WO2005107733A1 - 局所麻酔用皮膚外用製剤 - Google Patents

局所麻酔用皮膚外用製剤 Download PDF

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Publication number
WO2005107733A1
WO2005107733A1 PCT/JP2005/008383 JP2005008383W WO2005107733A1 WO 2005107733 A1 WO2005107733 A1 WO 2005107733A1 JP 2005008383 W JP2005008383 W JP 2005008383W WO 2005107733 A1 WO2005107733 A1 WO 2005107733A1
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WO
WIPO (PCT)
Prior art keywords
skin
fatty acid
external preparation
acid ester
local anesthetic
Prior art date
Application number
PCT/JP2005/008383
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
Rakan Matui
Masami Ishida
Tokuyuki Namiki
Original Assignee
Shiseido Company, Ltd.
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 Shiseido Company, Ltd. filed Critical Shiseido Company, Ltd.
Publication of WO2005107733A1 publication Critical patent/WO2005107733A1/ja

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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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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

Definitions

  • the present invention relates to an external preparation for skin containing a local anesthetic. More specifically, the present invention relates to an oil-based external preparation containing a local anesthetic, which has a high skin permeability of a local anesthetic, and is excellent in immediate effect and sustainability of a local anesthetic effect.
  • amide-type local anesthetic such as lidocaine
  • injection of an amide-type local anesthetic has been performed for local anesthesia.
  • subcutaneous or intradermal injections of amide-type local anesthetics have been actively performed to relieve patients of pain.
  • Amide-type local anesthetics can block nerve transmission at the application site and locally relieve pain, and are expected to make a significant contribution to improving the quality of life for patients and facilitating medical treatment.
  • injection of an amide-type local anesthetic is painful at the time of injection, and there has been a strong demand for improvement, especially in infants and the elderly.
  • the amide-type local anesthetic passes into the stratum corneum, which is a barrier for permeation, it is immediately transferred to the circulating blood. Therefore, a high skin penetration rate is required to maintain the anesthetic effect at the local skin.
  • the penetration rate of a drug into the skin depends on the concentration of the drug contained in the base.Therefore, especially when the concentration of the amide type local anesthetic in the base is low, the skin penetration rate is extremely low, and Is it possible to obtain a persistent anesthetic effect by application? I got it.
  • a patch containing a high concentration of a local anesthetic is provided, and the power to obtain an anesthesia effect of a certain cereal ⁇ If there is a problem such as skin irritation or itching, or if the treatment site is small When there is unevenness or unevenness, the patch has to be cut off according to the site, and the patch needs to be devised.
  • the present invention has been made in view of the above circumstances, and in a skin external preparation containing an amide-type local anesthetic, the skin sensitivity of the amide-type local anesthetic is enhanced, thereby improving the immediate effect of the local anesthetic effect. It is intended to provide an excellent preparation for external use on the skin. Disclosure of the invention
  • glycerin fatty acid ester sorbitan fatty acid ester, polyglycerin fatty acid ester, polyoxetylene glycerin fatty acid ester, and polyoxyethylene were used together with the amide type local anesthetic.
  • Apply to skin by blending one or more nonionic surfactants at room temperature, which are semi-solid or liquid, selected from the group consisting of alkyl ethers and polyethylene glycol fatty acid esters In doing so, they found that the skin permeability of the amide-type local anesthetic was significantly increased, and completed the present invention.
  • the external preparation for skin of the present invention comprises a amide type local anesthetic and a group consisting of glycerin fatty acid ester, sonolebitan fatty acid ester, polyglycerin fatty acid ester, polyoxetylene glycerin fatty acid ester, polyoxyethylene alkyl ether and polyethylene dalicol fatty acid ester. It is characterized by being an oily preparation containing one or two or more selected non-ionic surfactants which are semi-solid or liquid at normal temperature.
  • the specific nonionic surfactant mentioned above enhances the skin permeability of the amide-type local anesthetic when applied to the skin with an oil-based external preparation containing the amide-type local anesthetic, and improves the usability of the oil-based preparation.
  • the stability can be improved.
  • the nonionic surfactant has 12 to 18 carbon atoms in the alkyl group and has a calorie with ethylene oxide. It is a polyoxyethylene alkyl ether having a monole number of 2 to 10.
  • the compounding amount of the nonionic surfactant is 0.5 to 20 mass based on the total mass of the external preparation for skin. / 0 is preferred.
  • the amount of the amide-type local anesthetics is preferably 1 0-6 0 weight 0/0 relative to the total weight of the external skin preparation.
