JP5496684B2 - 局所使用のためのナノ粒子状麻酔薬組成物 - Google Patents
局所使用のためのナノ粒子状麻酔薬組成物 Download PDFInfo
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- JP5496684B2 JP5496684B2 JP2009553872A JP2009553872A JP5496684B2 JP 5496684 B2 JP5496684 B2 JP 5496684B2 JP 2009553872 A JP2009553872 A JP 2009553872A JP 2009553872 A JP2009553872 A JP 2009553872A JP 5496684 B2 JP5496684 B2 JP 5496684B2
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- poly
- anesthetic
- lidocaine
- prilocaine
- polymer
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- 230000037152 sensory function Effects 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000002344 surface layer Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- A61K9/00—Medicinal preparations characterised by special physical form
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Description
効率を示すという事実に関する文献も存在しない。同じ文脈において、ポリマーナノ粒子中の麻酔剤の製剤が、非ナノ粒子状の製剤と比較して、感覚消失時間の増大および優れた規定(definition)の麻酔効果につながり得るという本発明者らにより確認された驚くべき事実に関する文献も存在しない。
麻酔薬ナノ粒子は、表1に示される相の組成に従って調製した。
ヒドロゲルは、例1に従って調製したナノ粒子懸濁液に、0.25%、0.75%および1.5%の最終濃度でCarbopol(登録商標)940 (カルボキシポリメチレン)を組み込むことにより調製し、最終体積は、製剤 G 5-PCL-TWE、G 5-PCL-TWE 0.75%およびG 5-EUD-EPK (例1に従ってつくられた濃縮懸濁液 5-PCL-TWEおよび5-EUD-EPKからそれぞれ調製される) については最終的な表示割合5%の麻酔薬を得るように、製剤 G 3-PCL-TWE (例1に従ってつくられた濃縮懸濁液 3-PCL-TWEから調製される) については最終的な表示割合3%の麻酔薬を得るように、蒸留水を添加することにより調整した。
リドカインおよびプリロカインのナノ粒子を含有するヒドロゲルにより促されるインビボにおける感覚消失のパーセンテージ割合を、“Tail Flick”技術 (Kolesnikov Y. e col. “Evaluation of the tail formalin test in mice as a new model to assess local analgesic effects”. Brain Research, v. 1029, p. 217-223, 2004) および、比較のための市販製品 EMLA(登録商標) (AstraZeneca do Brasil Ltda.により製造される2.5% リドカインおよび2.5% プリロカインを含有するクリーム) を用いてマウスで決定した。
・ポジティブコントロールグループ (1グループ): 市販製品 EMLA(登録商標)の局所適用
・ネガティブコントロールグループ (1グループ): 薬剤なしのナノカプセルを含有するヒドロゲル
・試験グループ (4グループ): 表4に規定される麻酔薬の割合およびナノ粒子組成物に従った、リドカインおよびプリロカインを含有するナノ粒子を有するヒドロゲルの局所適用
ここで、TL=麻酔薬製剤の効果の下での潜伏時間;TB=ベースの潜伏時間;6=照射に対する最大の露出時間。
以下に、本願出願の当初の特許請求の範囲に記載された発明を付記する。
[1] 少なくとも一つの治療的に有効な量のポリマーナノ粒子中の局所麻酔剤、および少なくとも一つの粘度増強剤を含む、皮膚または粘膜への局所適用のための麻酔薬組成物。
[2] ナノ粒子の製造のために使用されるポリマーが、以下からなる群より選択される、[1]に記載の麻酔薬組成物:
ポリ(ε-カプロラクトン);メタクリル酸(methacrylate acid)の共重合体およびメタクリレートまたはアクリル酸エステル;ポリ(アルキルメタクリレート);ポリ(メチルメタクリレート);ポリ(ラクチド)、ポリ(ラクチド-グリコリド)、ポリ(グリコリド)、ポリ(カプロラクトン)、ポリ(アミド)、ポリ(無水物)、ポリ(アミノ酸)、ポリ(エステル)、ポリ(シアノアクリレート)、ポリ(ホスファジン)、ポリ(ホスホエステル)、ポリ(エステルアミド)、ポリ(ジオキサノン)、ポリ(アセタール)、ポリ(セタール)、ポリ(カルボネート)、ポリ(オルトカルボネート)、分解性ポリ(ウレタン)、キチン、キトサン、ポリ(ヒドロキシブチレート)、ポリ(ヒドロキシバレレート)、ポリ(マレイン酸)、ポリ(アルキレンオキサレート)、ポリ(アルキレンスクシネート)、ポリ(ヒドロキシブチレート-コ-ヒドロキシバレレート)、およびコポリマー、ターポリマー、酸化セルロース、またはこれら物質の組み合わせもしくは混合物。
[3] 局所麻酔剤が、以下からなる群より選択される、[1]または[2]に記載の麻酔薬組成物:
