A peptide derivative, composition and use thereof

Abstract

The present invention relates to the field of biotechnology, and in particular to a peptide derivative, a composition and its use. The present invention provides an application of biotin tripeptide-1, a composition and an application of the composition. The present invention can be used to prevent and / or treat the intrinsic and extrinsic symptoms of hair loss, can stimulate the synthesis of collagen IV and laminin 5, inhibit the expression of 5α-reductase, androgen receptor, transcriptional growth factor-β2 genes, delay hair follicle aging, improve hair follicle structure, fix hair in dermal follicles, enhance hair quality, and prevent hair loss; in addition, it can activate tissue repair gene expression and relieve inflammation.

Description

Technical Field

[0001] The present invention relates to the field of biotechnology, and in particular to a peptide derivative, a composition and use thereof. Background Art

[0002] There are about 100,000 hairs on the head, and the three cycles of each hair are not synchronized. As the body declines, most hair follicles close their microcirculation, and the hair follicles shrink and die. After middle age, these atrophied hair follicles increase and no longer participate in the three cycles. This is one of the reasons why hair becomes thinner after middle age. The three cycles of hair seem to be determined by the hair follicles, but in fact, they are the dermal papilla cells (DPC) at the bottom of the hair follicle. DPC plays an important role in the development of hair follicles. It can be said that without the division of DPC, hair follicles cannot be formed, and the three cycles of hair cannot be formed.

[0003] Other hair care and hair growth products on the market are mainly anti-hair loss products, and most of the products used to prevent and treat gray hair are mainly Chinese herbal extracts. Their efficacy is relatively single, and their mechanism of action needs to be further studied. The anti-hair loss and hair growth effects are not ideal. By promoting the expression of DPC, hair growth can be promoted more effectively. Therefore, it is very meaningful to develop a hair care and hair growth product that promotes the expression of DPC. Summary of the invention

[0004] In view of this, the present invention provides a peptide derivative, a composition and a use thereof, which have the effects of preventing hair loss and relieving inflammation.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides the use of a compound represented by formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof in the preparation of a product having the efficacy of preventing hair loss and protecting hair and / or relieving inflammation.

[0007] Vx-Xaa1-Xaa2-Xaa3 (I)

[0008] Wherein, Vx is a vitamin or vitamin derivative containing a carboxyl group, Xaa1 is an aliphatic amino acid, a polar amino acid or a neutral amino acid, Xaa2 is an amino acid containing a heterocyclic ring or a basic amino acid; Xaa3 is an aliphatic amino acid or a basic amino acid;

[0009] The anti-hair loss care comprises:

[0010] (1) Increase the number of effective hair follicles; and / or

[0011] (2) Preventing hair loss; and / or

[0012] (3) increasing the activity of hair papilla cells; and / or

[0013] (4) Upregulating the expression of collagen IV gene; and / or

[0014] (5) Upregulating the expression of laminin 5 gene; and / or

[0015] (6) inhibiting 5α-reductase; and / or

[0016] (7) down-regulating androgen receptor gene expression; and / or

[0017] (8) down-regulating 5α-reductase 2 gene expression; and / or

[0018] (9) down-regulate the expression of transcriptional growth factor-β2 gene;

[0019] The relief of inflammation includes inhibiting the secretion of TNF-α inflammatory factor.

[0020] In some specific embodiments of the present invention, in the above application, the Vx is vitamin H, the Xaa1 is glycine, the Xaa2 is L-histidine, and the Xaa3 is lysine.

[0021] In some specific embodiments of the present invention, in the above application, the compound is biotin tripeptide-1.

[0022] In some specific embodiments of the present invention, in the above application, the compound accounts for 0.02 wt% to 0.1 wt% of the net weight of the product.

[0023] The present invention also provides a composition comprising biotin tripeptide-1, Platycladus orientalis leaf extract and ectoine.

[0024] In some specific embodiments of the present invention, in the above composition, by weight, the biotin tripeptide-1 is 0.02 to 0.1 parts, the Platycladus orientalis leaf extract is 1 to 10 parts, and the tetrahydromethylpyrimidine carboxylic acid is 0.1 to 3 parts.

[0025] The present invention also provides a composition comprising biotin tripeptide-1, Platycladus orientalis leaf extract and sodium hyaluronate.

