JPH01163114A - Hair tonic - Google Patents

Abstract

PURPOSE:To provide a safe hair tonic exhibiting excellent effect in promoting hair growth, preventing falling-off of hair and suppressing dandruff and itchiness and containing one or more compounds selected from sialic acid and its derivative having excellent hair-tonic effect. CONSTITUTION:The objective hair tonic contains one or more compounds selected from sialic acid (preferably N-acetylneuraminic acid) and sialic acid derivative (preferably oligosaccharide bonded with sialic acid, protein bonded with sialic acid, lipid bonded with sialic acid or sialic acid salt). The sialic acid and its derivative are produced by extracting a milk raw material from the viewpoint of economy.

Description

[Detailed description of the invention] [Industrial application field] The present invention relates to a novel hair nourishing material.

[Conventional technology]

Traditionally, the causes of baldness and hair loss include activation of male hormones in organs such as hair roots and sebaceous glands, decreased blood flow to hair follicles, excessive secretion of sebum, production of oxides, and growth of bacteria on the scalp. Neurosis caused by abnormalities, genetic factors, stress, etc.
Possible causes include secondary to disease and aging.

For this reason, conventional hair growth agents generally contain compounds that have the effect of eliminating or alleviating the above-mentioned causes. For example, vitamins such as vitamin B, amino acids such as methionine, vasodilators such as acetylcholine derivatives, anti-inflammatory agents such as purple root extract, female hormones such as estradiol, skin-stimulating agents such as cephalanthine, etc. It is used in the prevention and treatment of alopecia.

[Problem that the invention seeks to solve]

However, the mechanism of hair loss and hair growth is extremely complex, and baldness and hair loss cannot be sufficiently prevented simply by inhibiting the activation of male hormones or increasing blood flow to hair follicles. Conventional hair restorers have been shown to be effective in preventing or improving dandruff, itching, and hair loss for only some people, but they still do not have satisfactory effects on hair growth, promoting hair growth, or preventing hair loss. has not been obtained.

In view of the above circumstances, the present inventors have conducted extensive research to obtain a substance that is effective against hair loss and has an excellent hair-nurturing effect. The present invention was completed based on the discovery that the present invention has the following properties.

[Means for solving problems]

That is, the present invention provides a hair nourishing agent containing one or more selected from the group consisting of sialic acid and sialic acid derivatives.

Hereinafter, the configuration of the present invention will be explained in detail.

The sialic acid used in the present invention is a known substance, and the N of polyhydroxymonoaminocarboxylic acid (neuraminic acid)
- A general term for acyl, N-acyl, and 0-acyl conductors,
Also called sialic acid.

Sialic acid is contained in various organisms, and usually constitutes cell surface carbohydrates and exists in glycosidic bonds at the terminals of glycoproteins and glycolipids. It is particularly abundant in the brain, nerves, blood, submandibular glands, mucin, and colostrum, but it is also present in free form in serum, body fluids, and urine.A typical sialic acid found most abundantly in living organisms. is N-acedelneuraminic acid (NANA: molecule Q
309), melting point 185-187℃, [α]'f-3
It is a white powder with an angle of 2°±2°.

The biological and pharmacological actions of sialic acid and sialic acid derivatives are known to be related to their contribution to negative charge on the cell surface, their involvement in specific cell recognition mechanisms, the red blood cell pre-existing reaction caused by viruses, and the homing phenomenon of blood proteins. ing. Recently, expectorant activity of sialic acid (Japanese Patent Application Laid-Open No. 61-684
18) Anti-inflammatory effect (Japanese Patent Application Laid-open No. 62-145015) and nutritional effect of sialic acid-binding oligosaccharides (Japanese Patent Application Laid-open No. 61-1
52233) etc. have been reported.

However, it is not yet known that it has a hair-nourishing effect. In the present invention, the term "hair nourishing effect" or "hair nourishing effect" refers to prevention of hair loss, promotion of hair body and hair growth, and neglect of hair growth.

