Composition for hair restoration, and pharmaceutical composition for hair restoration containing the same
The hair growth composition combining Polygonum multiflorum extract, silver nanoparticles, and tripeptide-1 copper addresses the limitations of existing compositions by significantly promoting hair growth and new hair follicle generation, as evidenced by enhanced hair coverage and follicle density in mouse studies.
Patent Information
- Application Number
- JP2024196986
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-11-14
- Filing Date
- 2024-11-11
- Publication Date
- 2025-05-26
AI Technical Summary
Current hair growth compositions for alopecia areata, such as those containing silver nanoparticles and Polygonum multiflorum extract, do not achieve optimal hair growth promotion and new hair follicle generation.
A hair growth composition is developed that includes a mixture of Polygonum multiflorum extract, silver nanoparticles, and tripeptide-1 copper, with specific mass/volume ratios of tripeptide-1 copper to the composition and the mixture containing Polygonum multiflorum extract and silver nanoparticles.
The composition effectively promotes hair growth, achieves a high hair coverage rate, and stimulates the growth of new hair follicles, as demonstrated by significant improvements in hair coverage rates and hair follicle density in mouse models.
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Abstract
Description
Technical Field
[0001] The present invention relates to a hair growth composition, particularly to a composition containing silver particles and Polygonum multiflorum extract, and also to a pharmaceutical composition for hair growth containing the composition.
Background Art
[0002] Alopecia areata refers to a skin disease that creates areas of hair loss on the scalp or other parts of the body. It often starts with small, smooth, circular areas of hair loss on the scalp and can progress to alopecia totalis or alopecia universalis.
[0003] Generally, alopecia areata is thought to be caused by the body's immune system attacking hair follicles. Other observations suggest that dihydroxytestosteron (DHT), a naturally occurring hormone in the body, can shorten the growth phase of hair, make the growing hair too thin to be visible, and may cause male genetic hair loss. If left untreated, it can result in the gradual recession of the hairline in men.
[0004] Alopecia areata can occur in people of any gender and race, and its onset can start in adolescence. Epidemiologically, hair loss affects 1.7% of the world's population, with over 4.7 million people in the United States alone being affected. The above situation can potentially shock an individual's appearance, confidence, quality of life, work, and study.
[0005] Conventionally, it is known that a composition of silver nanoparticles and Polygonum multiflorum extract can be used to improve alopecia areata (see Patent Document 1).
Prior Art Documents
Patent Documents
[0006]
Patent Document 1
Summary of the Invention
Problems to be Solved by the Invention
[0007] In the above field, the development and research of a hair growth composition having more excellent effects are targeted.
Means for Solving the Problems
[0008] In order to achieve the above object, the present invention provides a hair growth composition containing a mixture containing polygonum multiflorum extract and silver nanoparticles and tripeptide-1 copper, wherein the mass / volume ratio of the tripeptide-1 copper to the hair growth composition is 0.10 mg / mL or more and 0.20 mg / mL or less, and the mixture containing the polygonum multiflorum extract and silver nanoparticles contains silver nanoparticles, polygonum multiflorum extract, a stabilizer and a diluent.
Effects of the Invention
[0009] The hair growth composition of the present invention can effectively promote hair growth and obtain a high hair coverage rate and an effect of promoting the growth of new hair follicles.
Brief Description of the Drawings
[0010]
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Mode for Carrying Out the Invention
[0011] [Description of Embodiments of the Present Invention] The hair-growing composition according to one aspect of the present invention contains a mixture containing a polygonum multiflorum extract and silver nanoparticles, and copper tripeptide-1, and the mass / volume ratio of copper tripeptide-1 to the hair-growing composition is 0.10 mg / mL or more and 0.20 mg / mL or less, and the mixture containing the polygonum multiflorum extract and silver nanoparticles contains silver nanoparticles, a polygonum multiflorum extract, a stabilizer, and a diluent.
[0012] As is currently known, silver nanoparticles and polygonum multiflorum extract can be used to improve alopecia, but in the present invention, copper tripeptide-1 is further blended, and by controlling the proportion of the mixture containing polygonum multiflorum extract and silver nanoparticles and copper tripeptide-1, a more excellent hair-growing effect than expected is desired.
