Topical compositions

Abstract

To provide a pharmaceutical technique that improves solubility of glycyrrhetinic acid in an external composition, which contains the glycyrrhetinic acid as well as 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 ufenamate. The external composition can improve solubility of glycyrrhetinic acid.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for external use that contains 50% by weight or more of white petrolatum and has improved solubility of glycyrrhetinic acids. [Background technology]

[0002] White petrolatum has a moisturizing effect that prevents moisture from evaporating from the skin, and a barrier effect that protects the skin from irritation by forming a film on the skin, and topical compositions containing white petrolatum as a base are widely used for preventing or improving dry skin, sensitive skin, contact skin inflammation, etc.

[0003] Various formulations of topical compositions containing white petrolatum have been reported. For example, Patent Document 1 reports that an emulsion formulation for topical skin containing (A) ethanol, isopropanol, and / or diethylene glycol monoethyl ether, (B) white petrolatum, (C) a carboxyvinyl polymer and / or an alkyl-modified carboxyvinyl polymer, and (D) a phospholipid exhibits improved formulation stability and excellent intradermal retention of the active ingredient. However, the emulsion formulation for topical skin described in Patent Document 1 contains 0.1 to 20% by weight of white petrolatum, which is not a formulation that can fully exhibit the moisturizing and barrier effects of white petrolatum. To fully exhibit the moisturizing and barrier effects of white petrolatum, it is necessary to increase the amount of white petrolatum in the topical composition. However, topical compositions containing increased amounts of white petrolatum may result in reduced solubility of the active ingredient.

[0004] On the other hand, glycyrrhetinic acids such as glycyrrhetinic acid, its derivatives, and salts thereof are known to have anti-inflammatory and anti-allergic effects, and topical compositions containing glycyrrhetinic acids have been developed to date, but sufficient research has not been conducted into formulations that can stably incorporate glycyrrhetinic acids in topical compositions that contain a higher amount of white petrolatum. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2008-195712 Summary of the Invention [Problem to be solved by the invention]

[0006] The present inventors have conducted research to develop a topical composition containing glycyrrhetinic acids and a higher amount of white petrolatum, and have found that in topical compositions containing glycyrrhetinic acids together with 50% by weight or more of white petrolatum, the glycyrrhetinic acids do not dissolve sufficiently, making it difficult to formulate.

[0007] Therefore, an object of the present invention is to provide a formulation technique for improving the solubility of glycyrrhetinic acids in a topical composition containing 50% by weight or more of white petrolatum and glycyrrhetinic acids. [Means for solving the problem]

[0008] The present inventors have conducted extensive research to solve the above problems and have found that a topical composition containing 50% by weight or more of white petrolatum, glycyrrhetinic acids, and ufenamate can improve the solubility of glycyrrhetinic acids. Furthermore, the present inventors have found that the solubility of glycyrrhetinic acids can be further improved by further adding diphenhydramine and / or a salt thereof to the topical composition. Based on these findings, the present invention has been completed through further research.

[0009] That is, the present invention provides the following aspects. Item 1. 50% by weight or more of white petrolatum, At least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, its derivatives, and salts thereof; Ufenamart and A topical composition containing Item 2. The composition for external use according to Item 1, further comprising diphenhydramine and / or a salt thereof. Item 3. The composition for external use according to Item 1 or 2, which is an oleaginous ointment. [Effects of the Invention]

[0010] According to the topical composition of the present invention, the solubility of glycyrrhetinic acids can be improved even though it contains 50% by weight or more of white petrolatum, so that the moisturizing effect and barrier effect of white petrolatum can be effectively exerted while the medicinal effect of glycyrrhetinic acids can be exerted. DETAILED DESCRIPTION OF THE INVENTION

[0011] 1. External use ingredients The topical composition of the present invention is characterized by containing 50% by weight or more of white petrolatum, at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, its derivatives, and salts thereof, and ufenamate. The topical composition of the present invention will be described in detail below.

[0012] [White petrolatum] The topical composition of the present invention contains 50% by weight or more of white petrolatum as a base. By including such a high content of white petrolatum, the moisturizing effect and barrier effect of white petrolatum can be effectively exerted.

[0013] The content of white petrolatum in the topical composition of the present invention may be 50% by weight or more, specifically 50 to 99% by weight, preferably 55 to 99% by weight, and more preferably 55 to 95% by weight.

