WO2017068673A1 - Composition pharmaceutique pour la peau - Google Patents

Composition pharmaceutique pour la peau Download PDF

Info

Publication number
WO2017068673A1
WO2017068673A1 PCT/JP2015/079752 JP2015079752W WO2017068673A1 WO 2017068673 A1 WO2017068673 A1 WO 2017068673A1 JP 2015079752 W JP2015079752 W JP 2015079752W WO 2017068673 A1 WO2017068673 A1 WO 2017068673A1
Authority
WO
WIPO (PCT)
Prior art keywords
weight
aqueous gel
composition
carboxyvinyl polymer
skin
Prior art date
Application number
PCT/JP2015/079752
Other languages
English (en)
Japanese (ja)
Inventor
亮 赤松
史紀 鳴海
雅崇 藤川
Original Assignee
マルホ株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by マルホ株式会社 filed Critical マルホ株式会社
Priority to PCT/JP2015/079752 priority Critical patent/WO2017068673A1/fr
Priority to JP2017545806A priority patent/JP6925275B2/ja
Priority to PCT/JP2016/081234 priority patent/WO2017069230A1/fr
Publication of WO2017068673A1 publication Critical patent/WO2017068673A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone

Definitions

  • the present invention relates to a pharmaceutical composition for skin useful for the treatment of acne vulgaris. More specifically, the present invention relates to a pharmaceutical composition for skin comprising benzoyl peroxide.
  • Acne vulgaris is a skin disease commonly referred to as “acne”. Self-care with pharmaceuticals etc. is carried out because it greatly reduces quality of life in a well-regulated aspect because the face is a frequent occurrence site. It cannot be said that it is a good thing.
  • Benzoyl peroxide has been used in the treatment of acne vulgaris in many countries since the 1960s.
  • Patent Literature 1 and Patent Literature 2 disclose various compositions.
  • Patent Document 1 discloses a water-soluble preparation for topical application to the skin, which contains water, a water-miscible organic solvent, and benzoyl peroxide.
  • Example 1 of Patent Document 1 discloses a water-soluble gel preparation containing 5% by weight of propylene glycol as a water-miscible organic solvent and 1.75% by weight of carboxyvinyl polymer as a gelling agent.
  • Patent Document 2 discloses a delivery system comprising a pad and a liquid composition containing an insoluble dermatologically active ingredient.
  • the liquid compositions I to VII of Patent Document 2 disclose a liquid composition containing 6% by weight of glycerin 96%, 0.3% by weight of carboxyvinyl polymer, 0.5% by weight of sodium edetate, and other additives. ing.
  • the present inventors have found that by adding a chelating agent to the preparation, it is possible to remarkably suppress property changes during high-temperature storage, and to complete the present invention. It came. Furthermore, the aqueous gel agent excellent in the main ingredient stability can be provided by adjusting the content rate of the carboxyvinyl polymer in a formulation.
  • an aqueous gel comprising (a) 2 to 3.5% by weight of benzoyl peroxide (b) 0.4 to 2.2% by weight of carboxyvinyl polymer (c) a chelating agent.
  • the chelating agent (c) is one or more selected from the group consisting of sodium edetate, tetrasodium edetate, sodium metaphosphate, gluconic acid, malic acid, citric acid, and sodium citrate.
  • the dermatological composition according to the present invention suppresses a change in the properties of the preparation by the action of the chelating agent, and is excellent in the stability of the active ingredient in the preparation by adjusting the content of the carboxyvinyl polymer.
  • saved at 50 degreeC for 4 weeks is shown.
  • the vertical axis represents ⁇ BA (% by weight), and the horizontal axis represents carboxyvinyl polymer content (% by weight).
  • the relationship between the propylene glycol content of the composition and ⁇ BA when a composition containing 0.8% by weight of carboxyvinyl polymer is stored at 50 ° C. for 4 weeks is shown.
  • the vertical axis represents ⁇ BA (% by weight), and the horizontal axis represents propylene glycol content (% by weight).
  • the composition according to the present invention is a composition for skin containing benzoyl peroxide as an active ingredient.
  • Benzoyl peroxide can be prepared by adding a hydrogen peroxide solution to a sodium hydroxide solution to obtain a sodium peroxide solution, and adding benzoyl chloride thereto.
  • the content of benzoyl peroxide (a) is preferably 2 to 3.5% by weight, more preferably 2.3 to 2.7% by weight. 2.5% by weight is particularly preferred.
  • content rate means the ratio of the weight of each component with respect to the total weight of the composition of this invention.
  • the carboxyvinyl polymer (b) used in the present invention may be one conventionally used as a thickener in pharmaceuticals and the like.
  • Carboxyvinyl polymer is available from various manufacturers as an additive that complies with the “Pharmaceutical Additive Standard 2013”.
  • the content of the carboxyvinyl polymer (b) in the present invention is preferably 0.4 to 2.2% by weight, and more preferably 0.6 to 2% by weight. 0.6 to 1.8% by weight is more preferable, and 0.6 to 1.3% by weight is particularly preferable. Most preferably, it is 0.6 to 1% by weight.
  • the chelating agent (c) of the present invention is not limited to the following, but preferred examples of the chelating agent include sodium edetate, tetrasodium edetate, sodium metaphosphate, gluconic acid, malic acid, citric acid, And sodium citrate.
  • the content of the chelating agent is preferably 0.01 to 0.5% by weight, more preferably 0.02 to 0.4% by weight, and particularly preferably 0.05 to 0.4% by weight. Most preferably, it is 0.05 to 0.2% by weight.
  • These chelating agents may be used alone or in combination of two or more.
  • chelating agents are additives that meet any of the requirements of “Japanese Pharmacopoeia (JP16)”, “Pharmaceutical Additive Standard 2013”, “Quasi-drug Raw Material Standard 2006”, and “Food Additives Official Version 8”. Available from various manufacturers.
  • aqueous gel means an aqueous gel described in the Japanese Pharmacopoeia (JP16) General Rules for Preparations.
  • the water content is preferably 80 to 97% by weight, particularly preferably 90 to 97% by weight.
  • the dermatological composition according to the present invention preferably contains a polyol as a water-soluble component.
  • polyol is synonymous with “polyhydric alcohol” and refers to an alcohol containing more than one hydroxyl group.
