WO2021187593A1 - Composition contenant du valérate de bétaméthasone - Google Patents

Composition contenant du valérate de bétaméthasone Download PDF

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WO2021187593A1
WO2021187593A1 PCT/JP2021/011180 JP2021011180W WO2021187593A1 WO 2021187593 A1 WO2021187593 A1 WO 2021187593A1 JP 2021011180 W JP2021011180 W JP 2021011180W WO 2021187593 A1 WO2021187593 A1 WO 2021187593A1
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composition
polyoxyethylene
ether
component
stability
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PCT/JP2021/011180
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English (en)
Japanese (ja)
Inventor
博志 村里
宜孝 友田
洋一 岩田
文枝 純浦
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シオノギヘルスケア株式会社
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Priority to JP2022508439A priority Critical patent/JP7350985B2/ja
Publication of WO2021187593A1 publication Critical patent/WO2021187593A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • 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
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a betamethasone valerate-containing composition. More specifically, the present invention relates to an external preparation containing betamethasone valerate as an anti-inflammatory agent. The present invention also relates to a method for improving the pharmaceutical stability of a betamethasone valerate-containing composition.
  • corticosteroids are effective in improving symptoms such as itching, redness, and swelling of the skin with inflammation, and eczema (including eczema due to atopic dermatitis; the same applies hereinafter) and itching (sweat, buds). It includes pruritus caused by measles, rashes, insect bites, etc. The same shall apply hereinafter), and is widely used for the treatment of dermatitis, psoriasis, and the like.
  • the present inventors have found that when a polyoxyethylene alkyl ether is added when designing a preparation containing betamethasone valerate, the pH of the preparation decreases with time. In order to solve this problem, we have been studying diligently. By using betamethasone valerate and polyoxyethylene alkyl ether in combination with tocopherol or a derivative thereof, the above phenomenon is significantly improved and the pH is stabilized. It has been found that a maintained betamethasone valerate-containing preparation can be obtained.
  • the present invention has been completed by repeating further improvements based on these findings, and includes the following embodiments.
  • Betamethasone valerate-containing composition (I-1)
  • the component (B) is at least one selected from the group consisting of polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene cetostearyl ether and polyoxyethylene distyrylphenyl ether. , (I-1).
  • I-3) The composition according to (I-1) or (I-2), which further contains (D) a pH regulator.
  • (II) Stabilized production method of betamethasone valerate-containing composition (II-1) (A) Selected from the group consisting of betamethasone valerate, (B) polyoxyethylene alkyl ether and polyoxyethylene aryl phenyl ether. A production method in which the stability of a composition containing at least one of these substances is improved. The production method, which comprises a step of coexisting (C) tocopherol or a derivative thereof in the composition. (II-2) The production method according to (II-1), wherein the composition further contains (D) a pH adjuster.
  • the component (B) is at least one selected from the group consisting of polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene cetostearyl ether and polyoxyethylene distyrylphenyl ether. , (II-1) or (II-2). (II-4) The production method according to any one of (II-1) to (II-3), wherein the improvement in stability is suppression of a decrease in pH.
  • (III) Method for improving stability of betamethasone valerate-containing composition (III-1)
  • the method for improving stability which comprises coexisting (C) tocopherol or a derivative thereof in the composition.
  • (III-2) The method for improving stability according to (III-1), wherein the composition further contains (D) a pH adjuster.
  • III-3) The method for improving stability according to (II-1) or (II-2), wherein the method for improving stability is a method for suppressing a decrease in pH of the composition.
  • the component (B) is at least one selected from the group consisting of polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene cetostearyl ether and polyoxyethylene distyrylphenyl ether. , (II-1) to (II-3).
  • betamethasone valerate-containing composition having good pharmaceutical stability. More specifically, according to the present invention, the pH decrease caused by adding polyoxyethylene alkyl ether to the betamethasone valerate-containing composition is significantly suppressed by adding tocopherol or a derivative thereof. It is possible to provide a betamethasone valerate-containing preparation characterized by the above.
