Application of polylactic acid and derivative thereof in promoting hair growth
By applying polylactic acid microspheres or copolymer microspheres directly to the scalp, the high cost and significant side effects of existing hair loss treatments are resolved, achieving rapid and effective hair growth.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-09
- Publication Date
- 2026-03-10
AI Technical Summary
Existing hair loss treatments suffer from high surgical costs, short-lasting effects, and significant side effects from non-surgical methods. Furthermore, the transdermal absorption efficiency of medications is low, making it difficult to effectively promote hair growth.
Polylactic acid and its copolymers are used to prepare polylactic acid microspheres or copolymer microspheres, which are then applied directly to the scalp as a drug reservoir to promote hair growth.
It significantly increases the number of hair follicles and the rate of hair growth, improves hair weight and length, reduces inflammation, and provides a long-lasting therapeutic effect.
Smart Images
Figure CN121622734A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedicine, specifically relating to the application of polylactic acid and its derivatives in promoting hair growth. Background Technology
[0002] Hair plays vital roles in the human body, including protecting the body, enhancing appearance, and regulating body temperature. However, hair loss, a non-life-threatening condition, can significantly impact an individual's appearance, social interactions, and overall quality of life. Currently, hair loss is a prevalent problem affecting people of all ages and genders worldwide. According to the U.S. Food and Drug Administration (FDA), more than 800,000 people globally are affected by this issue. Therefore, research into the prevention and treatment of hair loss is an important area of focus for the medical and pharmaceutical industries.
[0003] Currently, hair loss treatment in my country can be categorized into hair transplantation and non-surgical hair maintenance based on whether surgery is involved. Surgical hair transplantation involves extracting hair follicles from the back of the head, a region rich in high-quality follicles, and transplanting them to bald or thinning areas. Compared to other non-transplant hair health treatments, hair transplantation is significantly effective for hair loss, alopecia areata, and baldness. However, transplanted hair is difficult to maintain permanently and largely depends on the recipient's physiological condition. Furthermore, the high cost and invasive nature of the treatment limit its clinical application. Therefore, only a small number of patients can afford hair transplantation. Non-surgical hair maintenance includes shampoos, topical or oral treatments that can address various basic scalp and hair problems, such as early-stage hair loss, hair quality issues, scalp itching, and oily scalp. However, these products often have poor therapeutic effects, are addictive, require long-term use, and have serious side effects such as sexual dysfunction, hirsutism, edema, cardiovascular adverse reactions, hormonal imbalances, and even psychological problems. Non-surgical hair maintenance products include minoxidil, finasteride, and immunosuppressive drugs.
[0004] To overcome the aforementioned shortcomings of existing technologies, a non-surgical treatment method with rapid therapeutic effects is gradually being used to improve scalp and hair problems. This new treatment can be seen as a form of daily management and care for the scalp and hair, similar to cosmetic maintenance and treatment of the face. This new treatment allows medication to be applied directly to the recipient area, solving the problems of low transdermal absorption efficiency of topical medications, the inability of oral medications to achieve local effects, and the high cost and short-lasting effects of hair transplantation. Furthermore, because drugs administered superficially to the skin have a lower clearance rate, the duration of drug action can be longer, and the scalp layer can act as a drug reservoir, resulting in a more sustained therapeutic effect. Summary of the Invention
[0005] To address the shortcomings of existing technologies, the present invention aims to provide a use of polylactic acid and its derivatives in promoting hair growth, and specifically provides the following technical solution:
[0006] A first aspect of the invention provides the use of polylactic acid and / or copolymers in the preparation of products that maintain or promote hair growth.
[0007] A second aspect of the invention provides the use of polylactic acid and / or copolymers in the preparation of products that increase the number of hair follicles in the growth phase.
[0008] In one embodiment, the molecular weight of the polylactic acid and its copolymers is 400 Da to 300 kDa;
[0009] In a preferred embodiment, the polylactic acid and its copolymers have a molecular weight of 1000 Da to 100 kDa; for example, 5000 Da.
[0010] In one embodiment, the polylactic acid includes L-polylactic acid, D-polylactic acid, and racemic polylactic acid; preferably L-polylactic acid.
[0011] In one embodiment, the polylactic acid copolymer includes one or more of polylactic acid-glycolic acid copolymer, polylactic acid-polyethylene glycol copolymer, polyethylene glycol-polylactic acid-glycolic acid copolymer, polylactic acid-chitosan copolymer, and lactide-caprolactone copolymer.