[0013] In the present invention, tripeptide-1 copper has a complex structure, with copper as the central atom and surrounded by molecules of three amino acids, glycine - histidine - lysine, around it. In one embodiment, tripeptide-1 copper with CAS No. 49557-75-7 is used. In another embodiment, tripeptide-1 copper with CAS No. 89030-95-5 is utilized.
[0014] Preferably, the mass / volume ratio of the silver nanoparticles to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be 0.0010 mg / mL or more and 0.10 mg / mL or less. More preferably, the mass / volume ratio of the silver nanoparticles to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be 0.0050 mg / mL or more and 0.020 mg / mL or less. Even more preferably, the mass / volume ratio of the silver nanoparticles to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be 0.0077 mg / mL or more and 0.014 mg / mL or less.
[0015] Preferably, the particle size of the silver nanoparticles may be 1 nm or more and 50 nm or less. More preferably, the particle size of the silver nanoparticles may be 1 nm or more and less than 20 nm. Even more preferably, the particle size of the silver nanoparticles may be 1 nm or more and less than 10 nm. In the present invention, the particle size refers to the diameter.
[0016] Preferably, the mass / volume ratio of the polygonum multiflorum extract to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be 0.10 mg / mL or more and 10.0 mg / mL or less. More preferably, the mass / volume ratio of the polygonum multiflorum extract to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be from 0.50 mg / mL to 5.00 mg / mL. Even more preferably, the mass / volume ratio of the polygonum multiflorum extract to the mixture containing the polygonum multiflorum extract and silver nanoparticles may be from 0.91 mg / mL to 1.82 mg / mL.
[0017] Preferably, the mass / volume ratio of the tripeptide-1 copper to the hair growth composition may be 0.10 mg / mL or more and 0.18 mg / mL or less. More preferably, the mass / volume ratio of the tripeptide-1 copper to the hair growth composition may be 0.10 mg / mL or more and 0.16 mg / mL or less.
[0018] Preferably, the polygonum multiflorum extract may be a polygonum multiflorum root extract.
[0019] Preferably, as a method for producing the polygonum multiflorum root extract, (a) polygonum multiflorum root and an alcohol-based solvent are mixed and extracted at a temperature of 40°C to 60°C for 24 hours to 72 hours, and the extracted polygonum multiflorum root is separated and removed to obtain a polygonum multiflorum root extract. Then, (b) the solvent is removed from the polygonum multiflorum root extract and dried to obtain a polygonum multiflorum root extract.
[0020] Preferably, the polygonum multiflorum may be dried polygonum multiflorum.
[0021] Preferably, the alcohol-based solvent may contain methanol, ethanol, or propanol. The concentration of the alcohol solvent may be 30% to 95% by volume.
[0022] Preferably, the solid-liquid ratio (mass:volume) of the polygonum multiflorum to the alcohol-based solvent is 1:1 to 1:30. For example, when the solid-liquid ratio (mass:volume) of the polygonum multiflorum to the alcohol-based solvent is 1:1, it represents the mixing of 100 g of polygonum multiflorum and 100 mL of the alcohol-based solvent. When the solid-liquid ratio (mass:volume) of the polygonum multiflorum to the alcohol-based solvent is 1:30, 100 g of polygonum multiflorum and 3000 mL of the alcohol-based solvent are mixed.
[0023] In this embodiment, the polygonum multiflorum extract used in the example is, for example, manufactured by GREENTECH BIOTECHNOLOGIES. The extraction method is to pulverize 100 g of dried polygonum multiflorum roots, immerse them in 1000 mL of a 50% by volume ethanol aqueous solution, and extract for 48 hours. Then, after filtration separation, a polygonum multiflorum root extract is obtained, and this polygonum multiflorum root extract is concentrated under reduced pressure and freeze-dried to obtain 10 g of a polygonum multiflorum root extract. In this case, the extraction rate of the polygonum multiflorum root extract is 10%.