  • Betamethasone valerate ester-containing composition and method for producing the same
  • the betamethasone valerate ester-containing composition of the present invention (hereinafter, also simply referred to as "the present composition") is the following (A), (B) and ( C) A composition containing a component. At least one selected from the group consisting of (A) betamethasone valerate (B) polyoxyethylene alkyl ether and polyoxyethylene aryl phenyl ether, and (C) tocopherol or a derivative thereof.
  • the solid composition may contain the following component (D) in addition to the components (A) and (B).
  • the solid composition may contain the following component (E) in addition to the components (A) to (C) or the components (A) to (D). (E) External base.
  • the component betamethasone valerate is an esterified steroid in which the hydroxyl group at the 17-position is valeryrylized and the hydroxyl group at the 21-position is acetylated.
  • the compound is a strong steroid with anti-inflammatory activity and is known to have the following indications: Eczema / dermatitis group (including progressive finger palmar keratoderma, female facial lichen planus, Vidal lichen, radiation dermatitis, sunlight dermatitis), dermatitis, pruritus group (lichen-like lichen, strophulus) , Including fixed urticaria), insect bites, psoriasis, palmoplantar pustulosis, lichen planus, glossy lichen planus, pore red erythema, gibelbara erythema, erythema (polymorphic exudative erythema, nodule) Erythema, Darier efferent ring erythema), erythema (including erythema due to malignant lymphoma), chronic discoid erythematosus, drug eczema / toxic eczema, circular
  • the amount of the component (A) contained in the present composition may be an amount that exerts a desired medicinal effect without interfering with the effect of the present invention, and can be appropriately set and adjusted within that range.
  • this composition is prepared as an external preparation (pharmaceutical preparation) for improving skin diseases (for example, eczema, prurigo, dermatitis or psoriasis) having symptoms such as itching, redness or swelling of the skin with inflammation.
  • the content of the component (A) in the present composition the range of 0.0002 to 10% by mass can be exemplified. It is preferably 0.002 to 2% by mass, and more preferably 0.01 to 0.3% by mass.
  • the component polyoxyethylene alkyl ether and polyoxyethylene arylphenyl ether are nonionic compounds having a surface active action.
  • the polyoxyethylene alkyl ether and polyoxyethylene arylphenyl ether targeted by the present invention can be blended in pharmaceutical products, quasi-drugs or cosmetics.
  • polyoxyethylene alkyl ethers include monoethers of polyoxyethylene having an addition molar number of 4 to 200 and an alkyl group having 8 to 22 carbon atoms. Be done. Among these are polyoxyethylene capryl ether, polyoxyethylene caprylyl ether, polyoxyethylene lauryl ether, polyoxyethylene myristyl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, and poly. Oxyethylene isosteyl ether, polyoxyethylene cetostearyl ether, polyoxyethylene behenyl ether and the like are included. Preferably, it is polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene cetostearyl ether, and more preferably polyoxyethylene cetyl ether, and polyoxyethylene stearyl ether.
  • polyoxyethylene arylphenyl ether examples include ethers of polyoxyethylene (EO) having an addition molar number of 4 to 200 and arylphenyl. These include polyoxyethylene distyrylphenyl ether, polyoxyethylene polystyrylphenyl ether and the like. It is preferably polyoxyethylene distyrylphenyl ether.
  • EO polyoxyethylene
  • components (B) may be used alone or in combination with the component (A), or two or more of them may be arbitrarily combined and used in combination with the component (A). When two or more kinds of the component (B) are used in combination, it is preferable to use the above-mentioned suitable polyoxyethylene alkyl ether as one kind.
  • the amount of the component (B) contained in the present composition may be an amount that exerts a desired surface-active action without interfering with the effects of the present invention, and can be appropriately set and adjusted within that range. Although not limited, it can be adjusted so as to lower the interfacial tension existing at the interface between the oil component and the water component and exert an action of finely dispersing the oil component in the water component.