  • the oily topical skin preparation of the present invention is preferably semi-solid or solid from the viewpoint of its usability and stability.
  • the external preparation for skin of the present invention can provide higher skin permeability of an amide-type local anesthetic when applied to the skin, and is excellent in immediate effect and sustainability of the local anesthetic effect. It is also excellent in usability and stability.
  • FIG. 1 is a graph showing the skin permeation rate of lidocaine in an external preparation containing various nonionic surfactants.
  • FIG. 2 is a graph showing the skin permeation rate of lidocaine in an external preparation containing POE (2) oleyl ether at each blending amount.
  • FIG. 3 is a graph showing the skin permeation rate of lidocaine in an external preparation containing lidocaine at each blending amount.
  • the external preparation for skin of the present invention contains an amide type local anesthetic and a specific nonionic surfactant as essential components.
  • amide-type local anesthetic used in the present invention examples include, for example, lidocaine, jib force-in, prilocaine, bupiva force-in, oral viva force-in, etide force-in, propitocaine, mepipa force-in, oxesasein, piberidinoacetyla. Ethyl minobenzoate and the like.
  • these amide-type local anesthetics can be used alone or in combination of two or more.
  • the amount of the amide-type local anesthetic in the external preparation for skin of the present invention is not particularly limited.
  • 1 0-6 is preferably 0 mass 0/0 relative to the total weight, more preferably 2 0-4 0 wt% Dearu. If the amount is less than 10% by mass, sufficient local anesthetic effect may not be obtained when applied to the skin, and if the amount exceeds 60% by mass, the stability of the preparation may be deteriorated.
  • the nonionic surfactant used in the present invention may be selected from glycerin fatty acid ester, sorbitan fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene alkynoleether, and polyethylene glycol fatty acid ester. Selected from the group consisting of
  • non-ionic surfactants which are semisolid or liquid at normal temperature and which can be used in the external preparation for skin of the present invention are exemplified below.
  • glycerin fatty acid ester examples include glyceryl monooleate and glyceryl monodistearate.
  • sorbitan fatty acid ester examples include sorbitan monolaurate, sorbitan monooleate, sorbitan sesquioleate, sorbitan trioleate, sonorebitan monoisostearate, and sorbitan sesquiisostearate.
  • polyglycerin fatty acid ester examples include diglyceryl monooleate, diglyceryl dioleate, diglyceryl monoisostearate, tetraglyceryl monooleate, hexaglyceryl monooleate, decaglyceryl disostearate, deglyceryl trioleate, Examples include depot glycerinol pentaisostearate, decaglyceryl pentaoleate, decaglyceryl monooleate, and decaglyceryl monoisostearate.
  • Polyoxyethylene (hereinafter, POE) glycerin fatty acid esters include, for example, POE hydrogenated castor oil, POE castor oil, POE glyceryl monooleate, and the like.
  • polyoxyethylene alkyl ether examples include POE lauryl ether, POE cetino ole ether, POE stealin ole ether, POE olein ole ether, and the like.
  • Polyethylene glycol (hereinafter, PEG) fatty acid esters include, for example, PEG monostearate, PEG monooleate, PEG diisostearate, PEG monolaurate, and the like.
  • the above-mentioned nonionic surfactants can be used alone or in combination of two or more.
  • the compounding amount of these nonionic surfactants in the external preparation for skin of the present invention is preferably 0.5 to 20% by mass, more preferably 1 to 1% by mass, based on the total mass of the external preparation for skin. 0 mass. / 0 . If the amount is less than 0.5% by mass, a sufficient effect of enhancing the permeability of the amide-type local anesthetic may not be obtained, and if the amount exceeds 20% by mass, the permeability is enhanced by increasing the amount of the compounding agent. No increase in effect is obtained, and it is not preferable in terms of safety on the skin.
  • the external preparation for skin of the present invention is an oily preparation.
  • oil-based preparation or "oil-based external preparation for skin” means a preparation containing an oil-based component as a main base and basically does not contain water. Some moisture may be contained as long as the object of the present invention can be achieved, such as moisture absorbed in the process.
  • the water content is preferably 10% by mass or less, more preferably 5% by mass or less, based on the total mass of the external preparation. Yes, more preferably 2% by mass or less.
  • the oily base component used in the external preparation for skin of the present invention is not particularly limited as long as it can be blended with an external preparation such as cosmetics, pharmaceuticals, and quasi-drugs.
  • an external preparation such as cosmetics, pharmaceuticals, and quasi-drugs.
  • Kisir Millis Synthetic ester oils such as phosphate myristyl, dimethylpolysiloxane, methylol Roh reflex Eni Honoré polysiloxane, Jifue - Honoré polysiloxane of sheet Liquid fats and oils such as corn oil, olive oil and rapeseed oil can be used in the external preparation for skin of the present invention.
  • Synthetic ester oils such as phosphate myristyl, dimethylpolysiloxane, methylol Roh reflex Eni Honoré polysiloxane, Jifue - Honoré polysiloxane of sheet Liquid fats and oils such as corn oil, olive oil and rapeseed oil can be used in the external preparation for skin of the present invention.
  • these oily base components can be used alone or in combination of two or more.
  • the amount of these oily base components in the external preparation for skin of the present invention is appropriately determined depending on the desired dosage form, the feeling of use when applied to the skin, and the like, and is not particularly limited. It is 20 to 80% by mass relative to the total mass of the preparation.
  • the formulation for external use on the skin of the present invention is not particularly limited as long as it is an oily formulation, and includes any formulation such as an oil-liquid system, a paste system, and an ointment system. It is preferably in the form or a solid.
  • a semi-solid or solid external preparation for skin can be prepared.
  • the compounding amount of the liquid oily base component in the external preparation for skin of the present invention is preferably 15 to 70% by mass, more preferably 30 to 70% by mass, based on the total mass of the external preparation for skin. 6 0 mass 0/0.
  • the amount is less than 15% by mass, it may be difficult to appropriately dissolve or disperse the topical anesthetic in a topical skin preparation. If the amount exceeds 70% by mass, the hardness may be too low, May drop when applied to skin, causing poor usability.
  • the external preparation for skin of the present invention may contain, in addition to the above specific nonionic surfactant, any surfactant usually used in external preparations for skin, as long as the effects of the present invention are not impaired.
  • the external preparation for skin of the present invention may contain, in addition to the amide-type local anesthetic, other optional components having a local anesthetic effect.
  • the method for preparing the external preparation for skin of the present invention is not particularly limited.
  • an amide-type local anesthetic and a nonionic surfactant are added to a heat-soluble oily base component, and the mixture is dissolved or dispersed by a stirring mixer. And cooled.
  • the topical skin preparation of the present invention may be used as a topical preparation for local anesthesia such as, for example, laser treatment, blood sampling, intravenous power injection, pain relief at the time of injection, post-herpetic neuralgia, trigeminal neuralgia, etc. It can be used for any purpose such as relieving causal pain, relieving pain and itch at skin wound sites such as soreness, rash, cuts and abrasions.
  • lidocaine was used as an amide-type local anesthetic.
  • all the compounding amounts are represented by mass% with respect to the total amount of the preparation.
  • the skin permeability of lidocaine in each preparation was measured by a skin permeability test using an abdominal depilated and excised skin of inVitro rats.
  • the method is as follows: (Method)
  • the receptor solution was stirred with a magnetic stirrer, and sampled in lmL every 2 hours until 10 hours later.
  • FIG. 1 shows the results.
  • the preparations of Examples 1 to 18 of the present invention containing a specific nonionic surfactant which is semisolid or liquid at normal temperature together with lidocaine are the same as the preparation of Comparative Example 1 containing no nonionic surfactant. In comparison, it resulted in significantly higher lidocaine skin penetration rates.
  • Examples 9 to 14 containing a polyoxyethylene alkynoleether having an alkyl group having 12 to 18 carbon atoms and an ethylene oxide addition mole number of 2 to 10 lidocaine skin The transmission speed was high.
  • Comparative Examples 2 to 4 containing nonionic surfactants (glyceryl monostearate, sorbitan monostearate, and POE (5) behe-leatenole) which are solid at room temperature showed that lidocaine permeated the skin through lidocaine.
  • the rates were comparable or rather low as in Comparative Example 1, which contained no nonionic surfactant.
  • POE Polyoxyethylene (The number in the box is the number of monocles with ethylene oxide.) The result is shown in figure 2. Compared with the formulation containing no nonionic surfactant, the skin permeation rate of lidocaine was significantly higher in the formulation containing 0.5 to 20% by mass of POE (2) oleyl ether. Was. In particular, in formulations containing 1% by mass or more of POE (2) oleyl ether, the skin permeation rate of lidocaine was remarkably high.
  • lidocaine as an amide-type local anesthetic, the effect of the compounding amount on its skin permeability was examined.
  • POE (2) oleinole ether was used as the nonionic surfactant
  • glycerinole monostearate was used as the nonionic surfactant.
  • Formulations containing the respective amounts of lidocaine were prepared according to the formulation shown in Table 3 below, and the skin permeation rate of lidocaine in each formulation was measured by the skin permeability test described above.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pain & Pain Management (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/JP2005/008383 2004-05-10 2005-04-26 局所麻酔用皮膚外用製剤 WO2005107733A1 (ja)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2004-139415 2004-05-10
JP2004139415A JP2005320282A (ja) 2004-05-10 2004-05-10 局所麻酔用皮膚外用製剤

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011121034A3 (en) * 2010-04-01 2012-05-31 Pharmanest Ab Water-free pharmaceutical compositions suitable for local anaesthetics

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006051818A1 (ja) * 2004-11-10 2006-05-18 Hisamitsu Pharmaceutical Co., Inc. 外用製剤及び貼付剤
ES2385737T3 (es) * 2004-11-10 2012-07-31 Hisamitsu Pharmaceutical Co., Inc. Fármaco para uso externo y parche adhesivo
JP2023027715A (ja) * 2021-08-17 2023-03-02 株式会社カネカ 医薬組成物、及び貼付剤

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0948739A (ja) * 1995-08-04 1997-02-18 Pola Chem Ind Inc 抗炎症医薬組成物
JPH0977662A (ja) * 1995-09-11 1997-03-25 Zeria Pharmaceut Co Ltd 軟膏剤
JP2000319168A (ja) * 1999-05-12 2000-11-21 Yuutoku Yakuhin Kogyo Kk 局所麻酔用テープ剤
JP2001072603A (ja) * 1999-09-03 2001-03-21 Zeria Pharmaceut Co Ltd 吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を配合した外用剤
JP2001131062A (ja) * 1999-11-02 2001-05-15 Yuutoku Yakuhin Kogyo Kk ミドドリン経皮適用剤
JP2003321347A (ja) * 2002-05-07 2003-11-11 Rohto Pharmaceut Co Ltd ゲル軟膏
JP2004051487A (ja) * 2002-07-16 2004-02-19 Ss Pharmaceut Co Ltd 経皮吸収製剤
JP2004083437A (ja) * 2002-08-23 2004-03-18 Shiseido Co Ltd 局所麻酔用固形状組成物
JP2004131472A (ja) * 2002-08-09 2004-04-30 Taisho Pharmaceut Co Ltd 痔疾治療用軟膏
JP2005029541A (ja) * 2003-07-11 2005-02-03 Shiseido Co Ltd 油中水型皮膚外用医薬品製剤

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2557657B2 (ja) * 1987-08-28 1996-11-27 エスエス製薬株式会社 経皮吸収促進基剤組成物
JPH10316590A (ja) * 1997-05-14 1998-12-02 Showa Denko Kk 局所麻酔用外用剤
JP2001058960A (ja) * 1999-08-19 2001-03-06 Yuutoku Yakuhin Kogyo Kk メラトニン経皮適用剤

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0948739A (ja) * 1995-08-04 1997-02-18 Pola Chem Ind Inc 抗炎症医薬組成物
JPH0977662A (ja) * 1995-09-11 1997-03-25 Zeria Pharmaceut Co Ltd 軟膏剤
JP2000319168A (ja) * 1999-05-12 2000-11-21 Yuutoku Yakuhin Kogyo Kk 局所麻酔用テープ剤
JP2001072603A (ja) * 1999-09-03 2001-03-21 Zeria Pharmaceut Co Ltd 吉草酸酢酸プレドニゾロン及び塩基性局所麻酔薬を配合した外用剤
JP2001131062A (ja) * 1999-11-02 2001-05-15 Yuutoku Yakuhin Kogyo Kk ミドドリン経皮適用剤
JP2003321347A (ja) * 2002-05-07 2003-11-11 Rohto Pharmaceut Co Ltd ゲル軟膏
JP2004051487A (ja) * 2002-07-16 2004-02-19 Ss Pharmaceut Co Ltd 経皮吸収製剤
JP2004131472A (ja) * 2002-08-09 2004-04-30 Taisho Pharmaceut Co Ltd 痔疾治療用軟膏
JP2004083437A (ja) * 2002-08-23 2004-03-18 Shiseido Co Ltd 局所麻酔用固形状組成物
JP2005029541A (ja) * 2003-07-11 2005-02-03 Shiseido Co Ltd 油中水型皮膚外用医薬品製剤

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011121034A3 (en) * 2010-04-01 2012-05-31 Pharmanest Ab Water-free pharmaceutical compositions suitable for local anaesthetics
CN102892408A (zh) * 2010-04-01 2013-01-23 帕玛内斯特公司 适于局部麻醉剂的无水药物组合物

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