  • the polyol used in the composition according to the present invention is not limited to the following, but preferred examples of the polyol include propylene glycol, dipropylene glycol, 1,3-butylene glycol, ethoxydiglycol, and polyethylene glycol. Etc.
  • a particularly preferred polyol is propylene glycol.
  • the content of the polyol is preferably 0.5 to 10% by weight, more preferably 0.5 to 5% by weight, particularly preferably 0.8 to 3.7% by weight, and most preferably 0.8 to 2% by weight.
  • These polyols can be obtained from various manufacturers as additives that meet any of “Japanese Pharmacopoeia (JP16)”, “Pharmaceutical Additive Standard 2013”, and “Quasi-drug Raw Material Standard 2006”.
  • the composition according to the present invention preferably contains 0.1 to 1% by weight of a pH regulator.
  • the pH adjuster used in the composition according to the present invention is not limited to the following, but preferred examples of the pH adjuster include potassium hydroxide, sodium hydroxide, monoethanolamine, diethanolamine, diisopropanolamine, Examples thereof include a pH regulator selected from the group consisting of ethanolamine, triisopropanolamine and the like. These pH regulators are additives that comply with any of the following standards: “Japanese Pharmacopoeia (JP16)”, “Pharmaceutical Additives Standard 2013”, “Quasi-drug Raw Material Standard 2006”, “Food Additives Official Version 8” Can be obtained from various manufacturers.
  • the pH of the composition according to the present invention is preferably 4 to 11, more preferably 4 to 8, and particularly preferably 4.5 to 6.5.
  • the composition for skin which concerns on this invention does not contain surfactant.
  • the surfactant is preferably less than 0.2% by weight, more preferably less than 0.1% by weight, and particularly preferably less than 0.05% by weight. Most preferably, no surfactant is included in the composition.
  • the dermatological composition according to the present invention is provided as an external preparation of an aqueous gel.
  • the affected area is washed once to several times a day, and then an appropriate amount is applied to the affected area.
  • composition for skin which concerns on this invention can contain the additive generally used for the external preparation for skin.
  • additives include antioxidants (ascorbic acid, dibutylhydroxytoluene, tocopherol acetate, etc.), stabilizers (l-menthol, etc.), preservatives (paraoxybenzoic acid esters, etc.), colorants (titanium oxide, etc.) Etc.).
  • the total amount of additives is preferably 5% by weight or less, more preferably 3% by weight or less, and particularly preferably 2% by weight or less.
  • composition of the present invention includes a composition obtained by arbitrarily combining them. Also included are compositions obtained by arbitrarily combining the weight percentages and weight ratios described for the essential components and optional components.
  • the upper limit value or the lower limit value of each numerical range can be arbitrarily combined.
  • a composition was prepared for the purpose of developing an aqueous gel containing benzoyl peroxide, which does not cause changes in the properties of the preparation.
  • Table 1 shows examples of the composition according to the present invention.
  • composition Sodium edetate was added and dissolved in water, and then the carboxyvinyl polymer was swollen to form a gel phase. Separately, benzoyl peroxide was dispersed in water and propylene glycol to form a main drug phase. The main drug phase was added to the gel phase and mixed, and an aqueous solution of a pH adjusting agent was added to the gel phase and mixed to prepare a uniform.
  • confirmation method of property change of composition A 1 g sample was placed on a watch glass placed on white paper, and the presence or absence of lumps was evaluated visually and touched.
  • composition Nos. 5, 8, and 11 were damped when stored at 50 ° C. for 2 weeks, but compositions No. 6, 7, 9 to which sodium edetate was added respectively. , 10 and 12 were not damped.
  • sodium edetate has an effect in suppressing property changes (damage).
  • the amount of benzoic acid in the preparation (weight%) after storing the composition in a thermostat set at 50 ° C. for a certain period was quantified, and the difference from the amount of benzoic acid (wt%) in the preparation at the start ⁇ BA ( % By weight). That is, it was judged that the smaller the ⁇ BA (% by weight), the better the main drug stability in the preparation.
  • FIG. 1 shows the correlation between carboxyvinyl polymer content and ⁇ BA in a composition containing 5% by weight propylene glycol.
  • the value of ⁇ BA decreased as the content of carboxyvinyl polymer in the composition decreased, that is, the main drug stability in the preparation tended to improve.
  • FIG. 2 shows the correlation between propylene glycol content and ⁇ BA in a composition containing 0.8 wt% carboxyvinyl polymer.
  • benzoyl peroxide in the composition is very easily decomposed, but by adjusting the content of carboxyvinyl polymer and further adjusting the content of propylene glycol, it is a gel agent with excellent stability of the active ingredient.
  • it is a gel agent with excellent stability of the active ingredient.
  • the dermatological composition containing benzoyl peroxide as an active ingredient according to the present invention does not change its properties even under high temperature storage, and can achieve excellent stability of the active ingredient in the preparation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention fournit une composition pharmaceutique pour la peau qui consiste en un gel aqueux contenant un peroxyde de benzoyle en tant que principe actif, dont la préparation pharmaceutique ne change pas de caractéristique y compris lors d'une conservation à température élevée, et qui possède une excellente stabilité de son agent principal. Plus précisément, la composition de l'invention consiste en un gel aqueux pour la peau, qui comprend 2 à 3,5% en masse de peroxyde de benzoyle, et 0,4 à 2,2% en masse d'un chélateur tel qu'un polymère carboxyvinyle et un édétate de sodium, ou similaire.
PCT/JP2015/079752 2015-10-21 2015-10-21 Composition pharmaceutique pour la peau WO2017068673A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/JP2015/079752 WO2017068673A1 (fr) 2015-10-21 2015-10-21 Composition pharmaceutique pour la peau
JP2017545806A JP6925275B2 (ja) 2015-10-21 2016-10-21 皮膚用の医薬組成物
PCT/JP2016/081234 WO2017069230A1 (fr) 2015-10-21 2016-10-21 Composition pharmaceutique pour la peau

