MLリソース：ボツリヌス毒素

MLリソース：ボツリヌス毒素,Botulinum toxin
【日本語版コメント1191】
　眼瞼けいれん、片側顔面痙攣、痙性斜頸の治療薬として日本でも承認されているボツリヌス毒素(ボトックス注)が、2004.7月に腋臭(わきが)多汗症治療薬としてFDA承認された。　この適応では、初めての快挙となる。
　腋臭(わきが)に悩む人は少なくないが、原因は腋下にある汗腺であるアポクリン腺やエクリン腺から分泌される汗が常在菌で分解され悪臭を放つもの。　制汗剤で不十分な場合、この治療法として、これまで主に外科手術が行われ、いくつかの術式のうち「剪除法」が唯一健保適用。　皮膚外科だけでなく、美容外科でも多く扱われてきた。
　今回採りあげたボトックス注は、神経をこのボツリヌス菌で麻痺させることによって汗の分泌を抑える。　日本の美容外科の多くで既に腋臭治療に使用されている。　ほぼ半年間の効果がある。

【日本語版コメントTo 1057,1131】

　日本ではしわ取りにコラーゲン注入が話題となってるが、１回の治療に５～１０万円と高価（６～１２か月で徐々に吸収）。　米国では８年以上前からボツリヌス毒素が効果があるというので眼瞼痙攣治療剤ボトツクス[アラガン社]が使われるようになり問題化したため、FDAは1994年11月18日付けで通達を出したほど。　しかし依然として多くの医療機関では使われている。それがとうとうBotox CosmeticとしてFDA正式承認された[2002.4.15]。　しかし、アラガン社の研修を終了した認定医のみ処方可。日本でもP2。　因みにBotox 2001年度世界売上$309.5 million(+29.2%) Myobloc[Elan] $11 million
【市場】
●Allergan
 ($Million)    2003          2002      2001          2000        1999   1998
※Botox        563.9(+28.2)  439.7     309.5(+29.2%) 239.5(+39)  175.8  125.3 botulinum toxin A
*註) Botox売上中でBotox Cosmetic 40%を占める(2002&2003各)。　世界シェア90%
●Elan Corporation, plc[IR]
($ million)    2003          2002      2001          2000
Myobloc         14.9(-24)     19.6      11.6           -(Botulinum Toxin Type B)
  Myobloc (Neurobloc in Europe)はElanにより開発。
  米国発売2000.12、欧州発売2001.3。　日本でE2014[エーザイ]P2
【製品】
Botox承認の日米比較(U=米国,J=日本の承認日)。
[BOTOX]Blepharospasm(uncontrollable blinking)眼瞼けいれん U1989/J1996.10.9
Strabismus(crossed eyes)斜視 U1989
Cervical Dystonia 痙性斜頸 U00.12.21/J01.6.20
hemifacial spasm 片側顔面痙攣 /J00.1
[BOTOX COSMETIC]Glabellar Lineslines (brow furrow)眉間のしわ U2002.4.15/P2
●US Botox Uses Under Investigation[米アラガン社] ...BOTOX関連情報、FAQ、添付文書を含む
　アラガン社は米国での承認拡大に向けての作業をしている。　1998年にはFDAに偏頭痛の治験申請を行い、その全世界の用途特許を申請。　偏頭痛臨床治験はフェーズ２段階。　またjuvenile cerebral palsy[若年性頸部麻痺]はフェーズ３。Upper Limb Spasticity[上肢痙性] P3, Hyperhydrosis[多汗症] P3, Chronic Tension Headache[慢性緊張性頭痛] P2
【ボツリヌスＡ毒素】
　アラガン㈱は1998年10月，眼瞼痙攣に対してボツリヌス療法を行っている医療機関の情報を提供する「眼瞼・顔面けいれん／痙性斜頸電話情報センター」を開設。0120-611094。　眼瞼痙攣に対するボツリヌス療法は，1989年に米国で承認されて以来，現在59か国で行われている。わが国では1997年 4 月に健康保険が適用された。同療法は，ボツリヌス毒素を利用するため，登録された医師だけが薬剤を使用できる。わが国の登録医師数は約200人。　わが国における眼瞼痙攣の患者数は，同社の調査（1995年）によると，およそ3,500人。40～70歳代の中高年層に発症率が高く，女性に多い（男女比＝ 1：2 ）とされる。●ボツリヌストキシン療法研究会内「眼瞼・顔面けいれん／痙性斜頸電話情報センター」を開設～アラガン～　●眼瞼けいれんに特効薬健保適用で利用拡大！

「眼瞼（がんけん）けいれん」... 上下のまぶたの筋丙がけいれんし、突然強いまばたきが起きたり、目を開けていられなくなるという難病。比較的まれな病気だが、患者は中高年の女性が多く、外出や運転が不安でできないなど日常生活にも文障を来す。●くすりと病気に関する情報：痙性斜頚に対して使用するボツリヌスＡ毒素とは？［北里大学］

【美容目的使用】
ボツリヌス毒素は1989年12月にOculinumとして眼瞼痙攣、斜視の治療薬としてFDA承認。商品名Botoxとして発売。　同剤は"皺とり"に使用されるようになり、1994年11月18日に、Ｆｅｄｅｒａｌ　Ｒｅｇｉｓｔｅｒ（官報）で、FDAは"その承認外の使用を"強力な毒性をもつ生物製剤を美容目的に使用することの言語道断な例"として非難した。●Botulinum Toxin: A Poison That Can Heal [FDA Consumer magazine (December 1995)]
　1997年3月第５５回米国皮膚科学会でUCLA Lowe教授により発表。BOTOXは眉間のしわに有効かつ安全で、コラーゲンや皮膚再生レーザーと同様の効果がある。● Botox: Nonsurgical Wrinkle Remover of the Future?
　BOTOXはしわ取りに有効で、１回の処置で4-6か月有効。　副作用は軽い頭痛程度。●Patient Information - Botox [New Zealand Dermatological Society]
【疫学資料】
「2002年度患者調査」閲覧第97表総患者数，傷病基本分類別を調べると、該当するH024眼瞼下垂　4千人(1999年度3千人)、Ｈ49麻痺性斜視 6千人(5)、Ｈ50その他の斜視 12千人(19)
Ｇ24ジストニー3千人中でG243けい性斜頚 1千人、G245眼瞼けいれん 1千人。
Ｌ74エクリン汗腺の障害(主に汗疹2) /Ｌ75アポクリン汗腺の障害(主に臭汗症1)

【臨床ガイドライン】
　ボツリヌス毒素治療に関する公式見解は● 83. CLINICAL USE OF BOTULINUM TOXIN from NIH Consens Statement 1990 Nov 12-14;8(8):1-20.　●最近では1998年米国家庭医学会が筋肉痙攣治療についてBotulinum Toxin Injections: A Treatment for Muscle Spasms / AAFP Patient Information Handoutの中で"１０年以上数千人に安全に使用されてきた。"として評価。
【主要サイト】
●NZ DermNet - Cosmetic Dermatology ...ニュージーランド皮膚科学会美容皮膚科サイト。　BOTOX, Collagen等の解説もある。
ボツリヌストキシン療法研究会
 http://www.botox.com/
http://www.botoxcosmetic.net/
http://www.myobloc.com/
●価格情報
botox injections - Botox Costs: - PlasticSurgery.com[www.plasticsurgery.com]
 - $300 to $1000. According to the Amercian Society of Plastic Surgeons,
 the average cost per Botox injection in 2001 was $388
Cost of Botox Injections
 - 米国では$350 USD程度
AMNews: June 24, 2002. Botox wrinkle: worries over supply, pricing ...
[1191]Botulinum Toxin Type A(BOTOX[Allergan])

[1057][1109][1191]●製品 Botulinum Toxin Type A(BOTOX[Allergan])

　日本語版註）Botulinum Toxin Type A(BOTOX[Allergan])<ボツリヌス毒素Ａbr> 　【別名】Ａ型ボツリヌス毒素, Botulinum Neurotoxin A ,Clostridium botulinum A Toxin ,Oculinum, AGN-191622　【開発元】Allergan　 [DBR_ID]35029,35237-1220
　【化学名】ボツリヌス菌によって産生される製造工程でウシ（心臓、血液、乳、骨格筋、膵臓）及びヒツジ（血液）由来成分を使用している; a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose and yeast extract
　【承認】FDA承認=Dec-1989[斜視,眼瞼痙攣]、21-Dec-2000[痙性斜頸]、19-Jul-2004[腋臭多汗症]　【製剤】Vials - Clostridium botulinum type A neurotoxin complex 100単位, Albumin (Human) 0.5mg, 塩化ナトリウム 0.9mg【適応】1)成人（１２才以上）におけるジストニー（組織における緊張亢進または緊張低下状態）を伴う斜視[strabismus]および眼瞼痙攣[blepharospasm]の治療。　良性本態性眼瞼痙攣あるいは第７神経障害を含む。　2)[追加; 21-Dec-2000]痙性斜頸[cervical dystonia]　3)[追加2004.7.19]腋臭多汗症[Axillary Hyperhidrosis]　【用法用量】患部に筋肉注射する。初回量として、眼瞼痙攣で1.25～2.5単位、痙性斜頸には最小単位(最大時100単位)を緊張筋に、腋臭・多汗症には、推奨量50単位。　【作用】末梢の神経筋接合部における神経終末内でのアセチルコリン放出抑制により、神経筋伝達を阻害し、筋弛緩作用を示しますが、伝達阻害された神経は、側副枝や側芽を作り、筋繊維上に新たな運動神経終板を形成します。また、毒素の作用をうけた運動神経終板の機能も回復します。よって本剤の効果は徐々に消失し、約3～4ヵ月で元の状態に戻るため、その作用は可逆的。　汗を分泌する汗腺はアポクリン腺とエクリン腺の２種類があり、脇の神経をこのボツリヌス菌で麻痺させることによって汗の分泌を抑える。　【特徴】　【製品情報】www.botox.com | www.botoxcosmetic.net　【添付文書】Botox |Botox Cosmetic　【EU】73か国で承認。　【日本】日本ではボトックス注［アラガン］が[適応]眼瞼けいれん、承認96.10.09薬価収載97.04.01; 00年1月に「片側顔面痙攣」が承認; 01年6月20日「痙性斜頸」追加承認　【製剤～日本】１瓶中Ａ型ボツリヌス毒素（botulinum toxin type A）100単位　【適応～日本】眼瞼痙攣、片側顔面痙攣[2000.1]、痙性斜頸[2001.6.20]　【用法用量～日本】1)眼瞼痙攣：通常、成人にはA型ボツリヌス毒素として初回1.25～2.5単位／部位を、1眼当たり眼輪筋6部位の筋肉内に注射する。　2)片側顔面痙攣：通常、成人にはA型ボツリヌス毒素として初回10mgを痙攣筋に筋肉内注射する　3)痙性斜頸：通常、成人にはA型ボツリヌス毒素として初回30～60単位を緊張筋に筋肉内注射する。　【製品情報～日本】ボトックス注100　【添付文書～日本】ボトックス注100添付文書　【その他】
●MeSH Data

National Library of Medicine - Medical Subject Headings
2001 MeSH
MeSH Descriptor Data

MeSH Heading Botulinum Toxins
Tree Number D24.185.926.123.179
Tree Number D24.185.926.640.075
Annotation / antag permitted but consider also BOTULINUM ANTITOXIN
Scope Note Toxins produced by Clostridium botulinum. There are at least seven different substances, most being proteins. They have neuro-, entero-, and hemotoxic properties, are immunogenic, and include the most potent poisons known. The most commonly used apparently blocks release of acetylcholine at cholinergic synapses.
Entry Term Botulin
Entry Term Clostridium botulinum Toxins
Entry Term Botulinum Toxin
See Also Botulism
Allowable Qualifiers AD AE AG AI AN BI BL CF CH CL CS CT EC GE HI IM IP ME PD PK PO RE SD ST TO TU UR
Pharm. Action Anti-Dyskinesia Agents
Registry Number 0
Previous Indexing Clostridium Botulinum (1966-1968)
Previous Indexing Toxins (1966-1968)
Online Note use BOTULINUM TOXINS to search BOTULINUM TOXIN 1969-77 (as Prov 1969-71)
History Note 78; was BOTULINUM TOXIN 1969-77 (Prov 1969-71)
Unique ID D001905
--------------------------------------------------------------------------------


MeSH Heading Botulinum Toxin Type A
Tree Number D24.185.926.123.179.050
Tree Number D24.185.926.640.075.050
Annotation / antag permitted but consider also ANTITOXINS
Scope Note A neurotoxin produced by Clostridium botulinum. When consumed in contaminated food it can cause paralysis and death. In its purified form, it has been used in the treatment of blepharospasm and strabismus.
Entry Term Botox
Entry Term Botulinum A Toxin
Entry Term Botulinum Neurotoxin A
Entry Term Clostridium botulinum A Toxin
Entry Term Oculinum
Allowable Qualifiers AD AE AG AI AN BI BL CF CH CL CS CT EC GE HI IM IP ME PD PK PO RE SD ST TO TU UR
Pharm. Action Neuromuscular Agents
Registry Number 0
Previous Indexing Botulinum Toxins (1982-1996)
History Note 97
Unique ID D019274
【日本語版コメント1191】
　眼瞼けいれん、片側顔面痙攣、痙性斜頸の治療薬として日本でも承認されているボツリヌス毒素(ボトックス注)が、2004.7月に腋臭(わきが)多汗症治療薬としてFDA承認された。　この適応では、初めての快挙となる。
　腋臭(わきが)に悩む人は少なくないが、原因は腋下にある汗腺であるアポクリン腺やエクリン腺から分泌される汗が常在菌で分解され悪臭を放つもの。　制汗剤で不十分な場合、この治療法として、これまで主に外科手術が行われ、いくつかの術式のうち「剪除法」が唯一健保適用。　皮膚外科だけでなく、美容外科でも多く扱われてきた。
　今回採りあげたボトックス注は、神経をこのボツリヌス菌で麻痺させることによって汗の分泌を抑える。　日本の美容外科の多くで既に腋臭治療に使用されている。　ほぼ半年間の効果がある。
　→詳細は参考資料●MLリソース：ボツリヌス毒素に纏めた。
＜日本語版コメント用要約＞
・A型ボツリヌス毒素が重度の腋臭(わきが)発汗 (原発性腋臭(わきが)多汗症) の治療薬としてFDAに承認された。
・一腋臭(わきが)あたり50単位を1～2 cmの間隔で10～15箇所に皮内注射する。
・1回の治療効果は6～7ヶ月以上持続する。
・効果が消失すればいつでも再投与できるが、繰り返し投与した場合の長期作用は明らかではない。
●承認データ：FDA

●2004.5.1 以降　Drugs@FDA

Drug Name(s)        =BOTOX COSMETIC  (BOTULINUM TOXIN TYPE A)
FDA Application No. =BLA # 103000
Active Ingredient(s)=BOTULINUM TOXIN TYPE A 
Company             =ALLERGAN
Dosage Form/Route   =VIAL; SINGLE-USE
Strength            =100U/VIAL
Label Information | FDA Talk papers
Approval History
 - Approval Date=	:Label 07/19/2004[添付文書]|Letter 07/19/2004[承認書]|Review

Action
date Supplement
Number Approval
Type Letters,
Reviews,
Labels,
Patient Package Insert 備考
07/19/2004 5050 Supplement Label
Letter 
12/21/2000 1004 Supplement Letter
Review 
04/12/2000 5000 Supplement Letter
Label
Review 
12/09/1991 0000 Approval 　 
BOTOX(R) (Botulinum Toxin Type A)ボツリヌス毒素Ａのオーファン指定
情報ソース●http://www.fda.gov/orphan/designat/recent.htm
Generic Name: Botulinum toxin type A
Trade Name: Botox
Orphan Indication: Treatment of blepharospasm associated with dystonia in adults (patients 12 years of age and above).成人（１２才以上）のジストニー（組織における緊張亢進または緊張低下状態）を伴う眼瞼痙攣の治療
Sponsor: Allergan, Inc.
Address: Irvine, CA
Contact: Mr. Peter Kresel
Phone: (714) 752-4500
Fax:
Designation Date: 03/22/1984
Marketing Approval Date: 12/29/1989
-------------------------
Trade Name: Botox
Orphan Indication: Treatment of strabismus associated with dystonia in adults (patients 12 years of age and above).
成人（１２才以上）のジストニー（組織における緊張亢進または緊張低下状態）を伴う斜視の治療
Sponsor: Allergan, Inc.
Address: Irvine, CA
Contact: Mr. Peter Kresel
Phone: (714) 752-4500
Fax:
Designation Date: 03/22/1984
Marketing Approval Date: 12/29/1989

-------------------------
情報ソース●http://www.fda.gov/orphan/designat/list.htm
Generic Name: Botulinum toxin type A
Trade Name: 
Orphan Indication: Treatment of cervical dystonia.
★頸部 [dystonia]失調〔症〕，ジストニー（組織における緊張亢進または緊張低下状態）
Sponsor: Allergan, Inc.
Address: ,
Contact: Dr. Juliet Singh
Phone: (714) 246-4380
Fax:
Designation Date: 08/20/1986
-------------------------
Generic Name: Botulinum toxin type A
Trade Name: Dysport
Orphan Indication: Treatment of essential blepharospasm.★本態性眼瞼痙攣
Sponsor: Porton International, Inc.
Address: Washington, DC
Contact: Dr. Paul Buday
Phone: (202) 223-3737
Fax: (202) 223-4131
Designation Date: 03/23/1989
-------------------------
Generic Name: Botulinum toxin type A
Trade Name: Botox
Orphan Indication: Treatment of dynamic muscle contracture in pediatric cerebral palsy patients.★脳性小児麻痺におけるdynamic筋痙縮の治療
Sponsor: Allergan, Inc.
Address: Irvine, CA
Contact: Mr. Peter Kresel
Phone: (714) 752-4500
Fax:
Designation Date: 12/06/1991
-------------------------
Generic Name: Botulinum toxin type A
Trade Name:
Orphan Indication: Treatment of synkinetic closure of the eyelid associated with VII cranial nerve aberrant regeneration.★第７脳神経異所性再生に伴う眼瞼の共同閉鎖の治療
Sponsor: Associated Synapse Biologics
Address: Boston, MA
Contact: Ms. Arvilla Trag
Phone: (617) 350-7800
Fax: (617) 234-6505
Designation Date: 09/15/1992
-------------------------
Generic Name: Botulinum toxin type A
Trade Name: Dysport
Orphan Indication: Treatment of spasmodic torticollis (cervical dystonia).★痙性斜頸(頸部失調症)の治療
Sponsor: Ipsen Limited
Address: U.K. SL6 4UH,
Contact: Dr. Paul Buday
Phone: (540) 891-4055
Designation Date: 08/12/1998
-------------------------
Generic Name: Botulinum toxin type B
Trade Name: NeuroBloc
Orphan Indication: Treatment of cervical dystonia.★頸部失調症の治療
Sponsor: Elan Pharmaceuticals, Inc.
Address: South San Francisco, CA
Contact: Mr. Charles Democko
Phone: (650) 877-7409
Fax: (650) 877-7699
Designation Date: 01/16/1992
-------------------------
Generic Name: Botulinum toxin type F
Trade Name:
Orphan Indication: Treatment of essential blepharospasm.★本態性眼瞼痙攣
Sponsor: Porton International, Inc.
Address: Washington, DC
Contact: Dr. Paul Buday
Phone: (202) 223-3737
Fax: (202) 223-4131
Designation Date: 12/05/1991
-------------------------
Generic Name: Botulinum toxin type F
Trade Name:
Orphan Indication: Treatment of spasmodic torticollis (cervical dystonia).★痙性斜頸(頸部失調症)の治療
Sponsor: Porton International, Inc.
Address: Washington, DC
Contact: Dr. Paul Buday
Phone: (202) 223-3737
Fax: (202) 223-4131
Designation Date: 10/24/1991
-------------------------
Generic Name: Botulism immune globulin
Trade Name:
Orphan Indication: Treatment of infant botulism.★幼児ボツリヌス中毒の治療
Sponsor: California Department of Health Services
Address: Berkeley, CA
Contact: Dr. Stephen Arnon
Phone: (510) 540-2646
Fax: (510) 540-3205
Designation Date: 01/31/1989
Disease/Condition: Achalasia
情報ソース●http://www.fda.gov/orphan/grants/patients.htm Description: This is a randomized, double-blind dose-response trial of botulinum toxin Type A (Botox) injection in 56 patients with achalasia. The efficacy of two doses will be compared (80 units versus 160 units).
Contact Person: Laura Steinam
Telephone: (409) 772-8209
E-mail: lsteinma@utmb.edu
（ａｋ‐ａ‐ｌａ′‐ｚｅ‐ａ）［Ｇ．　ａ‐欠性辞＋ｃｈａｌａｓｉｓ，　ａ　ｓｌａｃｋｅｎｉｎｇ］．
アカラシア，弛緩不能症，無弛緩〔症〕，噴門痙攣，噴門無弛緩〔症〕（弛緩しないことで，特に幽門や噴門などの内臓開口部または括約筋についていう）．
ｅｓｏｐｈａｇｅａｌ　ａｃｈａｌａｓｉａ

Orphan Products: New Hope for People with Rare Disorders
情報ソース●http://www.fda.gov/fdac/special/newdrug/orphan.html by John Henkel
Alice Parker remembers well the time not long ago when her eyes closed and didn't reopen.

