External emulsion composition

Abstract

To provide an external emulsion composition that includes tocopherol and / or a derivative thereof and has excellent emulsion stability.SOLUTION: An emulsion composition includes ufenamate together with tocopherol and / or a derivative thereof, but not including allantoin, so that it has excellent emulsion stability.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an emulsion composition containing tocopherol and / or a derivative thereof and having excellent emulsion stability. [Background technology]

[0002] Topical emulsion compositions can contain aqueous and oily components, can be used in a variety of formulations, and are excellent in terms of ease of compatibility with the skin, ease of application to the skin, and the like, and are also favorable in terms of feel when used, and therefore are widely used in the field of topical preparations.

[0003] On the other hand, tocopherol and its derivatives are widely used in topical preparations due to their antioxidant, immunostimulating, and blood circulation promoting effects, etc. However, when tocopherol or its derivatives are incorporated into an emulsion composition, separation of the oil and aqueous phases (phase separation) is likely to occur during storage, making it difficult to maintain a stable emulsion state.

[0004] Therefore, various formulation techniques for improving emulsion stability in emulsion compositions containing tocopherol and / or its derivatives have been investigated. For example, Patent Document 1 describes that the emulsifiability of emulsion compositions can be improved by using a tocopherol aminoalkyl carboxylic acid ester and / or a salt thereof having a substituent on the nitrogen atom as a tocopherol derivative. However, the technique of Patent Document 1 has the disadvantage that it can be applied only to specific tocopherol derivatives and cannot be applied to commonly used tocopherol derivatives such as tocopherol acetate. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2004-2278 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide an emulsion composition for external use which contains tocopherol and / or a derivative thereof and has excellent emulsion stability. [Means for solving the problem]

[0007] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that an emulsion composition for external use can be provided with excellent emulsion stability by containing ufenamate together with tocopherol and / or a derivative thereof, but not allantoin. The present invention was completed through further research based on this finding.

[0008] That is, the present invention provides the following aspects. Item 1. An emulsion composition for external use containing (A) tocopherol and / or a derivative thereof, and (B) ufenamate, and not containing (C) allantoin. Item 2. The emulsion composition for external use according to Item 1, further comprising (C) a monoterpene. [Effects of the Invention]

[0009] According to the emulsion composition for external use of the present invention, even though it contains tocopherol and / or a derivative thereof, phase separation during storage can be suppressed and excellent emulsion stability can be achieved. DETAILED DESCRIPTION OF THE INVENTION

[0010] 1. Emulsified composition for external use The emulsion composition for external use of the present invention is characterized by containing (A) tocopherol and / or a derivative thereof, and (B) ufenamate, and not containing (C) allantoin. The emulsion composition for external use of the present invention will be described in detail below.

[0011] [(A) Tocopherol and / or its derivatives] The emulsion composition for external use of the present invention contains tocopherol and / or a derivative thereof (sometimes referred to as component (A)).

[0012] Tocopherol is a well-known component known as vitamin E. Tocopherol derivatives are not particularly limited as long as they are pharmaceutically acceptable, and examples thereof include esters with carboxylic acids such as acetic acid, nicotinic acid, and succinic acid, and diesters with phosphoric acid. The tocopherol derivative may be any of the d-, l-, and dl-forms, with the dl-form being preferred. The tocopherol derivative may be any of the α-, β-, γ-, and δ-forms, with the α-form being preferred.

[0013] In the emulsion composition for external use of the present invention, one type selected from tocopherol and its derivatives may be used alone as component (A), or two or more types may be used in combination.

[0014] Of the components (A), preferred are tocopherol derivatives, more preferred are esters of tocopherol with carboxylic acid, even more preferred are tocopherol acetate, and particularly preferred are d-α-tocopherol acetate, l-α-tocopherol acetate, and dl-α-tocopherol acetate.

[0015] The content of component (A) in the emulsion composition for external use of the present invention is not particularly limited, but may be, for example, 0.01 to 15% by weight, preferably 0.01 to 10% by weight, more preferably 0.1 to 5% by weight, and even more preferably 1 to 5% by weight.