[0026] In some specific embodiments of the present invention, in the above composition, in parts by weight, the biotin tripeptide-1 is 0.02 to 0.1 parts, the Platycladus orientalis leaf extract is 1 to 10 parts, and the sodium hyaluronate is 0.01 to 0.1 parts.

[0027] The present invention also provides the use of the above composition in preparing products with the effects of preventing hair loss and protecting hair and / or relieving inflammation;

[0028] The anti-hair loss care comprises:

[0029] (1) Increase the number of effective hair follicles; and / or

[0030] (2) Preventing hair loss; and / or

[0031] (3) increasing the activity of hair papilla cells; and / or

[0032] (4) Upregulating the expression of collagen IV gene; and / or

[0033] (5) Upregulating the expression of laminin 5 gene; and / or

[0034] (6) inhibiting 5α-reductase; and / or

[0035] (7) down-regulating androgen receptor gene expression; and / or

[0036] (8) down-regulating 5α-reductase 2 gene expression; and / or

[0037] (9) down-regulate the expression of transcriptional growth factor-β2 gene;

[0038] The relief of inflammation includes inhibiting the secretion of TNF-α inflammatory factor.

[0039] The present invention also provides a product, comprising the above composition and acceptable auxiliary materials or additives.

[0040] In some specific embodiments of the present invention, the above product:

[0041] In the composition, the biotin tripeptide-1 accounts for 0.02wt% to 0.1wt% of the net weight of the product, the Platycladus orientalis leaf extract accounts for 1.0wt% to 10.0wt% of the net weight of the product, and the tetrahydromethylpyrimidine carboxylic acid accounts for 0.1wt% to 3.0wt% of the net weight of the product; or

[0042] In the composition, the biotin tripeptide-1 accounts for 0.02wt% to 0.1wt% of the net weight of the product, the Platycladus orientalis leaf extract accounts for 1.0wt% to 10.0wt% of the net weight of the product, and the sodium hyaluronate accounts for 0.01wt% to 0.1wt% of the net weight of the product.

[0043] The present invention also provides a method for preparing the above product, comprising the step of mixing the above composition with acceptable auxiliary materials or additives.

[0044] The present invention also provides a compound as shown in formula (I),

[0045] Vx-Xaa1-Xaa2-Xaa3, Formula (I)

[0046] Among them, Vx is a vitamin or vitamin derivative containing a carboxyl group, especially vitamin H, Xaa1 is an aliphatic amino acid, a polar amino acid, or a neutral amino acid, especially glycine, Xaa2 is an amino acid containing a heterocyclic ring or a basic amino acid, especially L-histidine, and Xaa3 is an aliphatic amino acid or a basic amino acid, especially lysine.

[0047] In some specific embodiments of the present invention, the above-mentioned compound, wherein the amino acid modification in the biotin tripeptide is selected from the group consisting of lysine and histidine methylation.

[0048] In some specific embodiments of the present invention, the above-mentioned compound, wherein in the biotin tripeptide, the amino acid sequence is Biotinoyl-Gly-His-Lys, its biologically active fragments, its salts, its combinations and / or its variants.

[0049] In some specific embodiments of the present invention, the above compound, molecular formula C 24 H 38 N8O6S, molecular weight is 566.67g / mol.

[0050] The present invention also provides a composition comprising the above compound, wherein the at least one compound is present in the range of WT% of the total weight of the composition and at a concentration of 0.05 μM or above.

[0051] In some specific embodiments of the present invention, the above composition further comprises a cationic surfactant.

[0052] In some specific embodiments of the present invention, the above composition, wherein the cationic surfactant is present in the range of WT% of the total weight of the composition.

[0053] In some specific embodiments of the present invention, the above composition has the effects of preventing hair loss and protecting hair, and relieving inflammation.

[0054] In some specific embodiments of the present invention, the above-mentioned composition comprises an additional active ingredient, and the active ingredient is selected from whitening agents, anti-redness agents, sunscreens and UV organic or inorganic filters, hydrating agents, moisturizers, wetting agents, scrubs, anti-wrinkle agents, anti-aging agents, anti-inflammatory agents, antioxidants, free radical scavengers, tanning agents, hair growth liquids, mascara, eyelash care liquid, anti-hair loss shampoo, and anti-hair loss shower gel (for pets).

