JP5921868B2 - Method for producing hair growth composition - Google Patents

Description

  The present invention relates to a method for producing a hair growth composition.

  Alopecia is thought to be caused by complex intertwining of various factors such as blood circulation failure, decreased hair matrix cell activity, and sex hormone imbalance, and blood circulation is promoted for products intended for hair growth and hair growth. A plurality of medicinal ingredients such as synthetic substances and natural animal and plant extracts having an action, a hair matrix activation action, a metabolism promotion action and the like are used. Among them, aromatic hair-growth ingredients have effective effects such as activation of hair papilla and hair matrix cells such as trans-3,4'-dimethyl-3-hydroxyflavanone, and peripheral blood flow promoting effects such as nicotinic acids. It is known to have and is recognized as an important component of hair restorers.

  Aromatic hair-growth components are often poorly water-soluble and are generally used after being dissolved in alcohol (for example, Patent Documents 1 and 2).

JP 2009-96777 A JP 2011-153122 A

In order to increase the hair-restoring and hair-growth effect, it is necessary to have a composition with a high alcohol content in order to blend the aromatic hair-growth component at a high concentration. However, alcohol tends to impair the feeling of use due to skin irritation. Moreover, when many auxiliary components are used in order to solubilize components, such as a hair-growth component, percutaneous permeability may be inhibited.
Therefore, the subject of this invention is providing the method of manufacturing the hair-growth composition excellent in the solubility to water.

The inventors of the present invention have studied various techniques for solubilizing aromatic hair-growth ingredients, and by heating the hair-growth ingredients and water-soluble aromatic compounds at 100 ° C. or higher in the presence of an aqueous medium, It has been found that the dissolution concentration of the hair-growth component increases, and that the composition that has undergone such treatment suppresses precipitation of the hair-growth component and maintains high solubility even at room temperature.
That is, this invention provides the manufacturing method of the hair-growth composition which includes the process of heat-processing (A) aromatic hair-growth component and (B) water-soluble aromatic compound at 100-180 degreeC in presence of an aqueous medium. Is.

  According to the present invention, it is possible to produce a hair-growth composition having excellent solubility in water. By using this hair-growth composition, the use of alcohol can be reduced or avoided, so that an aqueous product with little skin irritation can be provided.

In the manufacturing method of the hair-growth composition of this invention, the process of heat-processing (A) aromatic hair-growth component and (B) water-soluble aromatic compound at 100-180 degreeC in presence of an aqueous medium is included.
As the (A) aromatic hair-growth component used in the present invention, a poorly water-soluble component, for example, solubility in water at 25 ° C. is 1 g / L or less, further 0.5 g / L or less, and further 0.2 g / L In the following, those of 0.1 g / L or less are preferably applicable. Here, the solubility represents the number of grams of solute dissolved in 1 L of the solution, and the unit is [g / L].
Specifically, flavanonol derivatives such as trans-3,4′-dimethyl-3-hydroxyflavanone; nicotinic acids such as benzyl nicotinate, tocopherol nicotinate, β-butoxyethyl nicotinate; α-tocopherol, dl-α acetate -Vitamin E such as tocopherol, nicotinic acid tocopherol, natural vitamin E; minoxidil, bimatoprost, tafluprost, nonyl acid vanillylamide, hypericum herb extract, capsicum tincture and the like.
Among them, trans-3,4'-dimethyl-3-hydroxyflavanone, benzyl nicotinate, tocopherol nicotinate, β-butoxyethyl nicotinate, α-tocopherol, dl-α-tocopherol acetate, tocopherol nicotinate, natural vitamin E , Minoxidil, bimatoprost, tafluprost, nonylic acid vanillylamide, hypericum herb extract and chili tincture are preferred, and trans-3,4'-dimethyl-3-hydroxyflavanone is more preferred. The aromatic hair-growth component may be one kind or a mixture of two or more kinds.