[0012] In a preferred embodiment, the polylactic acid copolymer is a polylactic acid-hydroxyacetic acid copolymer.
[0013] In one embodiment, the preparation method of polylactic acid microspheres and polylactic acid copolymer microspheres includes the following steps:
[0014] 1) Mix polylactic acid or polylactic acid copolymer with a solvent to obtain a polylactic acid solution or a polylactic acid copolymer solution;
[0015] 2) Mix polylactic acid solution or polylactic acid copolymer solution with polyvinyl alcohol aqueous solution, emulsify at high speed, stir to remove solvent, and freeze dry to obtain polylactic acid microspheres.
[0016] In a preferred embodiment, the solvent is any one of dichloromethane, chloroform, ethyl acetate, acetone, or toluene, or a mixture of any two or more of them.
[0017] In a preferred embodiment, in step 1) above, the mass-volume ratio of polylactic acid or polylactic acid copolymer to solvent is 1g:5mL to 1g:30mL. In a more preferred embodiment, the mass-volume ratio of polylactic acid or polylactic acid copolymer to solvent is 1g:10mL to 1g:20mL, for example, 1g:15mL.
[0018] And / or, in step 2), the mass concentration of the polyvinyl alcohol aqueous solution is 0.05% to 5.0%, and in a preferred embodiment, the mass concentration of the polyvinyl alcohol aqueous solution is 0.1% to 2.0%, for example, 0.5%;
[0019] And / or, in step 2), the volume ratio of polylactic acid solution or polylactic acid copolymer solution to polyvinyl alcohol aqueous solution is 1:5 to 1:30. In a preferred embodiment, the volume ratio of polylactic acid solution or polylactic acid copolymer solution to polyvinyl alcohol aqueous solution is 1:10 to 1:20, for example 1:13 or 1:15.
[0020] And / or, in step 2), the high-speed emulsification rotation speed is 1000 rpm / min to 5000 rpm / min, for example 3000 rpm / min;
[0021] And / or, in step 2), the emulsification time is 5 to 20 minutes, for example, 10 minutes.
[0022] In one embodiment, the mass concentration of polylactic acid and its copolymers, polylactic acid microspheres, and polylactic acid copolymer microspheres in the pharmaceutical or cosmetic product is 0.1% to 80%. In a preferred embodiment, the mass concentration of polylactic acid and its copolymers, polylactic acid microspheres, and polylactic acid copolymer microspheres is 0.5% to 2%, for example, 0.5%, 1%, and 2%.
[0023] In one embodiment, the drug and / or cosmetic may optionally further include excipients;
[0024] In a preferred embodiment, the excipients include at least one of stabilizers, fillers, binders, and surfactants;
[0025] In a more preferred embodiment, the surfactant is selected from one or more of polyethylene glycol, sodium dodecyl sulfonate, Tween, and Span;
[0026] In a more preferred embodiment, the stabilizer is selected from one or both of carboxymethyl cellulose and mannitol;
[0027] In a more preferred embodiment, the filler is selected from one or more of lactose, mannitol, cyclodextrin, and sorbitol;
[0028] In a more preferred embodiment, the adhesive is selected from one or more of hydroxypropyl cellulose, methylcellulose, sodium hyaluronate, collagen, and polyvinylpyrrolidone;
[0029] In one embodiment, the drug and / or cosmetic may optionally be used in combination with other active ingredients that promote hair growth.
[0030] In a preferred embodiment, the other active ingredients are selected from one or more of hyaluronic acid, panthenol, pyridoxine hydrochloride, glutamine, etc.
[0031] In one embodiment, the method of administration of the drug includes, but is not limited to, injection, application, etc.
[0032] In one embodiment, the dosage form of the drug is an injection, an ointment, or the like.
[0033] In other aspects of the present invention, the hair loss is one or more of the following: androgenetic alopecia, neurogenic alopecia, endocrine alopecia, nutritional alopecia, physical alopecia, chemical alopecia, infectious alopecia, age-related alopecia, congenital alopecia, and / or seasonal alopecia.