ベンゾエートエステルまたはアミノ−エステル、アミノ−アミドアニリド、アミノ−エステルナフトエート、安息香酸、プラモキシン、ジクロニン、メキシレチン(mexylethine)、リドカイン、プリロカイン(prilocaine)、ブピバカイン(bupivacaine)、メピボカイン(mepivocaine)、エチドカイン(ethydocaine)、ブタニルカイン(butanylcaine)、トリメカイン(trimecaine)、あるいは、テトラカイン、ベンゾカイン、ロピバカイン(ropivacaine)、ジブカイン、プロカイン、クロルプロカイン(chlorprocaine)、ブタンベン(butambene)、ピクラート、ジブカイン、アルティカイン(articaine)およびキシロカイン、並びにこれらの塩、誘導体または混合物。
[4] 粘度増強剤が、以下からなる群より選択される、[1]または[2]に記載の麻酔薬組成物:
セルロースおよびその誘導体、ゴム、アミド、カルボキシポリメチレン、ポリ(エチレングリコール)、ポリ(ビニルピロリドン)。
[5] 50 Cpを超える粘度、好ましくは100 Cpを超える粘度を示す、[1]〜[4]の何れか1に記載の麻酔薬組成物。
[6] 約100000〜800000 Cpの粘度を示す、[1]〜[5]の何れか1に記載の麻酔薬組成物。
[7] 650000 Cp未満の粘度を示す、[1]〜[6]の何れか1に記載の麻酔薬組成物。
[8] 前記少なくとも一つの麻酔剤の濃度が、組成物の約0.5〜10%を構成する、[1]〜[7]の何れか1に記載の麻酔薬組成物。
[9] 少なくとも2つの麻酔剤の組み合わせを含む、[1]〜[8]の何れか1に記載の麻酔薬組成物。
[10] 前記麻酔剤が、リドカインおよびプリロカインからなる、[9]に記載の麻酔薬組成物。
[11] 約2.5%の濃度のリドカインおよび約2.5%の濃度のプリロカインを含む、[8]に記載の麻酔薬組成物。
[12] 皮膚または粘膜への局所適用のための局所麻酔薬組成物の調製における、少なくとも一つの局所麻酔剤をカプセル化しているポリマーナノ粒子の使用。
Claims (3)
- (i)以下の(a)〜(d)からなるポリマーナノカプセルの懸濁液であって、116〜198nmの平均粒径を有するポリマーナノカプセルの懸濁液:
(a)ポリ(ε-カプロラクトン)、ポリ(メタクリル酸)、Eudragit S100(登録商標)またはメチルポリメタクリレートからなる群より選択されるポリマー;
(b)リドカインおよびプリロカインの組合せ;
(c)SPAN 60(登録商標)、EPIKURON 170(登録商標)、TWEEN 80(登録商標)またはこれらの材料の混合物からなる群より選択される界面活性剤;
(d)水;および
(ii)粘度増強剤としての少なくとも一つのカルボキシポリメチレン
を含む、皮膚または粘膜への局所適用のための麻酔薬組成物。 - 麻酔剤の濃度が、0.5〜10%のリドカインおよび0.5〜10%のプリロカインである、請求項1に記載の麻酔薬組成物。
- 2.5%の濃度のリドカインおよび2.5%の濃度のプリロカインを含む、請求項2に記載の麻酔薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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BRPI0700832A BRPI0700832B8 (pt) | 2007-03-16 | 2007-03-16 | composição anestésica tópica compreendendo suspensão de nanocápsulas poliméricas de lidocaína e prilocaína |
BRPI0700832-5 | 2007-03-16 | ||
PCT/BR2008/000070 WO2008113144A1 (en) | 2007-03-16 | 2008-03-12 | Nanoparticulated anesthetic composition for topic use |
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JP2010521498A JP2010521498A (ja) | 2010-06-24 |
JP5496684B2 true JP5496684B2 (ja) | 2014-05-21 |
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US (1) | US8568788B2 (ja) |
EP (1) | EP2134334B1 (ja) |
JP (1) | JP5496684B2 (ja) |
AR (1) | AR065723A1 (ja) |
BR (1) | BRPI0700832B8 (ja) |
CL (1) | CL2008000728A1 (ja) |
CO (1) | CO6220944A2 (ja) |
EC (1) | ECSP099691A (ja) |
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PE (2) | PE20131337A1 (ja) |
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RU2497679C2 (ru) | 2008-10-02 | 2013-11-10 | Милан Инк. | Способ получения многослойного клеящегося ламинированного материала |
BR102012022036B1 (pt) * | 2012-08-31 | 2019-10-01 | Biolab Sanus Farmacêutica Ltda. | Nanopartícula polimérica de finasterida e minoxidil, processo de sua preparação, suspensão aquosa contendo a mesma, composição farmacêutica, e seu uso |
