JP7127979B2 - Compositions containing D-chiro-inositol - Google Patents

Description

The present invention relates to compositions containing D-chiro-inositol. The present invention also relates to an external preparation containing the composition.

Inositol (1,2,3,4,5,6-cyclohexanehexaol) has a structure in which each hydrogen atom on each carbon of cyclohexane is substituted with a hydroxyl group, and is known as a vitamin-like active substance. there is Inositol has nine stereoisomers depending on the combination of steric configurations of hydroxy groups.

Patent Document 1 discloses a hair restorer containing inositol as an active ingredient. As in Patent Document 1, "inositol" used in the prior art refers to myo-inositol (cis-1,2,3,5-trans-4 , 6-cyclohexanehexaol) (see, for example, Non-Patent Documents 1-3).

JP-A-2006-28026

Standards for Quasi-drug Ingredients 2006 Integrated Edition, Yakuji Nippo, p. 318 Pharmaceutical Excipients Standards 2003, Yakuji Nippousha, p. 101-102 Pharmaceutical Additives Encyclopedia 2000, Yakuji Nipposha, p. 26

Here, the present inventors have found that D-chiro-inositol, among stereoisomers of inositol, is a compound having water solubility among isomers of inositol.
However, while continuing research on compositions containing D-chiro-inositol in order to take advantage of these properties of D-chiro-inositol, D-chiro-inositol is an inositol stereoisomer in an aqueous solution. It was found that they tended to form precipitates. In particular, D-chiro-inositol has very low solubility in solvents other than water, and tends to form precipitates more easily in mixed solutions containing solvents other than water.

Accordingly, an object of the present invention is to provide a composition capable of suppressing precipitation of D-chiro-inositol.

The present inventors have made intensive studies to solve the above problems, and found that a composition containing D-chiro-inositol and a monoterpene is a composition capable of suppressing the precipitation of D-chiro-inositol. The present inventors have found that it is a product, and have completed the present invention.

That is, the present invention provides the following inventions.
[1] A composition comprising D-chiro-inositol and a monoterpene.
[2] The composition according to [1], wherein the content of monoterpene is 0.01 to 10 w/v% relative to the composition.
[3] The composition according to [1] or [2], wherein the content of D-chiro-inositol is 0.001 to 20 w/v% of the composition.
[4] The composition according to any one of [1] to [3], wherein the monoterpene is menthol.
[5] The composition according to any one of [1] to [4], wherein the menthol is l-menthol.
[6] The composition according to any one of [1] to [5], further comprising an aqueous monoalcohol solution having 1 to 3 carbon atoms.
[7] The composition according to [6], wherein the monoalcohol having 1 to 3 carbon atoms is ethanol.
[8] The composition according to any one of [1] to [7], further comprising a polyhydric alcohol.
[9] An external preparation containing the composition according to any one of [1] to [8].

According to the present invention, a composition capable of suppressing precipitation of D-chiro-inositol is provided.

Hereinafter, the present invention will be clarified by describing the composition of the present invention and specific embodiments thereof. However, the invention is not limited to the specific embodiments described below.

A composition of the present invention is a composition comprising D-chiro-inositol and a monoterpene.

D-chiro-inositol is not particularly limited, but for example, those extracted from naturally occurring buckwheat, beans, citrus fruits, etc., those produced from leguminous plants by fermentation and extracted, those synthesized chemically, and A commercial item is mentioned. Here, the extraction method is not particularly limited, and a known extraction method can be used.

The content of D-chiro-inositol in the composition of the present invention is not particularly limited, but is preferably 0.001 to 20 w/v%, more preferably 0.01 to 20 w/v%, still more preferably is 0.05 to 15 w/v%, still more preferably 1 to 10 w/v%, still more preferably 3 to 7 w/v%.

As used herein, "w/v %" means the weight percentage of D-chiro-inositol relative to the volume of the composition.
In addition, in the present specification, the expression “X to Y” means X or more and Y or less.

The composition of the present invention can be used as an external preparation. External preparations include, for example, cracks and chapped skin, prickly heat and sores, corns and calluses, dry skin and rough skin, wrinkles and blemishes, moisturizers, hair dyes, hair restorers, shampoos, Examples include rinses, conditioners, lotions, creams, milky lotions, hand creams, medicated soaps, packs, and the like.
By containing D-chiro-inositol, the composition of the present invention can obtain a composition imparted with vitamin-like action and hair growth activity, and may be used as a hair restorer. In addition, as shown in the examples below, the feeling of use of the monoalcohol preparations of Examples 1 to 3 can be improved by including D-chiro-inositol.
Specifically, the hair-restoring activity is activity related to promotion of hair shaft growth, hair growth, prevention of hair loss, etc., and preferably activity related to promotion of hair shaft growth and hair growth.