The water-soluble aromatic compound (B) used in the present invention preferably has a higher water solubility than the (A) aromatic hair-growth component used together. Specifically, the solubility of the component (B) in water at 25 ° C. is preferably 2 times or more, more preferably 5 times or more than the solubility of the component (A) in water at 25 ° C., More preferably, it is 10 times or more. More specifically, it is preferable that the solubility in water at 25 ° C. is 2 g / L or more, further 5 g / L or more, further 10 g / L or more, further 15 g / L or more, and further 20 g / L or more.
Examples of such water-soluble aromatic compounds include sugar adducts of poorly water-soluble polyphenols, methylated products of poorly water-soluble polyphenols, catechins, chlorogenic acids, water-soluble isoflavones, vanillin, glucosyl hesperidin, glucosyl Rutin, methyl hesperidin, catechins, chlorogenic acids, water-soluble isoflavones and vanillin are preferred. These can be used alone or in combination of two or more.

The sugar adduct of the poorly water-soluble polyphenols used in the present invention is a compound in which at least one sugar is bonded to the poorly water-soluble polyphenols.
As the poorly water-soluble polyphenols, phenolic substances in which one or more, and more than two, hydroxyl groups are bonded to the benzene ring are preferable, and examples thereof include plant-derived flavonoids, tannins, and phenolic acids. Specific examples include flavonols, flavanones, flavones, isoflavones, phenol carboxylic acids and the like. Of these, flavonols and flavanones are preferable, rutin, hesperidin and isoquercitrin are more preferable, and rutin and hesperidin are more preferable.
The poorly water-soluble polyphenols include not only aglycones but also glycosides in which sugars are bound to aglycones.
For example, a glycoside in which rutinose (L-rhamnosyl- (α1 → 6) -D-glucose) is β-bonded to the hydroxyl group at position 7 of hesperetin (5,7,3′-trihydroxy-4′-methoxyflavanone). Examples include hesperidin, apiin in which apiose and glucose are bound to apigenin, rutin in which rutinose is bound to quercetin, and quercitrin in which rhamnose is bound to quercetin.

The type of sugar that binds to the poorly water-soluble polyphenols is not particularly limited, but is preferably at least one selected from 4 to 6 carbon sugars such as glucose, galactose, fructose, rhamnose, xylose, arabinose, and erythrose. Moreover, the number of sugar bonds is preferably 1 to 10, more preferably 1 to 6. The sugar binding site to the poorly water-soluble polyphenols is a phenolic hydroxyl group or a sugar residue of a glycoside. The binding mode between the poorly water-soluble polyphenols and these sugars may be either α-bond or β-bond.
As the sugar adduct of the poorly water-soluble polyphenols, glucosyl hesperidin, glucosyl rutin, glucosyl quercetin and glucosyl isoquercitrin are preferable, and glucosyl hesperidin and glucosyl rutin are more preferable.
A sugar adduct of a poorly water-soluble polyphenol can be industrially produced by a known method using chemical synthesis or enzymatic reaction.
Commercially available preparations may be used as sugar adducts of poorly water-soluble polyphenols, such as “Hayashibara Hesperidin S” (Hayashibara Bioscience Institute), “Glucosylrutin P” (Toyo Seika Co., Ltd.) Etc.

  The methylated product of the poorly water-soluble polyphenols used in the present invention is a methylated product of the aforementioned poorly water-soluble polyphenols solubilized in water. The position and number of methylation are not particularly limited. Specific examples include methyl hesperidin, methyl quercetin, methyl resveratrol, methyl rutin and the like, and methyl hesperidin is preferred. Methyl hesperidin is known to mainly contain chalcone type compounds (1) and flavanone type compounds (2), and examples of the constituents include those having the structures shown below.

(In the formula, R represents a hydrogen atom or a methyl group.)
Here, methyl hesperidin as a pharmaceutical additive and a food additive is mainly handled as a mixture of the compounds (3) and (4).

(In the formula, Gl represents a glucose residue, Rh represents a rhamnose residue, and Gl-2 represents the 2-position of the glucose residue (including 3-position in the case of (3-1)), Rh- 2 represents position 2 of the rhamnose residue.)
Hesperidin methyl chalcone as a cosmetic raw material is handled as a compound represented by (5). In the case of a composition containing a large amount of chalcone type compound, it is also called hesperidin methyl chalcone.