[0034] In other aspects of the invention, the hair includes one or more of hair, eyebrows, beard, and eyelashes. Attached Figure Description
[0035] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used in conjunction with embodiments of the invention to explain the invention and do not constitute a limitation thereof. In the drawings:
[0036] Figure 1 The hair growth of mice in each group after administration in Example 3 of this invention;
[0037] Figure 2 This shows the hair growth of mice in each group after administration of the drug in Example 4 of the present invention. Detailed Implementation
[0038] The present invention will be explained below with reference to embodiments. Those skilled in the art will understand that the following embodiments are for illustrative purposes only and should not be considered as limiting the scope of the invention. Where specific techniques or conditions are not specified in the embodiments, they are performed according to the techniques or conditions described in the literature in the field or according to the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be obtained commercially.
[0039] Example 1: Preparation method of polylactic acid (PLLA) microspheres
[0040] 10 g of polylactic acid (PLLA) (molecular weight 10 kDa) was dissolved in 200 mL of dichloromethane. The polymer solution was then added to 2000 mL of a 1.0% (w / w) aqueous solution of polyvinyl alcohol. Emulsification was carried out at 5000 rpm for 15 min, followed by stirring for 6 hours to remove the dichloromethane, yielding PLLA microspheres. The prepared microspheres had a smooth surface and a particle size of 3–55 μm. Without being limited by theory, the inventors hypothesize that the smooth surface and particle size of the microspheres or particles disclosed herein are associated with a lower inflammatory response in treated patients. Compared to microspheres with a more inhomogeneous and rough structure, smooth-surfaced microspheres elicited a lower inflammatory response in treated patients. Microspheres that are too small are easily phagocytosed by macrophages, while microspheres that are too large elicited a greater inflammatory response in treated patients.
[0041] Example 2: Preparation method of polylactic acid-glycolic acid copolymer microspheres
[0042] 10 g of polylactic-co-glycolic acid copolymer (PLGA) (molecular weight 10 kDa) was dissolved in 200 mL of dichloromethane. The polymer solution was then added to 2000 mL of a 1% (w / w) aqueous solution of polyvinyl alcohol. Emulsification was carried out at 5000 rpm / min for 15 minutes, followed by stirring for 6 hours to remove the dichloromethane. After drying, polylactic-co-glycolic acid copolymer microspheres were obtained. The prepared microspheres had a smooth surface and a particle size of 3–55 μm. Without being limited by theory, the inventors hypothesize that the smooth surface and particle size of the microspheres or particles disclosed herein are associated with a lower inflammatory response in treated patients. Compared to microspheres with a more inhomogeneous and rough structure, smooth-surfaced microspheres elicited a lower inflammatory response in treated patients. Microspheres that are too small are easily phagocytosed by macrophages, while microspheres that are too large elicited a greater inflammatory response in treated patients.
[0043] Example 3: Establishment of androgenetic alopecia mouse model and screening of appropriate ratios
[0044] 1. Experimental Grouping
[0045] Grouping Group Mouse number Administration method Dosage Group A normal group 8 smear The corresponding volume of physiological saline Group B androgenetic alopecia model group 8 Intraperitoneal injection 100μL Group C 0.5% poly-L-lactic acid microspheres 8 smear 100μL Group D 1% poly-L-lactic acid microspheres 8 smear 100μL Group E 2% poly-L-lactic acid microspheres 8 smear 100μL
[0046] Note: The polylactic acid microspheres used in groups A, B, and C were poly-L-lactic acid microspheres prepared according to the method described in Example 1. The particle size of the prepared poly-L-lactic acid microspheres ranged from 3 to 55 μm. All concentrations mentioned herein are mass concentrations.
[0047] Except for the normal group mice which did not receive subcutaneous injection of dihydrotestosterone (DHT), all mice underwent daily intraperitoneal injections of DHT to establish an androgenetic alopecia model. The specific modeling methods and steps are as follows:
[0048] 1) Select C57BL / 6 mice and place them in a constant temperature room (24±2℃) with a dark-light cycle of 12 hours for 7 days for acclimatization.
[0049] 2) Establishment of androgenic alopecia mouse model (AGA model): Dihydrotestosterone was dissolved in corn oil (10 mg / ml, i.e., 1%). Except for the normal group, mice in other groups were injected intraperitoneally with 0.1 ml for 15 consecutive days, starting 4 days before hair removal, in order to establish the AGA model.