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2015/079752 WO2017068673A1 (fr) 2015-10-21 2015-10-21 Composition pharmaceutique pour la peau

Publications (1)

Publication Number Publication Date
WO2017068673A1 true WO2017068673A1 (fr) 2017-04-27

Family

ID=58556810

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/JP2015/079752 WO2017068673A1 (fr) 2015-10-21 2015-10-21 Composition pharmaceutique pour la peau
PCT/JP2016/081234 WO2017069230A1 (fr) 2015-10-21 2016-10-21 Composition pharmaceutique pour la peau

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/JP2016/081234 WO2017069230A1 (fr) 2015-10-21 2016-10-21 Composition pharmaceutique pour la peau

Country Status (2)

Country Link
JP (1) JP6925275B2 (fr)
WO (2) WO2017068673A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022118942A1 (fr) * 2020-12-04 2022-06-09 マルホ株式会社 Composition en émulsion à usage externe

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009503056A (ja) * 2005-08-02 2009-01-29 ソル − ゲル テクノロジーズ リミテッド 水不溶性成分の金属酸化物被覆
US20090191245A1 (en) * 2006-05-17 2009-07-30 Galderma Research & Development Reduced-irritant dermatological compositions comprising at least one naphthoic acid compound and benzoyl peroxide and treatment of keratinization disorders therewith
JP2011504923A (ja) * 2007-11-30 2011-02-17 ガルデルマ・リサーチ・アンド・デヴェロップメント 少なくとも１種のナフトエ酸誘導体、過酸化ベンゾイルおよび少なくとも１種の皮膜形成剤を含む組成物、その調製方法、およびその使用
US20120252897A1 (en) * 2011-03-29 2012-10-04 Glenmark Generics Limited Combination composition comprising benzoyl peroxide and adapalene