  • the content (total amount) of the component (B) in the present composition can be exemplified in the range of 0.1 to 10% by mass.
  • the lower limit amount is preferably 0.15% by mass or more, more preferably 0.2% by mass or more, and further preferably 0.3% by mass or more.
  • the range is preferably 0.25 to 7.5% by mass, more preferably 0.3 to 5% by mass, and further preferably 0.5 to 5% by mass.
  • the ratio of the component (B) to 100 parts by mass of the component (A) is not limited, but is, for example, in the range of 10 to 100,000 parts by mass, preferably 100 to 50,000 parts by mass, and more preferably 500 to 10,000 parts by mass, particularly. Preferably, 1000 to 5000 parts by mass can be exemplified.
  • Tocopherol or a derivative thereof may be a natural product or a synthetic product as long as it can be blended in pharmaceutical products, quasi-drugs or cosmetics.
  • Tocopherols include d- ⁇ -tocopherols, dl- ⁇ -tocopherols, ⁇ -tocopherols, ⁇ -tocopherols, and ⁇ -tocopherols.
  • tocopherol derivatives include tocopherol acetate (for example, d- ⁇ -tocopherol acetate, dl- ⁇ -tocopherol acetate), tocopherol nicotinic acid ester, tocopherol succinic acid ester, and tocopherol linolenic acid ester.
  • the derivative of tocopherol is preferably an ester of tocopherol (vitamin E ester), and more preferably an ester of tocopherol acetate.
  • These components (C) may be used alone or in combination with the components (A) and (B), or two or more of them may be arbitrarily combined and used in combination with the components (A) and (B). May be done.
  • the component (C) itself is a compound having an antioxidant action, a blood circulation promoting action, and the like, but in the present composition, in addition to at least one of these actions (preferably a blood circulation promoting action), it will be described later. As shown in the examples described above, it exerts an action of suppressing the pH lowering phenomenon of the composition caused by containing the above-mentioned components (A) and (B).
  • the amount of the component (C) contained in the present composition may be an amount that exhibits the desired medicinal effect and the above-mentioned effect, and can be appropriately set and adjusted within that range.
  • this composition is prepared as an external preparation (pharmaceutical preparation) for improving skin diseases (for example, eczema, prurigo, dermatitis or psoriasis) having symptoms such as itching, redness or swelling of the skin with inflammation.
  • the content of the component (C) in the present composition the range of 0.001 to 10% by mass can be exemplified. It is preferably 0.005 to 10% by mass, and more preferably 0.025 to 5% by mass.
  • the ratio of the component (C) to 100 parts by mass of the component (A) is not limited, but is, for example, in the range of 10 to 10000 parts by mass, preferably 30 to 7000 parts by mass, and more preferably 50 to 5000 parts by mass. can do.
  • the component pH adjusting agent may be an acid or base or a salt thereof, which can be blended in a drug, a quasi drug or a cosmetic, and is usually used for pH adjusting.
  • inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid or salts thereof; hydroxides of alkali metals or alkaline earth metals; inorganic substances such as carbonates, hydrogen carbonates; acetic acid, methanesulfonic acid, oxalic acid.
  • Organic acids or salts thereof; ethylamine, diethylamine, triethylamine, monoethanolamine, diethanolamine, triethanolamine, monoisopropanolamine, diisopropanolamine, triisopropanolamine, lysine, arginine and the like can be exemplified.
  • the pH of human skin is weakly acidic of about 4.5 to about 6.5, and the pH of healthy skin is about 5.5. Therefore, for example, this composition is used as an external preparation (pharmaceutical preparation) for improving skin diseases (eg, eczema, prurigo, dermatitis, psoriasis, etc.) having symptoms such as itching, redness or swelling of the skin with inflammation.
  • the content of the component (D) in the present composition may be any ratio as long as the present composition can be adjusted to the above pH range, preferably pH 5.0 to 6.0. As long as this is not particularly limited, the composition can be appropriately adjusted from the range of 0.01 to 10% by mass in 100% by mass of the present composition. It is preferably 0.05 to 5% by mass, and more preferably 0.1 to 1% by mass.