[0050] 3) Hair removal in experimental animals: After mice were anesthetized with isoflurane, rosin and paraffin were mixed in a 1:1 volume ratio and heated to melt. After the temperature dropped, the mixture was applied to the back of the mice. After solidification, the hair on the back of the mice was removed. The hair removal area was 2cm × 3cm. The mice were then fed under the original conditions after hair removal treatment, and each group continued to receive the corresponding pre-hair removal intervention for the specified number of days.
[0051] 2. Mice in each group were administered the drug for 15 days, and photographs were taken on days 1, 8, 11, and 15 after administration. Figure 1 ), and observe the hair growth of mice.
[0052] 3. On day 15 of drug administration, 10 newly grown hairs were randomly selected from the experimental area, and their lengths were measured and recorded using an electronic digital caliper.
[0053] 4. On day 15, shave all new hair in the experimental area with a shaver, collect the hair, weigh it using an electronic balance, and record the weight of the new hair.
[0054] 5. On day 15, mice were sacrificed to assess the model establishment and hair growth. Skin samples from the backs of mice were fixed with paraformaldehyde and stained with hematoxylin and eosin (HE) to observe the growth of hair follicle cells. The total number of hair follicle cells was counted in cross-sections of the skin at the same level.
[0055] 1) Dewaxing paraffin sections: First place them in xylene I for 20 min, then in xylene II for 20 min, then in a series of ethanol solutions for 5 min each, and finally rinse with tap water.
[0056] 2) Hematoxylin staining: Immerse the sections in the staining solution for 3-5 minutes, then rinse with tap water, then differentiate with differentiation solution, and finally rinse with tap water.
[0057] 3) Eosin staining: The sections were dehydrated in 85% and 95% ethanol gradient solutions for 5 minutes each, and then immersed in eosin staining solution for 5 minutes.
[0058] min;
[0059] 4) Dehydration and sealing: The sections were sequentially immersed in a gradient of ethanol for 5 min each, then xylene I for 5 min, followed by xylene II for 5 min, and then sealed with transparent neutral glue.
[0060] 5) Microscopic observation, image acquisition and analysis.
[0061] 6. Homogenize the remaining mouse skin, centrifuge at 3000 rpm for 10 min, and aliquot and freeze the supernatant. Determine the VEGF content in mouse skin strictly according to the mouse VEGF kit method.
[0062] 7. Experimental Results
[0063] 1. The hair growth in mice 15 days after administration is shown in the table below:
[0064] Table 1: Effects on the length of new hair regrowth in androgenetic alopecia mice
[0065]
[0066] Note: Compared with the androgenetic alopecia model group, * indicates p<0.05, which is statistically significant, and ** indicates p<0.01, which is statistically significant; compared with the androgenetic alopecia model group, # indicates p<0.05, which is statistically significant, and ## indicates p<0.01, which is statistically significant.
[0067] from Figure 1 As shown in Table 1, the results indicate that intraperitoneal injection of dihydrotestosterone can alleviate the growth of new hair in mice. Following drug treatment, on day 15, the poly-L-lactic acid microspheres accelerated hair growth and increased the length of new hair in mice with androgenetic alopecia. The 1% poly-L-lactic acid microsphere group exhibited the longest new hair growth.
[0068] 2. The weight of all newly grown hair in the experimental area on day 15 after drug administration to mice is shown in Table 2 below:
[0069] Table 2: Effects on the weight of newly grown hair in androgenetic alopecia mice
[0070]
[0071] Note: Compared with the androgenetic alopecia model group, * indicates p<0.05, which is statistically significant, and ** indicates p<0.01, which is statistically significant; compared with the androgenetic alopecia model group, # indicates p<0.05, which is statistically significant, and ## indicates p<0.01, which is statistically significant.
[0072] Table 2 shows that, compared with the normal group and the androgenic alopecia model group, intraperitoneal injection of dihydrotestosterone reduced hair weight in mice, successfully establishing a mouse model of androgenic alopecia. After drug treatment, the poly-L-lactic acid microsphere group alleviated the effects of androgenic alopecia in mice and increased the weight of newly grown hair. Among them, the 1% poly-L-lactic acid microsphere group showed the greatest increase in hair weight.
[0073] 3. The growth status of hair follicle cells in the dorsal skin of mice on day 15 after drug administration is shown in Table 3:
[0074] Table 3: Effects on the number of hair follicles in the anagen phase on the dorsal skin of mice
[0075]
[0076] Note: * indicates p<0.05, which is statistically significant; ** indicates p<0.01, which is statistically significant; compared with the androgenic alopecia model group, # indicates p<0.05, which is statistically significant; ## indicates p<0.01, which is statistically significant.