Compositions of the invention comprise a monoterpene. Precipitation of D-chiro-inositol can be suppressed by including monoterpene. In addition, by including a monoterpene in the composition of the present invention, it is possible to obtain a composition that is excellent in use feeling when used on human skin and imparts a refreshing feeling.

The monoterpene is not particularly limited, but monoterpene hydrocarbons such as limonene, pinene, and camphor; monoterpene alcohols such as citronellol, geraniol, linalool, menthol, terpineol, and borneol; monoterpenes such as citronellal, citral, and safranal. aldehydes; monoterpene ketones such as menthone, carbomentone, and ionone; Monoterpene alcohols are preferred, and menthol is more preferred. These monoterpenes may be d-, l-, or dl-forms. These may be used individually by 1 type, and may be used in combination of 2 or more type. In particular, menthol is not particularly limited, but l-menthol and d-menthol are preferred, and l-menthol is more preferred. A mixture of l-menthol and d-menthol may also be used.

The content of monoterpene in the composition of the present invention is not particularly limited, but while maintaining a cool feeling, it suppresses precipitation of D-chiro-inositol and is excellent in suppressing drooling and irritation of the composition. Therefore, it is preferably 0.01 to 10 w/v%, more preferably 0.05 to 2 w/v%, still more preferably 0.1 to 1.0 w/v%, still more preferably 0 .7 to 1.0 w/v%.

The composition of the present invention may further contain an aqueous monoalcohol solution having 1 to 3 carbon atoms.
By containing the C 1-3 monoalcohol aqueous solution, the composition of the present invention tends to be able to further suppress the precipitation of D-chiro-inositol.

Monoalcohols having 1 to 3 carbon atoms include methanol, ethanol, n-propanol and isopropanol, preferably ethanol and isopropanol, and more preferably ethanol.
Monoalcohols having 1 to 3 carbon atoms may be used singly or in combination of two or more.

The concentration of the monoalcohol having 1 to 3 carbon atoms in the monoalcohol aqueous solution having 1 to 3 carbon atoms in the composition of the present invention is not particularly limited, but the concentration of the monoalcohol having 1 to 3 carbon atoms may be set high. It is possible.
The concentration of the monoalcohol having 1 to 3 carbon atoms in the monoalcohol aqueous solution having 1 to 3 carbon atoms may be, for example, 60 v/v% or less, may be 30 to 70 v/v%, or may be 30 to 60 v/v%. may be 30 to 40 v/v%.

As used herein, “v/v %” means the volume percentage of monoalcohol having 1 to 3 carbon atoms to the volume of aqueous solution of monoalcohol having 1 to 3 carbon atoms.
In the present invention, the C 1-3 monoalcohol aqueous solution is composed of a C 1-3 monoalcohol and water.
Since the composition of the present invention contains water in the form of an aqueous monoalcohol solution having 1 to 3 carbon atoms, the D-chiro-inositol contained in the composition is water-soluble, so that the effect of the present invention can be more reliably achieved. tend to be obtainable.
Examples of water include pure water such as ion-exchanged water, ultrafiltrated water, reverse osmosis water, and distilled water, and water from which ionic impurities are removed as much as possible, such as ultrapure water.

The composition of the invention may further contain a polyhydric alcohol. By containing a polyhydric alcohol, it tends to be possible to obtain a composition imparted with antibacterial properties and moisturizing properties.
A polyhydric alcohol means an alcohol having two or more hydroxyl groups in the molecule.
Examples of polyhydric alcohols include, but are not limited to, glycerin, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol (1,2-propanediol), dipropylene glycol, trimethylolpropane, 1,3-propylene glycol ( 1,3-propanediol), isobutylene glycol (2-methyl-1,2-propanediol), 1,2-butanediol, 1,3-butylene glycol (1,3-butanediol), 1,4-butane Diol, 2-butene-1,4-diol, 1,2-pentanediol, 1,5-pentanediol, 2-methyl-2,4-pentanediol, 1,2-hexanediol, 1,6-hexanediol , 2-ethyl-1,3-hexanediol, 1,7-heptanediol, and 1,8-octanediol. Among these, glycerin and 1,3-butylene glycol are preferred.
Polyhydric alcohols may be used singly or in combination of two or more, preferably in combination of two or more.

The content of the polyhydric alcohol in the composition of the present invention is not particularly limited, but is usually 0.1 w/v% or more, preferably 0.5 w/v% or more, more preferably 0.5 to 30 w /v%, more preferably 0.5 to 20w/v%, and even more preferably 0.5 to 15w/v%.

The composition of the present invention may further contain additives generally accepted in pharmaceuticals, quasi-drugs, cosmetics and the like.
Examples of additives include, but are not limited to, excipients, stabilizers, corrigents, bases, dispersants, diluents, surfactants, emulsifiers, percutaneous absorption enhancers, pH adjusters, preservatives, Colorants, oils (fat, mineral oil, etc.), thickeners, polymers, film-forming agents, UV absorbers, cell activators, antioxidants, preservatives, cooling agents, deodorants, pigments, dyes, fragrances, Sugars, amino acids, vitamins, organic acids, organic amines, plant extracts and the like can be mentioned.