[0016] [(B) Ufenamart] The topical emulsion composition of the present invention contains ufenamate (sometimes referred to as component (B)). By allowing tocopherol and / or a derivative thereof and ufenamate to coexist in the topical emulsion composition of the present invention, emulsion destabilization caused by tocopherol and / or a derivative thereof can be suppressed, thereby providing excellent emulsion stability.

[0017] Ufenamate, also known as butyl flufenamate, is a known lipid-soluble nonsteroidal anti-inflammatory drug.

[0018] The content of component (B) in the emulsion composition for external use of the present invention is, for example, 1 to 20% by weight, and from the viewpoint of further improving emulsion stability, it is preferably 2 to 10% by weight, more preferably 3 to 7% by weight. From the viewpoint of further improving emulsion stability, the content of component (B) in the emulsion composition for external use of the present invention is even more preferably 5 to 7% by weight, particularly preferably 5% by weight.

[0019] In the emulsion composition for external use of the present invention, the ratio of component (B) to component (A) is determined depending on the content of each of these components, but for example, the ratio of component (B) is 0.01 to 100 parts by weight, preferably 0.1 to 10 parts by weight, and more preferably 0.2 to 5 parts by weight per part by weight of component (A).

[0020] [(C) Allantoin] The topical emulsion composition of the present invention does not contain allantoin (sometimes referred to as component (C)). The topical emulsion composition of the present invention can improve emulsion stability by containing tocopherol and / or a derivative thereof and ufenamate, but even if these components are contained, the emulsion stabilizing effect of the present invention is impaired when allantoin is contained.

[0021] [(D) Monoterpene] The topical emulsion composition of the present invention may further contain a monoterpene (sometimes referred to as component (D)). When tocopherol and / or a derivative thereof and a monoterpene are present together in the absence of ufenamate, emulsion stability is significantly reduced. However, the topical emulsion composition of the present invention can maintain excellent emulsion stability even when it contains a monoterpene.

[0022] Monoterpenes are known compounds that have a structure containing two isoprene units in the molecule and have cooling and refreshing effects.

[0023] The type of monoterpene used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but examples thereof include alcohol-based monoterpenes such as menthol, thymol, geraniol, linalool, borneol, cineole, and terpineol; aldehyde-based monoterpenes such as citral, citronellal, perillaldehyde, and safranal; and ketone-based monoterpenes such as camphor, menthone, carbomenthone, and ionone. When optical isomers exist, these monoterpenes may be d-, l-, or dl-isomers. These monoterpenes may be used alone or in combination of two or more.

[0024] In addition, in the present invention, an essential oil containing a monoterpene may be used as the monoterpene. The essential oil containing a monoterpene can be appropriately selected from known essential oils and used, and for example, essential oils containing menthol include peppermint oil, peppermint oil, spearmint oil, etc. In addition, when an essential oil containing a monoterpene is used, the description of the content or ratio of the monoterpene in this specification is a value converted into the amount of monoterpene contained in the essential oil.

[0025] Among these monoterpenes, from the viewpoint of further improving emulsion stability, menthol is preferred, and 1-menthol is more preferred.

[0026] When the topical emulsion composition of the present invention contains component (D), its content is not particularly limited, but may be, for example, 0.01 to 10% by weight, preferably 0.01 to 5% by weight, more preferably 0.1 to 5% by weight, and even more preferably 0.2 to 5% by weight, of the total amount of component (D).

[0027] When the topical emulsion composition of the present invention contains component (D), the ratio of component (D) to component (A) is determined depending on the respective contents of components (A) and (D), but for example, the ratio of component (D) is 0.001 to 20 parts by weight, preferably 0.01 to 10 parts by weight, and more preferably 0.05 to 5 parts by weight per part by weight of component (A).

[0028] [Polyhydric alcohol] The emulsion composition for external use of the present invention may contain a polyhydric alcohol, if necessary. The polyhydric alcohol used in the present invention is not particularly limited, as long as it is applicable to the skin, and examples thereof include 1,3-butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, and glycerin.

[0029] Among the polyhydric alcohols, 1,3-butylene glycol and glycerin are preferred. These polyhydric alcohols may be used alone or in combination of two or more.

[0030] When the external emulsion composition of the present invention contains a polyhydric alcohol, the content thereof is not particularly limited, but may be, for example, 0.1 to 40% by weight, preferably 1 to 30% by weight, and more preferably 5 to 25% by weight, of the total amount of polyhydric alcohol.