Methods for molding sialic acid and sialic acid derivatives include synthetic methods and natural extraction methods (raw materials: egg white, submandibular gland mucin, placenta extract, colominic acid obtained from Escherichia coli, etc.); The extraction method (Patent No. 1) 91212, Patent No. 1252988, JP-A-184197, etc.) is particularly preferred.

An example of producing the compound according to the present invention by the milk extraction method will be shown below. The milk used in the milk extraction method can be freely selected from cow's milk, milk, breast milk, etc. Furthermore, the concentration of sialic acid can be adjusted depending on the degree of purification, so the manufacturing method can be selected according to the purpose, usage, dosage form, and purpose. It is possible. Note that the present invention is not limited to this.

('M Example 1) Add 28 kg of hydrochloric acid to 10 tons of sialic acid cheese whey to adjust the pH to 2.
After adjusting the temperature, the mixture was heated at 92° C. for 60 minutes to perform hydrolysis. The resulting whey was hydrolyzed using a screw decanter to remove proteins coagulated by heating to obtain a sialic acid-containing liquid. Next, the sialic acid-containing solution was placed in a desalination tank of an electrodialyzer and desalted to a conductivity of 2 mS/cm, after which the dialysis was stopped and the concentration tank liquid was discarded. Next, put distilled water 301 into the concentration tank and increase the conductivity to 50μS again.
Dialysis was performed until /c+n.

After dialysis, concentrate and dry the concentration tank liquid to obtain a white powder of 600%
I got g. The free sialic acid purity of the powder thus obtained was about 97%.

(Example 2) Sialic acid salt The above-mentioned '& release sialic acid is prepared with caustic soda to obtain Na sialic acid. In addition, salts such as Mg, K, phosphoric acid, and amino acid salts can be selected and produced according to the purpose.

(Production Example 3) A filtrate prepared by ultrafiltrating sialic acid-bound oligosaccharide milk or cheese whey was concentrated under reduced pressure to a total solid content of 20%. After electrodialyzing 25 kg of this liquid until the electrical conductivity reached 20 μS/cm, it was passed through a column packed with DOWEX IX2 (2 kg) to adsorb oligosaccharides. Then add 2 to this column.
After removing neutral sugars through 0 kg of water, the oligosaccharides adsorbed on the column were eluted through 0.5 M hydrochloric acid. Adjust the pH of the obtained eluate to pl+ with 30% caustic soda.7.
After adjusting to 0, electrodialysis was performed again until the electrical conductivity reached 150 μS/cn+. The obtained dialysate was concentrated and dried to obtain 100 g of white powder.

The purity of the sialic acid-bonded oligosaccharide of the powder thus obtained was 90%.

(Production Example 4) Sialic acid-bound protein rennet casein card waste liquid 30ON was heat sterilized at 75°C for 30 minutes in a Fordra tank, cooled to 40°C, and pl+ was adjusted to 4.6 with concentrated hydrochloric acid. After leaving to stand for about 30 minutes, the precipitate was passed through a talarifier to return the pl+ to 7.0, and the clarified solution was concentrated using an RO membrane.
Desalted. After concentrating up to 10 times, water was added to the concentrated solution and it was concentrated again up to 10 times. The obtained concentrate was dried to obtain 1.3 kg of white powder. The purity of the sialic acid-bound protein in the powder thus obtained was about 80%.

(Production Example 5) Add 100 l of chloroform-methanol mixture (1:1) to 15 kg of sialic acid-bound lipid buttermilk powder! The mixture was added, stirred at room temperature for 30 minutes, and extracted. Next, the chloroform-methanol mixture was collected and passed through an ion exchange resin (DEAE-Toyopearl acetate type) lff to adsorb sialic acid-bound lipids.
After washing the resin with a chloroform-methanol mixture (1:1) 21, the sialic acid-bound lipids were eluted with a 0.5M sodium acetate-methanol solution 41. After concentrating the eluate to remove methanol, water 51 was added and ultrafiltration was performed to desalt and concentrate the sialic acid-bound lipids. After the concentrated solution containing sialic acid-bound lipids was dried in an evaporator, it was passed through a silica gel column (4, OX 50cm) to adsorb the sialic acid-bound lipids, and then chloroform 1j2. After sequentially washing with 1β of a chloroform-methanol mixture (4:1), the sialic acid-bound J lipid was eluted with a mixture of chloroform-methanol (2:8). The eluate was evaporated to dryness using an evaporator to obtain 15 g of white powder.