It was like her body had pulled shades over her sight and wouldn't let them go. Her eyes still worked fine, but, blocked by locked-shut eyelids, they couldn't perform. At age 49, afflicted with the rare muscle disorder blepharospasm, she became, in essence, blind.

"I was unable to function normally," says Parker (not her real name). "I was bumping into things." Her only relief came from wearing uncomfortable glasses with special devices that pry the eyelids open. Her bout with blepharospasm, which began in 1985 as overactive blinking, eventually became so debilitating she had to quit her job.

But today, thanks in part to a law passed 12 years ago, Parker has regained her sight and is working again. She's not cured, but an injectable biological product made possible by the Orphan Drug Act of 1983 allows her to lead a life close to normal.

Blepharospasm is an "orphan" disease--a rare disorder affecting a small population. According to the Benign Essential Blepharospasm Research Foundation, about 25,000 people have the disease in this country. Traditional treatments such as surgery haven't always worked and have left patients disfigured. Many sufferers once resigned themselves to a life of functional blindness.

But now, the biologic Botox> (botulinum toxin type A), aided in development by the Food and Drug Administration's Orphan Products Program, has rescued many patients with blepharospasm and other muscle disorders. Approved in 1989, is derived from the same deadly bacterium that causes botulism. Yet, injected in the proper dosage, it relaxes certain muscles seized by spasms.

Mitchell Brin, M.D., a New York neurologist who conducted pre-market clinical trials of botulinum toxin, says, "Before the toxin, less than 10 to 20 percent of [blepharospasm] patients could be helped. Now we can help more than 90 percent."

Adopting 'Orphans'

The Orphan Drug Act defines orphan products as ones used to treat diseases or conditions affecting fewer than 200,000 persons in the United States. Such small patient populations reduce profit potential for sponsors, so the act grants special privileges and marketing incentives. In the case of
Blepharospasm is one of more than 5,000 known rare disorders that together affect as many as 20 million Americans, according to estimates from rare-disease groups. For years, these conditions condemned patients to a life of pain and suffering. People with diseases such as hemophilia, multiple sclerosis, cystic fibrosis, rare cancers, and scores of other disorders could see little relief in sight. Companies were reluctant to invest the time and money necessary to develop treatments because the market was so small. Other outlets, such as research hospitals and universities, often lacked the capital and business expertise to develop treatments for limited pati

●Allergan

●Product Information ★BOTOX and BOTOX COSMETIC (botulinum toxin type A)
The most widely used botulinum toxin product in the world and the foundation for Allergan's global leadership in neurotoxin therapy. As the primary treatment for many focal movement disorders since the mid-1980's, indications for BOTOX have expanded as scientists and physicians recognize its broad applicability.
・Facial Aesthetics - (glabellar lines / brow furrow) - 13か国承認[日本～開発段階－Early/Late : glabellar lines]
・Cervical Dystonia[痙性斜頸] - (painful neck spasm) - 50か国承認[日本承認2001.6.20]
・Juvenile Cerebral Palsy[小児脳性麻痺] - (muscles of one or more limbs are permanently contracted and stiff making normal movement difficult in children) - 43か国承認
・Adult Spasticity[成人痙性] - (increased rigidity in a group of muscles, causing stiffness and restriction of movement) - 25か国承認[日本～開発段階－Early]
・Hyperhidrosis[発汗過多症，多汗症] - (excessive sweating) - 10か国承認
・Blepharospasm[眼瞼痙攣] - (abnormal muscle spasms / increased blinking) - 71か国承認[日本承認96.10.09]
・Strabismus[斜視] - (lazy eye, cross-eye or squint, strabismus can result in serious vision problems) -44か国承認
・片側顔面痙攣[日本承認2000.1]

●Presse Release
Jul 20, 2004★FDA Approves BOTOX -- Botulinum Toxin Type A -- for Treatment of Severe Underarm Sweating; New Approval Marks Fourth Therapeutic Indication for Allergan's BOTOX Over Last 15 Years
Jun 15, 2004★Allergan, Inc. Wins $1.5 Million BOTOX ® Trademark Infringement And Unfair Competition Case Against Mira Life Group, Inc.
Apr 30, 2003★BOTOX Cosmetic U.S. FDA Approval -- One Year Later
Mar 22, 2003★New Study Finds Men Need More Botox® Cosmetic
Feb 25, 2003★Allergan's BOTOX® Product Receives Approval In France For The Treatment Of Glabellar Lines (Brow Furrow)
Feb 4, 2003★Allergan To Vigorously Defend Frivolous Lawsuit Against BOTOX

●アラガン株式会社

●プレスルーム ●医療関係者のページボツリヌストキシン療法研究会：眼瞼・顔面けいれん／痙性斜頸のページ -http://www.btx-a.net/

●www.botox.com

http://www.botox.com/ ●Consumer Connection Resources Product Development Product updates Links Reimbursement Services Reimbursement FAQ E-Mail Insurance Tutorials BOTOX FAQ Approved Uses BOTOX - Blepharospasm BOTOX - Strabismus BOTOX - Cervical Dystonia BOTOX COSMETIC- Glabellar Lines Prescribing Information BOTOX BOTOX Cosmetic ●Health Professionals Resources Library Product Development Education and Trainings Links Reimbursement Services Reimbursement FAQ E-Mail Toolbox Updates Botox FAQ Product Information History and Development Mechanism and Action Toxin Structure Intracellular Targets Approved Uses BOTOX - Blepharospasm BOTOX - Strabismus BOTOX - Cervical Dystonia BOTOX COSMETIC- Glabellar Lines Prescribing Information Botox Botox Cosmetic ●Botox Fact sheet

●ボトックス注100

●ボトックス注100 作成又は改訂年月 **2001年7月改訂　新様式第4版/*2001年2月改訂　新様式第3版日本標準商品分類番号 871229 効能又は効果追加承認年月（最新）2001年6月国際誕生年月 1989年12月薬効分類名 A型ボツリヌス毒素製剤ボトックス注100　BOTOX-INJ.100 薬価基準収載年月 1997年4月販売開始年月 1997年4月組成成分・含有量１瓶中　A型ボツリヌス毒素100単位（1単位はマウス腹腔内投与LD50値）一般的名称 A型ボツリヌス毒素効能又は効果 1.眼瞼痙攣 2.片側顔面痙攣 3.痙性斜頸一般名 A型ボツリヌス毒素（botulinum toxin type A）輸入・発売元アラガン株式会社

●「ボトックス注１００」に痙性斜頸の効能取得　アラガン
薬事日報01/07/11
　アラガンは6月26日、Ａ型ボツリヌス毒素製剤「ボトックス注１００」の「痙性斜頸」に対する効能・効果の追加承認を6月20日付で取得したと発表した。

　痙性斜頸は、筋肉の不随意収縮により、頭部および頸部に異常姿位を来す運動障害であり、日本の患者数は全国で数千人とされている。日本ジストニア協会の調査では、20代から40代で発症率が高く、80％以上が50歳までに発症している。明確な病因は未だに不明だが、精神的ストレスや疲労で悪化したり、職業との関連性が疑われる症例も少なくないとされている。

　同剤を原因となっている筋に投与することにより、末梢神経終末から筋肉への神経伝達物質であるアセチルコリンの放出を抑え、異常な頭位や頸部疼痛を改善することができる。痙性斜頸は、これまでに症状を十分に改善し得る治療法はなく、同剤は治療の第一選択肢になり得るとしている。

　「ボトックス注１００」は、世界46カ国で痙性斜頸の承認を取得しており、米国でも2000年12月にＦＤＡから承認を得ている。同剤は「眼瞼痙攣」や「片側顔面痙攣」などの適応を持ち、これらに対して世界68カ国で承認され、2000年度の売り上げは2億3950万ドルに達している。

　日本では、96年10月に「眼瞼痙攣」、00年1月に「片側顔面痙攣」が承認されている。

■眼瞼けいれん・片側顔面けいれん　患者さんのホームページ

監修：榊原白鳳病院　目崎高広
※「ボツリヌストキシン療法研究会」は、国内における片側顔面けいれんに対するＡ型ボツリヌス毒素製剤の臨床試験に携わった医師により構成されています。
=======================================================
■眼瞼けいれん・片側顔面けいれん　患者さんのホームページ
代表：三井記念病院院長萬年徹
ボツリヌストキシン療法研究会は、国内において片側顔面けいれんに対するボツリヌス毒素製剤（AGN191622）の臨床試験に携わった医師により構成されています。
当臨床試験は、顔面神経が脳内で血管に圧迫されることによって生じる片側顔面けいれんの患者さんを対象として実施し、良い成績を得ております。

ボツリヌストキシン療法は、毒素を主成分とするお薬を目の周りや顔に注射する治療法ですので、病気や各種治療方法のみならずボツリヌストキシンについて熟知した医師によって治療が行われなくてはなりません。本研究会では、臨床試験からの長年にわたる豊富な治療経験を持つ医師が講師となり、ボツリヌストキシン療法を行う先生方を対象とした講習を実施しています。国内でボツリヌストキシン療法により、眼瞼けいれんや片側顔面けいれんの治療を行っている先生方は、皆さんこの講習を受講されております。
Research Society for Botulinum Toxin Therapy

●他のニュース
Canada Approves Botox (Botulinum Toxin Type A) For Axillary Hyperhidrosis
Allergan社は、「Botox（Ｒ）」（Ａ型ボツリヌス毒素）Purified Neurotoxin Complexが、
腋窩多汗症（過剰発汗）の治療のため、カナダ保健省のTherapeutic Products Programme
により承認を受けたと発表した。これは、眉間のしわの治療のため、４月にカナダで承認
されたAllergan社の「Botox Cosmetic（ＴＭ）」のすぐ後に続くものである
 FROM MedicalWave薬剤ニュース
[1191]■腋臭（わきが）
●わきが治療


治療法 内容 問題点
理学療法 エステなどで行われる電気分解法・電気凝固法などです。
毛根といっしょにアポクリン腺や皮脂腺を処理するのですが、これらを完全に破壊することが難しいので、数ヶ月で元にもどってしまうことが多いと言われています。 
薬物療法 制汗剤や殺菌剤が含まれた市販のデオドラント製品による方法です。いずれも汗や臭いを一時的に抑える効果があります。
一般に市販されている制汗剤には、スプレー、クリーム、ローションなどのタイプがあり、汗の分泌を抑えることよって臭いを防ぐというものです。しかし、これらはあくまでも一時的なもので、長くても６時間、ひどいわきがの人ならせいぜい1時間ほどしかもちません。
わきが臭を抑える薬も販売されています。これは皮脂を分解して、いやな臭いの元になる細菌を殺す作用のある抗生物質が使用されています。こちらも効果は６時間程度です。 制汗剤や消臭剤は使いすぎると、人によってはかぶれることもあります。また抗生物質の入っているものは抗生物質の副作用を引き起こす可能性がありますので、注意が必要です。また香り付きのものはわきが臭と混ざって、かえって悪臭になることもあるので、無香料タイプの方がいいでしょう。
一時しのぎに使うのは良いですが、本当に臭いをなくしたいという人はきちんとした治療を受けることをおすすめします。
ボトックス注射療法 わきの皮膚にボトックスという注射を打つ治療法です。
ボトックスは主にエクリン腺に付随する自律神経終末にはたらいて、汗を一定期間抑えるはたらきがあります。
汗の量を抑えることにより、汗の拡散を防ぐので、わきがの臭いも抑える作用があります。効果は６ヶ月ほどですが、数分で終わり手軽に出来ます。
美容外科などでよく行われています。 手軽で、それなりに効果もありますが、６ヶ月くらいしか効果が持続せず、1回10万円程度と高価なので、2～3回で手術ができる料金になってしまいます。手術は絶対にイヤだという人には向いているでしょう。
手術療法 　 わきがを完全に治すには、臭いを発するアポクリン腺を取り除いてしまう手術を受けるしかありません。 ●術後の合併症
手術後起こりうることとしては、わきに体液や血液が溜まったり(血腫)、わきの皮膚が一時的に硬くなったり、しびれたりすることがあります。しかし血腫は病院で取り除く処置をすることができ、わきの拘縮やしびれも時間と共に治っていくので、そんなに心配することはありません。またわきの皮膚に色素沈着が出ることがありますが、クリームなどで改善を図ることができます。
切除法 わきの下の有毛部の汗腺や皮脂腺、毛根を切り取り、縫い合わせます。傷が大きくなることと、ひきつれを起こしたり取り残しが発生してしまうこともあり、現在はほとんど行われていないようです。 
吸引法 わきの下の皮膚を数ミリ切開し、そこからエクリン腺やアポクリン腺を吸引しようとする方法です。皮膚の生着も早く、傷跡もほとんど残らないという長所はありますが、汗腺の一部が残ってしまうことがあり、再発する場合もあります。 
超音波法 わきの下の皮膚に穴を開け、直径２ミリ程度の超音波を発振する管を入れ、血管や神経を避けて、汗腺のみを破砕しながら吸引する方法です。術後の血腫形成や皮膚壊死などの心配が無く、皮膚の生着も早いですが、やけどや組織内水腫の合併症の報告もあり、また汗腺の一部が残ってしまうこともあります。 
削除法 わきの下の皮膚の一部を切開し、汗腺を削除するための特殊な器具を挿入し、アポクリン腺やエクリン腺、皮脂腺まで除去する方法です。しかし直接、汗腺の残存を確認できないので取り残しがでる可能性もあります。美容外科ではよく行われています。 
剪除法 わきの下の皮膚を3～4センチ切開し、皮下組織内のアポクリン汗腺を直接目で確認し、取り除く方法です。重度のわきがに対しては最も確実性の高い方法で、技術が十分であれば再発することはありません。またわきがの手術の中で唯一健康保険が適用される方法でもあります。ただ傷痕が残ったり、手術後の圧迫や経過がやや長いという欠点はあります。 [時間]６０分～９０分程度[費用]保険適用・・・３万～５万　保険適用なし・・・25万～30万
剪除法は、最も効果が高い方法と言われていますが、アポクリン腺を見分ける十分な経験や知識が必要で、担当する医師の技量でも差が出る手術です。技術が未熟であったり、短時間で終わらせようとすれば、汗腺の取り残しが生じ、不十分な結果になることもあります。

 from わきがWEBドットコム -http://www.wakigaweb.com/


●メモ
★手術
汗腺には、体温の調節のため汗を出すエクリン汗腺と、思春期に活動を始めるアポクリン
汗腺がある。わきの下から発する特有な汗のにおい「わきが」（腋臭症（えきしゅうしょ
う））は、アポクリン汗腺から生じる。 
　つまり手術はこの汗腺を除去しようとするもの。
　体温調節など、何らかの障害が問題となりそうだが、問題とされることはないようだ。



●関連サイト

腋臭は trans-methyl-2-hexenoic酸に低級脂肪酸やandrost-16-enesが修飾し，
足臭はイソ吉草酸，加齢臭は不飽和アルデヒド2-nonenalが原因物質であることが解明された．

●解説・トピックス
[Yomiuri医療相談室]わきがに悩む　手術で治るのか
[あなたの健康百科] わきがの手術療法～アンケート
[産経新聞：体の悩み聞いて効く]腋臭(わきが)



●専門サイト
わきがWEBドットコム -http://www.wakigaweb.com/
 - わきがでお悩みの方への情報提供サイト;　リンク集。
わきが多汗症研究所 -http://www.wakiga.jpn.org/
 - 昭和６１年１月設立。五味クリニックで診療。手術費用30万円

 - 

●美容外科系サイト
わきが・多汗症のすべて ...[城本クリニック] -http://www.wakiga-clinic.com/
 - 効果の高い剪除法を24万円で！
わきが治療、わきが手術[アサミ美容外科] -http://www.asami-wakiga.com/
 - [手術による治療]料金：290,000円（税込304,500円）[ボトックスによる治療]料金：59,000円（税込：61,950円）
わきが多汗症カウンセリングWeb[フォレストクリニック] -http://www.wakiga-web.net/
 - [ラジカル法]両側400,000円→320,000円 [ボトックス注入]両側120,000円→96,000円
わきが・多汗症治療専門サイト[湘南美容外科クリニック] -http://www.wakiga.jp/
 - [脱毛用レーザー]5回 150,000円→120,000円   [ボトックス]100,000円→50,000円
　 [マイクロ法トリプルサクション] 320,000円→288,000円 [吸引法]150,000円→142,500円
　　マイクロ法では1500人以上の実績。
お悩み解決！わきが・多汗症[共立美容外科] -http://www.wakigatakan.jp/
 -  [ローラークランプ法] \315,000 [ボトックス(多汗症)]\105,000～ 
Wakiga.com[聖心美容外科] -http://www.wakiga.com/
 - [マイクロリムーブ法] 25万円 [ボツリヌストキシン注入]初回20万円/2回目以降10万円
@beauty-わきが・多汗症について[ミクモクリニック] -http://www.wakiga.org/
 - [ミクモ式Ｗメソッド法手術]３５万円　[ボトックス注射]１５万円
[1131]●製品Botulinum Toxin Type A (Botox Cosmetic[Allergan])