  • compositions can be prepared as an external preparation by mixing the above-mentioned (A) to (C) components or (A) to (D) components together with (E) an external base. More preferably, it is an external preparation for skin.
  • the dosage form is not limited and may include dosage forms commonly used in pharmaceuticals, quasi-drugs or cosmetics. Examples thereof include liquids (including lotions, emulsions and aerosols), sticks, creams, ointments, plasters, gels, poultices, foams and powders. It is preferably a cream, an ointment, a liquid or a gel.
  • a conventional external base can be used depending on the shape (dosage form) of the present composition. As long as it does not interfere with the effects of the present invention, it may be a base that can be blended in pharmaceuticals, quasi-drugs or cosmetics, and is not particularly limited.
  • oils such as white vaseline, cetanol, honeywort, lanolin, paraffin, liquid paraffin; natural rubber, isoprene rubber, polyisobutylene, styrene-isoprene-styrene block copolymer, styrene-butadiene-styrene block copolymer, styrene.
  • -Rubber such as ethylene / butylene-styrene block copolymer, (meth) acrylic acid alkyl ester (co) polymer, poly (meth) acrylic acid ester, (meth) acrylic acid ester, polyisobutylene, polybutene, liquid polyisoprene, etc.
  • Water-soluble polymers such as carboxyvinyl polymer, starch acrylate, sodium polyacrylate, sodium carmellose; glycerin; macrogol; silicic anhydride and the like can be exemplified.
  • excipients for example, sugars such as sucrose; starch derivatives such as dextrin; cellulose derivatives such as carmellose sodium; water-soluble polymers such as xanthan gum
  • excipients for example, sugars such as sucrose; starch derivatives such as dextrin; cellulose derivatives such as carmellose sodium; water-soluble polymers such as xanthan gum
  • the content of the component (E) in the present composition may be adjusted so that the total amount of the present composition is 100% by mass, and is not limited, but less than 100% by mass, for example, 99.999% by mass.
  • the upper limit range can be exemplified. It is preferably 5 to 99.999% by mass, and more preferably 10 to 99.99% by mass.
  • composition contains the above-mentioned components (A) to (C), components (A) to (D), or (A) as long as the effects of the present invention are not impaired.
  • component (E) other pharmacologically active ingredients may be further contained.
  • Non-steroidal anti-inflammatory drugs, local anesthetics, antipruritic agents, blood circulation promoters, fungicides, skin protectants, antibiotics, moisturizers, and / or refreshing agents can be exemplified, but not limited.
  • compositions of the present invention may be used for skin diseases (eg, eczema, etc.) having symptoms such as itching, redness or swelling of the skin with inflammation.
  • skin diseases eg, eczema, etc.
  • an external preparation pharmaceutical preparation
  • this composition at least the components (A) to (C) or the components (A) to (D) among the above-mentioned components are mixed with the components (E) and / or (F) as necessary. Then, it can be produced by a production method having a step of coexisting at least the component (C) in the composition containing the component (A) and the component (B), and other than that, it is basically a conventional production method of an external preparation. Therefore, it can be produced in the form of an external preparation.
  • composition thus prepared in the form of an external preparation is used externally to improve skin diseases having symptoms such as itching, redness or swelling of the skin with inflammation (for example, eczema, prurigo, dermatitis or psoriasis). It can be suitably used as a preparation (pharmaceutical preparation).
  • the application is not limited and can be widely used on the skin in general, such as hands, feet, fingers, face, head, and body. It can also be applied to areas with thin skin such as the anus and the area around the genital area.
  • the amount and usage of these substances on the skin are not particularly limited, and they should be used by applying an appropriate amount to the outer skin such as the skin once to several times a day depending on the symptoms of the affected area and the content of the active ingredient. Can be done.
  • the present invention provides a method for improving the stability of a composition containing the above-mentioned component (A) (betamethasone valerate-containing composition). do.
