JP2019085339A - Composition containing d-chiro-inositol - Google Patents

Abstract

To provide a composition that can inhibit the precipitation of D-chiro-inositol.SOLUTION: A composition contains D-chiro-inositol and a C1-3 monoalcohol aqueous solution, with the C1-3 monoalcohol of 60 v/v% or less in concentrations.SELECTED DRAWING: None

Description

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

  Inositol (1,2,3,4,5,6-cyclohexanehexaol) has a structure in which one hydrogen atom on each carbon of cyclohexane is substituted by a hydroxy group, and is known as a vitamin-like substance There is. Inositol has nine stereoisomers depending on the combination of configuration of hydroxy group.

  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) as an additive for pharmaceuticals, quasi-drugs or cosmetics, etc. , 6-cyclohexanehexaol) is usually meant (see, for example, non-patent documents 1 to 3).

Unexamined-Japanese-Patent No. 2006-28026

Quasi-drug raw material standard 2006 integrated version, Pharmaceutical Daily, Inc., p. 318 Pharmaceutical additive specification 2003, Pharmaceutical Daily, Inc., p. 101-102 Drug Additives Reference 2000, Pharmaceutical Daily, Inc., p. 26

Here, the present inventor has found that D-chiro-inositol is a compound having water solubility among the isomers of inositol among the stereoisomers of inositol.
However, in order to make use of these properties of D-chiro-inositol, D-chiro-inositol is one of the stereoisomers of inositol in an aqueous solution while continuing research on compositions containing D-chiro-inositol. It has been found that it tends to form precipitates. In particular, D-chiro-inositol has a very low solubility in solvents other than water, and tends to form precipitates more easily in a mixed solution containing a solvent other than water.

  Then, an object of this invention is to provide the composition which can suppress precipitation of D-chiro- inositol.

  As a result of intensive studies to solve the above problems, the present inventors found that a composition containing D-chiro-inositol in a specific concentration of a C1-C3 monoalcohol aqueous solution is D-chiro. It has been found that the composition is capable of suppressing the precipitation of inositol, and the present invention has been completed.

That is, the present invention provides the following inventions.
[1] It comprises D-chiro-inositol and a C 1 to C 3 monoalcohol aqueous solution,
The composition whose density | concentration of a C1-C3 monoalcohol is 60 v / v% or less.
[2] The composition according to [1], wherein the content of D-chiro-inositol is 0.001 to 20 w / v% with respect to the composition.
[3] The composition according to [1] or [2], wherein the monoalcohol having 1 to 3 carbon atoms is ethanol.
The external preparation containing the composition in any one of [4] [1]-[3].

  According to the present invention, a composition capable of suppressing the 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 present invention is not limited to the specific embodiments described below.

  The composition of the present invention is a composition containing D-chiro-inositol and a C 1-3 monoalcohol aqueous solution.

  The D-chiro-inositol is not particularly limited, and examples thereof include those extracted from naturally occurring oats, beans, citrus and the like, those extracted and produced from leguminous plants by a fermentation method, and those synthesized chemically, A commercial item is mentioned. Here, the method of extraction 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%, and further preferably Is from 0.05 to 15 w / v%, more preferably from 1 to 10 w / v%, even more preferably from 3 to 7 w / v%.

As used herein, "w / v%" refers to the weight percentage of D-chiro-inositol relative to the volume of the composition.
Moreover, when it describes with "X-Y" in this specification, it means that it is X or more and Y or less.

The composition of the present invention can be used as an external preparation. As the external preparation, for example, an agent for cracking and tearing, an agent for heat and air, an agent for skin and octopus, an agent for swelling and skinning, an agent for wrinkles and spots, a moisturizing agent, a hair dye, a hair restorer, a shampoo, Examples include rinses, conditioners, lotions, creams, emulsions, hand creams, medicinal soaps, packs and the like.
By including D-chiro-inositol, the composition of the present invention can obtain a composition having a vitamin-like action or hair growth activity, and may be used as a hair growth agent. Moreover, as shown in the Example mentioned later, the usability | use_condition in a C1-C3 monoalcohol formulation can be improved by containing D-chiro-inositol.
Specifically, the hair growth activity is an activity related to hair shaft growth promotion, hair growth, hair loss prevention and the like, and preferably an activity related to hair trunk growth promotion and hair growth.

