JP7733992B2 - External composition - Google Patents

Description

The present invention relates to a topical composition containing 50% or more by weight of white petrolatum and having improved allantoin solubility.

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. Topical compositions containing white petrolatum as a base are widely used to prevent or improve dry skin, sensitive skin, contact skin inflammation, etc.

Various formulations of topical compositions containing white petrolatum have been reported in the past. 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) carboxyvinyl polymer and/or alkyl-modified carboxyvinyl polymer, and (D) phospholipids has 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, and is not formulated to 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 a higher amount of white petrolatum may result in reduced solubility of the active ingredient.

On the other hand, allantoin is known to have tissue repair activating, anti-inflammatory, and antipruritic effects, and topical compositions containing allantoin have been developed to date. However, no sufficient research has been conducted into formulations that can stably incorporate allantoin into topical compositions containing a higher amount of white petrolatum.

JP 2008-195712 A

The inventors conducted research to develop a topical composition containing allantoin and a higher amount of white petrolatum, and discovered that in topical compositions containing 50% by weight or more of white petrolatum and allantoin, the allantoin did not dissolve sufficiently, making it difficult to formulate.

The object of the present invention is to provide a formulation technology that improves the solubility of allantoin in a topical composition containing 50% by weight or more of white petrolatum and allantoin.

The inventors conducted extensive research to solve the above-mentioned problems and found that a topical composition containing ufenamate, along with 50% by weight or more of white petrolatum and allantoin, can improve the solubility of allantoin. Furthermore, the inventors discovered that the solubility of allantoin can be further improved by further adding diphenhydramine and/or a salt thereof to the topical composition. Based on these findings, the present invention was completed through further research.

That is, the present invention provides the following aspects.
Item 1. A composition for external use containing 50% by weight or more of white petrolatum, allantoin, and ufenamate.
Item 2. The topical composition 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.

The topical composition of the present invention contains 50% by weight or more of white petrolatum, yet can improve the solubility of allantoin, thereby effectively achieving the moisturizing and barrier effects of white petrolatum while also achieving the medicinal effects of allantoin.

1. Topical Composition The topical composition of the present invention is characterized by containing 50% by weight or more of white petrolatum, allantoin, and ufenamate. The topical composition of the present invention will be described in detail below.

[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 exhibited.

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

[Allantoin]
The topical composition of the present invention contains allantoin, a compound also known as 5-ureidohydantoin, which is a known drug known to have tissue repair activating effects, anti-inflammatory effects, antipruritic effects, and the like.

The content of allantoin in the topical composition of the present invention may be set appropriately depending on the level of medicinal effect that the topical composition is to have, but may be, for example, 0.005 to 2% by weight, preferably 0.01 to 1% by weight, more preferably 0.01 to 0.2% by weight, and even more preferably 0.1 to 0.2% by weight.

[Ufenamart]
The topical composition of the present invention contains ufenamate in addition to the above-mentioned components. By including ufenamate together with allantoin in a topical composition containing 50% by weight or more of white petrolatum, the solubility of allantoin can be improved.

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

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 more significantly improving the solubility of allantoin.

In the topical composition of the present invention, the ratio of ufenamate to allantoin is, for example, 0.1 to 5,000 parts by weight of ufenamate per 1 part by weight of allantoin, and from the viewpoint of more significantly improving the solubility of allantoin, preferably 1 to 500 parts by weight, more preferably 10 to 75 parts by weight, and even more preferably 20 to 50 parts by weight.

[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 allantoin can be further effectively improved.

Diphenhydramine is a known drug known to have antihistamine properties.

Diphenhydramine salts are not particularly limited as long as they are pharmaceutically acceptable, but examples include acid addition salts such as hydrochloride, citrate, succinate, tartrate, fumarate, maleate, salicylate, diphenyldisulfonate, tannate, lauryl sulfate, and sulfate.

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

Among diphenhydramine and its salts, diphenhydramine and diphenhydramine hydrochloride are preferred, and diphenhydramine is more preferred, from the viewpoint of more significantly improving the solubility of allantoin.

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% by weight of diphenhydramine and/or a salt thereof in total, and from the viewpoint of more significantly improving the solubility of allantoin, preferably 0.05 to 3% by weight, more preferably 0.01 to 1% by weight, and even more preferably 0.5 to 1% by weight.

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 allantoin is not particularly limited, but for example, the total amount of diphenhydramine and/or a salt thereof is 0.01 to 5,000 parts by weight per 1 part by weight of the total amount of allantoin, and from the viewpoint of more significantly improving the solubility of allantoin, the total amount is preferably 0.1 to 500 parts by weight, more preferably 1 to 25 parts by weight, and even more preferably 4 to 15 parts by weight.

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

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

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

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

When a polyhydric alcohol is contained in the topical composition of the present invention, its content is not particularly limited, but examples include a total amount of polyhydric alcohol of 0.01 to 40% by weight, preferably 0.05 to 10% by weight, and more preferably 0.01 to 5% by weight.

[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 may be, 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.

[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 may be appropriately determined depending on the type of additive used, etc.

The topical composition of the present invention may contain pharmacological ingredients in addition to the ingredients described above. Examples of such pharmacological ingredients include steroids, antihistamines, local anesthetics, anti-inflammatory agents, moisturizers, disinfectants, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, vitamins, and mucopolysaccharides. 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 concentrations may be appropriately determined depending on the type of pharmacological ingredient used, the desired effect, and other factors.

[Dosage form/preparation form]
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.

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

The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

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 specified amounts of other ingredients were added and thoroughly mixed to prepare the oleaginous ointments. Immediately after preparation, the oleaginous ointments were left to stand at room temperature for 30 minutes, after which the appearance was observed and the solubility of allantoin was evaluated on a 10-point scale from 1 to 10, with 10 points representing "completely dissolved allantoin powder," 5 points representing "some residual allantoin powder, but within an acceptable range for commercialization," and 1 point representing "significant residual allantoin powder remaining."

The results are shown in Tables 1 and 2. When ufenamate was not added, allantoin did not dissolve in oleaginous ointments containing 50% or more by weight of white petrolatum and allantoin, and significant amounts of undissolved allantoin were observed (Comparative Examples 1 and 2). In contrast, in ufenamate-containing oleaginous ointments containing ufenamate together with 50% or more by weight of white petrolatum and allantoin, the solubility of allantoin was improved, and the amount of undissolved allantoin was reduced (Examples 1 to 11). In particular, when ufenamate and diphenhydramine were added together with 50% or more by weight of white petrolatum and allantoin, the solubility of allantoin was significantly improved (Examples 3 to 5, 7, 9, and 11). Furthermore, in the oleaginous ointment in Example 4 in which diphenhydramine was replaced with diphenhydramine hydrochloride, the solubility of allantoin was significantly improved, as in Example 4.

Claims (2)

A composition for external use which is an oleaginous ointment and contains 50% by weight or more of white petrolatum, allantoin, and ufenamate. The topical composition according to claim 1, further comprising diphenhydramine and/or a salt thereof.