JP2003081866A - Hair-growing hydrogel containing cell growth factor protein - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hair-growing hydrogel preparation containing a cell growth factor protein, usable for the treatment of male baldness, etc., uninfluential to the part other than the treating part of the body and expectable to exhibit sufficient effect by the use of a small amount of the preparation. SOLUTION: An aqueous solution of glutaraldehyde having a concentration of 25 wt.% is dropped under stirring in an amount of 100 μl to 50 ml of 5 wt.% aqueous solution of gelatin, the obtained reaction solution is cast on a polyethylene dish and crosslinked and the produced gelatin hydrogel is divided into a number of small chips or fine beads having a diameter of 8 mm. An aqueous solution containing 7-70 μg of human recombinant bFGF in 20 μl of phosphate-buffered saline of pH 7.4 is impregnated in the gelatin hydrogel chips or beads and the obtained drug delivery preparation is embedded in the subcutaneous tissue of an animal. The blackness of the embedded skin, the revascularization under the skin, the change of trichocyst tissue and the growth of hair are evaluated after the embedding treatment.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a hair-growing hydrogel containing a cell growth factor protein, which can be applied to the treatment of androgenetic alopecia and the like to obtain preferable effects.

[0002]

2. Description of the Related Art A disease known as androgenetic alopecia (a male pattern is not limited to males but is merely a medical name) has been known. Generally, hair dermal papilla cells are qualitatively and functionally changed by some factors to cause a disorder in the hair cycle, and male hair loss pox occurs due to a shortened growth period in the hair cycle. In this androgenetic alopecia, atrophy of hair papilla cells and a decrease in blood flow have been observed,
It has been considered that improvement of this can alleviate or cure the symptoms.

[0003] On the other hand, it has been known that hair growth involves five types of cells that determine the properties of the hair and the hair cycle. It is not known if hair grows by the mechanism. However, among them, the above-described hair papilla cells have a function of inducing hair follicle structure from the skin to cause hair to grow, and there is a hypothesis that "hair will grow when the hair papilla cells are activated", It turns out that it seems to be the cell that is the center of hair growth. Therefore, it has been considered that the androgenetic alopecia may be treated by causing a protein, which is a growth factor of hair papilla cells, to act on the hair with androgenetic alopecia.

[0004] In recent years, research papers have been published which report that it was recognized that certain proteinaceous physiologically active substances have an action of improving the properties of hair exhibiting androgenetic alopecia. As described above, the existence of proteins (physiologically active substances) that activate any of the above-mentioned five types of cells is being discovered by allowing various proteins to act on these cells in vitro. For example, bFGF (Basic FG) is one of such proteins, and it has been shown in vitro that it activates dermal papilla cells.

When such a protein is adopted for treating androgenetic alopecia, the technique for treating androgenetic alopecia using the protein preparation is to administer a therapeutic drug orally or directly to the affected area. The method of application was known.

[0006]

However, protein preparations are generally excreted and eliminated from the site of administration via a simple diffusion mechanism. In addition, the rate of metabolism in the body is high due to decomposition by enzymes in the body, and its activity is lost early. Therefore, it is necessary to administer a large amount to maintain the in-vivo concentration required for treatment. However, this is thought to have a possibility of exerting a bad influence on a part other than the necessary part, and there are many problems.

Further, since protein preparations are extremely expensive drugs, administration of a large amount of such expensive drugs not only increases the cost of treatment but also causes side effects due to these drugs. It is also an obstacle to practical use.

The object of the present invention is to solve the above-mentioned conventional problems.
It is an object of the present invention to provide a protein preparation for hair-growth, which can be expected to have a sufficient effect even when used in a small amount without affecting the area other than the area required for treatment.

[0009]

First, the hair-growth hydrogel of the first aspect of the present invention is composed of a hydrogel impregnated with a cell growth factor protein so that the cell growth factor protein can be released slowly. The hydrogel is formed into a small piece that can be implanted under the skin, for example, as in claim 2, and, in the bead form in a solution that can be injected subcutaneously or into a blood vessel, as in, for example, claim 3. It is formed in.