[0031] [Thickener] The external emulsion composition of the present invention may contain a thickener as needed. The thickener used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include cellulose-based thickeners, polyvinyl-based thickeners, thickening polysaccharides, and acrylic acid-based thickeners. These thickeners may be used alone or in combination of two or more. Among these thickeners, polyvinyl-based thickeners are preferred.

[0032] Specific examples of polyvinyl thickeners include carboxyvinyl polymers, polyvinylpyrrolidone, and polyvinyl alcohol. Among these thickeners, polyvinyl alcohol is preferred, and carboxyvinyl polymers are more preferred.

[0033] When a thickener is contained in the emulsion composition for external use of the present invention, the content thereof is not particularly limited, but may be, for example, 0.0001 to 5 wt %, preferably 0.001 to 2 wt %, and more preferably 0.01 to 1 wt % in terms of the total amount of thickener.

[0034] [Oil-based base] The emulsion composition for external use of the present invention contains an oily base as a base component forming an oil phase. The oily base used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include hydrocarbon oils, vegetable oils, animal oils, cholesterol, fatty acid alkyl esters, fatty acids, higher alcohols, silicone oils, etc.

[0035] These oily bases may be used alone or in combination of two or more. Among these oily bases, hydrocarbon oils are preferred.

[0036] The hydrocarbon oil is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include liquid paraffin, α-olefin oligomer, petrolatum, etc. Among these hydrocarbon oils, liquid paraffin is preferred.

[0037] The content of the oily base in the emulsion composition for external use of the present invention may be appropriately set depending on the emulsion type, formulation form, etc., and may be, for example, 1 to 80% by weight, preferably 2 to 65% by weight, more preferably 5 to 25% by weight, of the total amount of the oily base.

[0038] [Aqueous base] The emulsion composition for external use of the present invention contains water as a base component that forms an aqueous phase. The content of water in the emulsion composition for external use of the present invention may be appropriately determined depending on the emulsion type, formulation form, etc., and may be, for example, 20 to 97% by weight, preferably 35 to 90% by weight, and more preferably 40 to 80% by weight.

[0039] [Surfactants] The emulsified composition for external use of the present invention preferably contains a surfactant to prepare it into an emulsified form. The type of surfactant used in the present invention may be appropriately selected depending on the type of emulsion, but a nonionic surfactant is preferred.

[0040] The nonionic surfactant used in the present invention may be appropriately selected depending on the emulsification type, but preferably includes polyoxyethylene sorbitan fatty acid esters. Specific examples of polyoxyethylene sorbitan fatty acid esters include polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan tristearate, and polyoxyethylene sorbitan monolaurate. Among these nonionic surfactants, polyoxyethylene sorbitan monooleate is preferred. These nonionic surfactants may be used alone or in combination of two or more.

[0041] The content of the surfactant in the emulsion composition for external use of the present invention may be appropriately set depending on the emulsion type, the type of surfactant used, etc., and may be, for example, 0.1 to 20% by weight, preferably 1 to 15% by weight, and more preferably 1 to 10% by weight.

[0042] [Other ingredients] In addition to the above-mentioned components, the emulsion composition for external use of the present invention may contain other commonly used additives as needed. Examples of such additives include pH adjusters, buffers, solubilizers, antiseptics, preservatives, antioxidants, stabilizers, fragrances, colorants, etc. When these additives are contained in the emulsion composition for external use of the present invention, the content thereof may be appropriately determined depending on the type of additive used, etc.

[0043] The topical emulsion composition of the present invention may contain pharmacological ingredients in addition to the above-mentioned ingredients. Examples of such pharmacological ingredients include antihistamines, local anesthetics, anti-inflammatory agents (other than component (B)), moisturizers, disinfectants, antibacterial agents, antipruritics, skin protectants, blood circulation promoters, and vitamins (other than component (A)). These pharmacological ingredients may be used alone or in combination of two or more. Furthermore, when these pharmacological ingredients are contained in the topical emulsion composition of the present invention, their concentrations may be appropriately determined depending on the type of pharmacological ingredient used, the desired effect, and the like.

[0044] [Emulsion type / formulation] The emulsion type of the external emulsified composition of the present invention may be either an oil-in-water type or a water-in-oil type, but is preferably an oil-in-water type.