[0024] In this embodiment, the stabilizer is a protein, a peptide, sodium borohydride or polyvinyl pyrrolidone. Here, the protein may be human serum proteins, transferrin. Preferably, when the stabilizer is polyvinyl pyrrolidone (PVP), the silver nanoparticles can be effectively stabilized. Preferably, based on the total volume of the hair growth composition, the concentration of the PVP is from 0.1 mM (millimoles per liter) to 1 mM, and in one embodiment, the concentration of the PVP may be 0.57 mM.
[0025] Preferably, the diluent may be selected from the group consisting of water, ethanol, dimethyl sulfoxide (DMSO), acetonitrile (ACN), Hepes buffer, phosphate buffer, Tris buffer, citrate buffer, serum, or any other kind of physiologically relevant solvent or solution and combinations thereof.
[0026] To achieve the above object, the present invention further provides a pharmaceutical composition for hair growth, which comprises a hair growth composition as described above and a pharmaceutically acceptable excipient. The pharmaceutical composition can be used as a medical product that can be a drug or a medical device. This medical product is administered to a subject in need thereof.
[0027] Preferably, the subject to which the pharmaceutical composition is administered may be a mammal. Examples of mammals include humans, dogs, cats, or rodents.
[0028] Preferably, the pharmaceutical composition may be for topical administration to the skin surface, and the pharmaceutical composition is administered to the skin surface by application.
[0029] Preferably, the dosing frequency of the pharmaceutical composition can be administered to humans once to three times a day and continuously administered for at least 7 weeks.
[0030] In the present invention, the pharmaceutically acceptable excipient is not particularly limited. For example, the pharmaceutically acceptable excipient can include, but is not limited to, water, propylene glycol, or a combination thereof.
[0031] The hair growth composition of the present invention can effectively promote hair growth and obtain a high hair coverage rate and a promoting effect on the growth of new hair follicles.
[0032] [Details of Embodiments of the Present Invention] The present invention will be further described by the following examples, but these examples do not limit the disclosure of the present invention. Those skilled in the art of the present invention can make some improvements and modifications without departing from the scope of the present invention.
[0033] <Composition for Hair Growth> (Description of Reagents) 1. The aqueous solution of silver nanoparticles is of the product model number "DA04-21" manufactured by LIWEI Nano Tech Co., Ltd., with CAS No. 7440-22-4, the concentration of silver nanoparticles being from 0.00085% by mass to 0.0015% by mass, and water being from 99.9985% by mass to 99.99915% by mass. 2. Polyvinylpyrrolidone is of the product model number "SI-PVP40-500G" manufactured by Youhe Trading Co., Ltd., with CAS No. 9003-39-8. 3. The Polygonum multiflorum extract is of the product model number "300558" manufactured by GREENTECH BIOTECHNOLOGIES, with the composition ratio being 49.0% by mass to 49.5% by mass of water, 49.0% by mass to 49.5% by mass of propylene glycol, and 1.0% by mass to 2.0% by mass of Polygonum multiflorum root extract. 4. For Tripeptide-1 Copper, the product model number is 1310CSB00010050, with CAS No. 49557-75-7, and it is purchased from Taiwan Epik Co., Ltd.
[0034] (Preparation Example 1) Preparation of a mixture containing Polygonum multiflorum extract and silver nanoparticles Put 100 mL of silver nano-aqueous solution (LIWEI Nano Tech Co., Ltd.'s "DA04-21", concentration of silver nanoparticles from 0.00085% to 0.0015% by mass) into a beaker with a handle and stir with a magnet. Here, the particle size of the silver nanoparticles in the silver nano-aqueous solution is less than 10 nm. Add 2.5 g of polyvinylpyrrolidone to the silver nano-aqueous solution in multiple portions slowly, mix and stir until the addition is complete, continue stirring until it is completely dissolved and the mixture becomes clear. Also, filter the polygonum multiflorum extract (GREENTECH BIOTECHNOLOGIES, 305558, concentration of polygonum multiflorum extract is from 1% to 2% by mass) through a 0.45-micron (μm) filtration cup, then take 10 mL of the filtered polygonum multiflorum extract and add it to the mixture to obtain a mixture containing polygonum multiflorum extract and silver nanoparticles. The mass / volume ratio of the silver nanoparticles to the mixture containing polygonum multiflorum extract and silver nanoparticles is from 0.0077 mg / mL to 0.014 mg / mL, the mass / volume ratio of the polygonum multiflorum extract to the mixture containing polygonum multiflorum extract and silver nanoparticles is from 0.91 mg / mL to 1.82 mg / mL, and the concentration of polyvinylpyrrolidone is about 0.57 mM.