The purity of the sialic acid-bound lipid in the powder thus obtained was 90% or more (resorcinol method) as determined by thin layer chromatography.

Next, safety tests were conducted on sialic acid and sialic acid derivatives, and the results are shown below.

Acute toxicity test ICR female mice (6 weeks old, For intraperitoneal administration, Ig 221/2 of each test substance was suspended in 0.5% sodium carboxymethylcellulose/physiological saline to a concentration of 2% by weight.
For oral administration, use a suspension of each test substance at 5% by weight in olive oil using an oral needle; for intraperitoneal administration, use 60 J/kg; for oral administration, 30-/kg was given. As a result, no deaths, no decreases in body weight, and no noteworthy toxic symptoms were observed during the 70-year observation period for all test substances, and no abnormalities were observed in the autopsy performed on the 7th day.

As is clear from these results, the acute toxicity value (LD50) of sialic acid and sialic acid derivatives is 1200 when administered intraperitoneally.
It was found to be highly safe, with an oral dose of 1500 mg/kg or more.

Next, the formulation of sialic acid and sialic acid derivatives for use as a hair nourishing agent will be described.

In addition to sialic acid and sialic acid derivatives, the hair tonic of the present invention also includes:
It can be used in a mixture with pharmaceutically acceptable excipients and other agents.

However, sialic acid has problems with stability against acids, alkalis, and light, and is not suitable for long-term storage, so it is preferable to use sialic acid derivatives with good stability.

Examples of the additive include carpronium chloride,
Vasodilators such as minoxidil and diadukizide, female hormones such as estradiol, amino acids such as methionine, vitamins such as B vitamins, herbal medicines such as Cordyceps sinensis, pentadecanoic acid, and their triglycerides, etc. Anti-androgen drugs such as oxendrone, hinokitiol, hexachlorophene, phenol, ZPT, tocopheryl retinoate, vitamin E/nicotinic acid ester, vitamin E/acetate, selenium sulfide, thioxolone, sulfur, resorcinol, tetrachlorosalicyl anilide, quaternary ammonium salts such as octadecyl Y.limethylammonium chloride, hexade'sildimethylbenzylammonium chloride,
Benzalkonium chloride, cetylpyridinium chloride,
Anti-dandruff agents such as undecylenic acid, trichlorocarbanilide and bithionol, derivatives such as glycyrrhizic acid and its ammonium salts, anti-inflammatory or cooling agents such as allantoin and menthol, salicylic acid, zinc and its compounds, lactic acid and its alkyl esters, vitamins drugs such as crude drug ingredients, animal and vegetable oils such as olive oil, macadamia nut oil, and squalane, hydrocarbon oils such as liquid paraffin, isopropyl myristate, cetyl isooctanoate,
Ester oils such as 2-ethylhexyl palmitate, waxes such as beeswax, oils such as higher fatty acids and higher alcohols, water, derivatives such as lactic acid and its ethyl ester, polyhydric alcohols such as polyethylene glycol and sorbitol, ethanol, etc. Lower alcohols, mucopolysaccharides (chondroitin sulfate, hyaluronic acid and their salts, etc.), pyrrolidone carboxylates, proteoglycans, collagen, humectants such as glycerin, surfactants, fragrances, antioxidants, ultraviolet absorbers, pigments. These can be used singly or in combination of two or more.

