Delivery system comprising collagen type xvii and methods of making and using the same

Abstract

The present application belongs to the technical field of skin care products, and particularly relates to a delivery system containing collagen type XVII, a preparation method and application thereof. The delivery system containing collagen type XVII comprises a penetration enhancer and an active substance; the penetration enhancer comprises hydroxyethyl deacetyl chitin, troxerutin and glucosyl hesperidin; and the active substance is collagen type XVII. The present application can promote hair growth, improve microcirculation, control oil, and optimize the scalp environment. Moreover, the formula of the present application is scientific and reasonable, has no adverse irritation reaction, has excellent tolerance in long-term and high-frequency use, and is suitable for daily hair loss prevention and maintenance and conditioning of various scalp problems.

Description

Technical Field

[0001] This invention belongs to the field of skin care technology, specifically relating to a delivery system containing type XVII collagen, its preparation method, and its application. Background Technology

[0002] Hair loss has become a widespread global problem, with a significantly younger age of onset. The huge market demand for hair regrowth products remains largely unmet. Currently, mainstream hair regrowth products are based on two main mechanisms of action: one is vasodilators, such as minoxidil, which have a single mechanism of action and side effects such as excessive shedding, scalp itching, and hirsutism; the other is 5α-reductase inhibitors, such as finasteride, primarily targeting androgenetic alopecia, but may cause systemic side effects such as sexual dysfunction, and has a high relapse rate after discontinuation. Therefore, the market urgently needs to develop safe and effective hair regrowth products based on new targets and mechanisms.

[0003] Recent scientific research has revealed that the decline in hair follicle stem cell function and the deterioration of the microenvironment surrounding the hair follicle are among the core pathological mechanisms of hair loss. In particular, the structural damage to the basement membrane in the hair follicle bulge area directly leads to the loss of anchorage of hair follicle stem cells, thereby triggering hair follicle miniaturization and hair loss. Type XVII collagen (also known as BP180) is a key transmembrane protein located on the hemidesmosomes of hair follicle stem cells, responsible for anchoring hair follicle stem cells to the basement membrane. It is crucial for maintaining the structural integrity of the hair follicle bulge area and the homeostasis of hair follicle stem cells. Studies have shown that the expression level of type XVII collagen decreases with age or external damage, and its deficiency is a key molecular event driving hair follicle miniaturization and leading to hair loss. Therefore, maintaining or supplementing type XVII collagen has become a highly promising new strategy for hair regrowth.

[0004] However, as a large transmembrane protein, type XVII collagen's active fragments or expression promoters are difficult to effectively penetrate the scalp's stratum corneum barrier and precisely deliver to the target area deep within the hair follicle, which constitutes a major technical challenge in this field. Therefore, developing a transdermal technology that can effectively overcome the scalp barrier and achieve targeted delivery of large molecular active ingredients (or their inducers) is of great significance for developing next-generation, highly effective, and safe hair growth products.

[0005] Chinese patent CN116496429B discloses a self-assembled transdermal delivery system based on hydroxyethyl deacetylated chitosan, its preparation, and its application. The system is prepared using chitin, 1,2-epoxybutane, and ethylene oxide as main raw materials. The resulting hydroxyethyl deacetylated chitosan has an average molecular weight of 7460 Da and is used as a penetration enhancer for active ingredients such as peptides, proteins, PCA, Zn, and ergothioneine. However, experiments have shown that while it can improve the transdermal absorption rate of collagen and sodium DNA to some extent when used alone, its effect is limited and requires further improvement. Summary of the Invention

[0006] To address the shortcomings of existing technologies, the present invention aims to provide a delivery system containing type XVII collagen, its preparation method, and its applications. The present invention utilizes a combination of hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin, which exhibits a synergistic effect, significantly promoting the transdermal penetration of type XVII collagen, thereby enhancing the hair growth-promoting effect of type XVII collagen as an active molecule.

[0007] The technical solution of this invention is: A delivery system comprising type XVII collagen, including a penetration enhancer and an active ingredient; said penetration enhancer includes hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin; The active ingredient is type XVII collagen.