[0035] (Example 1) Hair growth composition Mix the mixture containing polygonum multiflorum extract and silver nanoparticles with a tripeptide-1 copper aqueous solution at a concentration of 0.5 mg / mL, and set the volume ratio of the two to 2.5:1 to obtain the hair growth composition according to this example. In this example, 110 mL of the mixture containing polygonum multiflorum extract and silver nanoparticles and 44 mL of the tripeptide-1 copper aqueous solution were used. Here, the concentration of tripeptide-1 copper in the hair growth composition is 0.14 mg / mL.
[0036] (Comparative Examples 1 to 4) Hair growth composition Comparative Examples 1 to 4 are the same as Example 1 except for the volume ratio of the mixture containing the polygonum multiflorum extract and silver nanoparticles to the aqueous solution of tripeptide-1 copper at a concentration of 0.5 mg / mL. The volume ratios of the mixture of the polygonum multiflorum extract and silver nanoparticles to the aqueous solution of tripeptide-1 copper in Comparative Examples 1 to 4 are 20:1, 10:1, 5:1, and 1:1, respectively. The compositions of Example 1 and Comparative Examples 1 to 4 are shown in Table 1 below.
[0037]
Table 1
[0038] (Test Example 1: Hair Coverage Test) The following tests were conducted using Example 1 and Comparative Examples 1 to 4 as samples. After 6-week-old nude mice (Nu / Nu mice) were adaptively bred for 1 to 2 weeks, they were randomly grouped into groups of 5 mice each. A silicone splint (manufactured by Grace Bio-Labs (USA), product model number "SKU: 476687") was sutured to the back of each mouse. The outer diameter, inner diameter, and thickness of the silicone splint were 24 mm, 20 mm, and 0.5 mm, respectively. The hair-growing composition of the example, comparative example, or control group was administered to the skin of the mouse within the silicone splint on the back of the mouse every day for a total of 7 weeks, with a maximum amount of 40 μL. In this test example, administering a mixture containing the polygonum multiflorum extract and silver nanoparticles of Preparation Example 2 (without tripeptide-1 copper) to the back of a mouse was set as the positive control group, and applying no pharmaceutical to the back of the mouse was set as the negative control group. Also, applying an aqueous solution of 0.5 mg / mL tripeptide-1 copper to the back of the mouse was set as the tripeptide-1 copper control group. The mice were weighed once a week and their health status was checked. On the 0th, 7th, 14th, 21st, 28th, 35th, and 42nd days after the start of the test, that is, the 1st, 2nd, 3rd, 4th, 5th, 6th, and 7th weeks, the growth of the mouse hair was photographed. After anesthetizing the mice with 2.5% isoflurane, they were placed under a stereomicroscope imaging system (SZN71 Microscope system, Sunny, Hangzhou, Mainland China), and photos were taken using the built-in imaging software. Next, the hair coverage rate was analyzed with Image J software. The inner diameter range of the silicone sprint attached to the back of the mouse (i.e., the range of pharmaceutical administration) was frame-selected to calculate the total administration area, and then the hair growth range was frame-selected to calculate the range area of hair growth. The calculation formula for the hair coverage rate is (range area of hair growth ÷ total administration area) × 100%. The results of the hair coverage rates of Example 1, Comparative Examples 1 to 4, and the positive control group are shown in Figure 1.
[0039] As can be seen from the average results of the hair coverage rates of all the mice in each group in Fig. 1, no obvious hair coverage was observed in the administration ranges of each group from the first week to the third week. At the seventh week, the hair coverage rates of Comparative Example 1 to Comparative Example 4 and the control group were 30.6%, 19.8%, 16.4%, 11.8% and 22.0% respectively, while the hair coverage rate of Example 1 was 61.8%, which was the best result. Furthermore, by two-way analysis of variance (Two-way ANOVA (Tukey test)), it was confirmed whether there was a significant difference in the hair coverage rate results of each group at the seventh week compared to the positive control group. The results are shown in Table 2. Table 2 shows whether there is a significant difference between Example 1 and Comparative Example 1 to Comparative Example 4 compared to the positive control group. According to the results in Table 2, at the seventh week, only the hair coverage rate result of Example 1 showed a significant difference compared to any of Comparative Example 1 to Comparative Example 4 and the positive control group.