[0055] The present invention also provides the use of the above composition in preventing and / or treating the intrinsic and extrinsic symptoms of hair loss, stimulating the synthesis of collagen IV and laminin 5, inhibiting the expression of 5α reductase, androgen receptor, transcriptional growth factor-β2 genes, delaying hair follicle aging, improving hair follicle structure, fixing hair in dermal follicles, enhancing hair quality, preventing hair loss and activating tissue repair gene expression, relieving inflammation and reconstructing skin structure.

[0056] The present invention also provides the use of the composition in improving hair follicle structure, promoting hair growth and preventing hair loss.

[0057] The present invention also provides the use of the above composition in improving skin structure and maintaining skin tension and / or stiffness and / or elasticity.

[0058] The present invention also provides a method for preventing hair loss and effectively promoting hair growth, comprising using the above composition to promote the growth of eyelashes, eyebrows and hair.

[0059] The present invention also provides a method for effectively relieving inflammation and improving skin structure, comprising applying the above composition locally to the skin.

[0060] The peptide derivatives, compositions and uses thereof of the present invention have the following effects:

[0061] The experiment showed that the activity of hair papilla cells in the biotin tripeptide-1 sample group increased significantly, indicating that biotin tripeptide-1 has the ability to promote the proliferation of human papilla cells. After the application of biotin tripeptide-1, the expression of collagen IV gene and laminin 5 increased significantly, indicating that biotin tripeptide-1 has the ability to promote the expression of collagen IV gene and laminin 5 gene in hair papilla cells. The experiment also showed that after applying biotin tripeptide-1, the expression of androgen receptor gene in the biotin tripeptide-1 raw material group decreased significantly, indicating that the raw material has the ability to inhibit the expression of androgen receptor gene in hair papilla cells under the stimulation of dihydrotestosterone, and biotin tripeptide-1 significantly decreased the expression of 5α-reductase gene, indicating that the biotin tripeptide-1 raw material has the ability to inhibit the expression of 5α-reductase (SRD5A2) gene in hair papilla cells under the stimulation of dihydrotestosterone, and biotin tripeptide-1 significantly decreased the expression of transcription growth factor-β2 (TGF-β2) gene, indicating that the raw material has the ability to inhibit the expression of transcription growth factor-β2 (TGF-β2) gene in hair papilla cells under the stimulation of dihydrotestosterone.

[0062] The experiment also showed that after the administration of biotin tripeptide-1, the content of TNF-α inflammatory factor in cells was significantly inhibited, indicating that biotin tripeptide-1 has the ability to inhibit the secretion of TNF-α inflammatory factor. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below.

[0064] Figure 1 The results show the effects of the samples on the activity of hair papilla cells; "*" indicates significant difference compared with the blank control group, "*": p<0.05;

[0065] Figure 2 The statistical graph of ColⅣ gene expression is shown; "*" indicates significant difference compared with the blank control group, "**": p<0.001, "***": p<0.001;

[0066] Figure 3 shows the up-regulation rate of ColⅣ gene;

[0067] Figure 4 The Laminin 5 gene expression statistical chart is shown; "*" indicates a significant difference compared with the blank control group, "****": p<0.0001;

[0068] Figure 5 It shows the up-regulation rate of Laminin 5 gene;

[0069] Figure 6 Shows the 5α-reductase inhibition rate of the sample;

[0070] Figure 7 Shows the statistical graph of AR gene expression; "*" indicates significant difference compared with the blank control group, "*": p<0.05, "**": p<0.01;

[0071] Figure 8 It shows the inhibition rate of AR gene expression;

[0072] Fig. 9 The statistical graph of SRD5A2 gene expression is shown; "*" indicates significant difference compared with the blank control group, "***": p<0.001, "****": p<0.0001;

[0073] Fig.10 It shows the inhibition rate of SRD5A2 gene expression;

[0074] Fig.11 The statistical graph of TGF-β2 gene expression is shown; "*" indicates significant difference compared with the blank control group, "***": p<0.001, "****": p<0.0001;

[0075] Fig.12 It shows the inhibition rate of TGF-β2 gene expression;

[0076] Fig.13Shows the content of TNF-α inflammatory factor in macrophages; "*" indicates significant difference compared with the negative control group (LPS group), "**": p<0.01, "***": p<0.0001;

[0077] Fig.14 Indicates the inhibition rate of TNF-α inflammatory factor; "*" indicates significant difference compared with the blank control group, "**": p<0.01;

[0078] Fig.15 It shows the expression level of collagen Ⅳ gene in human hair papilla cells;

[0079] Fig.16 Shows the expression level of laminin 5 gene in human hair papilla cells. DETAILED DESCRIPTION

[0080] The present invention discloses a peptide derivative, a composition and its use. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0081] The biotin tripeptide-1 involved in the present invention is a commercially available product, product information: Shenzhen Readlin Biotechnology Co., Ltd., batch number: 20220601.