BOTULINUM TOXIN (BOTOX COSMETIC) FOR FROWN LINES
Botulinum toxin type A (Botox Cosmetic － Allergan) has received formal approval from the FDA for treatment of glabellar ("frown") lines in adults not more than 65 years old, and is being heavily advertised. Even before this approval, cosmetic use of botulinum toxin to reduce wrinkles on the face and neck had become a popular alternative to cosmetic surgery (Medical Letter 1999; 41:63). Botulinum toxin type A (Botox) and type B (Myobloc) are approved for treatment of cervical dystonia (Medical Letter 2001; 43:63), and type A has been approved since 1989 for treatment of strabismus and blepharospasm.
眉間のしわの治療薬・ボツリヌス毒素（BOTOX COSMETIC）
　A型ボツリヌス毒素Botulinum toxin type A（Botox Cosmetic － Allergan；日本ではアラガン社P2）が65歳以下の成人における両眉の間（「眉間」）のしわの治療薬として正式にFDAに承認され、大々的に宣伝されている。　承認前でも、顔および首のしわを減少させるためのボツリヌス毒素の美容領域における使用は、美容外科に代わる方法として人気が出てきていた（Medical Letter 1999; 41:63、通巻1057号、日本語版15(15)63,1999-7-16）。　A型ボツリヌス毒素（Botox）およびB型毒素（Myobloc）は頸部ジストニーcervical dystonia（痙性斜頸とも呼ばれる）の治療薬として承認されており（Medical Letter 2001; 43:63、通巻1109号、日本語版17(15)63,2001-7-23）、A型毒素は斜視および眼瞼痙攣の治療薬として1989年に承認されている。
結論　－　顔の眉間に直接注射するA型ボツリヌス毒素は、眉間のしわを減少させるか、または取り除くことができる。　注射部位および周辺の筋力低下により一過性の下垂が起こる可能性がある。　重症の頭痛が報告されている。　筋肉の脱神経を繰り返すと可逆性の萎縮を生じることがある。

　日本語版註）Botulinum Toxin Type A (Botox Cosmetic[Allergan])
　【別名】型ボツリヌス毒素, Botulinum Neurotoxin A ,Clostridium botulinum A Toxin ,Oculinum, AGN-191622 　【開発元】Allergan　[DBR_ID]35029,35237
【化学名】Each vial of BOTOXR COSMETIC contains 100 units (U) of Clostridium botulinum type A neurotoxin complex, 0.5 milligrams of albumin (human), and 0.9 milligrams of sodium chloride in a sterile, vacuum-dried form without a preservative.
【承認】FDA申請=、FDA承認=2002.4.15 ;【製剤】　【適応】BOTOXR COSMETIC is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients <65 years of age. 　【製品情報】http://www.botoxcosmetic.net/　【添付文書】http://www.botox.com/index.jsp?cc&prescribing-cosmetic　【日本】P2　【その他】For Intramuscular Injection Only
BOTOXR COSMETIC is to be reconstituted with 0.9% sterile, non-preserved saline (100 units in 2.5 mL saline) prior to intramuscular injection. The resulting formulation will be 4.0 U per 0.1 mL and a total treatment dose of 20 U in 0.5 mL. The duration of activity of BOTOX COSMETIC for glabellar lines is approximately 3-4 months.
【日本語版コメント】
承認データ：FDA

●CBER - Botulinum Toxin Type A, BOTOX COSMETIC, Allergan, Inc
http://www.fda.gov/cber/products/botuall041202.htm

Proper name: Botulinum Toxin Type A
Tradename: BOTOX COSMETIC
Manufacturer: Allergan, Inc, Irvine, CA, License #1145
Indication for Use: Temporary improvement in the appearance of moderate to sever
e glabellar lines associated with corrugator and/or procerus muscle activity in
adult patients < 65 years of age
Approval Date: 4/12/2002
Type of submission: Biologics license supplement
Approval Letter (Text), (PDF)
Label - (PDF)
Talkpaper:FDA APPROVES BOTOX TO TREAT FROWN LINES
Last Updated: 4/25/2002
■Allergan

●May 16, 2002 - ALLERGAN'S STATEMENT REGARDING TREATMENT WITH BOTOXR COSMETIC

(Irvine, CA, May 16, 2002) - Allergan, Inc. (NYSE: AGN) recently announced the approval of BOTOXR Cosmetic (botulinum toxin type A) for temporary improvement in the appearance of moderate to severe glabellar lines (brow furrow) in adult men and women 65 or younger by the U.S. Food and Drug Administration (FDA).
Since its approval, there has been a tremendous amount of press regarding the use of BOTOXR Cosmetic, which may have led to confusion regarding Allergan's marketing and promotion of BOTOXR Cosmetic. Allergan will responsibly and ethically market and promote BOTOXR Cosmetic. Allergan's position on the medical promotion of this brand includes the following:
1. BOTOXR Cosmetic should only be administered by or under the direction of a licensed and authorized healthcare professional who is trained and qualified to use BOTOXR Cosmetic.
2. BOTOXR Cosmetic should be administered in a medically appropriate environment as deemed suitable by the authorized healthcare professional.
3. Optimal results with BOTOXR Cosmetic are best assured when treatment is administered by well-trained and authorized professionals with an in-depth knowledge of the muscles that control facial expression, an understanding of the dynamics of aging, and the qualifications to determine the best aesthetic treatment option for each individual within a professional setting.
4. For these reasons, Allergan will responsibly market BOTOXR Cosmetic to aesthetic specialty physicians. These specialty physicians include dermatologists, plastic surgeons, facial plastic surgeons, oculoplastic surgeons, ophthalmologists and maxilofacial surgeons.
Allergan's long-term focus is to ensure that BOTOXR Cosmetic continues to deliver the aesthetic results our patients expect. Allergan will support the training of aesthetic specialty physicians to inject BOTOXR Cosmetic through a program entitled BOTOXR Cosmetic Physicians' Network. Only physicians can register for this training. Although some physicians may decide to employ supervised and authorized non-physician medical personnel to administer BOTOXR Cosmetic, Allergan encourages physicians to satisfy consumer desires by personally assessing and treating their facial aesthetic patients.
Side effects most often reported during clinical trials of BOTOXR Cosmetic included headache, respiratory infection, temporary eyelid droop, nausea and flu syndrome. Less frequently occurring adverse reactions included pain in the face, erythema (redness) at the injection site and muscle weakness. These events are thought to be associated with the injection and occurred within the first week. BOTOXR Cosmetic should not be used in the presence of infection at the proposed injection site(s).
Allergan's BOTOXR product is the only one of its type with over 10 years of successful clinical experience in therapeutic conditions. Full prescribing information for BOTOXR Cosmetic is available at www.botoxcosmetic.net
●April 15, 2002 - ALLERGAN’S BOTOXR COSMETIC RECEIVES APPROVAL BY THE FDA FOR THE TREATMENT OF GLABELLAR LINES (BROW FURROW)

- New Cosmetic Indication Underscores Product's Versatility -
(Irvine, CA, April 15, 2002) - Allergan, Inc. (NYSE: AGN) today announced that the U.S. Food and Drug Administration (FDA) has granted approval to BOTOXR COSMETIC (botulinum toxin type A) for the temporary improvement in the appearance of moderate to severe glabellar lines in adult men and women 65 or younger. The approval specifically applies to the vertical lines between the eyebrows. In conjunction with this approval, BOTOXR will be marketed for this use under the name BOTOXR COSMETIC with dosing specific to treat frown lines.
"The FDA's approval is an important corporate accomplishment. Our successful clinical work shows that BOTOXR COSMETIC is safe and effective for this aesthetic use," commented Lester J. Kaplan, Ph.D., Allergan's President of Research and Development and Global BOTOXR. "Along with the previous approvals in the U.S. for BOTOXR in the treatment of certain neurological disorders, this new indication firmly establishes the versatility of the product."
Neurological disorders for which BOTOXR therapy is currently approved in the U.S. include treatment of strabismus (crossed eyes), blepharospasm (uncontrollable blinking) and head position and neck pain associated with cervical dystonia (a movement disorder characterized by involuntary muscle contractions).
Most brow furrow lines are formed by excessive contraction of the two major muscles in the forehead, the corrugator and procerus muscles. BOTOXR COSMETIC works to relax these muscles by blocking nerve impulses that trigger wrinkle-causing muscle contractions, creating a smoothed and improved appearance between the brow. Administered in a few tiny injections of purified protein, this minimally invasive treatment is simple and quick and delivers dramatic results with minimal discomfort. Results can be seen as early as 24-48 hours and the effect lasts up to four months.
"BOTOXR COSMETIC treatments are one of the few procedures we do that result in high patient satisfaction within a short period of time. In fact, the American Society for Aesthetic Plastic Surgery (ASAPS) 2001 Statistics on Cosmetic Surgery listed BOTOXR COSMETIC injections as the fastest growing cosmetic treatment performed by surgeons in the United States. BOTOXR COSMETIC treatments have increased 46% since 2000 and were rated number one among the 8.5 million surgical and non-surgical cosmetic procedures performed in 2001," said Dr. Roberta D. Sengelmann, M.D., Assistant Professor, Dermatology and Otolaryngology at Washington University in St. Louis. "I have treated hundreds of patients with BOTOXR COSMETIC and the response from my patients has been overwhelmingly positive. Patients come to me saying they are often perceived by their friends, families, and colleagues as angry, stressed or worried due to the unwanted expressions from the lines between the brow. Within a few days after a BOTOXR COSMETIC treatment, patients look more refreshed and natural."
●ALLERGAN’S BOTOXR RECEIVES POSITIVE OPINION FOR APPROVAL IN FOURTEEN EUROPEAN COUNTRIES FOR FOCAL SPASTICITY IN ADULTS[2001.10.11]
(IRVINE, California, October 11, 2001)-- Allergan, Inc. (NYSE: AGN) today announced that BOTOXR Botulinum Toxin Type A has been granted a positive opinion by the European Commission for focal spasticity of the wrist and hand in adult post-stroke patients. This positive opinion represents the intent to approve BOTOXR for focal spasticity in post-stroke adults in 14 individual countries and is a key step in the approval process. Ireland served as the Reference Member State in the Mutual Recognition Process. The other countries involved are Austria, Belgium, Denmark, Finland, Germany, Greece, Iceland, Italy, Luxembourg, Norway, Portugal, Spain and Sweden.
●ALLERGAN’S BOTOXR RECEIVES JAPANESE GOVERNMENT APPROVAL FOR CERVICAL DYSTONIA[2001.6.25] IRVINE, California and TOKYO, Japan - June 25, 2001 - Allergan, Inc. (NYSE: AGN) today announced that BOTOXR (Botulinum Toxin Type A) Purified Neurotoxin Complex has been approved for use in cervical dystonia by the Ministry of Health and Labor Welfare, Japan.
Cervical dystonia, a disabling neurological movement disorder characterized by involuntary muscle contractions that force the head and neck into abnormal positions, is prevalent in thousands of patients in Japan. When injected into the affected muscles, BOTOXR decreases the severity of abnormal head position and neck pain associated with this condition by blocking the release of the neurotransmitter acetylcholine to the muscle resulting in a localized reduction in muscle activity. The most frequently reported adverse events noted in the clinical trials submitted to the Japan Ministry of Health were dysphagia and decrease of muscle tone. Caution should be exercised when administering BOTOXR to individuals who have a systemic impairment of neuromuscular synapses.
BOTOXR was first approved in Japan in 1996 for the treatment of blepharospasm (uncontrollable blinking) and subsequently approved for the treatment of hemifacial spasm in January 2000.
"We are pleased BOTOXR is now available in Japan for patients who have had limited options for the treatment of this disorder. BOTOXR has become the standard of care for treating cervical dystonia in many parts of the world and we are looking forward to that trend continuing in Japan," said Max Akedo, Managing Director Allergan KK.
BOTOXR has been approved for cervical dystonia by regulatory agencies in 45 other countries and endorsed for this indication by the American Academy of Neurology and the National Institutes of Health (NIH) since 1990.
"The approval of BOTOXR for cervical dystonia in Japan brings a proven treatment alternative to the many individuals in Japan who suffer from this disabling neurological disorder," said Lester J. Kaplan, President of Research and Development and Global BOTOXR. "Furthermore, this BOTOXR approval for cervical dystonia strengthens the Company’s emerging specialty pharmaceutical business in Japan, a very important strategic market for Allergan."
BOTOXR was approved for the treatment of abnormal head position and pain associated with cervical dystonia by the United States Food and Drug Administration in December 2000 and is approved in 46 other countries worldwide, including Japan. Caution should be exercised when administering BOTOXO to individuals with peripheral motor neuropathic diseases or neuromuscular junctional disorders.
BOTOXR global net product sales for the year ended 31 December 2000 were $239.5 million.
●www.botoxcosmetic.net
http://www.botoxcosmetic.net/
●Physicians
	Our Network
	About Botox Cosmetic
	Before & After
	Patient Materials
	Clinicals
	How-To
●Consumers
	About Botox Cosmetic
	Find a physician
	Results
	Testimonials
	Beauty Tips

●Full Prescribing Information
●FOR IMMEDIATE RELEASE:ALLERGAN’S BOTOXR COSMETIC RECEIVES APPROVAL BY THE FDA FOR THE TREATMENT OF GLABELLAR LINES(BROW FURROW)
New Cosmetic Indication Underscores Product’s Versatility
(Irvine, CA, April 15, 2002) --- Allergan, Inc. (NYSE: AGN) announced today that the U.S. Food and Drug Administration (FDA) has granted approval to BOTOXR COSMETIC (botulinum toxin type A) for the temporary improvement in the appearance of moderate to severe glabellar lines in adult men and women 65 years of age or younger. The approval specifically applies to the vertical lines between the eyebrows. In conjunction with this approval, BOTOXR will be marketed for this use under the name BOTOXR COSMETIC with dosing specific to treat frown lines.
"The FDA’s approval is an important corporate accomplishment. Our successful clinical work shows that BOTOXR COSMETIC is safe and effective for this aesthetic use," commented Lester J. Kaplan, PhD, Allergan’s President of Research and Development and Global BOTOXR. "Along with the previous approvals in the U.S. for BOTOXR in the treatment of certain neurological disorders, this new indication firmly establishes the versatility of the product."
Neurological disorders for which BOTOXR therapy is currently approved in the U.S. include treatment of strabismus (crossed eyes), blepharospasm (uncontrollable blinking), and head position and neck pain associated with cervical dystonia (a movement disorder characterized by involuntary muscle contractions).
Most brow furrow lines are formed by excessive contraction of the 2 major muscles in the forehead, the corrugator and procerus muscles. BOTOXR COSMETIC works to relax these muscles by blocking nerve impulses that trigger wrinkle-causing muscle contractions, creating a smoothed and improved appearance between the brows. Administered in a few tiny injections of purified protein, this minimally invasive treatment is simple and quick and delivers dramatic results with minimal discomfort. Results can be seen as early as 24 to 48 hours and the effect lasts up to 4 months.
"BOTOXR COSMETIC treatments are one of the few procedures we do that result in high patient satisfaction within a short period of time. In fact, the American Society for Aesthetic Plastic Surgery (ASAPS) 2001 Statistics on Cosmetic Surgery listed BOTOXR COSMETIC injections as the fastest growing cosmetic treatment performed by surgeons in the U.S. BOTOXR COSMETIC treatments have increased 46% since 2000 and were rated #1 among the 8.5 million surgical and non-surgical cosmetic procedures performed in 2001," said Dr. Roberta D. Sengelmann, MD, Assistant Professor, Dermatology and Otolaryngology at Washington University in St. Louis. "I have treated hundreds of patients with BOTOXR COSMETIC and the response from my patients has been overwhelmingly positive. Patients come to me saying they are often perceived by their friends, families, and colleagues as angry, stressed, or worried due to the unwanted expressions from the lines between the brows. Within a few days after a BOTOXR COSMETIC treatment, patients look more refreshed and natural."