(In the formula, R represents a hydrogen atom or a methyl group.)
The methyl hesperidin used in the present invention may contain both the chalcone type compound (1) and the flavanone type compound (2) shown above, or may contain only one of them.
In the present invention, more preferred methyl hesperidin includes a mixture of compound (3) and compound (4).
Methyl hesperidin is a known method, for example, hesperidin is dissolved in an aqueous sodium hydroxide solution, a corresponding amount of dimethyl sulfate is allowed to act on the alkaline solution, the reaction solution is neutralized with sulfuric acid, and extracted with n-butyl alcohol. It can be produced by distilling off and then recrystallizing with isopropyl alcohol (Saki Bath, Nippon Kagaku Kagaku, 79, 733-6 (1958)), but the production method is not limited to this.
Commercially available methyl hesperidin-containing preparations may be used as methyl hesperidin, for example, “Methyl Hesperidin” (Tokyo Chemical Industry Co., Ltd.), “Hesperidin Methyl Chalcone” (Sigma), “Methyl Hesperidin” (Hamari Pharmaceutical Co., Ltd.) Co., Ltd.).

  The catechins used in the present invention include non-epimeric catechins such as catechin, gallocatechin, catechin gallate and gallocatechin gallate, and epi-catechins such as epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate. It is a collective term. The content of catechins is defined based on the total amount of the above eight types.

As catechins, tea extracts may be used. As the tea extract, at least one selected from a tea extract, a concentrate thereof, and a purified product thereof can be used.
Here, the “tea extract” refers to an extract extracted from tea leaves using hot water or a water-soluble organic solvent, and has not been concentrated or purified. As the water-soluble organic solvent, for example, a lower alcohol such as ethanol can be used. As the extraction method, known methods such as kneader extraction, stirring extraction (batch extraction), countercurrent extraction (drip extraction), and column extraction can be employed.

  The tea leaves used for extraction can be roughly classified into non-fermented tea, semi-fermented tea, and fermented tea depending on the processing method. Examples of non-fermented tea include green tea such as sencha, bancha, gyokuro, mochi tea, kettle tea, stem tea, stick tea, and bud tea. Examples of the semi-fermented tea include oolong tea such as iron kannon, color type, golden katsura, and martial arts tea. Furthermore, examples of fermented tea include black teas such as Darjeeling, Assam, Sri Lanka and the like. These can be used alone or in combination of two or more. Among these, green tea is preferable from the viewpoint of the content of catechins.

The “tea extract concentrate” refers to removing a part of the water content of a solution extracted from hot leaves or a water-soluble organic solvent from tea leaves selected from non-fermented tea, semi-fermented tea and fermented tea. The concentration of catechins is increased, for example, by the method described in JP-A-59-219384, JP-A-4-20589, JP-A-5-260907, JP-A-5-306279, etc. Can be prepared. Examples of the form include various forms such as a solid, an aqueous solution, and a slurry. Commercially available products may be used as the concentrate of the tea extract, for example, green tea extraction such as “Polyphenone” from Mitsui Norin Co., “Theafranc” from ITO EN, “Sunphenon” from Taiyo Kagaku Co., Ltd. There is a liquid concentrate.
Purification of the tea extract or the like can be performed by purification using a solvent or a column.