The hair growth agent of the present invention can be in any form as long as it is suitable for obtaining medicinal effects, such as powder, granules, powder, tablets, capsules, syrups, suppositories, injections, and ointments. etc. Among these, external preparations are preferred from the point of view of ease of use, and may be in the official form as long as they can be applied externally.For example, external preparations such as lotions, liniments, milky lotions, creams, ointments, pasta, poultices, jellies, sprays, etc. Semi-solid preparations for external use can be mentioned.

In the hair growth agent of the present invention, the total amount of sialic acid and sialic acid derivatives as active ingredients is o,
ooot ~ 50% by weight, preferably o, ooi ~ 5ml
%. If it is less than 0.0001% by mass, sufficient effects tend to be difficult to obtain, and conversely, even if it exceeds 50% by weight, it is difficult to expect a significant increase in the effect.

When the hair tonic of the present invention is used externally, it is administered by transdermal administration, in which it is directly applied or sprayed on the skin.

In addition, the dosage of the hair tonic of the present invention cannot be limited to immediate hair removal as it may be administered in an amount outside the following range depending on age, individual differences, medical conditions, etc. Or the total amount of the sialic acid derivative for oral administration and transdermal administration is 0.001 to 200 per kg of body ff1) per day.
0 mg1 preferably 0.01 to 1000 mg,
This amount can be administered once or in several doses.

The method for formulating the hair growth agent and the hair growth effect according to the present invention will be specifically explained below with reference to Examples. Note that the present invention is not limited to this. Below, the compounding amount is % weight
It is.

(Method for producing a hair tonic) Na sialic acid and hydrogenated castor oil ethylene oxide (40 mol) adduct were added to 95% ethanol, stirred and dissolved, and then ion-exchanged water was added and mixed to produce the liquid hair tonic of Example 1. Obtained. Examples 2 to 5 and Comparative Example 1 were also obtained in the same manner as Example 1. The Na sialic acid and sialic acid derivatives used were those produced in Production Examples 2 to 5.

Table 1: Prescriptions of Examples 1 to 5 and Comparative Example 1 (hair growth effect test) Next, in order to investigate the hair growth effect of the hair growth agent of the present invention, (J) Trichogram test and (2) Road conversion rate test were conducted. Examples 1-5
and the hair growth agent of Comparative Example 1.

(1) Trichogram test The removed hair roots were observed under a microscope before and after using the hair tonic, and the number of hair roots in the resting phase was counted from the morphology of the hair roots, and the hair growth effect of the hair tonic was compared by increasing or decreasing the percentage. . Telogen hair roots are hair roots that have stopped growing, and people who complain of hair loss have a higher proportion of hair roots in the resting stage than normal people.
The hair-nourishing effect was evaluated based on the decrease in the number of telogen hair roots.

Each of the hair tonic test solutions of Examples 1 to 5 and Comparative Example 1 was applied to the scalps of 10 male subjects twice a day, 2 times a day, for 6 consecutive months, immediately before application, and after the end of the 6 month application. Immediately after, 100 hairs were removed from each subject and each hair root was examined. The rate of change in the percentage of telogen hair roots after use compared to before use of the hair tonic was determined, and a case where the percentage decreased by 15% or more was taken as an effective example, and the efficiency was determined. The results are shown in Table-2.

Table 2 Trichogram test results (2) On-road conversion rate test Three down hair sites on the head of each of the 30 subjects with androgenetic alopecia
At different locations, the conversion rate from downy hair to road surface was compared before and after application of each of the test solutions (Examples 1 to 5 and Comparative Example 1). On the street, hair other than downy hair, that is, length 1
It refers to hair that is 4 meters or longer, and the transition from downy hair to street hair means a hair-nourishing effect. The subjects were divided into 6 groups of 5 people per group, and each test solution was applied to the entire head of each group twice a day (morning and evening) for 4 months.

Immediately after the application of each test solution and immediately after the application of the 4 months, close-up photographs were taken of the above-mentioned down hair sites on the head to measure the conversion rate, and the conversion rate to the road was expressed as a percentage of the average of the three locations. To judge the hair growth effect, an average on-road conversion rate of 10% or more is considered effective, and 1
Less than 0% was judged as invalid.