Further, the hydrogel comprises, for example, a gelatin hydrogel as claimed in claim 4, and the gelatin hydrogel has at least dermal papilla cells as the cell growth factor protein as described in claim 5, for example. Is impregnated with bFGF which activates

Further, the hydrogel comprises collagen hydrogel as described in claim 6, for example, and this collagen hydrogel contains at least vascular endothelial cells as the cell growth factor protein as described in claim 7. It is impregnated with VEGF which activates.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. First, in the present invention, a cell growth factor protein that acts on hair growth and an amount that does not adversely affect other parts of the human body are provided so that the protein can provide the necessary local and effective action. Used in combination with various drug delivery systems. In the first embodiment described below as a cell growth factor protein, bFGF will be taken up and described.

Cell growth factor proteins that can be used for this purpose have a hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and angiogenic activity in addition to bFGF and vascular endothelial growth factor (VEGF) described below. Cell growth factors such as cytokines, interleukins,
Angiopoietin, transforming growth factor (TG
F) -α, epidermal growth factor (EGF) and the like. These proteins may be used alone or in combination of two or more.

Although bFGF is known as a factor that promotes the growth of dermal papilla cells and promotes the formation of capillaries, its effect on the hair of the head has not been known so far. However, if an effective administration method that modifies and improves the hair properties by administering this bFGF to the onset site of androgenetic alopecia, etc., is expected to have an unprecedented effect in the treatment of androgenetic alopecia, etc. it can. As described above, the method of changing the hair properties by the administration of bFGF or the application to the human scalp is completely new.

As the bFGF in this example, human recombinant bFGF having an isoelectric point of 9.6 is used. This human recombinant bFGF can be produced by using so-called biotechnology in which a human gene is put in E. coli and produced in E. coli.

Next, a drug delivery system using the above human recombinant bFGF is constructed. Drug delivery systems are roughly classified into four methods. That is, those that act directionally, those that promote absorption, those that prolong the life of the drug, and those that cause the drug to act gradually. In this example, a "slow-release" system in which the drug gradually acts is used.

For that purpose, first, an aqueous solution containing the above human recombinant bFGF (hereinafter, simply referred to as bFGF) in a predetermined ratio is prepared. As the aqueous solution, a phosphate buffered saline (pH: 7.4) (hereinafter referred to as PBS) was used, PBS containing no bFGF, PBS containing 0.7 μg of bFGF per 20 μl, bF per 20 μl.
PBS containing 7 μg of GF and PBS containing 70 μg of bFGF per 20 μl are prepared.

Then, acidic gelatin having an isoelectric point of 5.0 is dissolved in distilled water at 40 ° C. so as to have a concentration of 5 wt%, and 100 ml of a 25 wt% glutaraldehyde aqueous solution is added dropwise to 50 ml of this aqueous solution while stirring. The reaction solution was immediately cast on a polyethylene dish (8 × 8 cm 2) to carry out a crosslinking reaction at 4 ° C. for 24 hours. As a result, the amino group of gelatin and the aldehyde group of glutaraldehyde are chemically bonded to each other to crosslink between gelatin and gelatin, and a reaction in which water does not dissolve, that is, a crosslinking reaction is performed, and gelatin hydrogel is formed in the polyethylene dish. Is generated. The gelatin hydrogel thus obtained is punched with a punch having a diameter of 8 mm to produce a large number of microchips of gelatin hydrogel.

In the above crosslinking reaction, unreacted (that is, excess) aldehyde groups may remain in the gelatin hydrogel. If it is left as it is, when a protein is put in the hydrogel, the protein is bound to the residual aldehyde group, and the protein is denatured, so that the sustained release cannot be achieved. Therefore, it is necessary to inactivate or block the remaining aldehyde groups.

To this, small small molecules that react with the aldehyde group are added to transform the aldehyde group into another harmless substance. For this, a large number of gelatin hydrogel microchips obtained as described above are placed in a 0.1 M glycine aqueous solution and stirred at room temperature for 1 hour. As a result, the unreacted aldehyde groups in the gelatin hydrogel microchip react with glycine to chemically block the residual aldehyde groups. Thereafter, for the purpose of removing the remaining unreacted material from the hydrogel, washing with distilled water at room temperature for 1 hour was repeated twice, and the gelatin hydrogel microtips after the washing were washed with liquid nitrogen. The frozen product is freeze-dried.

