JP2022178154A - external composition - Google Patents

Abstract

To provide a pharmaceutical technique that improves solubility of glycyrrhetinic acid and can suppress separation of white petrolatum during its storage in an external composition, which contains the glycyrrhetinic acid as well as the white petrolatum of 50 wt.% or more.SOLUTION: An external composition contains white petrolatum of 50 wt.% or more and glycyrrhetinic acid as well as a polyhydric alcohol. The external composition can improve solubility of glycyrrhetinic acid and can suppress separation of white petrolatum during its storage.SELECTED DRAWING: None

Description

TECHNICAL FIELD The present invention relates to a composition for external use that contains 50% by weight or more of white petrolatum, has improved solubility of glycyrrhetinic acids, and can suppress separation of white petrolatum during storage.

White petrolatum has a moisturizing effect that prevents moisture from evaporating from the skin, and a barrier effect that protects against irritation by forming a film on the skin. It is widely used for prevention or improvement of skin, contact skin inflammation, etc.

Conventionally, various reports have been made on formulations of compositions for external use containing white petrolatum. For example, Patent Document 1 discloses (A) ethanol, isopropanol and/or diethylene glycol monoethyl ether, (B) white petrolatum, (C) carboxyvinyl polymer and/or alkyl-modified carboxyvinyl polymer, and (D) phosphorus It has been reported that lipid-containing external skin emulsified formulations have improved formulation stability and superior intradermal retention of active ingredients. However, the skin external emulsified preparation described in Patent Document 1 contains 0.1 to 20% by weight of white petrolatum, and is not a formulation that can sufficiently exhibit the moisturizing effect and barrier effect of white petrolatum. In order to sufficiently express the moisturizing effect and barrier effect of white petrolatum, it is necessary to increase the amount of white petrolatum in the composition for external use. Solubility may be reduced.

On the other hand, glycyrrhetinic acids such as glycyrrhetinic acid, derivatives thereof, and salts thereof are known to have anti-inflammatory and anti-allergic effects, and external compositions containing glycyrrhetinic acids have been developed. However, sufficient studies have not been conducted on formulations that can stably incorporate glycyrrhetinic acids in external compositions containing an increased amount of white petrolatum.

JP 2008-195712 A

The inventors of the present invention conducted studies to develop an external composition containing glycyrrhetinic acids and having an increased amount of white petrolatum, and found that an external composition containing 50% by weight or more of white petrolatum and glycyrrhetic acids, We have learned that glycyrrhetinic acids cannot be sufficiently dissolved, making formulation difficult. Furthermore, white petrolatum is a mixture of paraffins with different molecular weights, and it is known that part of white petrolatum becomes liquid and separates during storage. It was found that white petrolatum tends to separate during storage, and the storage stability is reduced.

Accordingly, an object of the present invention is to provide a formulation technique capable of improving the solubility of glycyrrhetinic acids and suppressing the separation of white petrolatum during storage in an external composition containing 50% by weight or more of white petrolatum and glycyrrhetinic acids. is.

The present inventors conducted intensive studies in order to solve the above problems, and found that an external composition containing 50% by weight or more of white petrolatum, glycyrrhetinic acids, and a polyhydric alcohol improves the solubility of glycyrrhetinic acids. , it was found that the separation of white petrolatum during storage can be suppressed. Furthermore, the present inventors have found that the composition for external use further contains diphenhydramine and/or a salt thereof, so that the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing the separation of white petrolatum during storage become remarkable. I found The present invention has been completed through further studies based on such findings.

That is, the present invention provides inventions in the following aspects.
Section 1. 50% by weight or more of white petrolatum;
at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, derivatives thereof, and salts thereof;
a polyhydric alcohol;
A topical composition containing
Section 2. Item 2. The composition for external use according to Item 1, further comprising ufenamate.
Item 3. Item 3. The composition for external use according to Item 1 or 2, further comprising diphenhydramine and/or a salt thereof.
Section 4. Item 4. The composition for external use according to any one of Items 1 to 3, wherein the polyhydric alcohol is a dihydric alcohol and/or a trihydric alcohol.
Item 5. Item 5. The composition for external use according to any one of Items 1 to 4, which is an oleaginous ointment.