[0082] The Platycladus orientalis leaf extract involved in the present invention is a commercially available product, product information: Guangzhou Baoyi Biotechnology Co., Ltd., batch number: 20221025.

[0083] The ectoine carboxylic acid involved in the present invention is a commercially available product, product information: Shenzhen Readline Biotechnology Co., Ltd., batch number: 20230405.

[0084] The sodium hyaluronate involved in the present invention is a commercially available product, product information: Bloomage Biotech Co., Ltd., batch number: 20230605.

[0085] Unless otherwise specified, the raw materials, reagents, consumables and instruments involved in the present invention are all common commercial products and can be purchased from the market.

[0086] The present invention will be further described below in conjunction with embodiments:

[0087] Example 1

[0088] The formula of the anti-hair loss and hair growth lotion is shown in Table 1, wherein group C is the active ingredient raw material. Preparation method: (1) Heat component A to 85 degrees, dissolve and stir evenly. (2) Add component B to a water pot, heat to 85 degrees, dissolve and stir evenly. (3) Add component A to component B, homogenize for 10 minutes, stir and keep warm for 30 minutes, then cool to 45 degrees. (4) Add components C, D, and E below 45 degrees and stir evenly.

[0089] Table 1

[0090]

[0091] Comparative Example 1

[0092] The formula of the anti-hair loss and hair growth lotion is shown in Table 2, and the preparation method is the same as that of Example 1.

[0093] Table 2

[0094]

[0095]

[0096] Effect Example 1

[0097] 1. Hair growth milk stability test

[0098] (1) Test method: The hair growth emulsions prepared in Example 1 and Comparative Example 1 were placed in a 4°C constant temperature refrigerator, a 37°C constant temperature incubator, and a 45°C constant temperature incubator for 3 months, and their appearance phenotype changes, such as obvious color change, solution stratification or precipitation, were observed.

[0099] (2) Test results: as shown in Table 3 below

[0100] Table 3: Stability of hair growth cream

[0101] Grouping 4℃ constant temperature refrigerator 37℃ constant temperature incubator 45℃ Constant temperature incubator Example 1 No delamination, no obvious discoloration No delamination, no obvious discoloration No delamination, no obvious discoloration Comparative Example 1 No delamination, no obvious discoloration No delamination, no obvious discoloration No delamination, no obvious discoloration

[0102] The results showed that the hair growth lotion had good stability.

[0103] 2. Animal Experiments on Hair Growth Lotion

[0104] Rats were randomly divided into 3 groups, 10 rats in each group, half of them were male and half were female. The back of the rat was evenly divided into 4 areas A, B, C, and D (2 cm × 2 cm) from the head to the tail with the spine as the midline, half on the left and half on the right. After removing all the hair, the hair growth lotion of Example 1 and Comparative Example 1 was applied to the right side of each group of rats, and the left side was applied with distilled water as a blank. After 28 days, a bunch of new hair was plucked from the applied area, and 10 longer hairs were selected by visual observation and measured with a vernier caliper, and the average value was taken as the hair growth length value of the rats in the area. The hair in the applied area was carefully removed, collected, and weighed, which was taken as the hair growth weight value of the rats.

[0105] Table 4: Rat hair growth length and rat hair growth weight

[0106] Grouping Blank Group Comparative Example 1 Example 1 Hair growth length (mm) 10.15 11.79 15.69 Hair growth weight value (mg) 32.11 40.75 51.16

[0107] The results showed that compared with the blank group, Comparative Example 1 promoted the hair growth of rats to a certain extent, and Example 1 had the best effect and effectively promoted the hair growth of rats, indicating that the hair growth cream prepared in this experiment has the effect of promoting hair growth.