[0077] As shown in Table 3, the experimental results indicate that intraperitoneal injection of dihydrotestosterone (DHT) induced androgenetic alopecia in mice. The number of hair follicles in the androgenetic alopecia model group was reduced. After drug treatment, the number of hair follicles on the back skin of mice in the poly-L-lactic acid microsphere group increased. Among them, the 1% poly-L-lactic acid microsphere group had the highest number of hair follicles in the growth phase on the back skin of mice, which played a role in alleviating androgenetic alopecia and promoting hair growth.
[0078] 4. The VEGF factor content in mouse skin on day 15 after drug administration is shown in Table 4:
[0079] Table 4: Vascular endothelial growth factor (VEGF) content in mouse skin
[0080]
[0081] Note: * indicates p<0.05, which is statistically significant; ** indicates p<0.01, which is statistically significant; compared with the androgenic alopecia model group, # indicates p<0.05, which is statistically significant; ## indicates p<0.01, which is statistically significant.
[0082] Vascular endothelial growth factor (VEGF) can act paracrinely on vascular endothelial cells in the dermis, inducing increased microvascular synthesis in local skin areas, providing nutrients to hair follicles, and promoting hair growth. Table 4 shows that the concentration of VEGF in the skin of mice in the androgenic alopecia model group was decreased compared to the normal group. After drug treatment, the VEGF content in mice in the poly-L-lactic acid microsphere group increased, indicating that poly-L-lactic acid microspheres can promote hair growth in mice by increasing VEGF secretion. Specifically, the 1% poly-L-lactic acid microsphere group significantly increased VEGF secretion in mice, promoting hair growth in androgenic alopecia mice.
[0083] Example 4: Establishment of androgenetic alopecia mouse model; testing the effect of a combination of polylactic acid and hair growth active substances on preventing hair loss or promoting hair regrowth.
[0084] 1. Experimental Grouping
[0085] Grouping Grouping Mouse number Administration method Dosage Group A normal group 8 smear The corresponding volume of physiological saline Group B androgenetic alopecia model group 8 Intraperitoneal injection 100μL Group C Minoxidil group 8 smear 100μL Group D Hyaluronic acid group 8 smear 100μL Group E Panthenol group 8 smear 100μL Group F Pyridoxine hydrochloride group 8 smear 100μL Group G glutamine 8 smear 100μL Group H Polylactic acid glycolic acid copolymer microspheres 8 smear 100μL Group I Poly-L-lactic acid group 8 smear 100μL Group J Poly-L-lactic acid + hyaluronic acid group 8 smear 100μL Group K Poly-L-lactic acid + panthenol group 8 smear 100μL Group L Poly-L-lactic acid + pyridoxine hydrochloride group 8 smear 100μL Group M Poly-L-lactic acid + glutamine 8 smear 100μL
[0086] Note: The polylactic acid used in groups I, J, K, and L is poly(L-lactic acid) microspheres prepared according to the method described in Example 1. The polylactic acid-glycolic acid copolymer microspheres used in group H are prepared according to the method described in Example 2. The molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer microspheres is 80:20. A microsphere concentration of 1% is chosen to achieve the effects described in the examples. Only one concentration in the examples is used as an example for detailed explanation; other concentrations are not described here.
[0087] Minoxidil is soluble in ethanol and propylene glycol. Unless otherwise specified, all other materials are soluble in physiological saline.
[0088] Except for the normal group mice which did not receive subcutaneous injection of dihydrotestosterone (DHT), all mice underwent daily intraperitoneal injections of DHT to establish an androgenetic alopecia model. The specific modeling methods and steps are as follows:
[0089] 1) C57BL / 6 mice were placed in a constant temperature room (24±2℃) with a 12-hour dark-light cycle for 7 days for acclimatization. 2) Establishment of the androgenic alopecia mouse model (AGA model): Dihydrotestosterone was dissolved in corn oil (10mg / ml, i.e., 1%).
[0090] Except for the normal group, all other groups of mice were injected intraperitoneally with 0.1 ml for 15 consecutive days, starting 4 days before hair removal, in order to establish the AGA model.