  • the stability of the composition containing the component (A) is lowered by blending the component (B) described above, and a phenomenon that the pH is lowered with time occurs. This phenomenon may occur beyond the buffering capacity even when the pH adjuster (component (D)) is blended in the composition containing the component (A).
  • the pH lowering phenomenon can be improved by coexisting the above-mentioned component (C) in the composition (composition containing components (A) and (B)).
  • the composition containing the components (A) and (B) may contain the above-mentioned component (D).
  • the pH decrease over time caused by blending the component (B) with betamethasone valerate-containing composition is suppressed.
  • a composition (measurement target) containing at least the components (A) to (C) or the components (A) to (D) has the same composition as the above except that the component (C) is not contained (comparison target).
  • the pH decrease that occurs over time is small, it is judged that the former composition has the pH decrease phenomenon suppressed by the inclusion of the component (C) and the stability is improved. be able to.
  • the presence or absence of a decrease in pH over time is determined by storing the composition to be measured and the composition to be compared in a dark place under constant temperature and humidity conditions of 40 ° C. and 75%, respectively, for about 0 to 6 months. It can be evaluated by measuring the pH with a pH meter over time during the period and comparing the degree of the pH decrease. For details, the description of the experimental example described later can be referred to.
  • a method for coexisting the component (C) in the composition containing the components (A) and (B) (or the components (A), (B) and (D) a method capable of obtaining the effect of the present invention is used. All you need is, and there are no restrictions. Although not limited, for example, the component (B) or the component (B) and the component (D) are dissolved in the component (E), the component (C) is mixed therein, and the component (B) and the component (C) are mixed.
  • a method may be used in which a coexistence state with the component or a coexistence state with the (B) component, the (D) component and the (C) component is formed, and the (A) component is dispersed therein.
  • component (F) and component (G) may be blended as other components as long as the effects of the present invention are not impaired.
  • a liquid agent if necessary, a liquid agent, a stick agent, a cream agent, an ointment agent, a gel agent, etc. It can also be prepared in the form of a conventional external preparation such as a plaster.
  • the ratio of each component in the composition, the compounding ratio, and the like are as described in (I) above, and the description can be incorporated herein by reference.
  • Betamethasone Benzoic acid ester Obtained from Sicor Tocopherol acetate (deer special grade): Obtained from Kanto Chemical Co., Ltd.
  • pH measurement sample (product temperature: 24.5 to 25.5 ° C.) prepared above is measured with a pH meter, and the pH of the test composition before storage is measured. The temporal stability of the test sample is evaluated from the difference (pH change) between the pH of the test composition and the pH of the test composition after storage.
  • Betamethasone valerate ester-containing composition A book in which the pH decrease over time is suppressed as compared with the betamethasone valerate ester-containing composition (cream) containing no C component (Comparative Examples 2 to 11).
  • the formulations of betamethasone valerate-containing compositions (creams) (Examples 2-11) of the present invention are shown in Tables 5-14.

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Abstract

La présente invention concerne une composition qui contient du valérate de bétaméthasone et qui présente une bonne stabilité de production. La composition contient (A) du valérate de bétaméthasone, (B) un polyoxyéthylène alkyl éther, et (C) du tocophérol ou un dérivé de celui-ci.
PCT/JP2021/011180 2020-03-19 2021-03-18 Composition contenant du valérate de bétaméthasone WO2021187593A1 (fr)

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JP2022508439A JP7350985B2 (ja) 2020-03-19 2021-03-18 ベタメタゾン吉草酸エステル含有組成物

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09110696A (ja) * 1995-10-18 1997-04-28 Sekisui Chem Co Ltd 皮膚疾患治療用外用剤
JP2002542293A (ja) * 1999-04-23 2002-12-10 レオ・ファーマ・アクティーゼルスカブ 医薬組成物
JP2006028123A (ja) * 2004-07-20 2006-02-02 Iwaki Seiyaku Co Ltd 乳剤性皮膚外用剤

Patent Citations (3)

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