[0008] Furthermore, the delivery system containing type XVII collagen comprises the following components and their mass fractions: 0.21 to 1.5 parts of penetration enhancer and 0.01 to 0.4 parts of active ingredient.

[0009] Furthermore, the delivery system containing type XVII collagen comprises the following components and their mass fractions: 0.26 to 1.5 parts of penetration enhancer and 0.05 to 0.2 parts of active ingredient.

[0010] Furthermore, the delivery system containing type XVII collagen comprises the following components and their mass fractions: 0.35-0.8 parts of penetration enhancer and 0.05-0.2 parts of active ingredient.

[0011] Furthermore, the delivery system containing type XVII collagen comprises the following components and their mass fractions: 0.55 parts of penetration enhancer and 0.05 parts of active ingredient.

[0012] Furthermore, the mass ratio of hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin in the penetration enhancer is 0.01-0.3:0.1-0.6:0.15-0.6.

[0013] Furthermore, the mass ratio of hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin in the penetration enhancer is 0.1-0.3:0.1-0.2:0.15-0.3.

[0014] Furthermore, the mass ratio of hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin in the penetration enhancer is 0.3:0.1:0.15.

[0015] Another object of the present invention is to provide a method for preparing the aforementioned delivery system containing type XVII collagen, comprising the following steps: (1) Hydroxyethyl deacetylated chitosan, troxerutin and glucosyl hesperidin are mixed evenly to obtain a penetration enhancer; (2) Mix the penetration enhancer and active ingredient evenly to obtain the product.

[0016] Another object of the present invention is to provide the application of the aforementioned delivery system containing type XVII collagen in the preparation of hair growth products.

[0017] Another object of the present invention is to provide a hair growth product comprising the aforementioned delivery system containing type XVII collagen.

[0018] Compared with the prior art, the present invention has the following advantages: (1) This invention can promote hair growth and improve microcirculation: After a 6-week, 10-time human test, the product of this invention can effectively activate dormant hair follicles and increase the number of new hairs in the hair loss area (especially the top of the head and hairline), showing a real improvement effect on diffuse hair loss and seborrheic alopecia.

[0019] (2) The present invention can refresh and control oil and optimize the scalp environment: The product provided by the present invention has good fat solubility and permeability, and is not easy to deposit on the scalp surface. It can be quickly absorbed under the action of the iontophoresis device. After use, the scalp feels refreshed and non-greasy, providing a clean and healthy physiological environment for hair follicle growth.

[0020] (3) The present invention is mild, safe and non-irritating: The formula of the present invention is scientific and reasonable, with no adverse irritant reaction. It has excellent tolerance to long-term and high-frequency use and is suitable for daily hair loss prevention and maintenance as well as conditioning of various scalp problems. Attached Figure Description

[0021] Figure 1 This is a before-and-after comparison image of a person with typical symptoms of seborrheic alopecia.

[0022] Figure 2 Before and after comparison images for individuals exhibiting typical symptoms of diffuse hair loss.

[0023] Figure 3 Before and after photos of hair follicles are shown for individuals exhibiting typical symptoms of seborrheic alopecia.

[0024] Figure 4 Before and after comparison of hair follicles for individuals exhibiting typical symptoms of diffuse hair loss. Detailed Implementation

[0025] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0026] Before further describing specific embodiments of the present invention, it should be understood that the scope of protection of the present invention is not limited to the specific embodiments described below; it should also be understood that the terminology used in the embodiments of the present invention is for describing specific embodiments and not for limiting the scope of protection of the present invention.

[0027] The XVII type collagen used in this invention has a molecular weight of 22kDa to 25kDa.

[0028] The material usage of the delivery systems containing type XVII collagen in Examples 1 to 5 and Comparative Examples 1-1 to 5-2 is shown in Table 1.

[0029] Table 1. Material usage (wt%) of the delivery systems containing type XVII collagen in Examples 1-5 and Comparative Examples 1-1-5-2.

