JP6579604B2 - Hair growth / hair growth promoter - Google Patents

Description

  The present invention relates to a hair growth / hair growth promoter comprising a bovine colostrum enzyme-treated product.

  Alopecia refers to the condition (symptoms) of hair loss due to various causes, but typical examples include androgenetic alopecia (baldness), seborrheic alopecia, erosive alopecia, senile alopecia , Alopecia areata, postpartum alopecia, mechanical (compressive) alopecia, hair loss etc. For the treatment of such alopecia, for example, use of a substance that inhibits the production of dihydrotestosterone (DHT) by inhibiting 5α-reductase activity (Patent Document 1) has been proposed. There is room for improvement.

  Patent Document 2 describes that an enzyme-treated product of human serum (β-galactosidase, or β-galactosidase and sialidase) has a macrophage activating action.

Japanese Patent Laid-Open No. 7-033673 International Publication No. 2013/038997

  The present invention intends to provide a hair-growth / hair growth-promoting agent comprising a bovine colostrum enzyme-treated product, a food / beverage product and a pharmaceutical comprising the same.

  As a result of intensive studies, the inventor has obtained a bovine colostrum enzyme-treated product obtained by a production method comprising a step of contacting bovine colostrum with a specific enzyme, that is, β-galactosidase, or β-galactosidase and sialidase. However, it discovered that it had the outstanding effect as a hair growth and hair growth promoter, and also repeated examination, and completed this invention.

That is, the present invention
[1] A hair growth / hair growth promoter comprising a bovine colostrum enzyme-treated product obtained by a production method comprising a step of contacting bovine colostrum with β-galactosidase,
[2] The hair growth / hair growth promoting agent according to the above [1], wherein the method for producing a bovine colostrum enzyme-treated product further comprises a step of contacting with sialidase,
[3] The hair-growth / hair growth-promoting agent according to the above [1] or [2], which contains a protein in an amount ranging from 0.02 μg to 40 mg for one administration.
[4] The hair-growth / hair growth-promoting agent according to any one of the above [1] to [3], which is a dosage form absorbed from the digestive tract,
[5] Symptoms to be administered include androgenetic alopecia (baldness), seborrheic alopecia, erosive alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) ) The hair growth / hair growth promoting agent according to any one of the above [1] to [4], which is alopecia or hair loss
[6] Male pattern alopecia (baldness), seborrheic alopecia, sputum alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) alopecia or hair loss Food or drink for prevention or improvement,
A food or drink comprising the hair growth / hair growth promoter according to any one of [1] to [5] above,
[7] Male pattern alopecia (baldness), seborrheic alopecia, sputum alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) alopecia or hair loss A medicinal product for prevention or treatment,
A pharmaceutical comprising the hair-growth / hair growth-promoting agent according to any one of [1] to [5] above,
About.

  Since the bovine colostrum enzyme-treated product according to the present invention has an excellent effect as a hair growth / hair growth promoter, it is useful for the prevention, improvement or treatment of alopecia. Therefore, if the bovine colostrum enzyme-treated product is used, foods and drinks useful for the prevention or improvement of alopecia and pharmaceuticals useful for the prevention or treatment of alopecia can be provided.

  Furthermore, since the bovine colostrum enzyme-treated product according to the present invention can be prepared by treating bovine colostrum with β-galactosidase, or β-galactosidase and sialidase, it has an advantage of being simple and low-cost.

Drawing substitute photographs (FIG. 1A and FIG. 1B, respectively) showing the top of the head on the administration start date (DAY1) and 30 days later (DAY30) when a bovine colostrum enzyme treatment product was administered to a 12-year-old man with alopecia areata It is. Drawing substitute photographs (FIG. 2A and FIG. 2B, respectively) showing the occipital region on the administration start date (DAY 1) and 30 days after (DAY 30) when a bovine colostrum enzyme treatment product was administered to a 12-year-old man with alopecia areata. is there. Drawing-substitute photographs (FIG. 3A and FIG. 3B, respectively) showing the hairline at the start of administration (DAY 1) and 31 days after (DAY 31) when a bovine colostrum enzyme treatment product was administered to a 23-year-old woman with alopecia areata (FIGS. 3A and 3B, respectively) ).

<Bovine colostrum>
The bovine colostrum used in the present invention refers to milk secreted by calves by the 10th day after calf delivery, preferably by 7 days, more preferably by the 5th day. is there. In the present invention, any bovine colostrum can be used regardless of the type of cow such as Holstein and Japanese Black.