●ALLERGAN’S BOTOXR COSMETIC RECEIVES APPROVAL BY THE FDA FOR THE TREATMENT OF GLABELLAR LINES (BROW FURROW)

- New Cosmetic Indication Underscores Product’s Versatility -
(Irvine, CA, April 15, 2002) --- Allergan, Inc. (NYSE: AGN) today announced that the U.S. Food and Drug Administration (FDA) has granted approval to BOTOXR COSMETIC (botulinum toxin type A) for the temporary improvement in the appearance of moderate to severe glabellar lines in adult men and women 65 or younger. The approval specifically applies to the vertical lines between the eyebrows. In conjunction with this approval, BOTOXR will be marketed for this use under the name BOTOXR COSMETIC with dosing specific to treat frown lines.
"The FDA’s approval is an important corporate accomplishment. Our successful clinical work shows that BOTOXR COSMETIC is safe and effective for this aesthetic use," commented Lester J. Kaplan, Ph.D., Allergan’s President of Research and Development and Global BOTOXR. “Along with the previous approvals in the U.S. for BOTOXR in the treatment of certain neurological disorders, this new indication firmly establishes the versatility of the product.”
Neurological disorders for which BOTOXR therapy is currently approved in the U.S. include treatment of strabismus (crossed eyes), blepharospasm (uncontrollable blinking) and head position and neck pain associated with cervical dystonia (a movement disorder characterized by involuntary muscle contractions).
Most brow furrow lines are formed by excessive contraction of the two major muscles in the forehead, the corrugator and procerus muscles. BOTOXR COSMETIC works to relax these muscles by blocking nerve impulses that trigger wrinkle-causing muscle contractions, creating a smoothed and improved appearance between the brow. Administered in a few tiny injections of purified protein, this minimally invasive treatment is simple and quick and delivers dramatic results with minimal discomfort. Results can be seen as early as 24-48 hours and the effect lasts up to four months.
"BOTOXR COSMETIC treatments are one of the few procedures we do that result in high patient satisfaction within a short period of time. In fact, the American Society for Aesthetic Plastic Surgery (ASAPS) 2001 Statistics on Cosmetic Surgery listed BOTOXR COSMETIC injections as the fastest growing cosmetic treatment performed by surgeons in the United States. BOTOXR COSMETIC treatments have increased 46% since 2000 and were rated number one among the 8.5 million surgical and non-surgical cosmetic procedures performed in 2001," said Dr. Roberta D. Sengelmann, M.D., Assistant Professor, Dermatology and Otolaryngology at Washington University in St. Louis. “I have treated hundreds of patients with BOTOXR COSMETIC and the response from my patients has been overwhelmingly positive. Patients come to me saying they are often perceived by their friends, families, and colleagues as angry, stressed or worried due to the unwanted expressions from the lines between the brow. Within a few days after a BOTOXR COSMETIC treatment, patients look more refreshed and natural.”
[略]
Allergan’s BOTOXR product is the only one of its type with over 10 years of successful clinical experience in therapeutic conditions. In 1989, BOTOXR therapy was approved in the U.S. for the treatment of strabismus and blepharospasm and, in December 2000, for the treatment of abnormal head position and neck pain associated with cervical dystonia. BOTOXR COSMETIC(R) was previously approved in Canada in April 2001 for the treatment of glabellar lines.
BOTOXR therapy is approved in 70 countries for a broad range of conditions, and is currently being investigated in the U.S. for the treatment of many different medical conditions including hyperhidrosis (excessive sweating), post-stroke spasticity, back spasm and headache.
[略]
[1109]●製品BOTULINUM TOXIN type B (Myobloc [Elan])

　日本語版註）BOTULINUM TOXIN type B (Myobloc vials [Elan Pharmaceuticals]) 　;【別名】(Neurobloc)[EU] 【開発元】Elan[IR] [DBR_ID]x
;【化学名】a sterile liquid formulation of a purified neurotoxin that acts at the neuromuscular junction to produce flaccid paralysis. The neurotoxin is produced by fermentation of the bacterium Clostridium botulinum type B (Bean strain) and exists in noncovalent association with hemagglutinin and nonhemagglutinin proteins as a neurotoxin complex.
FDA申請=、FDA承認=8-Dec-2000,米国発売=Dec 2000 ;EU発売=Mar.2001(Neurobloc)【適応】Treatment of cervical dystonia to reduce the severity of abnormal head position and neck pain　【製品情報】http://www.myobloc.com/ ; http://www.fda.gov/cber/products/botelan120800.htm　【添付文書】http://www.myobloc.com/cons/product_info/myobloc_pi.pdf ;http://www.elanpharmaceuticals.com/pdfs/uploaded/myoblocpi.pdf ; http://www.fda.gov/cber/label/botelan120800lb.pdf　【その他】

【日本語版コメント】
●「ボトックス注１００」に痙性斜頸の効能取得　アラガン
薬事日報01/07/11
　アラガンは6月26日、Ａ型ボツリヌス毒素製剤「ボトックス注１００」の「痙性斜頸」に対する効能・効果の追加承認を6月20日付で取得したと発表した。

　痙性斜頸は、筋肉の不随意収縮により、頭部および頸部に異常姿位を来す運動障害であり、日本の患者数は全国で数千人とされている。日本ジストニア協会の調査では、20代から40代で発症率が高く、80％以上が50歳までに発症している。明確な病因は未だに不明だが、精神的ストレスや疲労で悪化したり、職業との関連性が疑われる症例も少なくないとされている。

　同剤を原因となっている筋に投与することにより、末梢神経終末から筋肉への神経伝達物質であるアセチルコリンの放出を抑え、異常な頭位や頸部疼痛を改善することができる。痙性斜頸は、これまでに症状を十分に改善し得る治療法はなく、同剤は治療の第一選択肢になり得るとしている。

　「ボトックス注１００」は、世界46カ国で痙性斜頸の承認を取得しており、米国でも2000年12月にＦＤＡから承認を得ている。同剤は「眼瞼痙攣」や「片側顔面痙攣」などの適応を持ち、これらに対して世界68カ国で承認され、2000年度の売り上げは2億3950万ドルに達している。

　日本では、96年10月に「眼瞼痙攣」、00年1月に「片側顔面痙攣」が承認されている。
■MEDLINEplus: Dystonia

【主要サイト】
Dystonia Medical Research Foundation
承認データ：FDA
情報ソース●CBER - Botulinum Toxin Type B (Myobloc), Elan Pharmaceuticals
www.fda.gov/cber/products/botelan120800.htm

Product Approval Information - Licensing Action
--------------------------------------------------------------------------------
Proper name: Botulinum Toxin Type B
Tradename: MYOBLOC
Manufacturer: Elan Pharmaceuticals, South San Francisco, CA, License #1579
Indication for Use: Treatment of cervical dystonia to reduce the severity of abn
ormal head position and neck pain.
Approval Date: 12/08/2000
Type of submission: Biologics license application
--------------------------------------------------------------------------------
Approval Letter (Text), (PDF)
Labeling (PDF)
Statistical Review (PDF)
Supplemental Clinical Review (PDF)
Chemistry, Manufacturing, and Controls Section Review (PDF)
Clinical Review (PDF)
Last Updated: 7/23/2001


●EUDRA
Neurobloc INN:Botulinum Toxin Type B (Rev. 1)
●Product Approval Information:Botulinum Toxin Type B, MYOBLOC
December 8, 2000

Michael Scaife, Ph.D.
Vice President, Regulatory Affairs
Elan Pharmaceuticals
800 Gateway Boulevard
South San Francisco, CA 94080

Dear Dr. Scaife:
Your Biologics License Application for Botulinum Toxin Type B, "MYOBLOC", for the treatment of cervical dystonia, is approved this date. Elan Pharmaceuticals is hereby authorized to introduce or deliver into interstate commerce, botulinum toxin type B produced at your Neurobloc Production Facility, South San Francisco, CA location under Department of Health and Human Services U.S. License No. 1579.

MYOBLOC is indicated for the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia. In accordance with approved labeling, your product will bear the tradename MYOBLOC, and will be marketed in 3.5 mL single use vials containing 2500 U, 5000 U or 10,000 U per vial.

Under this authorization you are approved to manufacture MYOBLOC at the Neurobloc Production Facility (NPF) in South San Francisco, CA. Drug product will be shipped to a contract filling and packaging facility, [------------, --- ----------], for filling, labeling and packaging. Packaged MYOBLOC will be distributed by [--------------------------- ---------------------------.

The dating period for this product shall be 21 months from the date of manufacture when stored continuously at 2-8oC. The concentrated and diluted bulk products may each be stored for up to 12 months when stored continuously at 2-8oC. The date of manufacture shall be defined as the date of the last valid potency test on the final container product. This potency test should be initiated within 30 days of the filling date. Any extension of the dating period will require the submission of supporting data as a supplement to your biologics license application for review and approval. Alternatively, you may submit a stability protocol to be used in extension of dating as a supplement to your license application.

You are requested to submit to the Center for Biologics Evaluation and Research (CBER) samples of future formulated product together with the protocols showing the results of all applicable tests. No lots of product shall be distributed until notification of release is received from the Director, CBER.

We acknowledge your commitments dated November 7, 2000, November 17, 2000, November 21, 2000, and December 7, 2000, for the following postmarketing clinical and manufacturing studies and data:

You have agreed to initiate a postmarketing study to evaluate the safety and immunogenicity of MYOBLOC in patients with cervical dystonia. You have made the following commitments for timeframes of conducting the study and submission of related materials to CBER:

The study protocol will be finalized and submitted to CBER for review and comment by February 2001.
The study will be initiated by June 2001.
A total of 500 study subjects will be enrolled.
Enrollment of study subjects will be completed in approximately 3.5 years with the last subject to be entered by December 2004.
All study subjects will be followed until the 2-year clinical observation period for the last enrolled patient is completed in December 2006.
Closure and initiation of analysis of the database will occur in June 2007, with completion of database analysis by November 2007.
The Clinical Study final report will be completed and submitted to CBER by February 2008.
You have agreed to submit a complete testing data report from fermentation through the diluted bulk stage, for the next lot of product manufactured after the concentrated product lot designated D90001 and submission of the completed report by the end of December 2000.

You have agreed to perform stability studies on a lot of product in final container manufactured from a new lot of concentrated product (CP) near the end of its dating period. This lot of CP will be manufactured by April 2001 and will be held at 2-8oC for 12 months before compounding the diluted bulk for further manufacture by April 2002. The diluted bulk will be stored for a period of no less than 3 months but no more than 6 months at 2-8oC to simulate the upper limit of storage in routine manufacturing. Stability reports for the final container through the 21 month dating period will be submitted to CBER starting at the 3 month timepoint and then at 6 month intervals through July 2004.

You have agreed to monitor stability using one lot of MYOBLOC per year for each fill size (2500 U, 5000 U, and 10,000 U) in accordance with the current stability protocol.

This information will be placed in your biologics license application file for this product.

Changes in the manufacturing process, manufacturing facility, product testing, packaging or labeling for botulinum toxin type B (MYOBLOC) may require the submission of a supplement to your biologics license application for review and approval prior to implementation.

It is required that adverse experience reports be submitted in accordance with the adverse events reporting requirements for licensed biological products (21 CFR 600.80) and that distribution reports be submitted as described (21 CFR 600.81). All adverse experience reports should be prominently identified according to 21 CFR 600.80 and be submitted to the Center for Biologics Evaluation and Research, HFM-210, Food and Drug Administration, 1401 Rockville Pike, MD 20852-1448.

It is required that reports of errors and accidents in manufacture be submitted in accordance the error and accident reporting for licensed biological products (21 CFR 600.14). All error and accident reports should be promptly identified according to 21 CFR 600.14 and be submitted to the Director, Office of Compliance, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.

Please submit final printed labeling at the time of use and include implementation information on FDA Form 2567. Please provide a PDF-format electronic copy as well as original paper copies (ten for circulars and five for other labels). In addition, you may wish to submit draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2567 or Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Final printed advertising and promotional labeling should be submitted at the time of initial dissemination, accompanied by a FDA Form 2567 or Form 2253.

All promotional claims must be consistent with and not contrary to approved labeling. No comparative promotional claim or claim of superiority over other similar products should be made unless data to support such claims are submitted to and approved by the Center for Biologics Evaluation and Research.

Please acknowledge receipt of this letter to the Director, Division of Vaccines and Related Products Applications, HFM-475, Center for Biologics Evaluation and Research.
Sincerely yours,

    --- signature ---      --- signature ---
Karen Midthun, M.D.
Director, Office of Vaccines Research and Review
Center for Biologics Evaluation and Research Steven A. Masiello
Director
Office of Compliance and Biologics Quality
Center for Biologics Evaluation and Research
DEPARTMENT OF HEALTH AND HUMAN SERVICES,Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
--------------------------------------------------------------------------------
Last Updated: 1/15/2001
●

pharmalicensing.com: company news: FDA approves Elan's MYOBLOC
... FDA approves Elan's MYOBLOC, 12 Dec 2000 Elan Corporation, plc has announced that
the US FDA approved MYOBLOC (Botulinum Toxin Type B) Injectable Solution. ...

pharmalicensing.com: Elan Pharmaceutical Technologies: related ...
... 26 Jan 2001) Generex and Elan to form joint venture (5 Jan 2001) FDA approves Elan's
MYOBLOC (12 Dec 2000) FeRx and Elan to develop liver cancer treatment (30 ...

Elan Corporation
... Outlook for Remainder of 2000 and Calendar Year 2001 Dec-11-2000 FDA Approves Elan's
MYOBLOC(TM) Nov-10-2000 Elan Completes Acquisition of DURA Nov-6-2000 ...
www.prnewswire.com/gh/cnoc/comp/231593.html
●Myobloc[www.myobloc.com]
http://www.myobloc.com/cons/product_info/myobloc_pi.pdf

For Patient/Consumer
About Cervical dystonia
About Myobloc
Enroll in the solution program
WEB Resources
---
Dystonia Medical Research Foundation
(800) 377-DYST ? (312) 755-0198 ? www.dystonia-foundation.org
ST/Dystonia, Inc.
(715) 258-8756 ? www.spasmodictorticollis.org
WE MOVE
Worldwide Education and Awareness for Movement Disorders
(800) 437-MOV2 ? www.wemove.org

For Health Professionals
 ---要登録
●Elan Corporation, plc[IR]
($ million)    2003          2002      2001          2000
Myobloc         14.9(-24)     19.6      11.6           -(Botulinum Toxin Type B)
  Myobloc (Neurobloc in Europe)はElanにより開発。
  米国発売2000.12、欧州発売2001.3。
MYOBLOC (Botulinum Toxin Type B) Injectable Solution

●Elan Corporation
 --- 従業員4500人。 Ireland
http://www.elanpharmaceuticals.com/pdfs/uploaded/myoblocpi.pdf
NewsRoom
Elan reports 2001 financial results[2002.2.4]
Product Pipeline
Products
Annual reports
Amended Sections of form 20-f 2000 --- 22p-製品売上/Pipeline
US revenues for ZanaflexTM, SkelaxinTM, MaxipimeTM and AbelcetTM increased by 78%, 45%, 70% and 29%, to $162 million, $118 million, $86 million and $82 million, respectively, for 2001 compared to 2000. ZonegranTM and Myobloc revenues were $38 million and $11 million, respectively, for 2001.
●FDA approves Elan's Myobloc --- The First Type B Botulinum Toxin Therapy to be Approved
[2000.12.11]
DUBLIN, IRELAND, December 11, 2000 -- Elan Corporation, plc
(NYSE:  ELN) ('Elan') announced that the U.S. Food and Drug
Administration ('FDA') approved MYOBLOCT (Botulinum
Toxin Type B) Injectable Solution.

New MYOBLOC Ready-to-Use Solution is a liquid formulation
of botulinum toxin that does not require reconstitution and
is available in three convenient vial configurations of
2,500 Units, 5,000 Units and 10,000 units, providing
maximum flexibility for dosing.

Donal J. Geaney, Chairman and Chief Executive Officer of
Elan, commented, 'Our scientists have extensive experience
in the development of biological therapeutics, and we've
applied this expertise to the development of MYOBLOC,
resulting in the only botulinum toxin therapy available as
a ready-to-use solution.  We are excited to bring this new
product to physicians and their patients.'

Elan Corporation, plc is a leading worldwide specialty
pharmaceutical and drug delivery company headquartered in
Ireland, with its principal research, development,
manufacturing and marketing facilities located in Ireland,
the United States and Israel. Elan is focused on the
discovery, development and marketing of therapeutic
products and services in neurology, pain management and
oncology, and on the development and commercialization of
products using its extensive range of proprietary drug
delivery technologies. Elan shares trade on the New York,
London and Dublin Stock Exchanges.

The statements in this press release may include forward-
looking statements that involve risks and uncertainties
including the difficulty of predicting regulatory
approvals, as well as other risks and uncertainties
detailed from time to time in periodic reports, including
Elan's annual report of Form 20-F for the fiscal year ended
December 31, 1999, as amended by Elan's Form 20-F/A1, both
filed with the Securities and Exchange Commission.  Actual
results may differ from the forward-looking statements.
●Elan Exploring Potential Use of MYOBLOC(TM) (Botulinum Toxin Type B) in Spasticity, Pain and Dermatologic Applications[01.5.9]

biz.yahoo.com/prnews/010509/nyw088.html - MYOBLOC is the First New Botulinum Toxin Therapy in Over a Decade - PHILADELPHIA, May 9 /PRNewswire/ -- Elan Pharmaceuticals announced today that it is investigating the potential use of MYOBLOC(TM) (Botulinum Toxin Type B) Injectable Solution in a variety of spasticity, pain and dermatologic applications. The clinical benefits of botulinum toxin therapy in the treatment of various clinical disorders characterized by muscle hyperactivity, such as spasticity, was established more than 10 years ago by the National Institutes of Health. The potential market for the applications under investigation by Elan is considerable. ``The use of botulinum toxin has become an enormously popular form of therapy for a variety of applications, said Leslie Baumann, MD, University of Miami Cosmetic Center, Cedars Medical Center. ''MYOBLOC is an exciting new treatment option that doesn't need to be reconstituted nor kept frozen, an important consideration in administering botulinum toxin therapy.`` MYOBLOC for the Treatment of Cervical Dystonia MYOBLOC was recently approved for the treatment of cervical dystonia. It is the first new botulinum toxin therapy in a decade, and the only botulinum toxin formulated as a ready-to-use solution. Type B is an antigenically distinct serotype from botulinum toxin type A (Botox) and was FDA approved last December for the symptomatic treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with the disorder. MYOBLOC works by preventing the release of acetylcholine from the nerve ending to the overactive muscle. Involuntarily muscle contractions can cause pain, tightness and spasms. ``Clinical studies have demonstrated that MYOBLOC is a highly potent and long lasting botulinum toxin therapy and we are excited about evaluating type B's safety and efficacy in a variety of conditions,'' said Christopher O'Brien, Vice President, Medical Affairs, Elan. ``Additionally, because of the advanced manufacturing technique employed in producing the drug, the result is a toxin that is consistent, pure and stable.'' MYOBLOC is available in three convenient vial configurations of 2,500 units, 5,000 units and 10,000 units, all at the same concentration providing maximum flexibility for dosing. MYOBLOC is generally safe and well tolerated. The most frequently reported adverse events associated with MYOBLOC treatment were dry mouth, dysphagia (difficulty swallowing), dyspepsia (upset stomach), and injection site pain. These side effects are generally mild to moderate, temporary, clear up on their own, and more common with higher doses. If patients experience any side effects during treatment with MYOBLOC, they should contact their physician. Caution should be exercised when administering MYOBLOC to individuals with motor neuron diseases (e.g., amyotrophic lateral sclerosis) or neuromuscular junctional disorders (e.g., myasthenia gravis or Lambert-Eaton syndrome). Patients with neuromuscular disorders may be at increased risk of clinically significant systemic effects including severe dysphagia and respiratory compromise from typical doses of MYOBLOC. Elan Pharmaceuticals is a division of Elan Corporation, plc (NYSE: ELN - news). Elan is a leading worldwide fully integrated pharmaceutical company headquartered in Ireland, with its principal research, development, manufacturing and marketing facilities located in Ireland, the United States and Israel. Elan is focused on the discovery, development and marketing of therapeutic products and services in neurology, pain management, oncology, infectious disease and dermatology and on the development and commercialization of products using its extensive range of proprietary drug delivery technologies. Elan shares trade on the New York, London and Dublin Stock Exchanges.
SOURCE: Elan Pharmaceuticals

関連★Yahoo - Botulinum Toxin Type B Studies Demonstrate Long-Term ...[01.5.10]
... formulation' said Dr. James Callaway, VP Pharmaceutical Development, Elan Pharmaceuticals.
``MYOBLOC is produced using a manufacturing process that does not ...
biz.yahoo.com/prnews/010510/nyth023.html
●USP DrugGuide: BOTULINUM TOXIN TYPE A (Parenteral-Local)

: Prescrire Int 2001 Feb;10(51):12-4 Related Articles, Books, LinkOut Botulinum toxin type A and dynamic equinus in children with cerebral palsy: new indication. Better than repeat casts.
(1) Botox degrees , a product based on type A botulinum toxin, has received a new licensed indication in the local treatment of dynamic equinus in children with spasticity due to cerebral palsy. (2) Three placebo-controlled trials show that intramuscular injections of type A botulinum toxin reduce spastic equinus and substantially improve walking for at least 3 months. Two small trials, each involving 20 children, show no difference in effects between type A botulinum toxin and successive stretching casts. (3) In this setting the risk of adverse effects is smaller with type A botulinum toxin than with stretching casts. (4) Treatment with type A botulinum toxin is costly.
PMID: 11503850 [PubMed - indexed for MEDLINE]
解説