[0014] [Glycyrrhetinic acid] The topical composition of the present invention contains at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, its derivatives, and salts thereof. Glycyrrhetinic acids are known to have anti-inflammatory and anti-allergic effects.

[0015] The derivatives of glycyrrhetinic acid are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, and glycyrrhetinic acid monoglucuronide.

[0016] The salt of glycyrrhetinic acid and / or its derivative is not particularly limited as long as it is pharmaceutically acceptable, and specific examples include alkali metal salts such as sodium salts and potassium salts, and ammonium salts.

[0017] In the topical composition of the present invention, one or more glycyrrhizinic acids selected from glycyrrhetinic acid, derivatives of glycyrrhetinic acid, and salts thereof may be used as the glycyrrhizinic acid compound, or two or more may be used in combination.

[0018] Among these glycyrrhetinic acids, glycyrrhetinic acid is preferred.

[0019] The content of glycyrrhetinic acids in the topical composition of the present invention may be appropriately determined depending on the degree of medicinal effect that the topical composition is to have, and may be, for example, 0.005 to 5 wt %, preferably 0.01 to 2 wt %, more preferably 0.01 to 0.3 wt %, and even more preferably 0.1 to 0.3 wt % in total of glycyrrhetinic acids.

[0020] [Ufenamart] The topical composition of the present invention contains ufenamate in addition to the above-mentioned components. By including ufenamate together with glycyrrhetinic acids in a topical composition containing 50% by weight or more of white petrolatum, it becomes possible to improve the solubility of glycyrrhetinic acids.

[0021] Ufenamate, also known as butyl flufenamate, is a known lipid-soluble nonsteroidal anti-inflammatory drug.

[0022] The content of ufenamate in the topical composition of the present invention is, for example, 0.1 to 10% by weight, preferably 1 to 8% by weight, and more preferably 3 to 5% by weight, from the viewpoint of further improving the solubility of glycyrrhetinic acids.

[0023] 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 from the viewpoint of further improving the solubility of glycyrrhetinic acids, preferably 1 to 200 parts by weight, more preferably 5 to 50 parts by weight, and even more preferably 12 to 40 parts by weight.

[0024] [Diphenhydramine and / or its salts] The topical composition of the present invention may contain diphenhydramine and / or a salt thereof in addition to the above-mentioned components. By further including diphenhydramine and / or a salt thereof, the solubility of glycyrrhetinic acids can be further effectively improved.

[0025] Diphenhydramine is a known drug known to have antihistamine properties.

[0026] The salt of diphenhydramine is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include acid addition salts such as hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate, diphenyldisulfonate, tannate, lauryl sulfate, and sulfate.

[0027] These diphenhydramines and salts thereof may be used singly or in combination of two or more.

[0028] Among diphenhydramine and salts thereof, from the viewpoint of more significantly improving the solubility of glycyrrhetinic acids, preferred are diphenhydramine and diphenhydramine hydrochloride, and more preferred are diphenhydramine.

[0029] When diphenhydramine and / or a salt thereof is contained in the topical composition of the present invention, the content is not particularly limited, but may be, for example, 0.01 to 5 wt% in total of diphenhydramine and / or a salt thereof, and from the viewpoint of further improving the solubility of glycyrrhetinic acids, preferably 0.05 to 3 wt%, more preferably 0.01 to 1 wt%, and even more preferably 0.5 to 1 wt%.

[0030] When diphenhydramine and / or a salt thereof is contained in the topical composition of the present invention, the ratio of diphenhydramine and / or a salt thereof to glycyrrhetinic acids is not particularly limited, but for example, the total amount of diphenhydramine and / or a salt thereof is 0.01 to 1000 parts by weight per 1 part by weight of the total amount of glycyrrhetinic acids, and from the viewpoint of more significantly improving the solubility of glycyrrhetinic acids, it is preferably 0.1 to 100 parts by weight, more preferably 1 to 10 parts by weight, and even more preferably 3 to 8 parts by weight.

[0031] [Polyhydric alcohol] The topical composition of the present invention may contain a polyhydric alcohol, if necessary.

[0032] The polyhydric alcohol is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include dihydric alcohols such as propylene glycol, 1,3-butylene glycol, dipropylene glycol, and polypropylene glycol; and trihydric alcohols such as glycerin.

[0033] These polyhydric alcohols may be used alone or in combination of two or more.