The chlorogenic acids used in the present invention include 3-caffeoylquinic acid, 4-caffeoylquinic acid and monocaffeoylquinic acid of 5-caffeoylquinic acid, 3-feruloylquinic acid, and 4-feruloylquinic acid. And 5-feruloylquinic acid monoferuloylquinic acid and 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid dicaffeoylquinic acid Is a collective term. The content of chlorogenic acids is defined based on the total amount of the above nine types.
Further, chlorogenic acids may be in the form of a salt. Examples of the salt include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium and calcium, and organic amine salts such as monoethanolamine, diethanolamine and triethanolamine. , Basic amino acid salts such as arginine, lysine, histidine, ornithine and the like.
As the chlorogenic acids, a plant extract containing the same, a concentrate thereof, a purified product thereof, or the like can be used. Such plant extracts include, for example, sunflower seeds, apple immature fruits, fresh coffee beans, Simon leaves, pine cones, pine plant seed shells, sugarcane southern leaves, burdock, eggplant skin, Examples include those extracted from ume fruit, dandelion, and vines. Among these, raw coffee bean extract is preferable from the viewpoint of chlorogenic acid content and the like. The type of coffee tree may be any of Arabica, Robusta, Revelica and Arabsta. In addition, the method and conditions for extraction, concentration and purification are not particularly limited, and known methods and conditions can be employed.
Commercially available chlorogenic acid-containing preparations may be used as chlorogenic acids, and examples include flavor holder RC (Hasegawa Fragrance Co., Ltd.).
In the present invention, catechins, chlorogenic acids or methyl hesperidin can be used alone or in combination of two or more as component (B).

The water-soluble isoflavones used in the present invention are isoflavones extracted and purified from soybean germ using alcohol, and include daidzein, genistin, glycitin, and their malonyl glycosides and acetyl glycosides. . The kind of saccharide | sugar couple | bonded with daidzein, genistin, or glycitin is not restrict | limited in particular, The above-mentioned thing is mentioned.
A commercially available water-soluble isoflavone-containing preparation may be used as the water-soluble isoflavone, and examples include Soyaflavone HG (Fuji Oil Co., Ltd.).

Vanillin used in the present invention is a compound represented by the chemical name 4-hydroxy-3-methoxybenzaldehyde, molecular formula C ₈ H ₈ O ₃ . Vanillin includes isomers such as isovanillin and orthovanillin.
Vanillin can be obtained by extraction from a natural product containing the vanillin or a known synthesis method.

  The aqueous medium used in the present invention refers to water and an aqueous solution of an organic solvent. Examples of water include tap water, distilled water, ion exchange water, and purified water. The organic solvent is not particularly limited as long as it is uniformly mixed with water. As the organic solvent, alcohol having 4 or less carbon atoms is preferable, propanol and ethanol are more preferable, and ethanol is more preferable from the viewpoint of being applicable to cosmetics. When an organic solvent is used, the solubility of the (A) aromatic hair-growth component in water increases, but it is desirable to reduce the amount used from the viewpoint of irritation to the skin. The concentration of the organic solvent in the aqueous solution is preferably 0 to 60% by mass (hereinafter simply referred to as “%”), more preferably 0 to 30%, still more preferably 0 to 10%, and substantially 0%. preferable.

  (A) Since the aromatic hair-growth component has low solubility in water, it is preferably dispersed in an aqueous medium and subjected to a heat treatment in a slurry state. On the other hand, it is preferable to use (B) the water-soluble aromatic compound by dissolving it in an aqueous medium.

When using for heat processing, the heat processing raw material containing an aqueous solvent, (A) aromatic hair-growth component, and (B) water-soluble aromatic compound is prepared, and heat processing is performed.
The content of the (A) aromatic hair-growth component in the heat-treated raw material varies depending on the type, but is usually preferably 0.1 to 100 g / L, more preferably 0.5 to 50 g / L from the viewpoint of fluidity. Preferably, 0.7 to 20 g / L is more preferable, and 0.72 to 10 g / L is more preferable.

  From the viewpoint of fluidity, the content of the (B) water-soluble aromatic compound in the heat treatment raw material is preferably 0.1 to 200 g / L, more preferably 0.5 to 100 g / L, and 1 to 50 g / L. Is more preferable, and 2 to 10 g / L is more preferable.

  In the heat treatment raw material, the mass ratio [(A) / (B)] of the (A) aromatic hair growth component to the (B) water-soluble aromatic compound is the solubility of the hair growth composition obtained after the heat treatment and cooling. From the point, 0.005 to 20 is preferable, 0.01 to 15 is more preferable, 0.1 to 12 is still more preferable, and 2 to 10 is still more preferable.