According to the composition for external use of the present invention, the solubility of glycyrrhetinic acids can be improved while containing 50% by weight or more of white petrolatum. A medicinal effect can be expressed. In addition, according to the composition for external use of the present invention, separation of white petrolatum during storage can be suppressed, so that excellent storage stability can be provided.

1. Composition for external use The composition for external use of the present invention contains 50% by weight or more of white petrolatum, at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, derivatives thereof, and salts thereof, and a polyhydric alcohol. characterized by containing The composition for external use of the present invention is described in detail below.

[White Vaseline]
The composition for external use of the present invention contains 50% by weight or more of white petrolatum as a base. Thus, by including white petrolatum in a high content, it is possible to effectively express the moisturizing effect and barrier effect of white petrolatum.

The content of white petrolatum in the composition for external use of the present invention may be 50% by weight or more, specifically 50 to 99% by weight, preferably 55 to 99% by weight, more preferably 55 to 95% by weight. %.

[Glycyrrhetinic acids]
The composition for external use of the present invention contains at least one selected from the group consisting of glycyrrhetinic acid, derivatives thereof, and salts thereof as glycyrrhetinic acids. Glycyrrhetinic acids are known drugs known to have anti-inflammatory effects, anti-allergic effects, and the like.

The derivative of glycyrrhetinic acid is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and monoglucuronide glycyrrhetinate.

Salts of glycyrrhetinic acid and/or derivatives thereof are not particularly limited as long as they are pharmaceutically acceptable, and specific examples thereof include alkali metal salts such as sodium salts and potassium salts, and ammonium salts.

In the composition for external use of the present invention, as glycyrrhetinic acids, one of glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and salts thereof may be selected and used, or two or more thereof may be used in combination. .

Among these glycyrrhetinic acids, glycyrrhetinic acid is preferred.

The content of glycyrrhetinic acids in the composition for external use of the present invention may be appropriately set according to the degree of efficacy to be provided in the composition for external use. , preferably 0.01 to 2% by weight, more preferably 0.01 to 0.3% by weight, and still more preferably 0.1 to 0.3% by weight.

[Polyhydric alcohol]
The composition for external use of the present invention contains a polyhydric alcohol in addition to the components described above. In a composition for external use containing 50% by weight or more of white petrolatum, by including a polyhydric alcohol together with glycyrrhetinic acids, it becomes possible to suppress the separation of white petrolatum during storage while improving the solubility of glycyrrhetic acids. .

Polyhydric alcohols are not particularly limited as long as they are pharmaceutically acceptable. Examples include dihydric alcohols such as propylene glycol, 1,3-butylene glycol, dipropylene glycol and polypropylene glycol; trihydric alcohols such as glycerin; alcohol.

Among these polyhydric alcohols, dihydric alcohols are preferred, and propylene glycol and glycerin are more preferred.

These polyhydric alcohols may be used singly or in combination of two or more.

A suitable example of a combination of two or more polyhydric alcohols is a combination of propylene glycol and glycerin. By adopting the combination of propylene glycol and glycerin, it is possible to more significantly exhibit the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing the separation of white petrolatum during storage. When propylene glycol and glycerin are used in combination, their ratio is not particularly limited, but for example, 0.001 to 500 parts by weight, preferably 0.1 to 50 parts by weight of glycerin per 1 part by weight of propylene glycol, More preferably 0.5 to 20 parts by weight.

The content of the polyhydric alcohol in the composition for external use of the present invention is, for example, 0.01 to 40% by weight in terms of the total amount of the polyhydric alcohol. From the viewpoint of making the performance remarkable, it is preferably 0.5 to 25% by weight, more preferably 1 to 15% by weight.