[0034] Among these polyhydric alcohols, dihydric alcohols are preferred, and propylene glycol is more preferred.

[0035] When a polyhydric alcohol is contained in the topical composition of the present invention, the content is not particularly limited, but may be, for example, 0.01 to 40% by weight, preferably 0.05 to 10% by weight, and more preferably 0.01 to 5% by weight, of the total amount of polyhydric alcohol.

[0036] [water] The topical composition of the present invention may contain water as needed, as long as it can be prepared into a desired dosage form.When the topical composition of the present invention contains water, the content thereof is, for example, 5% by weight or less, preferably 4% by weight or less, 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 may be, for example, 0.01% by weight or more or 0.1% by weight or more.

[0037] [Other ingredients] In addition to the above-mentioned components, the topical composition of the present invention may contain other commonly used additives as needed.Such additives include, for example, 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, fragrances, etc.When these additives are contained in the topical composition of the present invention, the content thereof can be appropriately determined depending on the type of additive used, etc.

[0038] The topical composition of the present invention may contain pharmacological ingredients in addition to the above-mentioned ingredients. Examples of such pharmacological ingredients include steroids, antihistamines, local anesthetics, anti-inflammatory agents, moisturizers, disinfectants, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, vitamins, mucopolysaccharides, etc. These pharmacological ingredients may be used alone or in combination of two or more. Furthermore, when these pharmacological ingredients are contained in the topical composition of the present invention, their concentration may be appropriately determined depending on the type of pharmacological ingredient used, the desired effect, etc.

[0039] [Dosage form / preparation type] The formulation of the topical composition of the present invention is not particularly limited as long as it is applicable transdermally, and may be any of an oily ointment, a water-in-oil cream, etc., with an oily ointment being preferred.

[0040] Furthermore, the topical composition of the present invention may be in any formulation such as a topical drug for skin application (including quasi-drugs) or a cosmetic, as long as it is applied to the skin. [Example]

[0041] The present invention will be explained in more detail below by showing examples, but the present invention is not limited to these examples.

[0042] Oleaginous ointments were prepared with the compositions shown in Tables 1 and 2. Specifically, the oily bases shown in Tables 1 and 2 were heated to 80°C and mixed, and then the other ingredients were added in predetermined amounts and thoroughly mixed to prepare the oleaginous ointments. The oleaginous ointments immediately after preparation were allowed to stand at room temperature for 30 minutes, and then the appearance was observed. The solubility of glycyrrhetinic acid was graded on a 10-point scale from 1 to 10, with 10 points representing "completely dissolved glycyrrhetinic acid powder," 5 points representing "some residual glycyrrhetinic acid powder, but within an acceptable range for commercialization," and 1 point representing "not dissolved glycyrrhetinic acid powder with significant residual glycyrrhetinic acid."

[0043] The results are shown in Tables 1 and 2. When ufenamate was not added, glycyrrhetinic acid was not dissolved in oleaginous ointments containing 50% by weight or more of white petrolatum and glycyrrhetinic acid, and significant residual glycyrrhetinic acid was observed (Comparative Examples 1 and 2). In contrast, in oleaginous ointments containing ufenamate together with 50% by weight or more of white petrolatum and glycyrrhetinic acid, the solubility of glycyrrhetinic acid was improved, and the residual glycyrrhetinic acid was reduced (Examples 1 to 11). In particular, when ufenamate and diphenhydramine were added together with 50% by weight or more of white petrolatum and glycyrrhetinic acid, the solubility of glycyrrhetinic acid was significantly improved (Examples 3 to 5, 7, 9, and 11). Furthermore, in the oleaginous ointment in which diphenhydramine was replaced with diphenhydramine hydrochloride in Example 4, the solubility of glycyrrhetinic acid was significantly improved to the same extent as in Example 4.

[0044] [Table 1]

[0045] [Table 2]

Claims

1. 50% by weight or more of white petrolatum; at least one glycyrrhetinic acid selected from the group consisting of glycyrrhetinic acid, pyridoxine glycyrrhetinate, stearyl glycyrrhetinate, glyceryl glycyrrhetinate, glyceryl glycyrrhetinate, glycyrrhetinic acid monoglucuronide, and salts thereof; Ufenamart and The topical composition is an oleaginous ointment.

2. The topical composition according to claim 1, further comprising diphenhydramine and / or a salt thereof.

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