In the composition of the present invention, the concentration of the C 1-3 monoalcohol in the C 1-3 monoalcohol aqueous solution is 60 v / v% or less.
By dissolving D-chiro-inositol in a C1-C3 monoalcohol aqueous solution having 60 v / v% or less, precipitation of D-chiro-inositol can be suppressed.

In the present specification, “v / v%” means the volume percentage of a C 1-3 monoalcohol to the volume of a C 1-3 C monoalcohol aqueous solution.
In the present invention, the C1-C3 monoalcohol aqueous solution is composed of C1-C3 monoalcohol and water.
Since the composition of the present invention contains water as a monoalcohol aqueous solution having 1 to 3 carbon atoms, D-chiro-inositol contained in the composition is soluble in water, so that the function and effect of the present invention can be more reliably obtained. It tends to be obtainable.
Examples of water include pure water such as ion exchange water, ultrafiltered water, reverse osmosis water, and distilled water, and water from which ionic impurities have been removed as much as possible, such as ultrapure water.

The concentration of the monoalcohol having 1 to 3 carbon atoms in the aqueous monoalcohol solution having 1 to 3 carbons in the composition of the present invention is preferably 60 v / v% or less, preferably 5 v / v% or more. Preferably it is 8 v / v% or more, more preferably 10 v / v% or more, and even more preferably 30 v / v% or more. The concentration of the monoalcohol aqueous solution having 1 to 3 carbon atoms in the composition of the present invention is preferably 60 v / v% or less, preferably 50 v / v% or less, and more preferably 45 v / v% or less. More preferably, it is 40 v / v% or less, still more preferably 38 v / v% or less.
Although the density | concentration of the C1-C3 monoalcohol aqueous solution is not specifically limited, Preferably it is 8-45 v / v%, More preferably, it is 30-40 v / v%.

As a C1-C3 monoalcohol, they are methanol, ethanol, n-propanol, and isopropanol, ethanol and isopropanol are preferable and ethanol is more preferable.
A C1-C3 monoalcohol may be used individually by 1 type, and may be used in combination of 2 or more type.

The composition of the present invention may further comprise a polyhydric alcohol. The inclusion of a polyhydric alcohol tends to make it possible to obtain a composition having antibacterial and moisturizing properties. Moreover, in the composition of the present invention, the possibility of suppressing precipitation of D-chiro-inositol is increased by further including a polyhydric alcohol.
The polyhydric alcohol means an alcohol having two or more hydroxyl groups in the molecule.
The polyhydric alcohol is not particularly limited. For example, 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, - heptanediol, and 1,8-octanediol, and the like. Among these, glycerin and 1,3-butylene glycol are preferred.
A polyhydric alcohol may be used individually by 1 type, and may be used in combination of 2 or more type.

  The content of 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, and more preferably 0.5 to 30 w / V%, more preferably 0.5 to 20 w / v%, still more preferably 0.5 to 15 w / v%.

  The composition of the present invention may further comprise a monoterpene. While containing a monoterpene, while giving a refreshing feeling, it exists in the tendency which can obtain the composition excellent by precipitation suppression of D-chiro- inositol.

  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 Examples of such aldehydes include monoterpene ketones such as menthone, carbomentone and ionone. It is preferably a monoterpene alcohol, more preferably menthol. These monoterpenes may be any of d-, l- and dl-forms. These may be used alone or in combination of two or more. Especially as menthol, although it does not specifically limit, for example, 1-menthol and d-menthol are preferable, and 1-menthol is more preferable. It may be used as a mixture of l-menthol and d-menthol.

  The content of monoterpene in the composition of the present invention is not particularly limited, but in addition to imparting a refreshing sensation, it suppresses precipitation of D-chiro-inositol, and suppresses dripping and irritating feeling (pizziness) of the composition obtained. And from 0.01 to 10 w / v%, more preferably 0.05 to 2 w / v%, and still more preferably 0.1 to 1 or more, because they are excellent in suppressing separation of the monoterpene itself. It is 0 w / v%, and more preferably 0.7 to 1.0 w / v%.

The composition of the present invention may further contain additives generally accepted for medicines, quasi-drugs, cosmetics and the like.
The additives are not particularly limited, but, for example, excipients, stabilizers, odorants, bases, dispersants, diluents, surfactants, emulsifiers, percutaneous absorption enhancers, pH adjusters, preservatives, Colorant, oil (oil, fat, mineral oil, etc.), thickener, polymer, film-forming agent, UV absorber, cell activator, antioxidant, preservative, freshener, deodorant, pigment, dye, fragrance, Examples include saccharides, amino acids, vitamins, organic acids, organic amines, plant extracts and the like.