The method of heat-treating (A) the aromatic hair-growth component and (B) the water-soluble aromatic compound in the presence of the aqueous medium is not particularly limited, and a known method can be applied.
The temperature of the heat treatment is 100 to 180 ° C. from the viewpoint of improving the solubility and heat stability of the aromatic hair-growth component, more preferably 110 to 170 ° C., still more preferably 120 to 160 ° C., and 120 to 150 ° C. Is more preferable. Examples of the heating means include water vapor and electricity.

  The pressure during the heat treatment is preferably 0 to 10 MPa, more preferably 0.1 to 8 MPa, further preferably 0.1 to 6 MPa, further preferably 0.2 to 6 MPa, and further preferably 0.2 to 4 MPa in terms of gauge pressure. Preferably, 0.25 to 2 MPa is more preferable, 0.3 to 1.5 MPa is further preferable, and 0.3 to 0.6 MPa is further preferable. The gauge pressure is a pressure at atmospheric pressure of 0 MPa. Moreover, it is preferable to set it more than the saturated vapor pressure of water. Gas may be used for pressurization, and examples of the gas used include inert gas, water vapor, nitrogen gas, helium gas, and the like. The pressurization may be adjusted by a back pressure valve without using gas.

The heat treatment can be performed by any method such as a batch method, a semi-batch method, and a distribution method. Among these, the flow method is preferable in terms of easy control of the heat treatment time.
The heat treatment time is preferably 0.1 to 30 minutes after the aqueous medium reaches the temperature of the heat treatment, and further 0.2 to 15 minutes from the viewpoint of improving the solubility of the aromatic hair-growth component and heat stability. Further, 0.5 to 8 minutes is preferable.

When the flow method is used, the heat treatment time is an average residence time calculated by dividing the volume of the high-temperature and high-pressure part of the reactor by the supply rate of the aqueous medium.
The flow rate of the aqueous medium in the flow method varies depending on the volume of the reactor. For example, when the reactor volume is 100 mL, 3.3 to 200 mL / min is preferable, and 6.7 to 150 mL / min is more preferable. .

  In the manufacturing method of this invention, it is preferable to include the process of cooling the heat processing liquid obtained by heat-processing to 90 degrees C or less, Preferably it is 50 degrees C or less, More preferably, it is 30 degrees C or less. When obtaining a liquid hair restorer composition, 0 degreeC or more is preferable and 10 degreeC or more is preferable. During cooling, the heat treatment liquid may be mixed and stirred for 0.5 to 5 days, preferably 1 to 3 days. Moreover, when obtaining a solid hair-growth composition, you may use a heat processing liquid for freeze-drying or spray-drying.

  The cooling rate of the heat treatment liquid calculated from the time required to decrease from the heat treatment temperature to 90 ° C. is 0.2 ° C./s or more, further 0.5 ° C./s or more, 1 ° C./s or more, and further 3 It is preferably at least 5 ° C./s, and more preferably The higher the cooling rate, the more the solubility of the aromatic hair-growth component can be improved. For this reason, although the upper limit of a cooling rate is not specifically defined, 100 degree C / s or less, for example, 50 degrees C / s or less are preferable from viewpoints, such as restrictions of manufacturing equipment.

  Furthermore, it is preferable from the point which improves the solubility of the hair-restoration composition obtained to perform the process of removing the solid part which remains without melt | dissolving from a heat processing liquid. The method for removing the solid part is not particularly limited, and can be performed, for example, by centrifugation, decantation, or filtration.

  The form of the hair-growth composition of the present invention may be in the form of an aqueous solution, or may be in the form of a paste by adjusting the amount of water. In addition, it is possible to remove the water to form a solid state such as a powder, granule, or solid. Examples of means for adjusting and removing moisture include freeze drying, evaporation to dryness, and spray drying.

The hair-growth composition thus obtained can suppress precipitation of the aromatic hair-growth component even at room temperature despite the high content of the aromatic hair-growth component. Moreover, it is excellent in solubility in water.
The mass ratio [(A) / (B)] of the component (A) to the component (B) in the hair growth composition of the present invention is preferably 0.16 to 5 from the solubility point of the hair growth composition. 0.2-4 are more preferable, 0.3-3 are still more preferable, and 0.4-2 are more preferable.