[0030] Preparation method: 1. Preparation method of hydroxyethyl deacetylated chitosan: It was prepared by the preparation method described in Example 1 of CN116496429B.

[0031] 2. The preparation methods of Examples 1 to 5 and Comparative Examples 1-1 to 5-2 are as follows: the penetration enhancer and active ingredient are added to water and stirred evenly.

[0032] Experimental Example 1: Transdermal Efficacy Test This test is based on the piglet skin-Franz cell diffusion cell system. The permeability of different samples to Franz cell diffusion cells was carried out using piglet back skin to examine the transdermal ability of the samples to isolated piglet back skin.

[0033] The specific test steps are as follows: (1) Add receiving fluid to the receiving chamber: Use a pipette to draw 7.0 mL of receiving fluid (physiological saline) and inject it into the receiving chamber, and place the matching magnetic stir bar in the receiving chamber.

[0034] (2) Assembly and fixation of the test model: The piglet skin was fixed between the diffusion chamber and the receiving chamber of the Franz cell diffusion cell, with the stratum corneum of the piglet skin facing the diffusion chamber and the dermis facing the receiving chamber. After fixing the piglet skin, 0.5 mL of receiving solution (physiological saline) was added to the sampling tube using a pipette according to the liquid level in the sampling tube, so that the dermis of the piglet skin was in close contact with the receiving solution, and the total volume of the receiving solution was 7.5 mL.

[0035] (3) Fix the Franz cell diffusion cell in the transdermal absorption diffusion apparatus, turn on the electromagnetic stirrer and stir at a speed of 300 rpm, and maintain a constant temperature air bath of (32±1)℃.

[0036] (4) Sample loading: After the air bath temperature of the diffuser is constant, sample loading is performed. Use a syringe to draw 400 μL of test sample and add it to the surface of pig skin.

[0037] (5) Subcutaneous sample collection: Samples were collected at 8 h.

[0038] (6) Treatment of the un-permeated parts of the skin: After 8 hours of permeation, use a pipette to repeatedly blow and clean the surface of the piglet skin with physiological saline. Wash 3 times and bring the volume to 2.0 mL.

[0039] (7) Treatment of residual parts in the skin: After 8 h of infiltration, the pig skin was cut into pieces and placed in a 2.0 mL EP tube, and the volume was adjusted to 2.0 mL with physiological saline. The tube was then sonicated for 30 minutes.

[0040] (8) Quantitative analysis of total protein content was performed on samples taken at time points using the Coomassie Brilliant Blue method, and the permeability at each time point was calculated according to the following formula: P = Q / P0 × 100%; where P is the permeability, Q is the cumulative permeation amount at each time point in the receiving chamber, and P0 is the sample loading amount in the diffusion chamber (sample loading amount = sample volume × sample concentration).

[0041] The transdermal effects of the examples and comparative examples are shown in Table 2.

[0042] Table 2 Transdermal Effects of Examples and Comparative Examples

[0043] In Table 2, the synergy coefficient is calculated according to the King's method, and the calculation formula is as follows: q=E A+B / (E A +E B -E A E B ) Where q is the coordination coefficient, E A+BE represents the penetration rate of collagen of type XVII in Example X. A To compare the penetration rate of X-1 with the corresponding type XVII collagen, E B The penetration rate of the corresponding type XVII collagen was compared to that of the comparative example X-2.

[0044] As shown in Table 2, the synergy coefficients of Examples 1 to 3 are greater than 1.15, indicating a synergistic effect; the synergy coefficients of Examples 4 to 5 are between 0.85 and 1.15, indicating no synergistic effect. In other words, hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin only have a synergistic effect in promoting the penetration of type XVII collagen within the scope of this invention.

[0045] Experimental Example 2: Human Efficacy Test 1. Test Objects and Methods Subject selection: Two subjects who met the inclusion criteria were selected (male, one with diffuse hair loss and the other with typical symptoms of seborrheic alopecia, respectively), with the main hair loss areas located on the top of the head and the hairline at the front of the forehead.