●くすりと病気に関する情報：痙性斜頚に対して使用するボツリヌスＡ毒素とは？

Ｑ：痙性斜頚に対して使用するボツリヌスＡ毒素とは？（整形外科医師）

Ａ：痙性斜頚は、頚部筋群の異常緊張により収縮が持続するため発生する頭頚部の姿勢異常や不随意的運動症である。原因は不明とされ、薬物療法、理学療法、精神療法などが試みられているが、根治的療法はまだ確立されていない。
　最近、薬物療法の１つとして、ボツリヌス菌（Clostridium botulinum）によって産生されるボツリヌスＡ型毒素による顔面、頚部の異常運動疾患（斜視、痙性斜頚、顔面痙攣など）への対症療法が注目されている。米国では、１９６０年代にボツリヌスＡ毒素の精製に成功し、１９８４年より結晶ボツリヌスＡ型毒素（Oculinum）を用いて治療が行われている。本邦では、千葉県血清研究所で製造されており、現在、眼科領域において斜視、眼瞼痙攣に対して製造承認申請中である。神経内科領域においては斜頚、ジストニーに対して治験実施中である。このため、通常の方法での入手はまだ不可能である。
　ボツリヌス毒素は、ボツリヌス菌により産生される外毒素で、強力な神経毒作用をもっている。ボツリヌス菌は、免疫学的に８種類（Ａ，Ｂ，Ｃ₁，Ｃ₂，Ｄ，Ｅ，Ｆ，Ｇ）に分類されており、そのうちのＡ型ボツリヌス毒素が最も強力である。本毒素は、神経筋接合部の運動神経終末に存在するボツリヌス毒素の受容体に作用し、アセチルコリンの神経終末からの遊離を阻害して強力な筋肉麻痺作用をきたすと考えられている。
　適用は、痙攣する筋肉内あるいは該当部位の皮下に数箇所直接注射するが、この際、先端を除いてテフロン絶縁された注射針を用い筋電計監視下で投与する方法もある。筋肉活動の低下は２４時間以内に発現し、以後効果は増強し１週間前後でほぼ一定となる。痙攣抑止効果は平均３ヵ月持続する。
　本毒素は組織親和性が強く、血管内への移行はなく全身への影響は少ないとされ、全身性の副作用の報告はほとんどないと言われている。しかし、作用が注射部位に限定されるため、患部が広範囲の場合には注射箇所、投与量が増大するので注意を要する。局所での副作用として表情の変化、顔面膨脹感、眼瞼下垂などが報告されている。痙攣抑止効果の持続は３ヵ月と言われているため、治療はほぼ３ヵ月毎に繰り返される。繰り返し使用による効果はほぼ一定とされているが、減弱するという報告もあり、長期追跡調査が必要であると思われる。
　根治的療法でなく３～４か月ごとに再注射が必要となる点が問題ではあるが、本治療の出現以来、顔面神経切断術や筋吊り上げ術などほとんど行われなくなってきている。本治療法の導入により単独使用、ブロック療法との併用など顔面の痙攣疾患治療に効果が期待される。
【参考文献】
[1]岩重博康：医学のあゆみ，149, 626, 1989.
[2]久世照五、伊藤裕輔：臨床麻酔，15, 501, 1991.
[3]福島考徳、高見政美：神経進歩，34, 283, 1990.

●眼瞼けいれんに特効薬健保適用で利用拡大！

上下のまぶたの筋丙がけいれんし、突然強いまばたきが起きたり、目を開けていられなくなる「眼瞼（がんけん）けいれん」という難病がある。比較的まれな病気だが、患者は中高年の女性が多く、外出や運転が不安でできないなど日常生活にも文障を来す。全国で三千人から四千人が悩んでいるとみられている。

●毒をもって毒を制す
眼瞼けいれんは、目の開閉をしている眼輪筋が何らかの原因で収縮するばかりになってしまう病気。原因は不明だ。人込みの中とか、不安の強いときに発作的に起こることからこれまでは心身症的な治療が試みられてきたが、効果は少なく、良い治療法がなかった。米国で二十年ほど前に、食中毒菌ボツリヌスの毒素製剤で治療する方法が開発された。
日本では帝京大学の丸尾敏夫教授らが早くから研究し、毒素製剤が五年前に希少疾病用医薬品に指定された。一九九六年には中央薬事審議会が輸入販売を承認、昨年から健康保険でこの治療法が広く利用できるようになった。
「毒をもって毒を制すのことわざ通りの治療法だが、数カ月ごとに注射するだけでけいれんから解放される画期的な治療法。研修を積んだ医師に受診すれば、決して危険なことはないので、よく相談して利用してほしい」と丸尾教授は言う。
一回の注射で三、四カ月は効果が持続する。再発したら二カ月以上間隔をあけて注射を繰り返す。しかし、この治療法は、重症筋無力症、筋委縮性側索硬化症など全身の神経と筋肉の接合部に異常がみる病気の人、妊婦や授乳婦、薬剤過敏症の人などには、使えないことになっている。

●全例を登録観察
特効薬だが、正しく使う必要があるので、厚生省はメーカーに薬の臨床使用例を全例登録、十年間経過観察をすることを求めている。専門医団体が実施する講習会、実技セミナーを受講し登録した医師が、眼瞼けいれん治療に限ってこの薬を使用するよう指導している。
講習会などで学んだ眼科医、神経内科医約二百人が既に認定登録されており、アラガン社（東京）では今年十月から一年間フリーダイヤルで全国の患者に最寄りの登録医師を紹介している。「服瞼けいれん電話情報センター」はフリーダイヤル（0120）611094（月曜－金曜午前九時から午後五時、正午から午後一時除く）。
（参考文献：平成１０年１２月８日　中部経済新聞・メディカルニュース）

私の感想
「眼瞼けいれん」の治療といえば、先ずは安定剤内服、それで良くならなければ、脳神経外科で血管減圧術を行うというのがこれまでの慣習でしたが、これに新しい選択肢が加わったようですね。何よりも手術前に試みる治療手段が増えたということは大進歩です。

●Yomiuri On-Line/ミニ時典

◆ボツリヌス毒素（98年8月18日）
土壌などに生息するボツリヌス菌が食物に混入して繁殖する際に出す毒素。７種類の型があり、体内に入ると末端の運動神経をまひさせ、視力障害や呼吸困難などの中毒症状を引き起こす。治療しないと死亡率は２０～４０％。東京都は１５日、イタリア産瓶詰オリーブ漬けから毒素を検出、警戒を促した。
この菌は、室温下の無酸素状態で繁殖。高温で十分加熱すれば毒素は無毒化するが、国内では年数件程度の発生が報告。１９８４年には、熊本産「からしレンコン」が原因で、１１人の死者が出ている。
毒素の性質を逆手に取り、運動神経の異常が関係する病気の患部に毒素を注射する療法も試みられ、意思と無関係にまぶたが閉じる「眼瞼（がんけん）けいれん」などに成果を上げている。（中）

●顔面痙攣について

・・・顔面痙攣について・・・
顔面痙攣は顔の片側だけがぴくぴくと動いてしまう病気です。最初目のまわりがぴくぴくする状態からはじまり、やがてつぶろうと思わないのに片目がぎゅーとつぶってしまう状態になり、進行するとほっペタや口が片側にひきつれた様になります。緊張すると悪化するのが普通で、そのためもあってご本人が神経質なためにおこると思われていることもあるようです。じっさいには、これも三叉神経痛と同じようなしくみでおこる病気であることがわかってきました。つまり脳幹よりでる顔を動かす神経である顔面神経に脳の血管があたって症状を起こします。この血管を神経からはがしてずらしてあげれば病気は治癒します。三叉神経痛とちがって薬による治療はあまり効果がありませんが精神安定剤を服用すると症状が多少よくなることがあります。ブロック療法も効果がありますが、薬剤の効果は一時的なことが多く、手術治療が根治療法です。
参考サイト：東京大学医学部脳神経外科藤巻高光のホームページ

目のまわりにある筋肉がピクピクとけいれんすることがありますが、眼瞼けいれんといいます。これの範囲がひろがり、一側の顔面筋の一部または全体におよぶものを顔面けいれんといいます。眼瞼けいれんは大体は眼の疲労、使いすぎ、睡眠不足、などによるものですが、眼の病気、例えば角結膜異物とか、さかさまつげのようなもののときにもおこるものです。さて顔面けいれんですが、ひどくなると顔面が変化するほどのこともあります。原因として最近顔面神経が脳幹を出る所で血管に接触圧迫されていることが注目されています。治療方法として軽い眼瞼けいれんでは眼を休ませること、トランキライザー等でよいのですが、顔面けいれんでは薬物治療は無効のことも多く手術を行うことがあります。顔面神経の一部の切断も行われましたが、最近では開頭して顔面神経にあたっている血管を剥離し圧迫をとることが行われます。
参考文献：「やさしい脳神経外科の話」平塚秀雄

顔面けいれんは目や口もとがひきつったり勝手に動く困った症状です。ひどい場合は一日中けいれんをしっぱなしということもあります。この病気の大半は、顔面神経に脳の血管が接触しているために起ることをＰ・ジャネッタ米国ピッツバーグ大学教授が突き止めました。現在は血管と神経を離すジャネッタ手術でほとんど治ります。
参考文献：「脳ドック」福島孝徳・田辺　功

●眼瞼けいれん電話情報センターを開設～アラガン～[99.7]

　アラガン（株）はこのほど，眼瞼痙攣に対してボツリヌス療法を行っている医療機関の情報を提供する「眼瞼けいれん電話情報センター」を開設した。フリーダイヤル：0120-611094（月～金曜日の 9：00～17：00。ただし，12：00～13：00と休日を除く）。　眼瞼痙攣に対するボツリヌス療法は，1989年に米国で承認されて以来，現在59か国で行われている。わが国では1997年 4 月に健康保険が適用された。同療法は，ボツリヌス毒素を利用するため，登録された医師だけが薬剤を使用できる。わが国の登録医師数は約200人。　わが国における眼瞼痙攣の患者数は，同社の調査（1995年）によると，およそ3,500人。40～70歳代の中高年層に発症率が高く，女性に多い（男女比＝ 1：2 ）とされている。

■３３．発酵と腐敗
　鏡餅に赤・青などカラフルな斑点ができたり、食べ物が腐ったりするのは、微
生物の働きによるものです。その微生物の作用には発酵と腐敗があり、その多くは嫌気的に（酸素のない状態で）、物質が変換されることです。発酵は、味噌・
しょうゆ、酒、酢から、納豆、チーズ、ヨーグルトのように人にとって有用なもので、腐敗は迷惑なものというようなイメージが強いと思います。発酵は炭水化
物（糖類で窒素を含まないもの）が分解されること、腐敗は窒素を含んだタンパク質などの有機化合物が分解されることです。腐敗分解によって生じる物質には
アミノ酸などから臭いアミン類や硫黄化合物を生じます。
　発酵は、上に挙げた例のように古い歴史を持つものがたくさんあります。日本
は温度湿度ともに微生物の繁殖に適した気候なので、その利用技術も進んでいます。さらに最近では化学調味料（味の素など）のグルタミン酸ソーダなどのアミ
ノ酸もアミノ酸発酵で得られます。同じく旨味成分で植物性のグアニル酸（しいたけなど）や動物性のイノシン酸（カツオ節など）は核酸の一種ですが、これら
も核酸発酵によって得られているのです。
　そのほかの微生物を利用した物質生産では、ペニシリンに代表される抗生物質
がもっとも有名です。そのほかにもメタンやエチレンといった炭化水素がエネルギー源となることで注目されています。さらに近年では、有用なタンパク質やペ
プチドを大腸菌で作らせる方法が確立されました。そのタンパク質やペプチドをコードする遺伝子を大腸菌に組換え、生産させるのです。そうすることで、わず
かしか得られなかったものが、大量に得られ利用されるようになったのです。
　腐敗に関連して、かびが産生する毒の問題もあります。天然に存在する毒の中
で最も毒性が高いのがかび毒なのです。肝臓毒で発ガン性のアフラトキシンや神経毒のボツリヌストキシンなどもあるので、十分に注意しなければなりません。
●Botulinum Toxin: A Poison That Can Heal [FDA Consumer magazine (December 1995)]

by Luba Vangelova
［略］
ボツリヌス菌にはＡ－Ｇの７種ある。
1910年－1919年の間に、ボツリヌス菌毒素中毒による死亡率は70%であった。 1980年代までに、9%まで下落して、1993年には2%以下。

ボツリヌス菌毒素中毒は早期処置では、馬血清で作られた抗毒素により対処可能。しかしアナフィラキシー、生命にかかわるアレルギー反応のような重大な副作用がある。
［略］
ボツリヌス毒素は1989年12月にOculinumとして眼瞼痙攣、斜視の治療薬としてFDA承認。商品名Botoxとして発売。　同剤は"皺とり"に使用されるようになり、1994年11月18日に、Ｆｅｄｅｒａｌ　Ｒｅｇｉｓｔｅｒ（官報）で、FDAは"その承認外の使用を"強力な毒性をもつ生物製剤を美容目的に使用することの言語道断な例"として非難した。

●Use as Medicine
Meanwhile, purified botulism toxin is the first bacterial toxin to be used as a medicine. FDA licensed botulinum toxin as Oculinum in December 1989 for treating two eye conditions--blepharospasm and strabismus--characterized by excessive muscle contractions. It is now marketed under the trade name Botox.
Small doses of the toxin are injected into the affected muscles. As happens with botulism, the toxin binds to the nerve endings, blocking the release of the chemical acetylcholine, which would otherwise signal the muscle to contract. The toxin thus paralyzes or weakens the injected muscle but leaves the other muscles unaffected. The injections "block extra contraction [of the muscle] but leave enough strength for normal use," says Barbara Karp, M.D., deputy clinical director of the National Institutes of Health's National Institute of Neurological Disorders and Stroke.

The effect of Botox is shown in the above photos. At left, a patient with blepharospasm before injection with Botox is unable to open her eyes due to abnormal muscle contractions. At center, still pre-injection, she uses her fingers to keep her eyes open. At right, after injection, her eyes stay open without difficulty. (Photos courtesy Joseph Jankovic, M.D., professor of neurology, Baylor College of Medicine, Houston, Texas)
Although the two eye conditions are the only indications for which it is licensed, botulinum toxin has been used investigationally for a variety of other conditions. "The main disease [group] the toxin is being used for is dystonias--neurologic diseases involving abnormal muscle posture and tension," Karp says. Examples include spasmodic torticollis (contractions of the neck and shoulder muscles), oral mandibular dystonia (clenching of the jaw muscles), and writers' and musicians' cramps.

Other investigational uses include: spasmodic dysphonia (which results in speech that is difficult to understand), urinary bladder muscle relaxation (such as in cases where muscle contraction is severe enough to require catheterized urination), esophageal sphincter muscle relaxation, and the management of tics.
Experience shows that "it works better for some things than others," NIH's Karp says. For example, "it works better for disorders that involve small muscles than large muscles," she says. But for about 2 to 5 percent of patients, the injections simply don't work at all, she adds.

Injections usually have to be repeated, as the effects usually only last about three to four months, although sometimes they can last over a year. Because of this, up to 10 percent of patients eventually develop antibodies to the toxin; this is more likely in patients who receive higher doses at more frequent intervals. Therefore, the makers of the biologic recommend that its dosage be kept as low as possible.
There are seven different types of botulinum toxin, and the currently marketed therapeutic toxin is type A. NIH is studying whether patients who have become immune to injections of type A toxin can successfully be treated by toxins of other types. So far, the research indicates that using type F to treat people with antibodies to type A seems to work, Karp says.
Botulinum toxin has "an amazing safety record," says Bill Habig, Ph.D., the recently retired deputy director of FDA's division of bacterial products in the Center for Biologics Evaluation and Research. "Considering it's one of the most toxic materials known and there was a lot of concern about it, it's turned out to be very safe," he says.

Luba Vangelova is a writer in Takoma Park, Md.
Not for Wrinkles
Botulinum toxin type A has been promoted for use as a wrinkle remedy. Apparently, some practitioners have been injecting the substance to ease wrinkles by weakening face muscles. In a Nov. 18, 1994, Federal Register notice, FDA denounced the promotion of such unapproved use as "an egregious example of promoting a potentially toxic biologic for cosmetic purposes."