  Therefore, the hair-growth composition of the present invention can be used for various pharmaceuticals and cosmetics. In particular, it is useful to use for water-based products. Examples of water-based products include hair wash agents and hair restorers.

  The reason why the solubility of the aromatic hair-growth component can be improved by heat-treating the aromatic hair-growth component (A) and the water-soluble aromatic compound at 100 ° C. or higher is not clear, but from UV spectrum analysis, It is estimated as follows. Aromatic hair-growth ingredients and water-soluble aromatic compounds dissolve in water by having a structure in which each molecule self-associates, has a hydrophobic part, and has a hydrophilic part outward, although there is a difference in solubility. It is thought that there is. Here, when both components coexist in an aqueous medium and heat of 100 ° C. or higher is applied, the laminated structure collapses and falls apart, and the interaction between the aromatic hair-growth component and the water-soluble aromatic compound occurs. It is considered that a new laminated structure in which an aromatic hair-growth component and a water-soluble aromatic compound are mixed is created, and this laminated structure is maintained even after cooling, so that the solubility of the aromatic hair-growth component is dramatically improved. .

[Measurement of trans-3,4′-dimethyl-3-hydroxyflavanone and water-soluble aromatic compound]
Using a high-performance liquid chromatograph manufactured by Hitachi, Inc., a column Cadenza CD-C18 (4.6 mmφ × 150 mm, 3 μm) manufactured by Intact was installed, and the gradient method was performed at a column temperature of 40 ° C. The mobile phase A solution was 0.05 mol / L acetic acid aqueous solution, the B solution was acetonitrile, and the solution was fed at 1.0 mL / min. The gradient conditions are as follows.
Time (min) A liquid (%) B liquid (%)
0 85 15
20 80 20
35 10 90
50 10 90
50.1 85 15
60 85 15
The sample injection amount was 10 μL, detection was quantified by absorbance at a wavelength of 254 nm for trans-3,4′-dimethyl-3-hydroxyflavanone, a wavelength of 360 nm for methyl hesperidin, and a wavelength of 283 nm for others.

[Measurement of catechins]
A sample is appropriately diluted with distilled water, and a high-performance liquid chromatograph (model) manufactured by Shimadzu Corporation, equipped with a packed column for liquid chromatography L-column TM ODS (4.6 mmφ × 250 mm: manufactured by Chemical Substance Evaluation Research Organization). SCL-10AVP) and a gradient method at a column temperature of 35 ° C. The mobile phase A solution was a distilled aqueous solution containing 0.1 mol / L of acetic acid, the B solution was an acetonitrile solution containing 0.1 mol / L of acetic acid, the sample injection amount was 20 μL, and the UV detector wavelength was 280 nm. .
(Concentration gradient condition)
Time (min) A liquid (% (v / v)) B liquid (% (v / v))
0 97 3
5 97 3
37 80 20
43 80 20
43.5 0 100
48.5 0 100
49 97 3
62 97 3

[Measurement of chlorogenic acids]
(Analytical equipment)
HPLC (manufactured by Hitachi, Ltd.) was used. The model numbers of the unit units are as follows.
Liquid feeding unit (built-in degasser): L-2130,
Autosampler (with cooler): L-2200,
Column oven: L-2300
Separation column: Cadenza CD-C18, Size: 4.6 mm i. d. × 150 mm, 3 μm (Intact Corporation)
Detector (ultraviolet visible absorption photometer): L-2420:
(Analysis conditions)
Sample injection volume: 10 μL,
Flow rate: 1.0 mL / min,
UV absorption photometer detection wavelength: 325 nm (chlorogenic acids),
Eluent A: 5% acetonitrile containing 0.05 mol / L acetic acid, 0.01 mol / L sodium acetate, and 0.1 mmol / L HEDPO,
Eluent B: acetonitrile (concentration gradient condition)
Time (min) A liquid (% (v / v)) B liquid (% (v / v))
0 100 0
10 100 0
15 95 5
20 95 5
22 92 8
50 92 8
52 10 90
60 10 90
60.1 100 0
70 100 0

[Measurement of solubility of water-soluble aromatic compounds]
The slurry was dispersed in distilled water so as to have a slurry concentration of 4 to 300 g / L. After shaking and stirring at 25 ° C. for 3 days, the solid content was separated by a membrane filter having a pore size of 0.2 μm, and the filtrate was analyzed by HPLC.