In the composition for external use of the present invention, the ratio of the polyhydric alcohol to the glycyrrhetinic acid is, for example, 0.01 to 5000 parts by weight of the total polyhydric alcohol per 1 part by weight of the total glycyrrhetinic acid, improving the solubility of the glycyrrhetinic acid. 0.1 to 500 parts by weight, more preferably 1 to 50 parts by weight, is preferred from the viewpoint of exhibiting the effect and the effect of suppressing the separation of white petrolatum more remarkably.

[ufenamart]
The topical composition of the present invention may further contain ufenamate in addition to the components described above. By further containing ufenamate, it is possible to more significantly exhibit the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing the separation of white petrolatum during storage.

Ufenamate, also called butyl flufenamate, is an ingredient known as a fat-soluble non-steroidal anti-inflammatory drug.

When the composition for external use of the present invention contains ufenamate, the content thereof is, for example, 0.1 to 10% by weight. From the point of view, it is preferably 1 to 8% by weight, more preferably 3 to 5% by weight.

When ufenamate is included in the topical composition of the present invention, the ratio of ufenamate to glycyrrhetinic acids is, for example, 0.1 to 2000 parts by weight of ufenamate per 1 part by weight of the total amount of glycyrrhetinic acids, and the effect of improving the solubility of glycyrrhetinic acids. , and from the viewpoint of exhibiting the effect of suppressing the separation of white petrolatum more remarkably, it is preferably 1 to 200 parts by weight, more preferably 5 to 50 parts by weight.

[Diphenhydramine and/or its salt]
The composition for external use of the present invention may contain diphenhydramine and/or a salt thereof in addition to the components described above. By further including diphenhydramine and/or a salt thereof, it is possible to more significantly exhibit the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing the separation of white petrolatum during storage.

Diphenhydramine is a known drug known to have antihistamine properties.

The salt of diphenhydramine is not particularly limited as long as it is pharmaceutically acceptable. Examples include hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate, and diphenyldisulfone. Acid addition salts such as acid salts, tannates, lauryl sulfates, and sulfates can be mentioned.

These diphenhydramines and salts thereof may be used singly or in combination of two or more.

Among diphenhydramine and salts thereof, diphenhydramine, diphenhydramine hydrochloride, and more preferably diphenhydramine are preferred from the viewpoint of exhibiting the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing the separation of white petrolatum during storage more remarkably.

When diphenhydramine and/or a salt thereof is contained in the topical composition of the present invention, the content is not particularly limited. From the viewpoint of exhibiting a more pronounced effect of improving the solubility of white petrolatum and suppressing the separation of white petrolatum, preferably 0.05 to 3% by weight, more preferably 0.01 to 1% by weight, still more preferably 0.5 ~1% by weight.

When diphenhydramine and/or a salt thereof is contained in the composition for external use of the present invention, the ratio of diphenhydramine and/or a salt thereof to glycyrrhetinic acids is not particularly limited, but for example, per 1 part by weight of the total amount of glycyrrhetinic acids, diphenhydramine and / or the total amount of salts thereof is 0.01 to 1000 parts by weight, preferably 0.1 to 100 parts by weight, from the viewpoint of more significantly exhibiting the effect of improving the solubility of glycyrrhetinic acids and the effect of suppressing separation of white petrolatum, More preferably 1 to 10 parts by weight.

[water]
The composition for external use of the present invention may contain water, if necessary, as long as it can be prepared into a desired dosage form. When the composition for external use of the present invention contains water, its content is, for example, 5% by weight or less, preferably 4% by weight or less, and more preferably 1% by weight or less. When the topical composition of the present invention contains water, the lower limit of the water content is not particularly limited, but examples thereof include 0.01% by weight or more or 0.1% by weight or more.

[Other ingredients]
The composition for external use of the present invention may contain other commonly used additives, if necessary, in addition to the components described above. Examples of such additives include surfactants, thickeners, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters, fatty acids, higher alcohols, pH adjusters, buffers, solubilizers, chelating agents, preservatives. , preservatives, antioxidants, stabilizers, perfumes, and the like. When these additives are contained in the composition for external use of the present invention, the content thereof may be appropriately set according to the type of additive used.