BR102014028009B1 (pt) | 2014-11-10 | 2023-04-18 | Universidade Federal De Pelotas | Composições filmogênicas para bioadesivos anestésicos tópicos (bats) para liberação controlada de princípios ativos e bioadesivos anestésicos tópicos |
WO2019028339A1 (en) * | 2017-08-04 | 2019-02-07 | Eric Haas | MICROPARTICLES AND NANOPARTICLES OF ANESTHETIC AGENTS, AND METHODS OF MAKING AND USING THEM |
CN113244167B (zh) * | 2021-05-20 | 2022-11-29 | 河北科技大学 | 一种盐酸利多卡因凝胶及其制备方法 |
RU208882U1 (ru) * | 2021-08-25 | 2022-01-19 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Курская государственная сельскохозяйственная академия имени И.И. Иванова" | Раневая атравматическая повязка для животных |
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SE7713618L (sv) * | 1977-12-01 | 1979-06-02 | Astra Laekemedel Ab | Lokalanestetisk blandning |
FR2659554B1 (fr) * | 1990-03-16 | 1994-09-30 | Oreal | Composition pour le traitement cosmetique et/ou pharmaceutique des couches superieures de l'epiderme par application topique sur la peau et procede de preparation correspondant. |
DE4120760A1 (de) * | 1991-06-24 | 1993-03-04 | 3 M Medica Gmbh | Traegersysteme fuer arzneimittel |
JPH09255565A (ja) * | 1996-03-26 | 1997-09-30 | Daikyo Yakuhin Kogyo Kk | 皮膚局所麻酔用ヒドロゲルパッチ |
CA2271750C (en) | 1997-07-02 | 2004-04-27 | Euro-Celtique, S.A. | Prolonged anesthesia in joints and body spaces |
US5993836A (en) * | 1998-04-28 | 1999-11-30 | Castillo; James G. | Topical anesthetic formulation |
KR100463167B1 (ko) * | 2001-04-13 | 2004-12-23 | 주식회사 태평양 | 고분자 나노입자를 이용한 경피흡수제 및 이를 함유한외용제 조성물 |
US20070154527A1 (en) * | 2001-10-12 | 2007-07-05 | Monosoirx, Llc | Topical film compositions for delivery of actives |
US20080124400A1 (en) * | 2004-06-24 | 2008-05-29 | Angiotech International Ag | Microparticles With High Loadings Of A Bioactive Agent |
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EP2134334A4 (en) | 2013-04-24 |
HUE051155T2 (hu) | 2021-03-01 |
BRPI0700832B8 (pt) | 2021-05-25 |
AR065723A1 (es) | 2009-06-24 |
PL2134334T3 (pl) | 2021-03-08 |
CO6220944A2 (es) | 2010-11-19 |
WO2008113144A1 (en) | 2008-09-25 |
ECSP099691A (es) | 2010-02-26 |
CL2008000728A1 (es) | 2008-09-26 |
ES2804466T3 (es) | 2021-02-08 |
EP2134334A1 (en) | 2009-12-23 |
BRPI0700832B1 (pt) | 2017-12-26 |
PT2134334T (pt) | 2020-08-20 |
BRPI0700832A (pt) | 2008-11-04 |
US8568788B2 (en) | 2013-10-29 |
JP2010521498A (ja) | 2010-06-24 |
EP2134334B1 (en) | 2020-05-13 |
PE20081883A1 (es) | 2008-12-27 |
US20100086614A1 (en) | 2010-04-08 |
PE20131337A1 (es) | 2013-11-18 |
MX2009009853A (es) | 2010-02-18 |
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