<Enzyme>
The β-galactosidase used in the present invention is not particularly limited, and any known type can be used. Examples of such include those derived from Escherichia coli and bovine liver. Examples of commercially available products include catalog No. of Wako Pure Chemical Industries, Ltd. 072-04141, G1875 of SIGMA-ALDRICH, and the like. In the present invention, β-galactosidase may be used alone or in combination of two or more.

  The sialidase used in the present invention is not particularly limited, and any known type can be used. As such, for example, those derived from Clostridium perfringenes, those derived from Streptococcus 6646K, those derived from Vibrio cholerae, Arthrobacter ureafaciens (Arthrobacter ureafaciens) The thing of origin etc. are mentioned. Examples of commercially available products include SIGMA-ALDRICH product numbers (Sigma Prod. Nos.) N2876, N2133, N2904, N3001, N5631, Biochemical Biobusiness Code Number 120052, BioLabs Catalog numbers (Catalog #) P0720L, P0720S, and the like. In the present invention, the sialidase may be used alone or in combination of two or more.

<Enzyme treatment>
In the present invention, the contact (enzyme treatment) of bovine colostrum with β-galactosidase or sialidase makes contact with a sufficient amount of enzyme for a sufficient time, so that the enzyme reaction further proceeds substantially. It is preferable to carry out to such an extent that it does not occur. For this purpose, although it depends on the kind of enzyme, for example, catalog No. of Wako Pure Chemical Industries, Ltd. as β-galactosidase. When using 072-04141, it is sufficient to use 65 mU of enzyme for 100 μl of bovine colostrum. For example, when using the product number (N2876) of SIGMA-ALDRICH as sialidase, it is sufficient to use 65 mU of enzyme for 100 μl of bovine colostrum. In this case, it is sufficient to perform the enzyme treatment for 3 hours.

  Enzymatic treatment can be carried out in any vessel by adding these enzymes to bovine colostrum, but is commonly used in this field to adjust the total protein concentration in bovine colostrum if desired. Buffer may be added. Examples of such a buffer include physiological saline, phosphate buffered saline (SPB), Ringer's solution, and the like. The temperature of the enzyme treatment is not particularly limited as long as the enzyme exhibits activity, but it is usually around 37 ° C. where the enzyme exhibits high activity.

  The enzyme treatment is terminated by inactivating the enzyme by heating (heat treatment). Such heat treatment is not particularly limited as long as the enzyme can be inactivated. For example, the heat treatment can be performed by heating at a temperature around 60 ° C. for about 10 minutes. The specimen after the heat treatment may be concentrated if desired. The concentration can be performed using a commercially available device, for example, a centrifugal concentrator (for example, 10000MWCO YM-10 manufactured by MILLIPORE).

  The enzyme treatment can also be performed using an enzyme (immobilized enzyme) immobilized on a solid phase. A method for immobilizing an enzyme on a solid phase is known to those skilled in the art. For example, β-galactosidase and / or sialidase can be immobilized on agarose beads with a coupling agent such as cyanogen bromide. Examples of such immobilized enzymes include immobilized β-galactosidase G3M (Mo Bi Tec, # A3102), neuraminidase agarose Clostridium perfringens (manufactured by Welsh bacteria) (manufactured by SIGMA-ALDRICH, product number: N5254). ) Etc. are commercially available. The advantage of using an immobilized enzyme is that the enzyme can be recovered without being deactivated by heat treatment after the enzyme treatment, and foreign substances (proteins such as enzymes deactivated by heat treatment) by such recovery It is possible to reduce the existence of.

<Bovine colostrum enzyme-treated product>
The thus obtained bovine colostrum enzyme-treated product of the present invention may be further freeze-dried to form a solid or powder. Such a bovine colostrum enzyme-treated product is a novel composition useful for hair growth and hair growth promotion.

<Hair growth / hair growth promoter>
The bovine colostrum enzyme-treated product can be used as a hair growth / hair growth promoter by blending an adjuvant (carrier) that is acceptable in the food or pharmaceutical field, if desired. The hair growth / hair growth promoter can be a food or drink or a medicine containing the same.

<Pharmaceutical>
The bovine colostrum enzyme-treated product of the present invention can be prepared as a pharmaceutical composition as it is or by appropriately blending a pharmaceutically acceptable adjuvant (carrier). As such pharmaceutically acceptable adjuvants, any of those commonly used in this field can be suitably used. Specific examples include diluents, stabilizers, preservatives, buffering agents. , Excipients, binders, preservatives, disintegrants, lubricants, flavoring agents and the like. These adjuvants are appropriately blended according to the dosage form of the pharmaceutical composition.