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 in which the components are mixed is not particularly limited.
Moreover, the conditions in the case of mixing are not specifically limited, either, It can be set as the composition of this invention according to a conventionally well-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 for skin cosmetics, hair cosmetics and scalp cosmetics . More specifically, it may be in the form of an ointment, a pap, liniment, a lotion, a solution for external use, a spray, a cream, a gel, an emulsion, a hair tonic, a hair spray.

  The method of the present invention comprises the step of administering the composition of the present invention to a subject. The dose of D-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 100 mg. It is 10 mg.

  The number of administrations 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 ~ 2 times.

  The subject to which the composition of the present invention is administered is not particularly limited, and includes, for example, humans, animals such as domestic animals and pets, and the like.

  Hereinafter, the present invention will be described in more detail by way of 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, Ltd., hereinafter abbreviated as "DCI")
Ethanol (manufactured by Wako Pure Chemical Industries, Ltd., hereinafter abbreviated as "EtOH")
Glycerin (manufactured by Wako Pure Chemical Industries, Ltd.)
l-menthol (manufactured by Wako Pure Chemical Industries, Ltd., hereinafter abbreviated as "l-mentol")
Pure water

Example 1
Each component was diluted and mixed with pure water so as to obtain the compositions shown in Tables 1 and 2 below, and each composition was prepared as a formulation.

A. Formulation stability test The obtained formulation was evaluated for precipitation of DCI in each aqueous EtOH solution by the following method.
Preparations for each composition were prepared in 3 lots and induced precipitation of DCI by a low temperature cycle (12 hours incubation at 5 ° C, then 12 hours-20 ° C repeated for 14 days) and evaluated visually based on the following indexes: did. The evaluation results are shown in Table 1 (N number is 3).
No precipitation of crystals is seen in all Lots "「 "
Even with 1 Lot, slight precipitation of crystals was observed "○"
Even in 1 Lot, precipitation of crystalline material was observed "×"

  From the results in Table 1, it can be determined that the precipitation of DCI can be suppressed in an aqueous EtOH solution by setting the EtOH concentration to 60 v / v% or less. Also, instead of EtOH, the same trend as in EtOH with isopropanol was followed and the same tendency as in EtOH was observed.

B. Testing of feeling of use The feeling of use at the time of application with the EtOH preparation (feeling of squeaky feeling, stickiness and burning feeling) was evaluated for the obtained preparation by the following method.
Evaluation Monitor 10 persons applied 0.5 g of the preparation to the arm to evaluate the squeakiness, stickiness and burning feeling at the time of application. Specifically, the evaluation was scored by conducting a questionnaire by Visual Analogue Scale. The evaluation results are summarized in Table 2 (N number is 10) by averaging the questionnaire results and rounding off the second decimal place.
<Feeling of use>
・ No feeling of squeak, no problem as usability "1 point"
Strong feeling of squeaky, "10 points" which is a problem as usability
-Sticky feeling Feeling sticky feeling is felt enough, there is no problem as usability "1 point"
The feeling of stickiness is very small, and it is a problem as usability "10 points"
There is no burning sensation or burning sensation, and there is no problem as usability "1 point"
Burning sensation is strong, "10 points" that is a problem as usability

  From the results in Table 2, it was found that the squeakiness, stickiness and burning feeling by the EtOH preparation were improved by the addition of DCI. Also, instead of EtOH, the same trend as in EtOH with isopropanol was followed and the same tendency as in EtOH was observed.

Example 2
Each component was diluted and mixed with pure water so as to have the compositions shown in Tables 3 and 4 below, and each composition was prepared as a formulation.

A. Formulation stability test The obtained formulation was evaluated for precipitation of DCI at each concentration of glycerol by the following method.
Preparations for each composition were prepared in 3 lots and induced precipitation of DCI by a low temperature cycle (12 hours incubation at 5 ° C, then 12 hours-20 ° C repeated for 14 days) and evaluated visually based on the following indexes: did. The evaluation results are shown in Table 3 (N number is 3).
No precipitation of crystals is seen in all Lots "「 "
Even with 1 Lot, slight precipitation of crystals was observed "○"
Even in 1 Lot, precipitation of crystalline material was observed "×"

  From the results of Table 3, it can be judged that the precipitation of DCI can be effectively suppressed by blending glycerin. Also, in place of glycerin, it may be carried out in the same manner as in glycerin with propylene glycol (1,2-propanediol), dipropylene glycol, 1,3-propylene glycol, or 1,3-butylene glycol, The same tendency as the result was seen.