データ

●"眼瞼"を適応に含むもの。（Ａ型ボツリヌス毒素以外は"眼瞼(縁)炎"）
Ａ型ボツリヌス毒素、アズレン、抗生物質、合成抗菌剤、副腎皮質ホルモン、サルファ剤スルフイソキサゾール、ＦＡＤ、硫酸亜鉛の６７品目
アズレン	消炎剤
アモキシシリン	合成ペニシリン
アンピシリン	合成ペニシリン
Ａ型ボツリヌス毒素	眼瞼けいれん治療剤
エリスロマイシン	マクロライド系抗生物質
塩酸シプロフロキサシン	ピリドンカルボン酸系抗菌剤
塩酸セフォチアムヘキセチル	セフェム系抗生物質
塩酸セフカペンピボキシル	セフェム系抗生物質
塩酸セフメノキシム	セフェム系抗生物質
塩酸テトラサイクリン	テトラサイクリン系抗生物質
塩酸ドキシサイクリン	テトラサイクリン系抗生物質
塩酸バカンピシリン	アンピシリンエステル
塩酸ミノサイクリン	テトラサイクリン系抗生物質
塩酸ロメフロキサシン	新キノロン系抗菌剤
オフロキサシン	ニューキノロン系抗菌剤
クリンダマイシン	リンコマイシン系抗生物質
クロラムフェニコール	抗生物質
クロラムフェニコール・コリスチンメタンスルホン酸ナトリウム	混合感染症治療剤
注射用コハク酸プレドニゾロンナトリウム	糖質副腎皮質ホルモン
酢酸コルチゾン	副腎皮質ホルモン
酢酸デキサメタゾン	糖質副腎皮質ホルモン
酢酸パラメタゾン	合成副腎皮質ホルモン
酢酸ヒドロコルチゾン	糖質副腎皮質ホルモン
酢酸プレドニゾロン	糖質副腎皮質ホルモン
酢酸メチルプレドニゾロン	合成副腎皮質ホルモン
ジョサマイシン	マクロライド系抗生物質
スパルフロキサシン	持続性ニューキノロン抗菌剤
スルフイソキサゾール	サルファ剤
スルベニシリンナトリウム	合成ペニシリン
セファレキシン	セファロスポリン系抗生物質
セファロリジン	セファロスポリン系抗生物質
セフジトレンピボキシル	セフェム系抗生物質
セフジニル	セフェム系抗生物質
セフロキサジン	セフェム系抗生物質
セフロキシムアキセチル	セファロスポリン系抗生物質
テトラサイクリン	テトラサイクリン系抗生物質
デキサメタゾン	糖質副腎皮質ホルモン
トシル酸トスフロキサシン	ニューキノロン系抗菌剤
トブラマイシン	アミノグリコシド系抗生物質
トリアムシノロン	糖質副腎皮質ホルモン
トリアムシノロンアセトニド	副腎皮質ホルモン
ノルフロキサシン	ピリドンカルボン酸系抗菌剤
ヒドロコルチゾン	糖質副腎皮質ホルモン
ファロペネムナトリウム	ペネム系抗生物質
フェネチシリンカリウム	合成ペニシリン
フラビンアデニンジヌクレオチド	補酵素型ビタミンＢ２
フルオロメトロン	抗炎症合成副腎皮質ホルモン
フレロキサシン	持続型ニューキノロン剤
プラノプロフェン	プロピオン酸系鎮痛・消炎・解熱剤
プレドニゾロン	糖質副腎皮質ホルモン
プロピオン酸ジョサマイシン	マクロライド系抗生物質
ベタメタゾン	糖質副腎皮質ホルモン
ホスホマイシン	抗生物質
メタスルホ安息香酸デキサメタゾンナトリウム	糖質副腎皮質ホルモン
メチルプレドニゾロン	合成副腎皮質ホルモン
ラクトビオン酸エリスロマイシン・コリスチンメタンスルホン酸ナトリウム	複合抗生物質
硫酸亜鉛	局所収れん剤
硫酸ゲンタマイシン	アミノグリコシド系抗生物質
硫酸シソマイシン	アミノグリコシド系抗生物質
硫酸ジベカシン	アミノグリコシド系抗生物質
硫酸フラジオマイシン	アミノグリコシド系抗生物質
硫酸ベカナマイシン	アミノグリコシド系抗生物質
硫酸ミクロノマイシン	アミノグリコシド系抗生物質
リン酸デキサメタゾンナトリウム	糖質副腎皮質ホルモン
リン酸プレドニゾロンナトリウム	糖質副腎皮質ホルモン
リン酸ベタメタゾンナトリウム	糖質副腎皮質ホルモン
レボフロキサシン	ニューキノロン系抗菌剤・オフロキサシン光学異性体
臨床ガイドラインなど

● 83. CLINICAL USE OF BOTULINUM TOXIN

●83. CLINICAL USE OF BOTULINUM TOXIN
●National Institutes of Health Consensus Development Conference StatementNovember 12-14, 1990
This statement was originally published as:
Clinical Use of Botulinum Toxin. NIH Consens Statement 1990 Nov 12-14;8(8):1-20.
For making bibliographic reference to the statement in the electronic form displayed here,
it is recommended that the following format be used:
Clinical Use of Botulinum Toxin. NIH Consens Statement Online 1990 Nov 12-14 [cited year month day];8(8):1-20.

●抄録●[機械訳]

「ボツリヌス毒素臨床使用に関するNIH Consensus Development Conference」は神経学者、眼科学者、otolaryngologist、病理学者等の専門家で構成。　：ボツリヌスの毒素の作用機序、ボツリヌスの毒素治療の適応と禁忌、注射の一般技術およびその安全かつ効果的な使用、短期・長期の副作用および療法の問題点。
　パネルは（1）ボツリヌスの毒素療法が斜視[strabismus]、眼瞼痙攣[blepharospasm]、半顔面の痙攣[hemifacial spasm]、内転筋の痙攣性の発生困難[adductor spasmodic dysphonia]、顎を終りのoromandibularの筋緊張異常[jaw-closing oromandibular dystonia]、および頚の筋緊張異常[cervical dystonia]の治療に安全かつ効果的であること（2）ボツリヌス毒素は慢性神経障害に対して治癒させる[curative]ものではない（3）ボツリヌス毒素療法の妊娠、breast feeding、幼年時代の慢性使用に対する安全性は不明。；（4）ボツリヌス毒素の慢性使用の長期効果は不明；（5）ボツリヌス毒素は医師など専門家チームによって管理されるべきである。

●INTRODUCTION
Botulinum toxin is a complex protein produced by the anaerobic
bacterium Clostridium botulinum. Previously known only as a cause of a serious and often fatal paralysis acquired through ingestion of contaminated food, the toxin causes paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. Advantage can be taken of this neuromuscular blocking effect to alleviate muscle spasm due to excessive neural activity of central origin or to weaken a muscle for therapeutic purposes. In therapeutic applications, minute quantities of botulinum neurotoxin type A are injected directly into selected muscles.Local injections of botulinum toxin are effective in the treatment of strabismus, essential blepharospasm, and hemifacial spasm. The U.S. Food and Drug Administration recently has approved botulinum toxin for these indications. Clinical studies indicate that botulinum toxin injections also can provide useful symptomatic relief in a variety of other conditions characterized by involuntary spasms of certain muscle groups, notably in focal or segmental dystonia including spasmodic torticollis, oromandibular dystonia (orofacial dyskinesia, Meige syndrome), and spasmodic dysphonia. A few studies suggest that it also may be useful in treating writer's cramp and related occupational cramps of the hand, limb dystonia, anismus, and urinary detrusor-sphincter dyssynergia. The value of the toxin in treating other conditions such as spasticity due to brain or spinal cord lesions is under investigation.For most patients with these conditions, botulinum toxin injection provides significant but variable relief of symptoms that lasts for weeks to months. Repeated injections are required to sustain benefit over long periods of time. Conventional therapy for many of these conditions depends on minimally effective drugs or surgical procedures designed to denervate or destroy the involved muscles and has been generally unsatisfactory. Reports of the benefits of botulinum toxin have thus aroused great interest and hope among physicians, biomedical scientists, and patients.This new therapeutic agent has been used principally by highly specialized physicians in academic medical centers. Many of the data are recent. Controversies persist regarding the indications, contraindications, optimal methods of use, and the nature of the side effects. Long-term effects of chronic botulinum toxin therapy are unknown. Long-term followup of treated patients is necessary.

Additional research appears needed to clarify the metabolism and pharmacology of the toxin, assess new indications, and define optimal techniques of administration.To evaluate the developing experience
with botulinum toxin in the
treatment of various clinical disorders characterized by muscle
hyperactivity, the National Institute of Neurological Disorders and
Stroke and the Office of Medical Applications of Research of the
National Institutes of Health convened a Consensus Development
Conference on November 12-14, 1990. The conference was cosponsored
by the National Institute on Deafness and Other Communication
Disorders of the National Institutes of Health and the Food and
Drug Administration. After a day and a half of presentations by
experts from all over the world and discussion by the audience, a
consensus panel drawn from specialists in relevant fields, clinical
investigators, and public representatives considered the evidence
relative to the following questions:What are the mechanisms of action of botulinum toxin?What are the indications and contraindications of botulinum toxin therapy? How should it be handled to assure safe and effective use?What are its side effects and complications?What further research on botulinum toxin therapy is needed?

●はじめに●[機械訳]

ボツリヌスの毒素は嫌気性菌のバクテリアによって生産された複雑な蛋白質である、Clostridiumのボツリヌス。神経筋肉の接合の点でアセチルコリンの前染色体結合の公開を妨たげることによって汚染された食物、毒素の原因の麻痺の摂取を通って取得された重大な、しばしば致命的な麻痺の原因としてのみ前に知られていたとき。中央の起源の過度の神経の活性による筋肉の痙攣を軽くするか、治療の目的のための筋肉を弱めるために結果を妨たげるとき利点はこの神経筋について得られることができる。治療のアプリケーションで、ボツリヌスの神経毒のタイプの微小な量、選ばれた筋肉に直接に注入される。

ボツリヌスの毒素の局地の注入は斜視、本質的な眼瞼痙攣、および半顔面の痙攣の処置に効果があっている。米国の食品医薬品局は最近これらの適応症のためのボツリヌスの毒素を承認した。臨床の研究はボツリヌスの毒素の注入がまた種々の他の状態での有用な症候的な救済が、目だって痙攣性の斜頚、oromandibularの筋緊張異常（orofacialの運動障害、Meigeの症候）、および痙攣性の発生困難を含む焦点の、または部分的な筋緊張異常での、ある筋肉のグループの不本意な痙攣によって特徴づけたと規定することができると指示する。手、肢の筋緊張異常、anismu、および尿のdetrusorの括約筋dyssynergiaの職業のクランプを話す、少数の研究はそれがまた著者のクランプを取り扱うことに役に立っていることを提案する。脳か脊髄の損害による痙攣性のような他の状態を取り扱うことにおける毒素の値は調査の下である。

月まで、週の間に、あの最後、これらの状態でほとんどの患者にとって、ボツリヌスの毒素の注入は徴候の重要な、しかし可変的な救済を供給する。繰り返された注入は時間の長い時代を通じて利益を支持するように要求される。一般的に不十分であった、これらの状態の多くのための伝統的な療法は最小限で効果的な薬によるか、外科の手続きはdenervateに計画するか、複雑な筋肉を破壊した。ボツリヌスの毒素の利益の報告は内科医、生物医学の科学者、および患者のなかで偉大な利益および希望をこのように刺激した。

この新たに治療の剤は大学の医学の中央での非常に特殊化された内科医によって主に使われた。データの多くは最近である。論争は適応症、禁忌、有益な最適な方法および、副作用の性質に関して続く。慢性のボツリヌスの毒素の療法の長期の結果は知られていない。待遇された患者の長期のfollowupは必要である。付加的な調査は代謝および毒素の薬理学を解明して、適応症を新たに査定して、投与の最適なテクニックを定義するために必要とされるように見える。

筋肉の機能亢進によって特徴づけられた様々な臨床の無秩序の処置でのボツリヌスの毒素で発達させる経験を評価するために、「神経学無秩序国民協会」および「卒中」および医学アプリケーション調査国民事務所「健康設ける」は1990年11月12-14日に「同意発展会議」を召集した。会議は「難聴の上の国民協会」および国民他通信無秩序「健康設ける」および食品医薬品局によって共同スポンサーとなられた。専門家による1日およびある半分の贈呈のあと、世界および聴衆による議論、適切なフィールドでの専門家から引き抜かれた同意のパネル、臨床の調査者の上一面に、公共の代表者は以下の質問に対する証拠の親類を考慮した：

ボツリヌスの毒素の行動の機序は何であるか？
何がボツリヌスの毒素の療法の適応症および禁忌であるか？
どうそれは安全な、効果的な使用を保証しているために取り扱われるべきであるか？
何がその副作用および複雑化であるか？
そのうえボツリヌスの毒素の療法を研究することは必要とされるか？

[以下略]
●CONSENSUS DEVELOPMENT PANEL ［略］
●SPEAKERS［略］
●PLANNING COMMITTEE［略］
●CONFERENCE SPONSORS［略］

●Botulinum Toxin Management of Essential Infantile Esotropia[内斜視] in Children[Fulltext, Arch Ophthalmol. Nov 1997;115:1411-1418] (c) AMA 1997

Clinical Sciences - November 1997
Botulinum Toxin Management of Essential Infantile Esotropia in Children
Keith W. McNeer, MD; Mary G. Tucker, MD; Robert F. Spencer, PhD
Background: Infantile esotropia has an onset during early infancy when visual cortical connections are established for binocular fusion and stereopsis. The goal of early treatment is to achieve normal binocular alignment and a favorable sensory outcome.
Objective: To determine the long-term effects of the use of botulinum toxin for the management of infantile esotropia in children.
Patients: Seventy-six neurologically normal children ranging from 4 to 48 months of age were entered consecutively into the study after being given the initial diagnosis of infantile esotropia with a mean strabismic angle of 33 prism diopters.
Interventions: Simultaneous bilateral injections of 2.5 U of botulinum toxin type A were made into the medial rectus muscles under nitrous oxide and ethrane anesthesia. Patients were followed up for 12 to 95 months after the last injection. Forty patients required 1 bilateral injection and 36 patients required multiple bilateral injections to achieve a favorable motor outcome.
Results: Bilateral medial rectus muscle injections of botulinum toxin were effective in reducing the mean preinjection deviation of 33 PD to an average esotropic angle of 2 PD. Binocular alignment (±10 PD) was achieved in 68 patients (89%). Boys required significantly fewer injections than did girls. The secondary incidence of overacting inferior oblique muscles was significantly greater in boys, while girls had a significantly greater incidence of late-onset refractive errors.
Conclusion: Botulinum toxin is an effective treatment modality for the management of infantile esotropia in infants and children, producing binocular alignment of the visual axes.
Arch Ophthalmol. 1997;115:1411-1418
INFANTILE ESOTROPIA is a common form of strabismus that is manifested
during early infancy.[
［略］

●Botulinum Toxin Injections: A Treatment for Muscle Spasms / AAFP Patient Information Handout★筋肉痙攣治療
１０年以上数千人に安全に使用されてきた。 Botulinum Toxin Injections: A Treatment for Muscle Spasms

★What is botulinum toxin?
Botulinum toxin is a protein. It can stop some of the chemical messages that are sent from nerves. These messages cause muscles to contract in spasms (to tighten up). Botulinum toxin is used to stop muscle spasms because it blocks these messages.
Botulinum toxin is made by the same bacteria that causes food poisoning. A high dose of botulinum toxin could be fatal, just as food poisoning can be fatal. The dose people get in injections is very small, however. This dose is so small that it's unlikely you'll have any harmful effects from the toxin.
Botulinum toxin has been used safely in thousands of people. It has been used for more than 10 years.

★Why do I need botulinum toxin injections?
Your doctor may be considering botulinum injections to treat certain muscle spasms on your face or eyelids. It can also be used for some disorders of eye movement, such as lazy eye. Botulinum toxin is a standard treatment for spasmodic torticollis, a muscle spasm that causes the head and neck to pull in one direction.

★How are botulinum toxin injections given?
Botulinum toxin is mixed with salt water and injected into a muscle with a very small needle.
You may receive five to 10 injections.
You might have some soreness at the injection sites. If your injection sites get sore, you can take acetaminophen (brand name: Tylenol) or ibuprofen (brand names: Advil, Motrin, Nuprin). You can also put an ice pack on the painful area.

★Will I have any side effects?
You might have weakness in that muscle, muscle soreness that may affect your whole body, difficulty swallowing and a red rash that lasts for several days after the injections. Some people have severe weakness in the muscles that were injected. All side effects go away quickly.
This information provides a general overview on botulinum toxin and may not apply to everyone. Talk to your family doctor to find out if this information applies to you and to get more information on this subject.
Visit the AAFP Web site at
http://www.aafp.org/healthinfo for more useful information.
Permission is granted to reproduce this material for nonprofit educational purposes. Written permission is required for other uses, including electronic uses.
This Web page was last modified on July 13, 1998.
American Academy of Family Physicians

総説記事・文献

●BOTOX® Injections for Wrinkles[しわ]

★BOTOXは10年以上眼瞼や顔面痙攣に使用。　Dr. Felderは額の線やしわ、frown linesやカラスの足跡を減少・除去するのに使用している。　所用時間は10分、効果持続は3-4か月。　コラーゲンと違いアレルギーがない。
Dr. Felder performed over 5,000 eyelid surgeries. Call today for a complimentary consultation. Call 1-800-2-EYELID...";

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●BOTOX® Injections for Wrinkles
Dr. Felder has been using BOTOX® (Botulinum Toxin) for 10 years, for eyelid and facial spasms. Dr. Felder now uses it for reducing or eliminating forehead lines and wrinkles, frown lines and Crow's feet.
Dr. Felder can use BOTOX® at the same time as laser rejuvenation and with his no scar, no stitch cosmetic eyelid surgery. All of these techniques can give a tremendous added effect in decreasing the amount of wrinkles and improving the ultimate cosmetic result.
BOTOX® is a series of injections which take about 10 minutes and last an average of 3-4 months. After 3 or 4 injections, BOTOX® has been noted to have a long-lasting effect in the elimination of frown lines, forehead wrinkles and Crow's feet.
Unlike collagen, there are no allergies associated with BOTOX® and again, there may be long-lasting or permanent effect. The side effects, which most commonly involve bruising at the injection site, are minimal and temporary.
This is an excellent treatment for forehead lines, Crow's feet and frown lines.
If you are considering cosmetic eyelid surgery, laser resurfacing or BOTOX®, please feel free to ask Dr. Felder to see if you are a candidate for these exciting new techniques.

● Botox: Nonsurgical Wrinkle Remover of the Future?

1997年3月第５５回米国皮膚科学会でUCLA Lowe教授により発表。BOTOXは眉間のしわに有効かつ安全で、コラーゲンや皮膚再生レーザーと同様の効果がある。 Botox: Nonsurgical Wrinkle Remover of the Future?
SAN FRANCISCO, March 21, 1997 -- The past two decades have witnessed an increase of new options for reversing the effects of aging skin. Dermatologists and dermatologic surgeons have been instrumental in developing and refining techniques that have become widely accepted by an eager population.

Speaking at the American Academy of Dermatology's 55th Annual Meeting, Nicholas J. Lowe, M.D., Clinical Professor of Dermatology at UCLA, Santa Monica, California, spoke today about the use of botulinum toxic type A (Botox) in the treatment of hyperkinetic facial lines.※運動過多性顔面線

Botox, is a purified form of one of the most potent toxins known to man. In high doses it can cause the clinical disease botulism. However, in carefully administered low doses, it is very useful for treating hyperkinetic facial lines.

The structure and function of botulinum toxin was originally determined at Fort Derrick, Maryland from work which began during World War II in an attempt to understand and develop antitoxins to potential agents of biological warfare.

"Structurally, the toxin is composed of a heavy chain and a light chain, joined together by two disulfide bonds. The active neurotoxin is
formed by 'nicking' of one of these disulfide bonds," Dr. Lowe explained. 徹f clinical relevance is that botulinum toxin type A has been shown not to cross the blood-brain barrier and has no systemic risk at the amounts used.�

Local injections of botox have been used successfully to treat strabismus, blepharospasm and other hyperkinetic movement disorders. The active toxins work by causing a reversible muscle paralysis by blocking acetylcholine release at the neuromuscular function.

The "ideal" patients for this treatment have upper facial expression lines, like forehead lines, frown lines and crows feet which are caused by the use of small muscles in the face.Botox was injected using an electromyography (PMG) instrument connected to the delivery needle.

"The injections are in an upward and lateral direction from the middle inter-eyebrow area. These instruments are a very effective means of assuring the botox is delivered accurately into the body of the muscles," explained Dr. Lowe.

Patients injected with the drug had significant improvement in facial lines. Some patients improved for up to one year after treatments. Side effects are rare, and can be minimalized by the upward and lateral technique. Additionally, botox decreases the patient's ability to frown or squint, which prevents the progressive worsening of these lines over time. Therefore, the method can be considered both corrective and preventive.