The composition for external use of the present invention may contain pharmacological components in addition to the components described above. Such pharmacological components include, for example, steroids, antihistamines, local anesthetics, anti-inflammatory agents, moisturizers, bactericidal agents, antibacterial agents, antipruritic agents, skin protective agents, blood circulation promoting components, vitamins, mucopolysaccharides, and the like. is mentioned. These pharmacological ingredients may be used singly or in combination of two or more. When these pharmacological ingredients are contained in the composition for external use of the present invention, the concentration thereof may be appropriately set according to the type of the pharmacological ingredient to be used, the expected effect, and the like.

[Dosage form/Formulation]
The dosage form of the composition for external use of the present invention is not particularly limited as long as it is percutaneously applicable, and may be either an oil-based ointment, a water-in-oil type cream, or the like, but is preferably Oily ointments may be mentioned.

In addition, the composition for external use of the present invention may be in any formulation form, such as a pharmaceutical for external use on the skin (including quasi-drugs), a cosmetic, etc., as long as it is applied to the skin.

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these.

An oleaginous ointment having the composition shown in Test Example Table 1 was prepared. Specifically, after heating the oleaginous base shown in Tables 1 and 2 to 80° C. and mixing, predetermined amounts of other components were added and thoroughly mixed to prepare an oleaginous ointment.

The oleaginous ointment immediately after preparation was allowed to stand at room temperature for 30 minutes, and then its appearance was observed. 10 points from 1 to 10, with 5 points for "a state in which the powder of glycyrrhetinic acid is not dissolved and there is a significant undissolved residue". The solubility of glycyrrhetinic acid was evaluated in stages.

In addition, after storing the oleaginous ointment immediately after preparation at 50 ° C. for 2 weeks, the appearance was observed. 5 points for "the state where it becomes uniform and there is no separation and is within the allowable range in terms of commercialization", and 1 point for "the state where white petrolatum is significantly separated and does not become uniform even if it is shaken". The degree of separation of the white petrolatum was graded on a scale of 10 to 10.

Results are shown in Tables 1 and 2. When no polyhydric alcohol was blended, in an oil-based ointment containing 50% by weight or more of white petrolatum and glycyrrhetinic acid, glycyrrhetinic acid did not dissolve, significant undissolved residue was observed, and white petrolatum was significantly separated after storage. was also observed (Comparative Examples 1 and 2). On the other hand, in the oleaginous ointment containing 50% by weight or more of white petrolatum and glycyrrhetinic acid together with a polyhydric alcohol, the solubility of glycyrrhetinic acid is improved, and the separation of white petrolatum during storage can also be suppressed. (Examples 1-15). In particular, when ufenamate and/or diphenhydramine are blended with 50% by weight or more of white petrolatum and glycyrrhetinic acid, the solubility of glycyrrhetic acid is remarkably improved, and the separation of white petrolatum during storage is remarkably suppressed. (Examples 3-8, 10, 13 and 15). Further, in each oleaginous ointment in which propylene glycol was replaced with 1,3-butylene glycol in Examples 2, 7 and 10, the solubility of glycyrrhetinic acid was improved to the same extent as in Examples 2, 7 and 10. Furthermore, separation of white petrolatum due to storage could be suppressed.

Preparation Example A oleaginous ointment having the composition shown in Table 3 was prepared, and the solubility of glycyrrhetinic acid and the separation of white petrolatum during storage were evaluated in the same manner as in the above test examples. As a result, in all of the oleaginous ointments of Production Examples 1 to 8, the solubility of glycyrrhetinic acid was remarkably improved, and the separation of white petrolatum during storage was remarkably suppressed.

Claims (5)

50% by weight or more of white petrolatum;
at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, derivatives thereof, and salts thereof;
a polyhydric alcohol;
A topical composition containing 2. The composition for external use according to claim 1, further comprising ufenamate. 3. The composition for external use according to claim 1, further comprising diphenhydramine and/or a salt thereof. The composition for external use according to any one of claims 1 to 3, wherein the polyhydric alcohol is a dihydric alcohol and/or a trihydric alcohol. The composition for external use according to any one of claims 1 to 4, which is an oleaginous ointment.