B. Test of feeling of use The feeling of use at the time of application with a glycerin-containing EtOH preparation (feeling of entanglement and spread) was evaluated for the obtained preparation by the following method.
Evaluation The evaluation monitor evaluated the feeling of stiffness at the time of application applied to the hair with 0.5 g of the preparation and the spread feeling at the time of application applied to the arm. Specifically, the evaluation was scored by conducting a questionnaire by Visual Analogue Scale. The evaluation results are summarized in Table 4 (N number is 10) by averaging the questionnaire results and rounding off the second decimal place.
<Feeling of use>
-No feeling of stiffness. There is no problem as usability "1 point".
Strong tenacity, "10 points" that is a problem in usability
· Spreading feeling very easy to spread out, no problem as usability "1 point"
Very difficult to spread, there is a problem as usability "10 points"

  From the results in Table 4, the feeling of stiffness and spread by the EtOH preparation containing glycerin was improved by the addition of DCI. Also, in place of glycerin, it may be carried out in the same manner as in glycerin with propylene glycol (1,2-propanediol), dipropylene glycol, 1,3-propylene glycol, or 1,3-butylene glycol, The same tendency as the result was seen.

Example 3
Each component was diluted and mixed with pure water so as to obtain the compositions shown in Tables 5 to 8 below, and each composition was prepared as a formulation.

A. Formulation stability test The obtained formulations were evaluated for DCI precipitation at each concentration of DCI and l-mentol according to the following method.
Preparations for each composition were prepared in 3 lots, induced precipitation of DCI and separation of l-mentol by a low temperature cycle (12 hours incubation at 5 ° C, 12 hours-20 ° C repeated for 14 days), and visually It evaluated based on the index of. The evaluation results are shown in Tables 5 and 6 (N number is 3).
And precipitation in all of Lot, precipitation of crystals was not seen "◎"
Even with 1 Lot, slight precipitation of crystals was observed "○"
Even in 1 Lot, precipitation of crystalline material was observed "×"
And separation in all of Lot, the separation of l-mentol is not seen "◎"
Even with 1 Lot, slight separation of l-mentol was observed "○"
Even with 1Lot, separation of l-mentol was seen "×"

  From the results in Table 5, it can be judged that the precipitation of DCI can be effectively suppressed by blending l-mentol which is a monoterpene. Further, from the results of Table 6, it can be judged that the separation of the monoterpene l-mentol can be effectively suppressed by blending DCI.

B. Testing of feeling of use The feeling of use (dipping and irritation) at the time of application with the l-mentol-containing EtOH preparation was evaluated for the obtained preparation by the following method.
The evaluation monitor 10 applied 0.5 g of the preparation to the arm to evaluate dripping and irritation at the time of application. Specifically, the evaluation was scored by conducting a questionnaire by Visual Analogue Scale. The evaluation results are summarized in Tables 7 and 8 (N number is 10) by averaging the questionnaire results and rounding off the second decimal place.
<Feeling of use>
-Liquid drip It is hard to drip and there is no problem as usability "1 point"
Very easy to drip, there is a problem as usability "10 points"
・ There is no feeling of irritation and no problem as usability "1 point"
"10 points" which is very tingling and a problem as usability

  From the results of Tables 7 and 8, the dripping and the irritating feeling (pizziness) by the EtOH preparation containing the monoterpene l-mentol were improved by the addition of DCI.

  In addition, formulations prepared by diluting with water so that DCI 5 w / v%, EtOH 50 v / v%, glycerin 5 w / v% and l-mentol 1 w / v% do not have precipitation of ingredients, and have a feeling of squeaky, sticky, It was an excellent composition in terms of feeling in use such as burning feeling, feeling of swelling, feeling of spreading, dripping and feeling of irritation.

Claims (4)

D-chiro-inositol and C1-C3 monoalcohol aqueous solution containing
The composition whose density | concentration of a C1-C3 monoalcohol is 60 v / v% or less.   The composition according to claim 1, wherein the content of D-chiro-inositol is 0.001 to 20 w / v% with respect to the composition.   The composition according to claim 1, wherein the monoalcohol having 1 to 3 carbon atoms is ethanol.   The external preparation containing the composition as described in any one of Claims 1-3.