It should be noted that although reagents other than those mentioned above are not described, they were used without being particularly purified. Further, before being used in animal experiments, gas sterilization with ethylene oxide gas is performed.

Following the above, 20 μl of each of the four kinds of PBS obtained as described above was individually added dropwise to the freeze-dried gelatin hydrogel drying chip, and then the mixture was allowed to stand at 4 ° C. for 24 hours. . As a result, bFGF
PBS not containing, PBS containing 0.7 μg of bFGF,
PBS containing 7 μg of bFGF or 70 μg of bFGF
A large number of 4 types of gelatin hydrogel swelling chips, each containing enough and evenly containing PBS containing swollen bFGF as if swelling like konjac, were produced.

Thus, a gelatin hydrogel impregnated with bFGF is prepared. When this hydrogel is put into a living body, bFGF is decomposed by oxygen decomposition of the hydrogel.
Is released from the hydrogel. This is a drug delivery system for sustained release of bFGF. bFG
An F-free hydrogel was prepared as a control.

By the way, there are various methods for investigating whether or not a drug for promoting the growth of hair is working (working) on cells related to hair, and one of them is to observe the color of the cells. There is a way. That is, there is a method of viewing that if the drug works, the melanin pigment is deposited inside the cell to darken the cell color, and if the cell color remains unchanged, the drug does not work. For this, the blackness of the back of the skin of the experimental body is generally examined. Some experimental mice (eg C3H / He
, Etc.) are often used in hair experiments, as this color change is well known and is synchronized with the hair cycle.

Another method is to check the number of capillaries in the vicinity of cells related to hair. That is, this is a method in which the drug is working if the number of capillaries is increasing, and the drug is not working if the number of capillaries is unchanged.

In this example, bF produced by the above method
Various experimental results using a gelatin hydrogel swelling chip containing no GF or impregnated with bFGF are observed and evaluated according to the above-described two investigation methods. This will be described below.

In this experiment, C3H / He male mice of 29 days old (back hair of the second growth phase) or 45 days old (also second regression phase) were used. Also, these mice were carefully selected so as to minimize individual differences.

Under Nembutal anesthesia, these mice were shaved on their backs, and the hairs were removed using a depilatory to synchronize the hair cycle, and then subcutaneously on the back 3 cm above the root of the tail. The above-mentioned four types of gelatin hydrogel swelling chips having a diameter of 8 mm were embedded in each mouse.

On the other hand, for comparison, an aqueous solution of bFGF before being included in gelatin hydrogel, that is, bFGF
-Free PBS, PBS containing 70 μg bFGF
Were administered to each group to prepare a group of mice. The dose of each PBS was 100 μl for each mouse, and in this case as well,
S was subcutaneously administered to the back 3 cm above the base of the tail of the mouse.

These hydrogel implants and bFGF
For the administration of PBS solution, 5 mice were used for one experimental group. And 10 days after the above administration treatment,
The mice were sacrificed and the dorsal skin around the treatment site was collected and evaluated.

First, the blackness of the back surface of the skin is evaluated. FIG. 1 is a diagram showing the evaluation results of the blackness of the back surface of the skin as an experimental result using the bFGF-impregnated gelatin hydrogel swelling chip (hereinafter, simply referred to as gelatin hydrogel) in the first embodiment. In this evaluation, the back side of the skin of 5 × 5 mm2 around the treatment site was sampled with a scanner, and 3 different sites per animal were measured using NI Image Image analysis software. Black is 100 and white is 0. Of the blackness of 3
The average of the measured values was calculated for (locations) × 5 (animals) = 15 (number of measurements).

As a result, as shown in the figure, the back surface of the skin was dark in the administration group treated with gelatin hydrogel impregnated with 7 μg of bFGF and the administration group treated with gelatin hydrogel impregnated with 70 μg of bFGF. . On the other hand, in the administration group treated with gelatin hydrogel containing little or no bFGF (0.7 μg of bFGF), the back surface of the skin is white, and even if 70 μg of bFGF is sufficiently contained, it is an aqueous solution (PBS). The back surface of the skin was similarly white in the administration group in the case of No. 2 and the group administered with a simple aqueous solution containing no bFGF (PBS containing 0 μg of bFGF).