The composition of the present invention is not particularly limited and can be produced by mixing the components included in the present invention. The order of mixing each component is not particularly limited.
Also, the conditions for mixing are not particularly limited, and the composition of the present invention can be obtained according to a conventionally known method.

When the composition of the present invention is used as an external preparation, it can be used as pharmaceuticals, quasi-drugs, cosmetics, etc. For example, it can be used in skin cosmetics, hair cosmetics, and scalp cosmetics. . More specifically, it can be in the form of ointments, poultices, liniments, lotions, liquids for external use, dusting agents, creams, gels, milky lotions, hair tonics, and hair sprays.

The methods of the invention comprise administering the compositions of the invention to a subject. The dose of chiro-inositol per administration to a subject is not particularly limited, but is preferably 0.005 to 200 mg, more preferably 0.05 to 100 mg, and still more preferably 0.5 to 10 mg. be.

The frequency of administration of the composition of the present invention to a subject is not particularly limited, but is preferably 1 to 6 times per day, more preferably 1 to 3 times per day, and still more preferably 1 time per day. ~2 times.

Subjects to which the composition of the present invention is administered are not particularly limited, but examples thereof include animals such as humans and domestic animals and pets.

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

The components used in this example are as follows.
D-chiro-inositol (manufactured by Wako Pure Chemical Industries, hereinafter abbreviated as "DCI")
Ethanol (manufactured by Wako Pure Chemical Industries, Ltd., hereinafter abbreviated as “EtOH”)
l-menthol (manufactured by Wako Pure Chemical Industries, Ltd., hereinafter abbreviated as “l-mentol”)
Pure water

Each component was diluted with pure water and mixed so as to have the composition shown in Tables 1 to 4 below, and each composition was prepared as a formulation.

A. Formulation Stability Test The obtained formulations were evaluated for precipitation of DCI at each concentration of DCI and l-mentol by the following method.
Prepare 3 lots of formulations for each composition, induce precipitation of DCI and separation of l-mentol by a low temperature cycle (after 12 hours of 5 ° C incubation, 12 hours -20 ° C for 14 days). was evaluated based on the index of Evaluation results are shown in Tables 1 and 2 (N number is 3).
・Precipitation
No precipitation of crystals is observed in all lots "◎"
Even in 1 lot, a small amount of crystals precipitated "○"
"X" that precipitation of crystals was observed even in 1 lot
・Separation
Separation of l-mentol is not seen in all lots "◎"
Even in 1 lot, a slight separation of l-mentol was observed "○"
Separation of l-mentol was observed even in 1 lot "×"

From the results in Table 1, it can be judged that the precipitation of DCI can be effectively suppressed by blending l-mentol, which is a monoterpene. Moreover, from the results in Table 2, it can be judged that the addition of DCI can effectively suppress the separation of l-mentol, which is a monoterpene.

B. Test of feeling in use The feeling in use (dripping and irritation) of the EtOH preparation containing l-mentol was evaluated by the following method.
Ten evaluation monitors applied 0.5 g of the preparation to the arm and evaluated dripping and irritation during application. Specifically, the evaluation was scored by conducting a questionnaire using the Visual Analogue Scale. By averaging the questionnaire results and rounding off to the second decimal place, the evaluation results are summarized in Tables 3 and 4 (the N number is 10).
<Usage feeling>
・Dripping
It is hard to drip, and there is no problem in usability "1 point"
Very easy to drip, problematic usability "10 points"
・Stimulation
There is no tingling sensation, and there is no problem in usability "1 point"
"10 points" which is a problem for usability due to a very tingling feeling

From the results in Tables 3 and 4, the addition of DCI improved the dripping and stinging sensation (tingling sensation) caused by the EtOH preparation containing the monoterpene l-mentol.

In addition, a formulation prepared by diluting with water to 5 w/v% DCI, 50 v/v% EtOH, 5 w/v% glycerin, and 1 w/v% l-mentol did not cause precipitation of the components, dripping and irritation. The composition was excellent in terms of feel during use.

Claims (8)

D-chiro-inositol and a monoterpene ,
A composition that is an external preparation . The composition according to claim 1, wherein the monoterpene content is 0.01-10 w/v% relative to the composition. The composition according to claim 1 or 2, wherein the content of D-chiro-inositol is 0.001-20 w/v% relative to the composition. A composition according to any preceding claim, wherein the monoterpene is menthol. A composition according to any one of claims 1 to 4, wherein the menthol is l-menthol. The composition according to any one of claims 1 to 5, further comprising an aqueous monoalcohol solution having 1 to 3 carbon atoms. The composition according to claim 6, wherein the C1-C3 monoalcohol is ethanol. A composition according to any preceding claim, further comprising a polyhydric alcohol.