[0091] 3) Hair removal in experimental animals: After mice were anesthetized with isoflurane, rosin and paraffin were mixed in a 1:1 volume ratio and heated to melt. After the temperature dropped, the mixture was applied to the back of the mice. After solidification, the hair on the back of the mice was removed. The hair removal area was 2cm × 3cm. The mice were then fed under the original conditions after hair removal treatment, and each group continued to receive the corresponding pre-hair removal intervention for the specified number of days.
[0092] 4) The specific dosing regimens for each group are as follows:
[0093] Group A received daily application of saline solution.
[0094] Group B received daily intraperitoneal injections of dihydrotestosterone (1% concentration).
[0095] Group C applied minoxidil (1% concentration) daily.
[0096] Group D applied hyaluronic acid (1% concentration) daily.
[0097] Group E applied panthenol (1% concentration) daily.
[0098] Group F applied pyridoxine hydrochloride (1% concentration) daily.
[0099] Group G applied glutamine (1% concentration) daily.
[0100] Group H applied polylactic acid glycolic acid copolymer microspheres (concentration 1%) daily.
[0101] Group I applied poly-L-lactic acid microspheres (1% concentration) daily.
[0102] Group J received daily application of a combination of poly-L-lactic acid microspheres (1% concentration) and hyaluronic acid (1% concentration).
[0103] Group K received daily application of a combination of poly-L-lactic acid microspheres (1% concentration) and panthenol (1% concentration).
[0104] Group L received daily application of a combination of poly-L-lactic acid microspheres (1% concentration) and pyridoxine hydrochloride (1% concentration).
[0105] Group M received daily application of a combination of poly-L-lactic acid microspheres (1% concentration) and glutamine (1% concentration).
[0106] The poly-L-lactic acid microspheres used were all poly-L-lactic acid microspheres with a particle size of 3-55 μm prepared in Example 1.
[0107] 2. Mice in each group were administered the drug for 15 days, and photographs were taken on days 1, 8, 11, and 15 after administration. Figure 2 ), and observe the hair growth of mice.
[0108] 3. On day 15 of drug administration, 10 newly grown hairs were randomly selected from the experimental area, and their lengths were measured and recorded using an electronic digital caliper.
[0109] 4. On day 15, shave all new hair in the experimental area with a shaver, collect the hair, weigh it using an electronic balance, and record the weight of the new hair.
[0110] 5. On day 15, mice were sacrificed to assess the model establishment and hair growth. Skin samples from the backs of mice were fixed with paraformaldehyde and stained with hematoxylin and eosin (HE) to observe the growth of hair follicle cells. The total number of hair follicle cells was counted in cross-sections of the skin at the same level.
[0111] 6) Dewaxing paraffin sections: First place them in xylene I for 20 min, then in xylene II for 20 min, then in a series of ethanol solutions for 5 min each, and finally rinse with tap water.
[0112] 7) Hematoxylin staining: Immerse the sections in the staining solution for 3-5 minutes, then rinse with tap water, then differentiate with differentiation solution, and finally rinse with tap water.
[0113] 8) Eosin staining: The sections were dehydrated in 85% and 95% graded ethanol solutions for 5 min each, and then immersed in eosin staining solution for 5 min.
[0114] min;
[0115] 9) Dehydration and sealing: The sections were placed in a gradient of ethanol for 5 min each, then xylene I for 5 min, then xylene II for 5 min, and finally sealed with transparent neutral glue.
[0116] 10) Microscopic observation, image acquisition and analysis.
[0117] 6. Homogenize the remaining mouse skin, centrifuge at 3000 rpm for 10 min, and aliquot and freeze the supernatant. Determine the VEGF content in mouse skin strictly according to the mouse VEGF kit method.
[0118] Example 5 Experimental Results
[0119] 1. The hair growth in mice 15 days after administration is shown in the table below:
[0120] Table 5: Effects on the length of new hair regrowth in androgenetic alopecia mice
[0121]
[0122] Note: Compared with the androgenetic alopecia model group, * indicates p<0.05, which is statistically significant, and ** indicates p<0.01, which is statistically significant; compared with the androgenetic alopecia model group, # indicates p<0.05, which is statistically significant, and ## indicates p<0.01, which is statistically significant.