Example 1
Trans-3,4'-dimethyl-3-hydroxyflavanone (hereinafter t-flavanone, purity 99% or more) and monoglucosyl hesperidin preparation (GHES, Hayashibara Hesperidin S (trade name), manufactured by Hayashibara Biochemical Laboratories, Inc., Monoglucosyl hesperidin content 74%) was added to distilled water to prepare a heat-treated raw material, which was uniformly stirred in a slurry supply tank. The concentration of t-flavanone in the heat treatment raw material was 1 g / L, and it was in a dispersed state. The concentration of monoglucosyl hesperidin was 0.19 g / L, and it was in a dissolved state (the dissolved amount of the monoglucosyl hesperidin preparation was 0.25 g / L). The liquid in the slurry supply tank was supplied at a rate of 100 mL / min to a stainless steel flow reactor (with a volume of 100 mL, manufactured by Nitto Koatsu Co., Ltd.), and heat treatment was performed at 150 ° C. (average residence time 1 minute). The pressure was adjusted to 0.6 MPa (gauge pressure) with an outlet valve. The heat treatment liquid is extracted from the reactor outlet, cooled to room temperature (25 ° C.) with a heat exchanger, passed through a sintered metal filter with a pore diameter of 7 μm, and the pressure is returned to atmospheric pressure with the outlet valve to collect the heat treatment liquid. did. The cooling rate obtained from the cooling time from 150 ° C. to 90 ° C. was 8 ° C./s.
The recovered liquid was shaken and stirred at room temperature for 3 days, and then the solid part was filtered off to obtain a t-flavanone composition as a t-flavanone-containing aqueous solution. Table 1 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and monoglucosyl hesperidin in the composition.

Example 2
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that the heating temperature was 120 ° C. and the gauge pressure was 0.3 MPa. Table 1 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and monoglucosyl hesperidin in the composition.

Comparative Examples 1 and 2
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that the heating temperature was 80 ° C. or 25 ° C. and the gauge pressure was 0 MPa. Table 1 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and monoglucosyl hesperidin in the composition.

Comparative Example 3
t-Flavanone was dispersed in water at 25 ° C. at 1 g / L, and after stirring for 3 days with shaking, the solid part was separated by filtration. The results of measuring the t-flavanone concentration in the liquid part are shown in Table 1.

Example 3
Instead of the monoglucosyl hesperidin preparation, a methyl hesperidin preparation (methyl HES, manufactured by Hamari Pharmaceutical Co., Ltd., methyl hesperidin content 100%) was used, and the methyl hesperidin concentration in the heat-treated raw material was 0.25 g / L. Except for the above, a t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and methyl hesperidin in the composition.

Comparative Example 4
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 3 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and methyl hesperidin in the composition.

Example 4
Instead of a monoglucosyl hesperidin preparation, a glucosyl rutin preparation (G rutin, glucosyl rutin P (trade name), Toyo Seika Co., Ltd., glucosyl rutin content 100%) is used, and the glucosyl rutin concentration in the heat treatment raw material is 0. A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that the amount was changed to .25 g / L. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and glucosyl rutin in the composition.

Comparative Example 5
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 4 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and glucosyl rutin in the composition.

Example 5
Instead of the monoglucosyl hesperidin preparation, a preparation obtained by purifying coffee bean extract as chlorogenic acids (chlorogenic acid content 40%), and the concentration of chlorogenic acids in the heat-treated raw material is 0.1 g / L (coffee bean extract A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that the amount of the purified preparation dissolved was 0.25 g / L). Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and chlorogenic acids in the composition.

Comparative Example 6
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 5 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and chlorogenic acids in the composition.