[0046] Testing cycle and method: For the first two weeks, use the product obtained in Example 3 of this invention once a week, and for the next four weeks, use it twice a week for a total of 6 weeks. Use a micro-source gel-infused device for application, focusing on areas of hair loss.

[0047] Evaluation indicators: Observe and record changes in hair volume, hair follicle activity (new hair growth), scalp sebum secretion, and irritation response in the bald areas of the subjects.

[0048] 2. Comparative analysis before and after the test (1) Macroscopic improvement in hair volume: Before and after comparison of typical symptoms of seborrheic alopecia, as shown in the figure. Figure 1 As shown in the image, the overall comparison before and after use is for individuals with typical symptoms of diffuse hair loss. Figure 2 As shown. Figure 1 , Figure 2 As shown, when subjects used the product obtained in Example 3 of this invention, the hair density and visual coverage of the balding areas on the top of the head and forehead were improved. In particular, after the test period ended, new, fine, soft hair was clearly visible growing in the sparse areas on the top of the head and forehead of the subjects.

[0049] (2) Improvement of microscopic hair follicles and scalp environment: Before and after comparison of hair follicles in patients with typical symptoms of seborrheic alopecia, as shown in the figure. Figure 3 As shown, the before-and-after comparison of hair follicles in individuals with typical symptoms of diffuse hair loss is as follows. Figure 4 As shown. Figure 3 , Figure 4 The "left" in this context refers to the left side of the forehead. Figure 3 , Figure 4 The "right" in this context refers to the right side of the forehead, making it easier to distinguish between before and after. For example... Figure 3 , Figure 4 As shown, with the increase in usage frequency, the sebum secretion on the scalp surface of the subjects was effectively controlled, and the environment around the hair follicle pores remained clean and free of clumps, indicating that the product of the present invention has a good ability to regulate the scalp microecology and balance oil.

[0050] (3) Comfort of use: The product has a clear texture and is absorbed quickly. No adverse reactions such as itching, redness, or stinging were observed during the entire test period, which proves that the product of this invention has extremely high biocompatibility and safety.

Claims

1. A delivery system comprising type XVII collagen, characterized in that, It includes penetration enhancers and active ingredients; the penetration enhancers include hydroxyethyl deacetylated chitosan, troxerutin, and glucosyl hesperidin; The active ingredient is type XVII collagen.

2. The delivery system comprising type XVII collagen according to claim 1, characterized in that, It includes the following components and their mass fractions: 0.21~1.5 parts of penetration enhancer and 0.01~0.4 parts of active ingredient.

3. The delivery system comprising type XVII collagen according to claim 2, characterized in that, It includes the following components and their mass fractions: 0.26~1.5 parts of penetration enhancer and 0.05~0.2 parts of active ingredient.

4. The delivery system comprising type XVII collagen according to claim 3, characterized in that, It includes the following components and their mass fractions: 0.35~0.8 parts of penetration enhancer and 0.05~0.2 parts of active ingredient.

5. The delivery system comprising type XVII collagen according to claim 1, characterized in that, The mass ratio of hydroxyethyl deacetylated chitosan, troxerutin and glucosyl hesperidin in the penetration enhancer is 0.01-0.3:0.1-0.6:0.15-0.

6.

6. The delivery system comprising type XVII collagen according to claim 5, characterized in that, The mass ratio of hydroxyethyl deacetylated chitosan, troxerutin and glucosyl hesperidin in the penetration enhancer is 0.1-0.3:0.1-0.2:0.15-0.

3.

7. The method for preparing a delivery system containing type XVII collagen according to any one of claims 1-6, characterized in that, Includes the following steps: (1) Hydroxyethyl deacetylated chitosan, troxerutin and glucosyl hesperidin are mixed evenly to obtain a penetration enhancer; (2) Mix the penetration enhancer and active ingredient evenly to obtain the product.

8. The use of the delivery system containing type XVII collagen according to any one of claims 1-6 in the preparation of hair growth products.

9. A hair growth product, characterized in that, The delivery system comprising type XVII collagen as described in any one of claims 1-6.

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