"Botulinum toxin type A appears to be safe and effective for the treatment of glabellar frown lines. Botox may be combined with collagen and skin rejuvenation lasers. Studies are currently underway for treating other hyperkinetic facial lines," Dr. Lowe said.※BOTOXは眉間のしわに有効かつ安全で、コラーゲンや皮膚再生レーザーと同様の効果がある。

The American Academy of Dermatology is the largest medical society representing physicians who specialize in treating hair, skin and nail conditions.

●Patient Information - Botox [New Zealand Dermatological Society]
BOTOXはしわ取りに有効で、１回の処置で4-6か月有効。　副作用は軽い頭痛程度。 Botulinum toxin (Botox) is a toxin produced by the bacterium Clostridium botulinum. It causes muscle paralysis.

●What can Botox be used for?
Botox was originally introduced for the safe and effective treatment of muscle spasms. In patients treated for hemifacial spasm it was noted that facial wrinkling decreased over the treated muscle. This experience lead to the development of Botox for the treatment of facial wrinkles. People often dislike their central frown line, which is caused by concentrating, squinting, or frowning. Botox injections can successfully reduce its prominence.
Botox can also be used to lessen crow's feet and other expression lines.

●How is Botox administered?
Tiny quantities of the toxin are injected directly into the muscles of facial expression. It takes three small injections between the eyebrows to treat the frown line.The treated muscles weaken over the following week or so. Most people do not notice anything. They simply become aware that they are no longer able to contract the frown muscles. They can still lift their eyebrows normally and blink without problems. The injection is almost painless.
It is important to remain upright for four hours after the injection. The treated areas should not be touched.
The effect lasts between four and six months. Treatment can be repeated as required.

●Side effects and risks
Some people have a slight headache after treatment for several hours.The most common significant complication, which is rare, is 眼瞼下垂"ptosis". This is a drooping of the eyelid caused by the Botox tracking into the eyelid muscle. It generally lasts just a few days, but more prolonged weakness is possible.
Botox injections cannot be used in pregnancy or when breast feeding.
1998 New Zealand Dermatological Society. Last updated 12th July 1998

● Botulinum Toxin Effective Against Excessive Sweating[発汗]

CHICAGO, IL -- March 17, 1998 -- Injections of botulinum toxin can successfully eliminate excessive sweating caused by the disorder known as focal hyperhidrosis, according to an article in this month's issue of the journal Archives of Dermatology.

Markus Naumann, M.D., and colleagues from the Bayerische Julius-Maximilians-Universität, in Würzburg, Germany, studied 11 patients who underwent treatment with botulinum toxin for focal hyperhidrosis. Hyperhidrosis produces excessive sweating in the palms, feet, armpits or all three. It may produce an unpleasant body odor, which can cause social embarrassment.

Treatments include anticholinergic drugs and topical applications of acids, aldehydes and metal salts, such as aluminum chloride. If these treatments prove ineffective, invasive or surgical procedures may be warranted.

The researchers injected botulinum toxin type A (Botox) in the patients' palms, soles and axillae (armpits).

"In all patients, botulinum toxin completely abolished sweating in the injected areas within three to seven days," they write. "Within the follow-up period of up to 20 weeks (range, 12 to 20 weeks), no clinical hyperhidrosis could be discovered in eight of 11 patients. However, 16 weeks after injection, small areas of clinically inapparent restored axillary sweating were observed in three patients, all of whom were successfully reinjected four weeks later."

Botulinum toxin is a potent neurotoxin that blocks cholinergic nerve terminals. Earlier studies have shown its effect in reducing sweat production in normal volunteers. The bacterium clostridium botulinum can cause the rare, but serious form of poisoning known as botulism.

All of the patients in the study were severely disabled with respect to their occupation and social activities because of the disorder. All had previously tried drug therapy, but had failed to experience any improvement in their symptoms. For all the patients, a successful treatment with botulinum toxin would provide an alternative to surgery.

The researchers found that the botulinum toxin injection was well tolerated by the majority of the patients in the study. There were few adverse effects, and those that did occur were mild.

Despite a marked decline in sweat production, patients with armpit sweating did not notice a significant reduction of unpleasant odor after the botulinum injection. The researchers suggest this is because of the different transmitters involved in two types of sweat glands -- one of which is unaffected by botulinum toxin.

The botulinum toxin (Botox) used in the study is currently being evaluated as an orphan drug in the United States. Since it has not yet been tested sufficiently in pregnancy, in particular, the researchers say it must not be given at this stage to women of childbearing age without contraception, or to pregnant women, or nursing mothers.

"Intracutaneous administration of botulinum toxin is a novel, safe and simple treatment for many patients with focal hyperhidrosis," they write. "It carries the potential to replace current invasive surgical procedures."

●WJB - BOTOX (Botulinum Toxin A)
THE FIRST NON-SURGICAL THERAPY THAT SAFELY AND EFFECTIVELY REVERSES THE SIGNS OF AGING

BOTOX (BOTULINUM TOXIN A) is a purified biological protein that is produced,
under rigorous laboratory conditions, by the growth of Clostridium Botulinum
bacterium. Botulinum Toxin A eliminates most wrinkles[しわ] around the eyes and
forehead[額]; such as, crows feet[カラスの足], forehead and frown lines[しかめ面の時の線], and it's unique protein
composition can prevent new wrinkles from forming.
Prior to Botulinum Toxin or Collagen, surgery was the only effective procedure used
to correct some of the age-related changes of the face. Not everyone, however, is an
acceptable candidate for elective surgery, so Collagen, which is a "filler material",
became the non-surgical procedure of choice to treat wrinkles. It can effectively fill
out areas of depression or redundant facial folds, but it cannot treat the underlying
cause of the deep wrinkle: muscle tension that pulls the skin inward.
Botulinum Toxin A has been proven to be the most effective, non-surgical aesthetic
technique for eliminating the dynamic facial wrinkles of the upper portion of the face.
In fact, Botulinum Toxin A is the definitive non-surgical treatment for crow's feet, and
to date, there have been no reported cases of allergic reactions.
Together with his colleagues, Dr. William Binder has refined and published strict
dosage guidelines and procedural protocols to ensure that the Botulinum Toxin A
injection procedure is safe and effective for all of his patients. Dr. Binder has co-
authored the first three articles to appear in the medical literature on the use of
Botulinum Toxin A for the treatment of facial lines. (Reprints are available upon
request.) Botulinum Toxin A is easily administered during a routine office visit. A
simple injection directly into the facial muscle weakens and reduces the muscular pull
on the skin, eliminating the ability to form deep expression lines on the face.
Although not a permanent cure, the effectiveness of Botulinum Toxin A can last up to
6 months, making it today's most successful non-surgical procedure. The treated areas
not only have a more youthful and rested appearance, but patients have actually
remarked about how much more relaxed they feel after their Botulinum Toxin
treatments.
R - Botox is a registered trademark of Allergan, Inc., Irvine, Ca.

PATIENT SQUINTING WITH THE
 DEVELOPMENT OF CROW'S FEET
AFTER BOTOX PATIENT IS TRYING
TO SQUINT & IS UNABLE TO PRODUCE
 CROW'S FEET (4 MONTHS POST OP)

PATIENT FROWNING BEFORE BOTOX
PATIENT IS TRYING TO FORM
FROWN LINES 5 MONTHS AFTER
 BOTOX--AND CANNOT

PATIENT FROWNING BEFORE BOTOX
PATIENT IS TRYING TO FORM
FROWN LINES 6 MONTHS AFTER
 BOTOX--AND CANNOT
Copyright ©1996 William J. Binder, M.D., F.A.C.S. - All Rights Reserved
ニュース・トピックス

●12〈眼瞼痙攣治療剤〉 A型ボツリヌス毒素

［販売名］ボトックス（アラガン）［副作用（重大な副作用）］眼：重篤な角膜露出，持続性上皮欠損，角膜潰瘍，角膜穿孔の報告がある。〈参考〉企業報告

■インフォシークボツリヌス毒素の検索結果......日本語サイト( 99件中)
くすりと病気に関する情報: di00011.html
Q:痙性斜頚に対して使用するボツリヌスA毒素とは?(整形外科医師) A:痙性斜頚は,頚部筋群の異常緊張により収縮が持続するため発生する頭頚部の姿勢異常や不随意的運動症である.原因は ...http://www.ahs.kitasato-u.ac.jp:8080/docs/ts/html/di_pro/di00011.html(Size 2.8K) 更新日: 1998.05.28

リンク＆リソース

■MEDLINEplus: Dystonia
Contents of this page:
From the NIH
General/Overviews
Alternative Therapy
Clinical Trials
Specific Conditions/Aspects
Treatment
Organizations
Children

The primary NIH organization for research on Dystonia is the
 National Institute of Neurological Disorders and Stroke
Search MEDLINE for recent research articles on
・ Dystonia
You may also be interested in these MEDLINEplus related pages:
・ Movement Disorders
・ Brain and Nervous System

●From the National Institutes of Health
Dystonias (National Institute of Neurological Disorders and Stroke)
Dystonias (National Institute of Neurological Disorders and Stroke)

●General/Overviews
Dystonia (We Move)
Dystonia (MedicineNet, Inc.)
Forms of Dystonia (Dystonia Medical Research Foundation)

●Alternative Therapy
Dystonia: Complementary Therapy (Dystonia Medical Research Foundation)

●Clinical Trials
ClinicalTrials.gov: Dystonia (National Institutes of Health)

●Specific Conditions/Aspects
Benign Essential Blepharospasm (National Institute of Neurological Disorders and Stroke)
Blepharospasm (Dystonia Medical Research Foundation)
Causes of Dystonia (Dystonia Medical Research Foundation)
Cervical Dystonia (Dystonia Medical Research Foundation)
Disorders Related to Dystonia (Dystonia Medical Research Foundation)
Genetics of Dystonia (Dystonia Medical Research Foundation)
Oromandibular Dystonia (Dystonia Medical Research Foundation)
Paroxysmal Dystonia (Dystonia Medical Research Foundation)
Prognosis of Dystonia (Dystonia Medical Research Foundation)
Secondary Dystonia (Dystonia Medical Research Foundation)
Writer's Cramp (Dystonia Medical Research Foundation)
Yips: More Than a Putting (Golf) Problem (Mayo Foundation for Medical Education and Research)

●Treatment
Botulinum Toxin Type A (BTX-A) for Dystonia (We Move)
Botulinum Toxin Type B (BTX-B) for Dystonia (We Move)
Dystonia: Approaches to Treatment (We Move)
Oral Medications (Dystonia Medical Research Foundation)
Other Medications Used to Treat Dystonia (We Move)
Surgery (Dystonia Medical Research Foundation)

●Organizations
Dystonia Medical Research Foundation
National Institute of Neurological Disorders and Stroke
We Move

●Children
Dopa-Responsive Dystonia (Dystonia Medical Research Foundation)
Early-Onset Generalized Dystonia (Dystonia Medical Research Foundation)
Last updated: 23 July 2001
●MEDLINEplus: Plastic & Cosmetic Surgery
Contents of this page:
News
General/Overviews
Coping
Pictures/Diagrams
Rehabilitation
Research
Specific Conditions/Aspects
Treatment
Dictionaries/Glossaries
Directories
Journals/Newsletters
Organizations
Statistics
Children
Teenagers

Search MEDLINE for recent research articles on
Plastic & Cosmetic Surgery:
・General
・Blepharoplasty (eyelid)
・Face lift (rhytidoplasty)
・Liposuction (fat removal)
・Rhinoplasty (nose)


You may also be interested in these MEDLINEplus related pages:
・Botox
・Breast Implants/Breast Reconstruction
・Scars
・Varicose Veins
 ・Procedures and Therapies
●Latest News
Happiness with Skin Resurfacing May Sag Over Time (10/23/2003, Reuters Health)
●General/Overviews
Cosmetic Plastic Surgery: Procedures at a Glance (American Society of Plastic Surgeons)
Facts on Dermatologic Surgery Procedures (American Society for Dermatologic Surgery)
Plastic Surgery and Total Patient Care (American Society of Plastic Surgeons)
●Coping
Psychological Aspects: Your Self-Image and Plastic Surgery (American Society of Plastic Surgeons)
●Pictures/Diagrams
Before and After Images: Liposuction (American Society for Dermatologic Surgery)
Before and After Photos of Dermatologic Surgery Procedures (American Society for Dermatologic Surgery)
Before and After: Procedure Example Photos (American Academy of Facial Plastic and Reconstructive Surgery)
●Rehabilitation
Camouflage Cosmetics: Makeup Techniques after Plastic Surgery (American Society of Plastic Surgeons)
What Is the Recovery from Plastic Surgery Like? (American Society of Plastic Surgeons)
●Research
IV Sedation with Local Anesthesia Proven Safe for Office-Based Plastic Surgery (American Society of Plastic Surgeons)
●Specific Conditions/Aspects
Abdominal Reduction (Abdominoplasty) (Mayo Foundation for Medical Education and Research)
Alterations of the Jaws (Cosmetic Orthognathic Surgery) (Mayo Foundation for Medical Education and Research)
Facial Implant Surgery (Mayo Foundation for Medical Education and Research)
Find a Plastic Surgeon: Make the Right Choice (American Society of Plastic Surgeons)
Laser Hair Removal: Zapping Unwanted Hair (Mayo Foundation for Medical Education and Research)
Laser Resurfacing (American Society for Dermatologic Surgery)
Lipoplasty/Liposuction (American Society of Plastic Surgeons)
Also available in: Spanish
Liposuction Information (Food and Drug Administration)
Plastic Surgery of the Ear (Otoplasty) (American Academy of Otolaryngology--Head and Neck Surgery)
Rhinoplasty: Surgery of the Nose (American Society of Plastic Surgeons)
Also available in: Spanish
Saving Face: The Nips and Tucks of Facelifts (Mayo Foundation for Medical Education and Research)
Understanding Blepharoplasty: Surgery of the Eyelids (American Academy of Facial Plastic and Reconstructive Surgery)
Understanding Forehead & Brow Lift Surgery (American Academy of Facial Plastic and Reconstructive Surgery)
Understanding Mentoplasty: Surgery of the Chin (American Academy of Facial Plastic and Reconstructive Surgery)
What Is a Facial Plastic Surgeon? (American Academy of Facial Plastic and Reconstructive Surgery)
What Is the Difference between Cosmetic and Reconstructive Surgery? (American Society of Plastic Surgeons)
What You Should Know about the Safety of Outpatient Plastic Surgery (American Society of Plastic Surgeons)
●Treatment
Skin Augmentation (Mayo Foundation for Medical Education and Research)
Wrinkle Treatment: When You Don't Want a Face-Lift (Mayo Foundation for Medical Education and Research)
●Dictionaries/Glossaries
Glossary of Terms (American Academy of Facial Plastic and Reconstructive Surgery)
●Directories
Find a Plastic Surgeon (American Society of Plastic Surgeons)
●Journals/Newsletters
Facial Plastic Surgery Today (American Academy of Facial Plastic and Reconstructive Surgery)
●Organizations
American Academy of Facial Plastic and Reconstructive Surgery
American Society for Dermatologic Surgery
American Society of Ophthalmic Plastic and Reconstructive Surgery
American Society of Plastic Surgeons
●Statistics
2000/2001/2002 National Plastic Surgery Statistics (American Society of Plastic Surgeons)
2001 Average Surgeon/Physician Fees: Cosmetic Patients (American Society of Plastic Surgeons)
6.6 Million Americans Get a Nip, Tuck, and Lift with Cosmetic Plastic Surgery in 2002 (American Society of Plastic Surgeons)
AAFPRS 2002 Statistics on Trends in Facial Plastic Surgery (American Academy of Facial Plastic and Reconstructive Surgery)
More Than 6 Million Reconstructive Plastic Surgery Patients Treated in 2002 (American Society of Plastic Surgeons)
●Children
What Is a Pediatric Plastic Surgeon? (American Academy of Pediatrics)
●Teenagers
Teens Turn to Facial Plastic Surgery to Improve Self-Esteem (American Academy of Facial Plastic and Reconstructive Surgery)
Page last updated: 24 October 2003
Topic last reviewed: 28 April 2003

主要サイト

■NZ DermNet - Cosmetic Dermatology
ニュージーランド皮膚科学会美容皮膚科サイト。　BOTOX, Collagen等の解説もある。
Laser Resurfacing
Laser Eyelid Surgery
Facial Red Vein and Vascular Birth Mark Treatments
Chemical Peeling
Leg Vein Therapies
Brown Spot and Mole Removal
Botox Treatments
Fruit Acid Facial Treatments
Collagen Replacement Therapy
Please note that NZ DermNet does not supply an on-line personal consultation service.
New Zealand Dermatological Society Last updated 28th October 1998
●From Toxin to Therapeutic Agent[米アラガン社]
BOTOX関連情報、FAQ、添付文書を含む Product Info
Product Use
Product FAQs
Patient Resources
Global Contacts
Prescribe Information

From Toxin to Therapeutic Agent
Clostridium botulinum produces 7 distinct toxins, types A through G. Botulinum toxin type A is the most potent of the 7 serotypes produced by the anaerobic bacterium Clostridium botulinum. Minute quantities of botulinum toxin type A offer significant potential in treating a wide variety of disorders associated with muscle overactivity.

●History of Botulinum Toxin Type A
Work with botulinum toxin type A as a therapeutic agent to treat human disease began in the late 1960s through the collaboration of Alan B. Scott, MD, of the Smith-Kettlewell Eye Research Foundation and Edward J. Schantz, PhD, director of food microbiology and toxicology at the University of Wisconsin. This is when botulinum toxin type A was first considered not as an agent of human sickness and disease but as a powerful therapeutic agent to treat symptoms of neurological disorders.

In 1989, the rights to a form of botulinum toxin type A, currently commercialized under the trade name BOTOX(R), were acquired by Allergan, Inc. In December of that same year, BOTOX(R) was approved for use in strabismus and blepharospasm associated with dystonia in patients 12 years of age and above. Through the collaboration of Drs. Scott and Schantz, and the pioneering efforts of Allergan, BOTOX(R) was added to the armamentarium of drugs used to treat these conditions.
Mechanism of Action?Blockade of Neuromuscular Transmission in the Treatment of Blepharospasm and Strabismus

At a normal neuromuscular junction, a nerve impulse triggers the release of acetylcholine, which causes the muscle to contract. Hyperactive muscle contraction is characterized by excessive release of acetylcholine at the neuromuscular junction. The use of BOTOX(R) (Botulinum Toxin Type A) Purified Neruotoxin Complex can be effective in reducing the excessive activity by blocking the release of acetylcholine at the neuromuscular junction.

BOTOX(R) is injected directly into the muscles surrounding the eye. It exerts its effect on the peripheral nerve terminal at the neuromuscular junction by blocking the release of acetylcholine. Affected terminals are inhibited from stimulating muscle contraction, resulting in a reduction in muscle tone.
Clinical effects of BOTOX(R) are usually seen within 1 week of injection. The typical duration of symptomatic relief averages 12.5 weeks. Repeat injections of BOTOX(R) may be required to maintain the desired clinical effect.