Example 6
Instead of the monoglucosyl hesperidin preparation, a water-soluble isoflavone-containing preparation (Soyaflavone HG (trade name), manufactured by Fuji Oil Co., Ltd., water-soluble isoflavone content 52%) is used, and the water-soluble isoflavone concentration in the heat treatment raw material is A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that the amount was 0.13 g / L (the dissolution amount of the water-soluble isoflavone-containing preparation was 0.25 g / L). Table 2 shows the heat treatment conditions and the measurement results of the t-flavanone and water-soluble isoflavone concentrations in the composition.

Comparative Example 7
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 6 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the heat treatment conditions and the measurement results of the t-flavanone and water-soluble isoflavone concentrations in the composition.

Example 7
Instead of the monoglucosyl hesperidin preparation, a vanillin preparation (manufactured by Wako Pure Chemical Industries, 98% purity) is used, and the vanillin concentration in the heat treatment raw material is 0.25 g / L (the dissolution amount of the vanillin preparation is 0.25 g / L) A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 1 except that. Table 2 shows the heat treatment conditions and the results of measuring the t-flavanone and vanillin concentrations in the composition.

Comparative Example 8
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 7 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the heat treatment conditions and the results of measuring the t-flavanone and vanillin concentrations in the composition.

Example 8
In place of the monoglucosyl hesperidin preparation, an epigallocatechin gallate preparation (TEAVIGO manufactured by DMS Nutritional Products, EGCG content 100%) was used as a catechin, and the concentration of catechins in the heat treatment raw material was 0.25 g / L. Obtained a t-flavanone composition as a t-flavanone-containing aqueous solution in the same manner as in Example 1. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and catechins in the composition.

Comparative Example 9
A t-flavanone composition was obtained as a t-flavanone-containing aqueous solution in the same manner as in Example 8 except that the heating temperature was 25 ° C. and the gauge pressure was 0 MPa. Table 2 shows the results of measuring the heat treatment conditions and the concentrations of t-flavanone and catechins in the composition.

As is apparent from Tables 1 and 2, according to the method of the present invention, a t-flavanone composition having a high t-flavanone content can be obtained, and the solubility of t-flavanone can be remarkably increased. .
Moreover, when the t-flavanone composition obtained in Examples 1 to 8 was stored at room temperature for 1 month, a stable dissolved state was maintained without precipitation.

Claims (6)

In the presence of an aqueous medium, (A) an aromatic hair-growth component having a solubility in water at 25 ° C. of 1 g / L or less and (B) a water-soluble aromatic compound having a solubility in water at 25 ° C. of 2 g / L or more , The step of heat treatment at 100 to 180 ° C. under the condition that the mass ratio [(A) / (B)] of (A) to (B) is 0.01 to 15, and the heat treatment obtained by heat treatment A step of cooling the liquid from the heat treatment temperature to 90 ° C. or less under a condition that the cooling rate calculated from the time required for the heat treatment temperature to be lowered to 90 ° C. is 3 ° C./s or more . The aromatic hair-growth component of (A) is a flavonol derivative, and the water-soluble aromatic compound of (B) is a sugar adduct of a poorly water-soluble polyphenol, or methyl of a poorly water-soluble polyphenol. , Catechins, chlorogenic acids, water It is one or more selected from sexual isoflavones and vanillin, and poorly water-soluble polyphenols are phenolic substance bound hydroxyl groups two or more benzene rings, the manufacturing method. (A) The method for producing a hair-growth composition according to claim 1, wherein the aromatic hair-growth component is trans-3,4'-dimethyl-3-hydroxyflavanone . (B) Hair growth according to claim 1 or 2, wherein the water-soluble aromatic compound is one or more selected from glucosyl hesperidin, glucosyl rutin, methyl hesperidin, catechins, chlorogenic acids, water-soluble isoflavones and vanillin. A method for producing a composition. The method for producing a hair-growth composition according to any one of claims 1 to 3, wherein the temperature of the heat treatment is 120 to 180 ° C. A hair-growth composition obtained by the production method according to any one of claims 1 to 4 . (B) The hair restorer composition of Claim 5 whose mass ratio [(A) / (B)] of the (A) aromatic hair restorer component with respect to a water-soluble aromatic compound is 0.16-5.