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH08245370A (ja) * 1995-03-03 1996-09-24 Noevir Co Ltd 水中油型乳化組成物
JP2000204020A (ja) * 1999-01-13 2000-07-25 Pola Chem Ind Inc 唇用の化粧料
FR2823669B1 (fr) * 2001-04-23 2004-03-26 Oreal Procede pour augmenter le seuil de tolerance d'une peau sensible ou intolerante
EP1923041A1 (fr) * 2006-10-20 2008-05-21 Symrise GmbH & Co. KG Utilisation des C10-C14 alcane-diols pour la préparation d'une composition pour la prophylaxe et/ou le traitement des pellicules induites par Malassezia, ainsi que des compositions comprenant des C10-C14 alcane-diols
BRPI0913326C1 (pt) * 2008-06-05 2021-05-25 Dow Pharmaceutical Sciences formulação farmacêuticas tópicas contendo uma baixa concentração de peróxido de benzoíla em suspensão aquosa e um solvente orgânico miscível em água
US8575189B2 (en) * 2008-10-08 2013-11-05 Takata Seiyaku Co., Ltd. Tacrolimus preparation for external applications
JP2014040385A (ja) * 2012-08-21 2014-03-06 Shiseido Co Ltd 乳化化粧料
PT2919747T (pt) * 2012-11-13 2019-01-16 Galderma Sa Composição de lavagem de bpo
CN104853746B (zh) * 2012-11-27 2018-02-23 索尔-格尔科技有限公司 用于治疗红斑痤疮的组合物
US9855211B2 (en) * 2013-02-28 2018-01-02 Novan, Inc. Topical compositions and methods of using the same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009503056A (ja) * 2005-08-02 2009-01-29 ソル − ゲル テクノロジーズ リミテッド 水不溶性成分の金属酸化物被覆
US20090191245A1 (en) * 2006-05-17 2009-07-30 Galderma Research & Development Reduced-irritant dermatological compositions comprising at least one naphthoic acid compound and benzoyl peroxide and treatment of keratinization disorders therewith
JP2011504923A (ja) * 2007-11-30 2011-02-17 ガルデルマ・リサーチ・アンド・デヴェロップメント 少なくとも１種のナフトエ酸誘導体、過酸化ベンゾイルおよび少なくとも１種の皮膜形成剤を含む組成物、その調製方法、およびその使用
US20120252897A1 (en) * 2011-03-29 2012-10-04 Glenmark Generics Limited Combination composition comprising benzoyl peroxide and adapalene

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022118942A1 (fr) * 2020-12-04 2022-06-09 マルホ株式会社 Composition en émulsion à usage externe

Also Published As

Publication number Publication date
JP6925275B2 (ja) 2021-08-25
WO2017069230A1 (fr) 2017-04-27
JPWO2017069230A1 (ja) 2018-08-09

Similar Documents

Publication Publication Date Title
US10350166B2 (en) Non surface active agent non polymeric agent hydro-alcoholic foamable compositions, breakable foams and their uses
RU2621615C2 (ru) Фармацевтическая композиция, содержащая луликоназол
JP5345937B2 (ja) 抗真菌組成物
WO2020028820A1 (fr) Compositions topiques et procédés de préparation et d'utilisation
JPWO2009031642A1 (ja) 医薬組成物
CA3078783A1 (fr) Composition pharmaceutique topique d'adapalene et de minocycline
JP4690672B2 (ja) 乳剤性皮膚外用剤
EP3446693B1 (fr) Compositions pharmaceutiques et formulations comprenant de l´acétate d'aluminium pour application topique avec effet astringent et antimicrobien
WO2017068673A1 (fr) Composition pharmaceutique pour la peau
HU223075B1 (hu) Tiagabint, illetve sóját tartalmazó gyógyszerkészítmény és eljárás annak előállítására
EP1526849B1 (fr) Formulations topiques contenant du ketoprofene stabilisees au sulisobenzone
JP6503626B2 (ja) 医薬組成物
JP6503627B2 (ja) 医薬液体組成物
JP2016023170A (ja) 外用組成物
JP4686144B2 (ja) 油脂性軟膏剤
JP2008184445A (ja) アダパレン含有外用剤組成物
JP6543945B2 (ja) 乳化組成物
JP6084579B2 (ja) タクロリムスを含有する水中油型クリーム状組成物
CN116942602B (zh) 一种枸橼酸托法替布药物组合物
JP5980171B2 (ja) アダパレン含有外用剤組成物
US20230037905A1 (en) Topical composition comprising tofacitinib and fingolimod
JP4060347B2 (ja) ２２−オキサ−１α，２５−ジヒドロキシビタミンＤ３を含有する水中油型乳剤性ローション剤
JP2011068695A (ja) ミノキシジル含有製剤
JP2019206498A (ja) 外用医薬組成物
KR20170137117A (ko) 피부용의 의약 조성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15906679

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15906679

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP