WO2005082334A1 - 徐放性クリーム剤 - Google Patents
徐放性クリーム剤 Download PDFInfo
- Publication number
- WO2005082334A1 WO2005082334A1 PCT/JP2005/002926 JP2005002926W WO2005082334A1 WO 2005082334 A1 WO2005082334 A1 WO 2005082334A1 JP 2005002926 W JP2005002926 W JP 2005002926W WO 2005082334 A1 WO2005082334 A1 WO 2005082334A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sustained
- release
- fatty acid
- cream
- release cream
- Prior art date
Links
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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/10—Dispersions; Emulsions
Definitions
- the present invention relates to a sustained release cream.
- Drug administration methods include intravenous injection, oral administration, and transdermal administration.
- transdermal administration is characterized in that it can avoid the first-pass effect in the liver and is simple to administer.
- Dosage forms for preparations for transdermal administration include patches, ointments and lotions.
- Ointments and lotions have the problem that the duration of the drug effect is short because the drug is released more quickly than patches.
- an external preparation comprising non-porous polymer fine particles containing a drug and a spreadable base and dispersing the non-porous polymer fine particles in the spreadable base has been proposed (Patent Document 1).
- Patent Document 1 Japanese Patent Application Laid-Open No. 2003-089631
- an object of the present invention is to provide a cream preparation which is improved in stickiness and extensibility and has excellent usability, and which can release the active ingredient for a long period of time. It is here.
- the present invention provides an oil phase containing 10 to 25% by mass of an oil phase based on the total amount of the preparation, and the content of the liquid fatty acid ester contained in the oil phase as a whole.
- a sustained-release cream preparation characterized by a standard of 25 to 60% by mass.
- the cream having the above composition has a feeling of use when applied to the skin or the like (eg, stickiness, growth, etc.). , Dry, and twisted) and can release the active ingredient continuously for a long time.
- liquid fatty acid ester is a saturated fatty acid monoester having 17 to 32 carbon atoms and / or a saturated dicarboxylic acid diester having 12 to 16 carbon atoms.
- the liquid fatty acid ester is at least one compound selected from the group consisting of isopropyl myristate, otatyl dodecyl myristate, isopropyl palmitate, cetyl 2-ethylhexanoate, diisopropyl adipate and getyl sebacate. Les, especially preferred to be.
- the sustained-release cream of the present invention preferably contains an antifungal drug as an active ingredient.
- the antifungal drug is preferably a benzylamine compound, an imidazole compound, or an arylamine compound.
- Particularly preferred antifungals are a benzylamine-based compound butenafine hydrochloride, an imidazole-based compound neticonazole hydrochloride, and an arylamine-based compound terbinafine hydrochloride.
- the sustained-release cream of the present invention preferably contains a therapeutic agent for contusion vulgaris, particularly ibuprofenpiconol, as an active ingredient.
- a therapeutic agent for contusion vulgaris particularly ibuprofenpiconol
- the active ingredients are these drugs, the effect of sustained release becomes more remarkable.
- FIG. 1 is a graph showing the relationship between elapsed time and the cumulative release rate (%) of butenafine hydrochloride
- FIG. 2 is a graph showing the relationship between elapsed time and the amount of butenafine hydrochloride released per unit time (mg), (a) showing Comparative Example 1 and (b) showing Example 1.
- the sustained-release cream of the present invention comprises a liquid fatty acid ester, an oily base, a surfactant, And a drug (active ingredient).
- the sustained-release cream of the present invention contains 10 to 25% by mass of the oil phase based on the total amount of the preparation, and the content of the liquid fatty acid ester contained in the oil phase is based on the entire oil phase. 25-60% by mass.
- the sustained-release cream of the present invention has an excellent feeling upon use and is capable of continuously releasing the active ingredient for a long time due to its power and strength.
- the oil phase contains a liquid fatty acid ester and an oily base.
- the sustained-release cream agent of the present invention contains higher alcohols, fatty acid esters, silicone oils, gelling agents, etc., these are also included in the oil phase.
- the sustained-release cream of the present invention can release the contained drug continuously for a long time regardless of whether the contained drug is water-soluble or fat-soluble.
- the feeling of use is excellent.
- This effect is caused by the fact that the sustained release cream of the present invention simply adjusts the content of the oil phase and also adjusts the content of the liquid fatty acid ester, which is a component contained in the oil phase. It is thought that it is.
- liquid fatty acid esters have a polar part (ester bond) and a non-polar part (alkyl group). It is thought that it is easy to stay in the cream with reduced oil phase content.
- the sustained-release cream of the present invention should have a liquid fatty acid ester content of 2560% based on the whole oil phase.
- the liquid fatty acid ester refers to a fatty acid ester that is liquid at normal temperature and normal pressure, and includes a saturated fatty acid monoester having 17 to 32 carbon atoms, a saturated dicarboxylic acid diester of 12 to 16 carbon atoms, or a mixture thereof. It is preferable that Here, the carbon number is the same as the carbon number of the fatty acid. It refers to the total number of carbon atoms of alcohol.
- the liquid fatty acid ester is isopropyl myristate, otatyl dodecyl myristate, isopropyl palmitate, and 2-ethylhexane from the viewpoint that the balance between the polar portion and the non-polar portion has an excellent sustained release effect. It is preferably at least one compound selected from the group consisting of cetyl acid, diisopropyl adipate and getyl sebacate.
- oil base examples include liquid paraffin, vaseline, paraffin wax, squalane and the like.
- the surfactant may be an anionic surfactant, a nonionic surfactant, a cationic surfactant, or an amphoteric surfactant.
- anionic surfactant include polyoxyethylene alkyl phosphate and sodium alkyl sulfate.
- nonionic surfactants include sorbitan sesquioleate
- Sorbitan trioleate sorbitan monostearate, sorbitan monolaurate, and sorbitan fatty acid esters such as polyoxyethylene sorbitan stearate; Of polyoxyethylene ether.
- examples of the cationic surfactant include benzethonium chloride and benzalkonium chloride.
- the drug contained in the sustained-release cream of the present invention may be fat-soluble or water-soluble. Regardless of the nature of the drug, the sustained release cream of the present invention can release the drug continuously for a long time.
- the drug contained in the sustained-release cream of the present invention is preferably an antifungal drug.
- the sustained-release cream of the present invention is effective as a therapeutic agent for athlete's foot, and can maintain its effect for two days or more by one application.
- the antifungal agent butenafine hydrochloride, which is preferably a pendinoleamine compound, is particularly preferable.
- Butenafine hydrochloride as a drug This is because, when it is contained, the sustained release effect of the sustained release cream becomes remarkable.
- Butenafine hydrochloride is a fat-soluble compound, and its physicochemical properties are shown in Table 1.
- the content of butenafine hydrochloride is usually 0.1 to 10% by mass, and preferably 115% by mass, based on the whole preparation, from the viewpoint of efficacy as an antifungal agent.
- imidazole-based compounds such as neticonazole hydrochloride and arylamin-based compounds such as terbinafine hydrochloride are also preferable. This is because the sustained-release cream preparation of the present invention containing these drugs has a remarkable sustained-release effect.
- the content of neticonazole hydrochloride and terbinafine hydrochloride is usually 0.1 to 10% by mass, and preferably 115 to 15% by mass, based on the whole preparation, from the viewpoint of efficacy as an antifungal agent.
- the drug contained in the sustained-release cream of the present invention is preferably a remedy for acne vulgaris (rapeseed), particularly ibuprofen piconol.
- the sustained-release terminator of the present invention is effective as a remedy for bruises on vulgaris, and can maintain its effect for two days or more with a single application.
- the sustained-release cream of the present invention may contain, in addition to the above components, higher alcohols, fatty acid esters, silicone oils, polyhydric alcohols or derivatives thereof, gelling agents, and the like.
- the higher alcohol is an alcohol having 10 to 22 carbon atoms, and is preferably a cetyl alcohol monoester, stearinoreanoreco nore, setosteolinorenorenocore, oreoleinorenorecole, or behenyl alcohol. is there.
- the fatty acid ester is an ester of a higher fatty acid. Esters are mentioned.
- Examples of the polyhydric alcohol or a derivative thereof include glycerin, ethylene glycol, Examples include propylene glycol, 1,3-butylene glycol, dipropylene glycol, polyethylene glycol and polypropylene glycol, and esters or ethers thereof.
- Examples of the gelling agent include carboxybutyl polymer and hydroxyethyl cellulose.
- Hydroxypropinoresenololose methinoresenorelose, etinoresenorelose, phorenoxymethyl cellulose and the like.
- the cream for external use of the skin of the present invention is a pH adjuster usually added to the cream for external use on skin
- An antioxidant a preservative, a preservative, a humectant, a chelating agent, a fragrance, and other additives.
- the cream for external use on the skin of the present invention can be produced by mixing and emulsifying each component according to a conventional method.
- a cream formulation containing butenafine hydrochloride as an active ingredient was manufactured by a conventional method according to the formulation in Table 2 (the values in Table 2 represent% by mass based on the whole formulation unless otherwise specified). More specifically, the water phase and the oil phase were each heated to 80 ° C, and the two were mixed and emulsified while sufficiently stirring. Thereafter, the mixture was cooled to room temperature while stirring, whereby a cream was obtained.
- the dissolution test of butenafine hydrochloride from the creams of Comparative Example 1 and Examples 1-2 was performed by a method according to the dissolution test “paddle method” described in the Japanese Pharmacopoeia (14th revision). More specifically, it is as follows. Dip the cell coated with the cream in the test solution, The test solution above the cell was stirred with a paddle at a constant rotation speed. A test solution was collected at regular intervals, and the amount of butenafine hydrochloride contained therein was quantified by HPLC (high performance liquid chromatography) to calculate the release rate of butenafine hydrochloride from the cream.
- HPLC high performance liquid chromatography
- Table 3 shows the cumulative release rate (%) of butenafine hydrochloride at each elapsed time (hour).
- Figure 1 is a graph showing the relationship between the elapsed time and the hydrochloride Butena cumulative release rate of fins (%), (a) is Comparative Example 1, (b) is Example 1, (c) is Example 2 Is shown.
- FIG. 2 is a graph showing the relationship between the elapsed time and the amount of butenafine hydrochloride released per unit time (mg), (a) showing Comparative Example 1 and (b) showing Example 1.
- the sustained-release cream of the present invention is capable of controlling the release of a drug from a preparation, and is considered to have the characteristics of a sustained-release preparation.
- the cream of Comparative Example 1 is a formulation that is administered once a day, the cream of Example 1 is a formulation that exhibits a sufficient therapeutic effect when administered once every two days. Likely to become
- the sensory test was used to compare the feeling of use of the cream of Example 3 and the cream of Comparative Example 2. Appropriate amounts of both creams were applied to the backs of the hands of 20 subjects, and the feeling of use was evaluated. There were five evaluation items: good spreadability, good paniticing, quick drying, low stickiness and overall preference. They were asked to respond with similar or similar strengths. The results are shown in Table 4.
- the sustained-release cream of the present invention improves stickiness and extensibility, has excellent feeling in use, and can release the active ingredient continuously for a long time. Was confirmed.
- a sustained-release cream preparation which is improved in stickiness and extensibility, has excellent usability, and can release the active ingredient continuously for a long time.
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- 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)
- Oil, Petroleum & Natural Gas (AREA)
- Emergency Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2006510434A JP4731472B2 (ja) | 2004-02-27 | 2005-02-23 | 徐放性クリーム剤 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2004054591 | 2004-02-27 | ||
JP2004-054591 | 2004-02-27 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2005082334A1 true WO2005082334A1 (ja) | 2005-09-09 |
Family
ID=34908798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2005/002926 WO2005082334A1 (ja) | 2004-02-27 | 2005-02-23 | 徐放性クリーム剤 |
Country Status (3)
Country | Link |
---|---|
JP (1) | JP4731472B2 (ja) |
TW (1) | TW200531707A (ja) |
WO (1) | WO2005082334A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10086008B2 (en) * | 2013-10-09 | 2018-10-02 | Revolution Pharma Llc | Topical antifungal compositions and methods of use thereof |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5815909A (ja) * | 1981-07-22 | 1983-01-29 | Toko Yakuhin Kogyo Kk | 抗真菌外用剤 |
JPS58167508A (ja) * | 1982-03-19 | 1983-10-03 | レ−ム・フアルマ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | 抗糸状菌治療調剤の製法 |
JPS58172312A (ja) * | 1982-04-02 | 1983-10-11 | Toa Eiyou Kagaku Kogyo Kk | ニフエジピン外用剤 |
JPH04275235A (ja) * | 1991-03-01 | 1992-09-30 | Hisamitsu Pharmaceut Co Inc | 吸収促進剤およびこれを含有する外用剤 |
JPH09309827A (ja) * | 1996-05-22 | 1997-12-02 | Pola Chem Ind Inc | 抗真菌外用剤 |
JP2001026553A (ja) * | 1999-07-09 | 2001-01-30 | Lion Corp | 外用剤組成物 |
JP2001213772A (ja) * | 2000-01-28 | 2001-08-07 | Health Science Center:Kk | 皮膚塗布剤組成物 |
WO2003045391A1 (en) * | 2001-11-29 | 2003-06-05 | 3M Innovative Properties Company | Pharmaceutical formulations comprising an immune response modifier |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07126164A (ja) * | 1993-10-29 | 1995-05-16 | Taisho Pharmaceut Co Ltd | 持効性抗真菌剤 |
JP3081766B2 (ja) * | 1994-05-06 | 2000-08-28 | 東興薬品工業株式会社 | 角質貯留型抗真菌外用組成物 |
JPH11152226A (ja) * | 1997-11-20 | 1999-06-08 | Zenyaku Kogyo Kk | 持続型抗白癬剤組成物 |
-
2005
- 2005-02-23 JP JP2006510434A patent/JP4731472B2/ja active Active
- 2005-02-23 WO PCT/JP2005/002926 patent/WO2005082334A1/ja active Application Filing
- 2005-02-25 TW TW094105949A patent/TW200531707A/zh unknown
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5815909A (ja) * | 1981-07-22 | 1983-01-29 | Toko Yakuhin Kogyo Kk | 抗真菌外用剤 |
JPS58167508A (ja) * | 1982-03-19 | 1983-10-03 | レ−ム・フアルマ・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | 抗糸状菌治療調剤の製法 |
JPS58172312A (ja) * | 1982-04-02 | 1983-10-11 | Toa Eiyou Kagaku Kogyo Kk | ニフエジピン外用剤 |
JPH04275235A (ja) * | 1991-03-01 | 1992-09-30 | Hisamitsu Pharmaceut Co Inc | 吸収促進剤およびこれを含有する外用剤 |
JPH09309827A (ja) * | 1996-05-22 | 1997-12-02 | Pola Chem Ind Inc | 抗真菌外用剤 |
JP2001026553A (ja) * | 1999-07-09 | 2001-01-30 | Lion Corp | 外用剤組成物 |
JP2001213772A (ja) * | 2000-01-28 | 2001-08-07 | Health Science Center:Kk | 皮膚塗布剤組成物 |
WO2003045391A1 (en) * | 2001-11-29 | 2003-06-05 | 3M Innovative Properties Company | Pharmaceutical formulations comprising an immune response modifier |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10086008B2 (en) * | 2013-10-09 | 2018-10-02 | Revolution Pharma Llc | Topical antifungal compositions and methods of use thereof |
Also Published As
Publication number | Publication date |
---|---|
TW200531707A (en) | 2005-10-01 |
JP4731472B2 (ja) | 2011-07-27 |
JPWO2005082334A1 (ja) | 2007-10-25 |
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