From the evaluation of the blackness of the back surface of the skin in the above experimental results, the administration of gelatin hydrogel impregnated with 7 μg of bFGF or gelatin hydrogel impregnated with 70 μg of bFGF was significantly black compared with other experimental groups. The degree is getting higher. From this, it is revealed that the sustained release of bFGF brings about a significant change in hair growth. In this experimental group, the color of the back surface of the skin is black when the hair cycle is in the growing phase, and the color becomes white as it shifts to the catagen. That is, the sustained release of bFGF had an effect on the hair cycle and was effective in suppressing the transition to the catagen, that is, extending the growing phase.

FIG. 2 is a diagram showing the evaluation results of the number of capillaries in the skin. In this evaluation, the number of new blood vessels at 3 randomly selected points (1 × 1 mm 2) was measured on the 5 × 5 mm 2 skin section around the treatment site collected above, and 3 (location) × 5 (animal) = 15 (measured number) was averaged.

As a result, as shown in the figure, in the PBS administration group containing no bFGF and the PBS administration group containing 70 μg of bFGF, the number of capillaries per 1 mm square was
2.3 ± 1.0 (pieces) and 2.1 ± 0.5, respectively
It was (book). That is, it was found that the administration in the form of an aqueous solution did not show a large difference in the number of capillaries whether or not bFGF was contained.

On the other hand, in the gelatin hydrogel administration group impregnated with 7 μg of bFGF and the gelatin hydrogel administration group impregnated with 70 μg of bFGF, the number of capillaries per 1 mm square was 7.7 ± 3.9 (pieces). ) And 8.9 ± 4.2 (pieces), and the number of capillaries was significantly increased as compared with the above-mentioned aqueous solution administration group. Although the same gelatin hydrogel was used, the administration group containing no bFGF and the administration group containing only 0.7 μg did not show a significant increase in the number of capillaries as compared with the above-mentioned aqueous solution administration group. .

From the evaluation result of the number of capillaries, bFG
Gelatin hydrogel impregnated with 7 μg of F or bFGF
It is shown that the administration of gelatin hydrogel impregnated with 70 μg of A. can promote angiogenesis in hair follicle tissue. It is known that increasing blood flow at the site is important for hair growth, and it is revealed that the sustained release of bFGF brings about a significant change in hair growth.

FIG. 3 is a diagram showing the evaluation results of the area occupied by the hair follicle tissue of the skin. In this evaluation, one skin section of 5 × 5 mm 2 around the treatment site was sampled as above.
After fixing with 0% formaldehyde, it was embedded in paraffin, and a section having a thickness of 4 μm was prepared in the horizontal direction with respect to the surface of the epidermis. E. Dyeing was performed.

The area occupied by the hair follicle tissue in the area of 1 × 1 mm 2 was measured from the section of this sample where the hair follicle tissue size was maximized. In this measurement, 3 points are measured for one section, and in this case also 3 (points) × 5
The average of the measured values was calculated for (number of animals) = 15 (number of measurements).

As a result, as shown in the figure, in the administration group treated with gelatin hydrogel impregnated with 7 μg of bFGF, the area occupied by hair follicles per unit area of tissue was significantly increased as compared with the aqueous solution administration group. Was. Similarly, even in the gelatin hydrogel-administered group, in the gelatin hydrogel-administered groups with other impregnation degrees, the hair follicle occupied area seems to be slightly increased as compared with the aqueous solution-administered group, but a significant increase. It wasn't what you would expect.

It is known that an increase in hair follicle tissue size is caused by activation of cells such as dermal papilla cells and an increase in the number of cells, and that these changes are key to hair growth. Conceivable. From the evaluation result of the hair follicle occupied area, it is found that administration of gelatin hydrogel impregnated with 7 μg of bFGF brings about a significant change in hair growth.

Although the specific results are not shown here, the same experiment as that shown in FIGS. 1 to 3 was conducted using 45 days old C3H / He mice. As a result, an effective effect on hair growth was observed only in the group in which gelatin hydrogel impregnated with 7 or 70 μg of bFGF was embedded. The blackness of the back surface of the skin was high, and the transition from the regression phase to the growth phase was promoted. Similarly, the number of new blood vessels around the hair follicle tissue was significantly increased. The occupied area of hair follicle tissue also increased significantly. Thus, it was found that the sustained release of bFGF has a positive effect on hair growth regardless of the hair cycle.