Table-3 On-road conversion rate test results (results) From the test results in Tables-2 and 3, sialic acid and sialic acid derivatives have excellent hair-nourishing effects, and combinations of two or more types of sialic acid and sialic acid derivatives It was also recognized that a synergistic effect could be obtained. In both tests, no subjects complained of side effects, and many subjects said that dandruff and itching had been suppressed, indicating that it was a highly safe hair growth agent.

Next, various embodiments will be shown. Hereinafter, the blending amount is expressed as weight %.

Example 6 W10 emulsified hair tonic (% by weight) Polyoxyethylene (60 mol) Addition hydrogenated castor oil 2.0 Glycerin 10.0 Dipropylene glycol 10.0 1.3-Butylene glycol 5,0 Polyethylene glycol 1
500 5.0 Cetyl Isooctanate
10.0 Squalane
5.0 Vaseline 2.
0 Propyl paraben 2.0 Carboxy vinyl polymer hexametaphosphate Sodium 0.03 Caustic potash 0.12 Sodium sialic acid
1.0 ion exchange water
Remaining Example 7 Cream-like hair nourishing agent (wt%) Sialic acid-bonded oligosaccharide
5.0 sialic acid binding protein
2.0 Sial-linked lipid 0.00
01 Liquid paraffin 5.0 Cetostearyl alcohol 5.5 Glyceryl monostearate 3. OIEO (20 mol) -
2- Octyl dodecyl ether 3.0 Propylparaben 0.3 Fragrance
0.1 glycerin
8.0 Dipropylene glycol 20.0 Polyethylene glycol 4000
5.0 Sodium hexametaphosphate
0.005 ion exchange water
Remaining Example 8 Tablets, Cial fiJ. A tablet containing 50 mg of C a , 50 mg of sialic acid-bound oligosaccharide, 50 mg of sialic acid-bound lipid, 50 mg of sialic acid-bound protein and 100 n+g of microcrystalline cellulose was prepared according to a conventional method, and sugar-coated with syrup gelatin precipitated calcium carbonate. Ta. This tablet is used in a single dose of 1 to 10 tablets.

Example 9 Granules 20 g of sialic acid-bonded oligosaccharides, 80 g of lactose, 10 g of water and 90 g of microcrystalline cellulose were uniformly mixed, crushed, granulated, dried and sieved to obtain granules. This granule is used in a single dose of 0.5 to 10 g.

Example 10 Capsule sialic acid-bound protein 100nw and microcrystalline cellulose 1
00■ and lactose 200■ are uniformly mixed. The capsules are used in a single dose of 1 to 10 capsules.

Example 1) 2.5 g of sialic acid-bonded oligosaccharide was kneaded with 47.5 g of Plastihose 50W consisting of soft liquid paraffin (95%) and polyethylene (5%), and the mixture was degassed under reduced pressure to obtain an ointment: y゛. Ta. This ointment is applied to the trunk 4-5 times a day.

〔Effect of the invention〕

The hair growth agent of the present invention is highly safe and has excellent effects on hair growth, hair loss prevention, and suppressing itchiness and itchiness.

Patent applicant: Shiseido Co., Ltd. Snow Brand Milk Products Co., Ltd.

Claims (4)

[Claims] (1) A hair nourishing agent containing one or more selected from the group consisting of sialic acid and sialic acid derivatives. (2) The hair growth agent according to claim (1), wherein the sialic acid derivative is a sialic acid-bonded oligosaccharide, a sialic acid-bonded protein, a sialic acid-bound lipid, or a sialic acid salt. (3) The hair growth agent according to claim (1) or (2), which uses sialic acid or a sialic acid derivative obtained by extraction from milk. (4) The hair tonic according to claim (1), (2) or (3), wherein the sialic acid is N-acetylneuraminic acid.