[0123] from Figure 1 As shown in Table 1, the results indicate that intraperitoneal injection of dihydrotestosterone can alleviate the growth of new hair in mice. Following drug treatment, on day 15, the poly-L-lactic acid microsphere group accelerated hair growth and increased the length of new hair in androgenic alopecia mice. Both poly-L-lactic acid and other active combination groups significantly increased hair length, with the poly-L-lactic acid microsphere and hyaluronic acid combination group exhibiting the longest new hair growth.
[0124] 2. The weight of all newly grown hair in the experimental area on day 15 after drug administration to mice is shown in Table 26 below:
[0125] Table 6: Effects on the weight of newly grown hair in androgenetic alopecia mice
[0126]
[0127] Note: Compared with the androgenetic alopecia model group, * indicates p<0.05, which is statistically significant, and ** indicates p<0.01, which is statistically significant; compared with the androgenetic alopecia model group, # indicates p<0.05, which is statistically significant, and ## indicates p<0.01, which is statistically significant.
[0128] Table 6 shows the experimental results: Comparing the normal group and the androgenic alopecia model group, intraperitoneal injection of dihydrotestosterone reduced hair weight in mice, successfully establishing a mouse model of androgenic alopecia. After drug treatment, the poly-L-lactic acid microsphere group alleviated the effects of androgenic alopecia in mice and increased the weight of newly grown hair. Both the poly-L-lactic acid microsphere and other active combination groups significantly increased hair weight.
[0129] 3. The growth status of hair follicle cells in the dorsal skin of mice on day 15 after drug administration is shown in Table 7:
[0130] Table 7: Effects on the number of hair follicles in the anagen phase on the dorsal skin of mice
[0131]
[0132]
[0133] Note: * indicates p<0.05, which is statistically significant; ** indicates p<0.01, which is statistically significant; compared with the androgenic alopecia model group, # indicates p<0.05, which is statistically significant; ## indicates p<0.01, which is statistically significant.
[0134] As shown in Table 7, the experimental results indicate that intraperitoneal injection of dihydrotestosterone induced androgenetic alopecia in mice. The number of hair follicles in the androgenetic alopecia model group was reduced. After drug treatment, the number of hair follicles in the anagen phase on the back skin of mice was significantly increased in both the poly-L-lactic acid microsphere group and the poly-L-lactic acid microsphere and other active combination groups. This can alleviate the symptoms of androgenetic alopecia and promote hair growth.
[0135] 4. The VEGF content in mouse skin on day 15 after drug administration is shown in Table 8:
[0136] Table 8: Vascular endothelial growth factor (VEGF) content in mouse skin
[0137]
[0138]
[0139] Note: * indicates p<0.05, which is statistically significant; ** indicates p<0.01, which is statistically significant; compared with the androgenic alopecia model group, # indicates p<0.05, which is statistically significant; ## indicates p<0.01, which is statistically significant.
[0140] Vascular endothelial growth factor (VEGF) can act paracrinely on vascular endothelial cells in the dermis, inducing increased microvascular synthesis in local skin areas, providing nutrients to hair follicles, and promoting hair growth. Table 4 shows that the concentration of VEGF in the skin of mice in the androgenic alopecia model group was decreased compared to the normal group. After drug treatment, the VEGF content in mice in the poly-L-lactic acid microsphere group increased significantly, indicating that poly-L-lactic acid microspheres can promote hair growth in mice by increasing VEGF secretion. Both poly-L-lactic acid microspheres and other active combination groups significantly increased VEGF secretion in mice, promoting hair growth in androgenic alopecia mice.
[0141] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.
Claims
1. Use of polylactic acid and / or copolymer in the preparation of a product for maintaining or promoting hair growth.
2. Use of polylactic acid and / or copolymer in the preparation of a product for increasing the number of anagen hair follicles.
3. Use according to claim 1 or 2, characterized in that, The polylactic acid and / or polylactic acid copolymer is prepared into microspheres, preferably, the molecular weight of the polylactic acid and / or polylactic acid copolymer is 400 Da to 300 kDa; more preferably, the molecular weight of the polylactic acid and / or polylactic acid copolymer is 5000 Da to 100 kDa; most preferably, the molecular weight of the polylactic acid and / or polylactic acid copolymer is 5000 Da to 20 kDa.
4. Use according to claim 1 or 2, wherein the compound is ###0002### The molecular weight of the polylactic acid and / or polylactic acid copolymer is 15000 Da.