FIG. 4 is a diagram showing the evaluation results for the length of hair. In this evaluation, the hair was carefully pulled out from the root of the collected skin section of 5 × 5 mm 2 around the treatment site under a microscope using tweezers, and its length was measured with a ruler. In this measurement, for each herd,
The length of 50 pieces in total was measured by removing 10 pieces from each animal, and the average was obtained.

As a result, as shown in the figure, the hair length was significantly significantly increased in the administration group treated with gelatin hydrogel impregnated with 7 μg of bFGF as compared with the aqueous solution administration group. Further, in the gelatin hydrogel-administered group impregnated with bFGF at other concentrations, a significant increase was observed as compared to the 7 μg-impregnated administration group, compared with the aqueous solution administration group.

From the evaluation result of the length of the hair, b
Gelatin hydrogel or bF impregnated with 7 μg of FGF
It was found that administration of gelatin hydrogel impregnated with 70 μg of GF causes a significant change in hair growth.

Next, a second embodiment will be described.
In the second embodiment described below, vascular endothelial growth factor (VEGF), which acts on cells other than angiogenic action and dermal papilla cells, will be described as a cell growth factor protein. V
Although human recombinant VEGF is used as EGF, this human recombinant VEGF can also be produced by biotechnology in which a human gene is put in E. coli and produced in E. coli. In this case also, the above human recombinant VE
A drug delivery system using GF is used,
In this case as well, a sustained release system within the drug delivery system will be constructed.

First, an aqueous solution containing the above human recombinant VEGF (hereinafter, simply referred to as VEGF) in a predetermined ratio is prepared. In this example, PB having a pH of 7.4 as an aqueous solution
Using S, PBS containing no VEGF and PBS containing 2 μg of VEGF per 20 μl are prepared.

Next, a collagen Type I sponge sheet (hereinafter simply referred to as collagen sponge) is prepared,
This collagen sponge is thermally crosslinked at 105 ° C. for 24 hours, and further chemically crosslinked with 0.2 wt% glutaraldehyde 0.05 acetic acid water bath at 4 ° C. for 24 hours. The crosslinked collagen sponge is washed with distilled water three times and freeze-dried. And, this freeze-dried collagen sponge is 1.0 × 1.0 × 0.3
Cut into cm ³ pieces and make many collagen sponge chips. These are sterilized with ethylene oxide gas.

Subsequently, each of the above-obtained two kinds of 20 μl of PBS was individually dropped on the above-mentioned freeze-dried collagen sponge chip, and then allowed to stand at 4 ° C. for 24 hours. As a result, a large number of two types of collagen sponge swollen chips, each containing swollen PBS containing no VEGF or PBS containing 2 μg of VEGF, are produced.

Thus, a hydrogel comprising a swollen collagen sponge impregnated with VEGF is prepared. Also in this case, when this collagen hydrogel is put into a living body, VEGF is gradually released from the hydrogel due to oxygen decomposition of the collagen hydrogel. This is V
It is a drug delivery system for sustained release of EGF. In this case as well, collagen hydrogel containing no VEGF was prepared as a control.

In this experiment, C3H / He male mice of 29 days old were used. Again, these mice were carefully selected to minimize individual differences. Then, under Nembutal anesthesia of these mice, the hair on their backs was shaved and the hair cycle was synchronized by removing the hairs with a depilatory, and then subcutaneously on the back 3cm above the base of the tail, The size described above is 1.0 × 1.0 × 0.
2 kinds of 3cm ³ collagen sponge swelling tip,
Each mouse was implanted.

Also in this second embodiment, for comparison, an aqueous solution of VEGF before being included in the collagen sponge, that is, PBS containing no VEGF, and 20 μm
A group of mice was prepared in which PBS containing 2 μg of VEGF per 1 was administered. The dose of each PBS is 1 for each mouse
00 μl, and again each PBS was administered subcutaneously on the back 3 cm above the base of the tail of the mouse. For these doses, 5 mice were used per experimental group. Then, 10 days after the above administration treatment, the mice were sacrificed and the dorsal skin around the treatment site was collected and evaluated.