  The above-mentioned pharmaceutical composition can be formulated into an appropriate dosage form to make a pharmaceutical product. The pharmaceutical composition and pharmaceutical of the present invention are effective for the prevention and treatment of alopecia. The dosage form of the pharmaceutical is not particularly limited, and may be an oral preparation or a parenteral preparation. Examples of parenteral preparations include injections, infusions, nasal drops, ear drops, suppositories, enteral nutrients and the like. For example, examples of the injection include those in administration forms such as intravenous injection, subcutaneous injection, intradermal injection, intramuscular injection, intraperitoneal injection, etc. Among them, intramuscular injection is preferable. On the other hand, as oral preparations, powders, granules, tablets (including sublingual tablets), capsules, pills, intestinal solvents, liquids for internal use (including suspensions, emulsions, syrups, etc.), inhalants Etc.

  The dose of the bovine colostrum enzyme-treated product according to the present invention varies depending on the age, sex, body weight and symptoms, administration method, etc. of the subject of administration, but typical examples include, for example, this bovine colostrum enzyme-treated product. The total amount of protein contained in adults is about 0.02 μg or more, preferably about 0.2 μg or more, more preferably about 2 μg or more, more preferably about 20 μg or more, more preferably about 50 μg per administration per adult. And about 40 mg or less, preferably about 20 mg or less, more preferably about 13 mg or less, more preferably about 10 mg or less, more preferably 2 mg or less. A preferred dosage range is, for example, about 0.02 μg to about 40 mg, preferably about 0.2 μg to about 20 mg, more preferably about 2 μg to about 13 mg, more preferably about 20 μg to about 10 mg, more preferably about It may be in the range of 50 μg to about 2 mg. In the present specification, the amount of protein is calculated based on the protein concentration determined by the absorbance at a wavelength of 570 nm.

  When the bovine colostrum enzyme-treated product according to the present invention is administered at a dose per administration as described above, a typical administration interval and administration frequency are 1-2 times / day. The dose and the administration interval can be appropriately changed within a range in which the total amount of protein to be administered is equivalent with the total amount of protein contained in the pharmaceutical composition as an index. In addition, administration for the purpose of prevention may be carried out at the same dose as that for improvement or treatment, or about half the dose may be used as a guide.

  The bovine colostrum enzyme-treated product according to the present invention can be used in combination with other hair growth / hair growth promoters. When used in combination, the dose of the bovine colostrum enzyme-treated product according to the present invention is appropriately adjusted in consideration of the efficacy, effect, and dose of the other hair growth / hair growth promoter.

<Quasi-drug>
The bovine colostrum enzyme-treated product according to the present invention can be made into a quasi-drug composition by blending the auxiliary agent as necessary, and further, the quasi-drug composition. Can be further processed into a quasi-drug comprising the same. The quasi-drug composition or quasi-drug can take various forms such as solution, suspension, syrup, granule, cream, paste, jelly, etc. Accordingly, it can be formed into a desired shape. Both quasi-drug compositions and quasi-drugs can be prepared by conventional methods. The amount of bovine colostrum enzyme-treated product used in the quasi-drug composition or quasi-drug of the present invention is not particularly limited. Those appropriately set with reference to can be adopted.

<Food &Drink>
The bovine colostrum enzyme-treated product according to the present invention is usually used in foods and drinks such as the above-mentioned adjuvants, sweeteners, spices, seasonings, preservatives, preservatives, bactericides, and antioxidants as necessary. It can be set as the composition for food-drinks by mix | blending various additives suitably, Furthermore, this food-drinks composition can be further processed and it can be set as the food-drinks containing this. The composition for food or drink or food or drink can take various forms such as solution, suspension, syrup, granule, cream, paste, jelly, etc. It can also be formed into a shape. In addition, the food and drink can take various forms such as bread, noodles, confectionery, beverages, soups, and processed foods. Preparation of the composition for food / beverage products and food / beverage products can be carried out according to a conventional method.

  Since the bovine colostrum enzyme-treated product of the present invention has an effect as a hair growth / hair growth promoter, the composition for food or drink or the food or drink of the present invention has an effect on prevention, improvement, etc. of alopecia. . In this case, the amount of the bovine colostrum enzyme-treated product used in the composition for food or beverage of the present invention or food and beverage is not particularly limited, but is the same as the dose in the case of the above pharmaceutical product, or the above Those appropriately set with reference to can be adopted.

  Such foods and drinks of the present invention can be administered orally such as so-called health foods, health drinks, functional foods, functional nutritional foods, health supplements, nutritional supplements (supplements), special purpose foods, foods for specified health use, etc. Or other non-human animals (work livestock, hounds, racehorses, pets, other animals).