5. The use according to claim 3, wherein the compound is ###0002### The size of the microspheres is 50 nm to 100 μm; preferably, the size of the microspheres is 1 μm to 100 μm; more preferably, the size of the microspheres is 3 μm to 55 μm.
6. Use according to claim 1 or 2, wherein the compound is ###0002### The polylactic acid comprises one or more of levorotatory polylactic acid, dextrorotatory polylactic acid, and racemic polylactic acid; preferably, the polylactic acid is levorotatory polylactic acid.
7. Use according to claim 1 or 2, wherein the compound is ###0002### The polylactic acid copolymer comprises one or more of polylactic acid-glycolic acid copolymer, polylactic acid-polyethylene glycol copolymer, polyethylene glycol-polylactic acid-glycolic acid copolymer, and lactide-caprolactone copolymer; preferably, the polylactic acid copolymer is polylactic acid-glycolic acid copolymer.
8. Use according to claim 1 or 2, wherein the compound is ###0002### The concentration of L-lactic acid in the polylactic acid copolymer is at least 20%, preferably, the concentration of L-lactic acid in the polylactic acid copolymer is 20% to 80%.
9. The use according to claim 3, wherein the compound is ###00003### 3 The method for preparing polylactic acid microspheres or polylactic acid copolymer microspheres comprises the following steps: 1) mixing polylactic acid or polylactic acid copolymer with a solvent to obtain a polylactic acid solution or a polylactic acid copolymer solution; 2) mixing the polylactic acid solution or the polylactic acid copolymer solution with an aqueous polyvinyl alcohol solution, high-speed emulsifying, stirring to remove the solvent, and freeze-drying to obtain polylactic acid microspheres.
10. Use according to claim 9, wherein The solvent is any one of dichloromethane, chloroform, ethyl acetate, acetone, or toluene, or a mixture of any two or more thereof.
11. The use according to claim 9, wherein In step 1), the mass-volume ratio of polylactic acid or polylactic acid copolymer to solvent is 1 g:5 mL to 1 g:30 mL; and / or, in step 2), the mass concentration of the aqueous polyvinyl alcohol solution is 0.05% to 5.0%; and / or, in step 2), the volume ratio of the polylactic acid solution or the polylactic acid copolymer solution to the aqueous polyvinyl alcohol solution is 1:5 to 1:30; and / or, in step 2), the rotation speed of high-speed emulsifying is 1000 rpm / min to 5000 rpm / min; and / or, in step 2), the emulsifying time is 5 to 20 minutes.
12. The use according to claim 11, wherein the compound is ###00010### or a pharmaceutically acceptable salt thereof. In step 1), the mass-volume ratio of polylactic acid or polylactic acid copolymer to solvent is 1 g:10 mL to 1 g:20 mL, preferably, the mass-volume ratio of polylactic acid or polylactic acid copolymer to solvent in step 1) is 1 g:15 mL.
13. Use according to claim 1 or 2, wherein the compound is ###0002### When administered, the mass concentration of polylactic acid and / or polylactic acid copolymer is 0.1% to 80%, preferably, when administered, the mass concentration of polylactic acid and / or polylactic acid copolymer is 0.5% to 2%.
14. Use according to claim 1 or 2, wherein The product is a medicine and / or a cosmetic.
15. The use according to claim 14, wherein the compound is ###0002### The medicine and / or cosmetic can optionally further include an excipient, including at least one of a stabilizer, a filler, a binder, and a surfactant.
16. The use of claim 14, wherein, The medicine and / or cosmetic can optionally be further used in combination with other active ingredients having the effect of promoting hair growth.
17. The use according to claim 16, wherein The other active ingredients include, but are not limited to, hyaluronic acid, panthenol, pyridoxine hydrochloride, glutamine, etc.
18. Use according to any one of claims 14 to 17, wherein The administration mode of the medicine includes, but is not limited to, intravenous injection, in situ injection, subcutaneous injection, oral administration, smearing, etc.
19. Use according to any one of claims 14 to 17, wherein The dosage form of the medicine is injection, ointment, cream, etc.
20. The use of claim 1, wherein, The alopecia is one or more of androgenetic alopecia, neurogenic alopecia, endocrine alopecia, nutritional alopecia, physical alopecia, chemical alopecia, infectious alopecia, senile alopecia, congenital alopecia, and / or seasonal alopecia.
21. The use of claim 1, wherein, The hair includes one or more of head hair, eyebrow, beard, and eyelash.