First, the blackness of the back surface of the skin is evaluated. FIG. 5 is a diagram showing an evaluation result of the blackness of the back surface of the skin as an experimental result using the VEGF-impregnated collagen sponge swelling chip (hereinafter, simply referred to as collagen hydrogel) in the second embodiment. In this evaluation, the back side of the skin of 5 × 5 mm ² around the treated site was scanned with a scanner, and three different sites were measured for each animal using NI Image Image analysis software. Evaluate the blackness of the back side, and
The average of the measured values was calculated for (locations) × 5 (animals) = 15 (number of measurements).

As a result, as shown in the figure, the back surface of the skin was black in the administration group treated with collagen hydrogel impregnated with 2 μg of VEGF. On the other hand, the administration group treated with collagen hydrogel not containing VEGF, VE
The administration group treated with PBS not containing GF was, of course, expected, but the administration group treated with PBS containing 2 μg of VEGF also had a white skin back surface.

From the evaluation of the blackness of the back surface of the skin in the above experimental results, the administration of collagen hydrogel impregnated with 2 μg of VEGF significantly increased the blackness as compared with the other experimental groups. From this, it is revealed that the sustained release of VEGF brings about a significant change in hair growth. Also in this experimental group, the color of the back surface of the skin is black when the hair cycle is in the growth period, and the color becomes white with the transition to the catagen period. That is, the sustained release of VEGF exerted an action on the hair cycle and was effective in suppressing the transition to the catagen, that is, in prolonging the growth period.

FIG. 6 is a diagram showing the evaluation result of the number of blood vessels in the skin. In this evaluation, the number of new blood vessels at three randomly selected points (1 × 1 mm ² ) was measured on one sampled skin section of 5 × 5 mm ² around the treatment site, and 3 (location) × 5 ( The average of the measured values was obtained for 15 animals (the number of animals).

As a result, as shown in the figure, the number of blood vessels per mm 2 in the PBS administration group containing 2 μg of VEGF was significantly increased as compared with the PBS administration group containing no VEGF. The number of blood vessels per 1 mm square in the collagen hydrogel-administered group impregnated with 2 μg of VEGF was further significantly increased as compared with the PBS-administered group containing 2 μg of PEG.

The results of evaluation of the number of blood vessels also show that administration of collagen hydrogel impregnated with 2 μg of VEGF can promote angiogenesis in hair follicle tissue.
As mentioned above, it has been found that increasing blood flow at the site is important for hair growth.
It is found that the sustained release of GF brings about a significant change in hair growth.

FIG. 7 is a diagram showing the evaluation results of the area occupied by the hair follicle tissue of the skin. In this evaluation, one skin section of 5 × 5 mm ² around the treatment site was sampled as above.
After fixing with 0% formaldehyde, it was embedded in paraffin, and a section having a thickness of 4 μm was prepared in the horizontal direction with respect to the surface of the epidermis. E. Dyeing was performed.

The area occupied by the hair follicle tissue in the area of 1 × 1 mm ² was measured from the section of this sample at the site where the hair follicle tissue size was maximized. In this measurement, 3 points are measured for one section, and in this case also 3 (points) × 5
The average of the measured values was calculated for (number of animals) = 15 (number of measurements).

As a result, as shown in the figure, in the administration group treated with collagen hydrogel impregnated with 2 μg of VEGF, the area occupied by hair follicles per unit area of tissue was V
There was a significant increase compared with the administration group treated with PBS containing 2 μg of EGF. When VEGF was not contained, neither collagen hydrogel nor PBS showed a significant increase.

From the evaluation result of the occupied area of the hair follicle, VE
It was found that administration of collagen hydrogel impregnated with 2 μg of GF brings about a significant change in hair growth.
FIG. 8: is a figure which shows the evaluation result regarding the length of a hair. In this evaluation, one piece of the treatment site peripheral portion 5 × 5 collected above was used.
From the mm ² skin section, the hair was carefully pulled out from the root of the hair using tweezers under a microscope, and its length was measured with a ruler. 1 per animal per flock in this measurement
A total of 50 pieces without 0 pieces were measured and the average thereof was obtained.

As a result, as shown in the figure, in the administration group treated with 2 μg of VEGF-impregnated collagen hydrogel, the hair length was significantly increased as compared with the aqueous solution administration group. Further, an increase in hair length was also seen in the aqueous solution administration group containing 2 μg of VEGF, but this was not significant.