[0045] The formulation of the emulsified composition for external use of the present invention is not particularly limited, and examples thereof include external pharmaceuticals such as creams, emulsions, lotions, liniments, aerosols, etc. Of these, creams are preferred.

[0046] [Manufacturing method] The emulsion composition for external use of the present invention can be produced according to a known formulation method for emulsion preparations depending on the emulsion type. For example, a method for producing the emulsion composition for external use of the present invention includes separating the components to be contained into water-soluble components and oily components, preparing an aqueous phase containing the water-soluble components and an oily phase containing the oily components, and emulsifying them according to a known method. [Example]

[0047] The present invention will be explained in more detail below by showing examples, but the present invention is not limited to these examples.

[0048] Test Example 1 An external emulsion composition (oil-in-water cream) having the composition shown in Table 1 was prepared by the following method. Specifically, first, predetermined amounts of the oil phase components, l-menthol, ufenamate, and dl-α-tocopherol acetate shown in Table 1 were mixed and dissolved at a temperature of 70 to 80°C to prepare an oil phase composition. Separately, predetermined amounts of the aqueous phase components and allantoin shown in Table 1 were mixed to prepare an aqueous phase composition. Next, the oil phase composition heated to 70 to 80°C was mixed with the aqueous phase composition heated to 70 to 80°C and emulsified to prepare an external emulsion composition (oil-in-water cream).

[0049] None of the obtained topical emulsion compositions showed phase separation immediately after preparation. Immediately after preparation, 45 g of each topical emulsion composition was filled into a glass bottle and stored at 50°C under light-shielded conditions for 2 days. After 2 days of storage, each topical emulsion composition was centrifuged (3,000 rpm, 10 minutes). The emulsified state after centrifugation was observed and the emulsion stability was scored on a 10-point scale from 1 to 10, with 1 point representing "significant phase separation, with a clear boundary between the oil and aqueous phases" and 10 points representing "no phase separation at all." A score of 8 or higher indicates that phase separation was sufficiently suppressed and is deemed acceptable for practical use.

[0050] The results are shown in Table 1. In topical emulsion compositions that did not contain dl-α-tocopherol acetate, no phase separation was observed even after storage, and the emulsified state was stably maintained (Reference Example 1). On the other hand, in topical emulsion compositions that did not contain ufenamate, when dl-α-tocopherol acetate was included, phase separation was observed after storage (Comparative Examples 1 to 4). When dl-α-tocopherol acetate and l-menthol were also included, phase separation became more pronounced after storage, further reducing emulsion stability (Comparative Examples 3 and 4). Furthermore, in topical emulsion compositions that contained dl-α-tocopherol acetate and allantoin, phase separation was pronounced after storage, regardless of the presence or absence of ufenamate (Comparative Examples 5 and 6). In contrast, in topical emulsion compositions that contained dl-α-tocopherol acetate and ufenamate, phase separation was suppressed after storage, and the emulsified state was stably maintained (Examples 1 to 4). Furthermore, in the external emulsion composition of Example 3, in which the l-menthol content was changed to 5 wt%, phase separation after storage was suppressed and the emulsified state was stably maintained. Furthermore, in the external emulsion composition of Example 3, in which the dl-α-tocopherol acetate content was changed to 5 wt%, phase separation after storage was suppressed and the emulsified state was stably maintained.

[0051] [Table 1]

[0052] Prescription example Topical emulsion compositions with the compositions shown in Tables 2 and 3 were prepared, and the emulsion stability after storage was evaluated in the same manner as in Test Example 1. Phase separation after storage was suppressed in all of the topical emulsion compositions of Formulation Examples 1 to 6, and the emulsified state was stably maintained. Note that, in the topical emulsion compositions of Formulation Examples 1 to 6 that did not contain ufenamate, phase separation was observed after storage.

[0053] [Table 2]

[0054]

Table 3

Claims

1. An oil-in-water emulsion composition for external use, containing (A) an ester of tocopherol and a carboxylic acid, (B) ufenamate, and (D) a monoterpene, and not containing (C) allantoin.

2. An external emulsion composition as described in claim 1, containing 0.01 to 15% by weight of the (A) component and 1 to 20% by weight of the (B) component.

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