[0040]
Table 2
[0041] (Test Example 2: Calculation of hair follicle number) After sacrificing all the mice in Test Example 1, the skin tissues of the mice were embedded in paraffin and cut into sections with a thickness of 3 μm on a slide glass for hematoxylin and eosin stain (H&E). Then, immunohistochemistry (IHC) was used for histopathological analysis. Hematoxylin and eosin staining was performed, and the stained glass was scanned using a glass panoramic scanner (OLYMPUS / VS 200). Two fields of view of each section were randomly selected under the condition of a magnification of 80 times, and the results of observing and measuring the hair follicles are shown in Figs. 2 to 9.
[0042] Figures 2 to 9 are sections of the negative control group, positive control group, tripeptide-1 copper control group, Comparative Example 1, Comparative Example 2, Comparative Example 3, Example 1, and Comparative Example 4, respectively. The arrows in each figure are examples of circular hair follicles. Among them, as shown in Figure 8, the number of hair follicles in the sections of the group treated in Example 1 was significantly superior to the number of hair follicles in each of the other groups (Figures 2 to 7 and Figure 9), and the hair follicles were more densely distributed. Therefore, the hair growth composition of the present invention can effectively promote the growth of new hair follicles.
[0043] From the above, the hair growth composition of the present invention can effectively promote hair growth in nude mice, has a high hair coverage rate, and can promote the generation of new hair follicles.
[0044] Various modifications and changes based on the present invention will not clearly depart from the scope and gist of the present invention for those skilled in the art. Although the present invention has been described with respect to specific preferred embodiments, it must be understood that the present invention should not be limited to such specific concrete facts. In fact, various modifications obvious to those skilled in the art in implementing the aspects described in the present invention are also included in the scope of the patent application.
Claims
1. A mixture comprising an extract of Polygonum multiflorum and silver nanoparticles; Tripeptide-1 copper and Contains the mass / volume ratio of the tripeptide-1 copper to the hair growth composition is 0.10 mg / mL or more and 0.20 mg / mL or less; The mixture containing the Polygonum multiflorum extract and silver nanoparticles comprises silver nanoparticles, Polygonum multiflorum extract, a stabilizer and a diluent.
2. The hair growth composition according to claim 1, wherein the mass / volume ratio of the silver nanoparticles to the mixture containing the Polygonum multiflorum extract and silver nanoparticles is 0.0010 mg / mL or more and 0.10 mg / mL or less.
3. The hair growth composition according to claim 1, wherein the silver nanoparticles have a particle size of 1 nm or more and 50 nm or less.
4. The hair growth composition according to claim 1, wherein the mass / volume ratio of the Polygonum multiflorum extract to the mixture containing the Polygonum multiflorum extract and silver nanoparticles is 0.10 mg / mL or more and 10.0 mg / mL or less.
5. The hair growth composition according to claim 1, wherein the Polygonum multiflorum extract is Polygonum multiflorum root extract.
6. 2. The hair growth composition according to claim 1, wherein the stabilizer is a protein, a peptide, sodium borohydride or polyvinylpyrrolidone.
7. 2. The hair growth composition of claim 1, wherein the diluent is selected from the group consisting of water, ethanol, dimethylsulfoxide, acetonitrile, Hepes buffer, phosphate buffer, Tris buffer, citrate buffer, serum, and combinations thereof.
8. A pharmaceutical composition for hair growth comprising the hair growth composition according to any one of claims 1 to 7 and a pharma- ceutical acceptable excipient.
9. The pharmaceutical composition for hair growth according to claim 8, wherein the subject of administration of the pharmaceutical composition is a mammal.
10. The pharmaceutical composition for hair growth according to claim 9, wherein the pharmaceutical composition is for application to the skin surface.
Citation Information
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