From the result of evaluation of the length of this hair, V
It was found that administration of collagen hydrogel impregnated with 2 μg of EGF brings about a significant change in hair growth.
As described above, it was found that the use of gelatin hydrogel impregnated with bFGF or collagen hydrogel impregnated with VEGF subcutaneously promotes hair growth.

In each of the above-described embodiments, mice are used for the experiments, but it goes without saying that the same effect can be obtained when applied to human scalp. In addition, both gelatin hydrogel and collagen hydrogel are being experimented in the form of chips (small pieces) that are embedded subcutaneously, but the shape of the microbeads that are dispersed subcutaneously or in a solution that can be injected into blood vessels You may produce it. Examples of shapes other than beads include films, tubes, disks, powders, particles, and fluid liquids. It is known that any shape exerts a hair growth action regardless of the sustained release property of the cell growth factor.

The material for the hydrogel is not limited to gelatin and collagen, and examples thereof include proteins such as gelatin, collagen and fibrin, polysaccharides such as alginic acid and hyaluronic acid, or their derivatives. A derivative, a mixture thereof, a complex formed by a chemical bond, or the like may be used.

The hydrogel impregnated with the above-mentioned factors relating to hair growth may be used as an external medicine by sticking it to the affected area.

[0068]

As described in detail above, according to the present invention, the blackness of the skin can be controlled by the administration of hydrogel impregnated with factors related to hair growth such as bFGF-impregnated gelatin hydrogel and VEGF-impregnated collagen hydrogel. ,
It has a remarkable growth effect on the number of capillaries on the skin, the area occupied by the hair follicle tissue, the length of the hair, etc. It can be expected to have similar effects even when applied to the human scalp, so it is simple, inexpensive and epoch-making It is possible to provide a hydrogel for hair-growth that provides various effects.

[Brief description of drawings]

FIG. 1 is a diagram showing an evaluation result of blackness of a back surface of a skin as an experimental result using a bFGF-impregnated gelatin hydrogel according to the first embodiment.

FIG. 2 is a diagram showing an evaluation result of the number of capillaries in the skin, which is an experimental result using the bFGF-impregnated gelatin hydrogel in the first embodiment.

FIG. 3 is a diagram showing an evaluation result of an area occupied by a hair follicle tissue of the skin as an experimental result using the bFGF-impregnated gelatin hydrogel in the first embodiment.

FIG. 4 is a diagram showing evaluation results of hair length as experimental results using the bFGF-impregnated gelatin hydrogel in the first embodiment.

FIG. 5 is a diagram showing an evaluation result of blackness of the back surface of the skin as an experimental result using the VEGF-impregnated collagen hydrogel in the second embodiment.

FIG. 6 is a diagram showing an evaluation result of the number of blood vessels in the skin as an experimental result using the VEGF-impregnated collagen hydrogel in the second embodiment.

FIG. 7 is a diagram showing the evaluation results of the area occupied by hair follicle tissue of the skin as an experimental result using the VEGF-impregnated collagen hydrogel in the second embodiment.

FIG. 8 is a diagram showing an evaluation result of hair length as an experimental result using the VEGF-impregnated collagen hydrogel in the second embodiment.

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Claims (7)

[Claims] 1. A hair-growth hydrogel comprising a hydrogel impregnated with a cell growth factor protein so as to be released slowly. 2. The hydrogel for hair growth according to claim 1, wherein the hydrogel is formed into a small piece that can be implanted subcutaneously. 3. The hair-growth hydrogel according to claim 1, wherein the hydrogel is formed into beads in a solution that can be injected subcutaneously or into a blood vessel. 4. The hair-growth hydrogel according to claim 1, 2 or 3, wherein the hydrogel is a gelatin hydrogel. 5. The hair-growing hydrogel according to claim 4, wherein the gelatin hydrogel is impregnated with at least bFGF that activates dermal papilla cells as a cell growth factor protein. 6. The hair-growth hydrogel according to claim 1, 2 or 3, wherein the hydrogel is a collagen hydrogel. 7. The collagen hydrogel is impregnated with VEGF which activates at least vascular endothelial cells as a cell growth factor protein.
The described hydrogel for hair growth.