  Such pharmaceuticals, quasi-drugs, and foods and drinks according to the present invention have a dosage form that absorbs bovine colostrum enzyme treated product, which is an active ingredient, from the digestive tract, preferably from the oral cavity or intestinal tract (for example, the above-mentioned It is preferably in the form of sublingual tablets or enteric solvents.

<Alopecia>
In the present invention, alopecia refers to a state (symptom) in which hair is reduced due to various causes. Typical alopecia includes, for example, androgenetic alopecia (baldness), seborrheic alopecia, erosive alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) ) Alopecia, hair loss (mental illness) and the like. Of these, alopecia areata is preferred.

  The present invention will be described in detail based on examples, but the present invention is not limited to these examples.

<Preparation of bovine colostrum enzyme-treated product>
1 g of solid bovine colostrum (colostrum Mune 2550) was dissolved in 100 ml of 50 mM SPB (15.601 g NaH ₂ PO ₄ .2H ₂ O and 35.814 g Na ₂ HPO ₄ · 12H ₂ O in 500 ml distilled water. 200 mM SPB (pH 7.0) was prepared and diluted to 50 mM SPB. The colostrum was centrifuged at 8,000 rpm and 4 ° C. for 1 hour. The supernatant was sequentially filtered with G2 membrane, 8 μm, 5 μm, 1.2 μm, and 0.2 μm (Millipore, Nitrocellulose filter). The filtrate was dialyzed with a hollow fiber membrane (Asahi Kasei Chemicals Corporation, pencil type module SEP-0013).

  1 mg of β-galactosidase (manufactured by Wako Pure Chemical Industries, Catalog No. 072-04141) immobilized with formyl resin (TOYOPEARL, AF-Formy-650M) was added per 1 mg of colostrum, and 1 at 37 ° C. Incubated for hours. After incubation, the reaction solution was filtered through a G2 membrane, and the immobilized enzyme in the reaction solution was removed. The filtrate was filtered at 0.2 μm. When the protein concentration was determined by measuring absorbance at a wavelength of 570 nm (using a calibration curve prepared for BSA (bovine serum albumin, SIGMA, A4503)), 0.747 g of protein was recovered from 1 g of bovine colostrum ( Sample 1).

  The specimen 1 was rapidly frozen with chilled methanol and then allowed to stand at −80 ° C. to be completely frozen. This was vacuum-dried to obtain a bovine colostrum enzyme-treated product. A part of the solution was redissolved and the protein concentration was determined by measuring absorbance at a wavelength of 570 nm (using a calibration curve prepared for BSA (bovine serum albumin, SIGMA, A4503)). From 1 g to 0.628 g of bovine colostrum Of protein was recovered.

<Test example>
Using the bovine colostrum enzyme-treated product prepared above, an enteric capsule adjusted so that the amount of protein contained therein was 1.0 mg was prepared by a conventional method. The enteric capsule was administered to the subject twice daily in the morning and evening. The results are shown in Table 1.

  ADVANTAGE OF THE INVENTION According to this invention, the hair growth and the hair growth promoter which comprise a cow colostrum enzyme processed material, the food-drinks and pharmaceutical which contain it can be provided.

Claims (7)

A method for producing a hair growth / hair growth promoter containing the treated bovine colostrum, wherein the bovine colostrum is obtained as a bovine colostrum enzyme-treated product by contacting bovine colostrum with β-galactosidase in a buffer solution . The method for producing a hair-growth / hair growth-promoting agent according to claim 1, further comprising a step of bringing the bovine colostrum enzyme-treated product into contact with sialidase . The method for producing a hair-growth / hair growth-promoting agent according to claim 1 or 2, which is a bovine colostrum enzyme-treated product containing a protein in an amount ranging from 0.02 µg to 40 mg / kg for a single administration . The method for producing a hair growth / hair growth promoting agent according to any one of claims 1 to 3, wherein the bovine colostrum enzyme-treated product is in a dosage form to be absorbed from the digestive tract . Symptoms to be administered include androgenetic alopecia (baldness), seborrheic alopecia, erosive alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) alopecia Or it is hair loss, The manufacturing method of the hair growth and hair growth promoter of any one of Claims 1-4 . A male pattern baldness (baldness), seborrhea containing the treated bovine colostrum, which is obtained as a bovine colostrum enzyme treated product by contacting bovine colostrum with β-galactosidase in a buffer. A method for producing a food or drink or a pharmaceutical product for the prevention or improvement of sexual alopecia, fertility alopecia, senile alopecia, alopecia areata, postpartum alopecia, mechanical (compressive) alopecia or hair loss . The method for producing a food or drink or pharmaceutical product according to claim 6, further comprising a step of bringing the bovine colostrum enzyme-treated product into contact with sialidase .