Muscles treated with BOTOX(R) eventually recover as new nerve sprouts develop. A nerve sprout establishes a new neuromuscular junction, and neuromuscular transmission gradually returns over a period of several months.
The most frequently reported side effects with BOTOX(R) include drooping of the eyelids, superficial punctate keratitis, and eye dryness. Reduced blinking can lead to corneal exposure. Sedentary patients should be cautioned to resume activity slowly following BOTOX(R) injections.

●Clinical Development
BOTOX(R) is currently in various stages of clinical development for a number of neuromuscular treatments. If successful, these treatments could offer new tools with potential to significantly improve a patient's ability to perform the activities of daily living.
Allergan's BOTOX(R) (Botulinum Toxin Type A) Purified Neurotoxin Complex is used in the treatment of certain neuromuscular disorders characterized by involuntary muscle contractions or spasms. Allergan markets BOTOX(R) in the United States and in 61 other countries. The approved indications for BOTOX(R) in the United States are for the treatment of blepharospasm (the uncontrollable contraction of the eyelid muscles that can force the eye closed and result in functional blindness) and strabismus (misalignment of the eyes) in people 12 years of age and over. For approved uses outside of the United States, please contact our global offices.

Allergan is working to expand the approved indications for BOTOX(R) in the United States. In 1998, Allergan exercised its option to acquire the exclusive worldwide rights to US and foreign patents for the use of botulinum toxin type A to treat migraine headaches and filed an investigational new drug application with the FDA for the migraine headache indication for BOTOX(R). Clinical development for the migraine and tension headache indications is currently in phase 2. In addition, Allergan has orphan drug designations from the FDA for 2 other uses for BOTOX(R): cervical dystonia and juvenile cerebral palsy. phase 3 clinical trials will soon be underway in the United States for the juvenile cerebral palsy indication, and Allergan expects to seek supplemental approval for the cervical dystonia indication during 1999. If Allergan gains approval for one or both uses before any other manufacturer of the same designated botulinum toxin serotype, the company will be entitled to 7 years of exclusive marketing in the United States for those uses. BOTOX(R) is also currently in phase 3 clinical development in the United States for hyperfunctional facial lines (cosmetic brow furrows) and will soon be in phase 3 for adult spasticity poststroke and in phase 2 for back pain.
　アラガン社は米国での承認拡大に向けての作業をしている。　1998年にはFDAに偏頭痛の治験申請を行い、その全世界の用途特許を申請。　偏頭痛臨床治験はフェーズ２段階。　またcervical dystonia and juvenile cerebral palsyの２適応のオーファン指定を得ている。　後者のフェーズ３はまもなく開始予定。　前者は1999年中に承認見込み。　またBOTOXは米国内で３適応の臨床試験を実施しており。 1)hyperfunctional facial lines (cosmetic brow furrows)顔面線過剰（美容上の額の溝） 2)adult spasticity poststroke成人痙性後発作（フェーズ３準備中）　3)back pain背部痛（フェーズ２）

●Manufacture and Storage
BOTOX(R) is supplied sterile in glass vials, each containing 100 units. BOTOX(R) must be diluted with sterile, nonpreserved saline immediately prior to its injection.

●Summary
The clinical use of BOTOX(R) represents one of the most dramatic role reversals in modern medicine: a potent biologic toxin transformed into a therapeutic agent.

BOTOX(R) offers potential as a powerful and versatile tool in the treatment of a wide variety of disorders characterized by muscle hyperactivity.
Click here for full prescribing information.
c1999 Allergan, Inc. All rights reserved.

●The Facial Plastic Surgery Center: Botox - Dr. Scott Gilbert
BOTOXの注射は１回$35.00と安価 BOTOX^(R) reacts with the nerve messaging system. When injected under the skin into the forehead area, BOTOX acts as an interceptor for transmission of nerve signals. BOTOX short-circuits the "contract" message being sent to the muscles to produce wrinkling and spasmodic tendencies. What does this mean? No wrinkling! BOTOX stands for Botulinum Toxin Type A. Before Botox TreatmentEven though it sounds bad, BOTOX is a safe and effective purified protein produced by the bacterium Clostriduim Botulinum. Clinical research over the past 10 years has found BOTOX to be beneficial in treatment of forehead wrinkles, frown lines, and crow's feet. Injections of BOTOX are inexpensive -- around $35.00 ea -- and the results are well worth it! Most patients will begin a series with about 10 injections. Repeat treatment can occur about 2-3 months later, with fewer injections -- usually about 4 or 5. Over the course of one year, you can expect the duration of BOTOX to have a cumulative effect. After First Botox TreatmentAfter Second Botox Treatment

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Blinking Eye, Oculoplastics, Blepharoplasty, Eyelid SurgeryWhat is EyePlastics^{^{^(R)}}?
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■Welcome to Cosmetic Surgery Network. Your friendly
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All of the surgeons listed within this
  service are board-certified and members of their respected surgical  societies. You can search for a surgeon by the geographical area in USA or  Canada.

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help.

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Plastic Surgery Network
Interesting Links:

●Medical /Surgical Societies and Organizations:

American Society for Aesthetic Plastic Surgery
Lipoplasty Society of North America

American Academy of Facial Plastic and Reconstructive Surgery, AAFPRS

British Association of Plastic Surgeons
French Society of Aesthetic Plastic Surgery
The Spanish Society for Plastic, Reconstructive and Esthetic Surgery
Australian Society of Plastic Surgeons
International Confederation for Plastic Surgery and Aesthetic Surgery (IPRAS)
Brazilian Society of Plastic Surgery
The Iberolatinoamerican Federation of Plastic Surgery
Sociedad Argentina de Cirurgia Plastica Estetica y Reparadora
Netherlands Society of Plastic Surgery
The Turkish Plastic Surgery Association
The John Staige Davis Society of Plastic Surgeons of Maryland.
PHILIPPINE SOCIETY FOR COSMETIC SURGERY
Educational and humanitarian arm of IPRAS (IPRAF)
National Institutes of Health
Department of Health and Human Services
Centers for Disease Control

American College of Surgeons
American Dental Association
American Medical Association
American Academy of Orthopedic Surgeons
American Association of Plastic Surgery
American Board of Plastic Surgery
American Board of Medical Specialties
American Association for Hand Surgery
Food and Drug Administration
National Cancer Institute
AMERICAN BOARD OF FACIAL PLASTIC AND RECONSTRUCTIVE SURGERY

●On line Surgical Journals:
Brazilian Journal of Plastic Surgery
Burns.
International Journal of Plastic & Aesthetic Surgery (IJPAS)
Microsurgery
Plastic and Reconstructive Surgery
The Canadian Journal of Plastic Surgery
The Electronic Journal of Handsurgery
The Electronic Journal of Surgery and Specialistic Medicine

●Departments of Plastic and Reconstructive Surgery:
University of Kentucky
Indiana University Medical Center
Mount Sinai Hospital New York
The University of Texas, Medical Branch
The University of Minnesota
Duke University in Durham, NC
The Medical College of Virginia
The University of Wisconsin
The University of Missouri-Columbia
The Mount Vernon Hospital
The University of Michigan Medical Center
The Mayo Clinics
Johns Hopkins Dept. of Plastic and Reconstructive Surgery
Brown University Plastic Surgery department
Baylor College of Medicine's site in Houston
Vanderbilt University
Iowa University Hospital.
University of Washington
Case Western Reserve University in Cleveland
Northwestern University Medical School Chicago
M.S. Hershey Medical Center, Penn State
Department of surgery in Toronto Canada

Ankara University , Dept. of Plastic Surgery
The University hospital of Bochum Germany
The University Hospital of Graz, Austria
National University Hospital, Singapore
McGill University
The Keio University in Japan
Darthmouth Hitchcock Medical Center
Maatschap voor Plastische en Reconstructieve chirurgie Regio Zuid-Oost Brabant, the Netherlands
Queen Victoria Hospital, Sussex UK
Katholieke Universiteit Nijmeg
●Special Links:

Interplast
PLink

The Un-Official Plastic Surgery
Integrated (3+3 years) Residency Site
Medline Search

Surgical and Medical Products:
 Check
our 1999 Comprehensive
Directory for Plastic/Cosmetic Surgery
 Products, Service, Supplies and Suppliers.

1999 Plastic Surgery Conferences, Meetings and Workshops.
 Check
our 1999 Comprehensive
 Directory

Plastic Surgery and Show Business.
Cleberitites and Plastic Surgery.
 Find out what some of your favorite celebrities, movie stars, TV hosts, models and others probably had undergone.

E! Online - The Hot Spot - Specials - Plastic Surgery.

The Mr. Showbiz Plastic Surgery Lab.

Cool sites on the Internet.
High Tech Solutions ( Los Angeles Service and Business Directory)

●Worldwide Plastic Surgeons' Web Sites:
 Please send us your e-mail with your web site address
 to be included.
 __________________
 Argentina, Australia, Brazil,
Belgium, Chile, China, Colombia,
Costa Rica, Cuba, Denmark,
El-Salvador, France, Germany,
Greece, India, Ireland, Israel,
Italy, Japan, Jordan, Kuwait,
Lebanon, Malaysia, Mexico,
Morocco, Netherlands,
New Zeland, Norway, Pakistan,
Philippines, Poland,
Portugal, Russia, Saudi Arabia,
Singapore, South Africa,
Spain, Sweden, Switzerland,
Syria, Thailand, Tunisia,
Turkey, Ukraine, United
 Arab Emirates, United Kingdom.

Australia:
Dr. Paul O'Keeffee.

Dr. V Zielinski.

Austria:
The
Schwarzl Outpatient Clinic
 Dr. Johann Umschaden and Dr. Helmut Hohlehner.
http://www.schwarzl-tagesklinik.at/englisch/
Brazil:
Dr Julio Dante Bonetti,from uberlandia, Brazil
Dr Wagner de Moraes, from Rio de Janeiro, Barazil
Dr Domingos Quintella de Paola, from Rio deJaneiro Brazil
Dr Ody Silveira Junior, from Londrina - PR - Brazil
Dr Ivo Pitanguy, from Rio de Janeiro, Brazil
Colombia:
Dr. José Henrique Mantilla Martín. M.D., P.S.

Dr Maria Teresa Perlaza

Costa Rica:
Dr. Arnoldo Fournier.

Drs. Noe Rosenstock and Clara Lieberman.
Dr. Jose Cohen.
Dr. Alejandro Lev.
Dr. Carlos A. Centeno Ramírez or Dr. Gustavo Chavarría León.
Dr. Rodrigo Araya, MD, San José, Costa Rica
Egypt
DR. HISHAM EL MINAWI

Netherland:

Esthetische Chirurgie en Laser Centrum. Amsterdam
 Jan van Goyen Kliniek
Poland:
Professor
Stanislaw B.Bartkowski, M.D.,Ph.D.
Dr.Andrew M.Bartkowski and Associates
c/o The American Medical and Research Center,Inc.
3-B Private Plastic Surgery Clinic
3 Nowowiejska Street,
30-052 Krakow, Poland
Phone/Fax 0048-12-636-64-36
 E-mail Address: AMBartkow@Aol.com

Spain:
Dr Joaquim Suñol, from Barcelona, Spain
Dr Victor Mari Suarez , from Barcelona, Spain

Sweden:
Dr Per Gunnar Opitz, from Malmö, Sweden

Taiwan:
Dr Tien-Hsing Chen, from Kaohsiung, Taiwan

Turkey:
Dr. Kutlu Sevin, from Ankara, Turkey
Dr. Aydin Saray, from Ankara, Turkey
Dr Ali Riza Erçöçen, from Ankara, Turkey

United Kingdom:
Mr Keith W. Cullen, from east Grinstead,
England
Dr H.J.C.R. Belcher, from Sussex, UK
Yugoslavia:
Mens
Sana Clinic for Plastic, Reconstructive and Aesthetic Surgery, owner Dr.
Zoran Lekic.
Address: Zarkovacka 44, 11000 Belgrade, Yugoslavia.
Tel./Fax. : +381 11 354 61 69, 54 51 58
http://www.menssana.co.yu
 E-mail: office@menssana.co.yu
㈱フクミ・メディカルメディア Fukumi Corporation MedicalMedia
〒101-0032 東京都千代田区岩本町２－４－１０共同ビル（岩本町２丁目） tel.03-5687-2890 fax.03-5687-2918　URL:www.fukumi.co.jp/mm/ 　E-Mail: fmed@fukumi.co.jp

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------------------------------------------------
関連●--------------------------------
●MLリソース：美容外科手術
●MLリソース:角膜屈折矯正手術
●MLリソース：刺青[Tatoo]除去
●MLリソース:レーザー脱毛
------------------------------------------------
●2004
★★1191★20/19★04.09.13★076★腋臭多汗症に対するボツリヌス毒素 (Botox)/2p●MLリソース：ボツリヌス毒素[1057_add]
-------------------------------------------------
●2002
★★1131★18/11★02.05.27★047★眉間のしわの治療薬・ボツリヌス毒素（BOTOX COSMETIC）/2p●リソース：ボツリヌス毒素,Botulinum toxin type A[187KB]
-------------------------------------------------
●2001
★★1109★17/15★01.07.23★063★頸部ジストニー治療薬ボツリヌス毒素/1p●リソース：ボツリヌス毒素,Botulinum toxin type A[187KB]
-------------------------------------------------
●1999
★1057★15/15★99.07.16★063★ボツリヌス毒素の美容への利用/2p●1057追加メモ[141KB]
-------------------------------------------------
作成：1999.8.1　最終更新:2004.10.27 小菅博之
The Medical Letter日本語版
●追加メモ to 1057,1109,1131,1191
On Drugs and Therapeutics

このページは［The Medical Letter日本語版］の補足データとして添付しています。　［The Medical Letter］は新薬の厳正な評価誌であり、ここに収録される製品は新しくＦＤＡ承認された新薬に対する評価を中心としています。
　企画意図の第一は、収録製品についての米国内・世界での背景情報です。　例えば、各製品の承認関連データ、競合品との、あるいは市場での位置づけ、疫学データなど。　第二は、日本での該当製品や市場の情報。　市場の主要製品売上、開発中の治験薬等。　調査項目としては、■製品■解説■データ■臨床ガイドラインなど■総説記事・文献■ニュース・トピックス■リンク■主要サイト■その他

Action date	Supplement Number	Approval Type	Letters, Reviews, Labels, Patient Package Insert	備考
07/19/2004	5050	Supplement	Label Letter
12/21/2000	1004	Supplement	Letter Review
04/12/2000	5000	Supplement	Letter Label Review
12/09/1991	0000	Approval

治療法		内容	問題点
理学療法		エステなどで行われる電気分解法・電気凝固法などです。毛根といっしょにアポクリン腺や皮脂腺を処理するのですが、これらを完全に破壊することが難しいので、数ヶ月で元にもどってしまうことが多いと言われています。
薬物療法		制汗剤や殺菌剤が含まれた市販のデオドラント製品による方法です。いずれも汗や臭いを一時的に抑える効果があります。一般に市販されている制汗剤には、スプレー、クリーム、ローションなどのタイプがあり、汗の分泌を抑えることよって臭いを防ぐというものです。しかし、これらはあくまでも一時的なもので、長くても６時間、ひどいわきがの人ならせいぜい1時間ほどしかもちません。わきが臭を抑える薬も販売されています。これは皮脂を分解して、いやな臭いの元になる細菌を殺す作用のある抗生物質が使用されています。こちらも効果は６時間程度です。	制汗剤や消臭剤は使いすぎると、人によってはかぶれることもあります。また抗生物質の入っているものは抗生物質の副作用を引き起こす可能性がありますので、注意が必要です。また香り付きのものはわきが臭と混ざって、かえって悪臭になることもあるので、無香料タイプの方がいいでしょう。一時しのぎに使うのは良いですが、本当に臭いをなくしたいという人はきちんとした治療を受けることをおすすめします。
ボトックス注射療法		わきの皮膚にボトックスという注射を打つ治療法です。ボトックスは主にエクリン腺に付随する自律神経終末にはたらいて、汗を一定期間抑えるはたらきがあります。汗の量を抑えることにより、汗の拡散を防ぐので、わきがの臭いも抑える作用があります。効果は６ヶ月ほどですが、数分で終わり手軽に出来ます。美容外科などでよく行われています。	手軽で、それなりに効果もありますが、６ヶ月くらいしか効果が持続せず、1回10万円程度と高価なので、2～3回で手術ができる料金になってしまいます。手術は絶対にイヤだという人には向いているでしょう。
手術療法		わきがを完全に治すには、臭いを発するアポクリン腺を取り除いてしまう手術を受けるしかありません。	●術後の合併症手術後起こりうることとしては、わきに体液や血液が溜まったり(血腫)、わきの皮膚が一時的に硬くなったり、しびれたりすることがあります。しかし血腫は病院で取り除く処置をすることができ、わきの拘縮やしびれも時間と共に治っていくので、そんなに心配することはありません。またわきの皮膚に色素沈着が出ることがありますが、クリームなどで改善を図ることができます。
	切除法	わきの下の有毛部の汗腺や皮脂腺、毛根を切り取り、縫い合わせます。傷が大きくなることと、ひきつれを起こしたり取り残しが発生してしまうこともあり、現在はほとんど行われていないようです。
	吸引法	わきの下の皮膚を数ミリ切開し、そこからエクリン腺やアポクリン腺を吸引しようとする方法です。皮膚の生着も早く、傷跡もほとんど残らないという長所はありますが、汗腺の一部が残ってしまうことがあり、再発する場合もあります。
	超音波法	わきの下の皮膚に穴を開け、直径２ミリ程度の超音波を発振する管を入れ、血管や神経を避けて、汗腺のみを破砕しながら吸引する方法です。術後の血腫形成や皮膚壊死などの心配が無く、皮膚の生着も早いですが、やけどや組織内水腫の合併症の報告もあり、また汗腺の一部が残ってしまうこともあります。
	削除法	わきの下の皮膚の一部を切開し、汗腺を削除するための特殊な器具を挿入し、アポクリン腺やエクリン腺、皮脂腺まで除去する方法です。しかし直接、汗腺の残存を確認できないので取り残しがでる可能性もあります。美容外科ではよく行われています。
	剪除法	わきの下の皮膚を3～4センチ切開し、皮下組織内のアポクリン汗腺を直接目で確認し、取り除く方法です。重度のわきがに対しては最も確実性の高い方法で、技術が十分であれば再発することはありません。またわきがの手術の中で唯一健康保険が適用される方法でもあります。ただ傷痕が残ったり、手術後の圧迫や経過がやや長いという欠点はあります。	[時間]６０分～９０分程度[費用]保険適用・・・３万～５万　保険適用なし・・・25万～30万剪除法は、最も効果が高い方法と言われていますが、アポクリン腺を見分ける十分な経験や知識が必要で、担当する医師の技量でも差が出る手術です。技術が未熟であったり、短時間で終わらせようとすれば、汗腺の取り残しが生じ、不十分な結果になることもあります。