[0108] Example 2

[0109] The formula of the anti-hair loss and hair growth liquid is shown in Table 5. Preparation method: (1) Heat water, glycerin, butylene glycol, hyaluronic acid, and β-glucan to 85 degrees, dissolve and stir evenly. (2) Cool to 45 degrees, add biotin tripeptide-1, phenoxyethanol, 1,2-hexanediol, Platycladus orientalis leaf extract, and essence, and stir evenly.

[0110] Table 5

[0111] Serial number Raw material name percentage% 1 water TO 100 2 glycerin 5.00 3 Butanediol 5.00 4 Sodium Hyaluronate 0.03 5 β-Glucan 0.03 6 Biotin Tripeptide-1 0.02 7 Phenoxyethanol 0.50 8 1,2-Hexanediol 0.50 9 Oriental Platycladus orientalis leaf extract 3.00 10 essence 0.02

[0112] Comparative Example 2

[0113] The formula is shown in Table 6. Preparation method: (1) Heat water, glycerin, butylene glycol, hyaluronic acid, and β-glucan to 85 degrees, dissolve and stir evenly. (2) Cool to 45 degrees, add phenoxyethanol, 1,2-hexanediol, Platycladus orientalis leaf extract, and essence, and stir evenly.

[0114] Table 6

[0115] Serial number Raw material name percentage% 1 water TO 100 2 glycerin 5.00 3 Butanediol 5.00 4 Sodium Hyaluronate 0.03 5 β-Glucan 0.03 6 Phenoxyethanol 0.50 7 1,2-Hexanediol 0.50 8 Oriental Platycladus orientalis leaf extract 3.00 9 essence 0.02

[0116] Effect Example 2

[0117] Anti-hair loss and hair growth liquid performance test indicators:

[0118] Effects on scalp:

[0119] The hair loss testers were randomly divided into groups, and their age, gender and hair loss conditions were evenly distributed, namely, a blank group, a comparative example group 2 and an embodiment group 2, with 30 people in each group. The blank group used clean water once in the morning and evening every day, took 5g of clean water each time, gently patted with the fingertips of both hands, inserted the fingers into the hair, and applied the clean water to the scalp at the hair loss site, and massaged for 10 minutes. Similarly, the comparative example group 2 and the embodiment group 2 used the anti-hair loss and hair growth liquid prepared by the corresponding scheme in the same way, respectively, once a day in the morning and evening, took 5g each time, gently patted with the fingertips of both hands, inserted the fingers into the hair, and applied the hair growth liquid to the scalp at the hair loss site, and massaged for 10 minutes. The test time was 12 weeks. During the test, all testers did not use other anti-hair loss and hair growth products except the anti-hair loss and hair growth liquid (Example 2, Comparative Example 2) used for the test.

[0120] (1) Effective scalp hair follicle density

[0121] A test area of ​​5cm×5cm was selected at the hair loss area on the test person’s head, and a hair follicle analyzer was used to test the hair follicle density of the hair loss person before and after use. The test period was 12 weeks, with testing every 2 weeks. The test results are shown in Table 7.

[0122] Table 7: Effective hair follicle density of scalp

[0123]

[0124] From the data in the table, it can be seen that after the testers in Example 2 used the anti-hair loss and hair growth liquid prepared by us, the effective hair follicle density continued to increase with the use time, and was significantly higher than that of the control group 2 and the blank group, thereby proving that this hair loss product can effectively increase the number of effective hair follicles, and further proves that it has the effect of effective hair growth.

[0125] (2) Anti-hair loss effect

[0126] The number of hair loss of the test subjects at week 0 and week 12 after using the anti-hair loss and hair growth liquid was counted. The specific method was to prepare a double-layer gauze of 1m×1m and spread it out, then comb the hair, collect and count the hair attached to the gauze, and the results are shown in Table 8.

[0127] Table 8: Number of hair loss

[0128]

[0129]

[0130] As can be seen from Table 8, after using the anti-hair loss product prepared by this scheme for 12 weeks, the amount of hair loss of the test subjects in Example 2 group was significantly reduced compared with before use (week 0), and the downward trend was significantly better than that of the comparative example 2 group and the blank group, proving that the anti-hair loss and hair growth liquid can effectively prevent hair loss.

[0131] (3) Hair growth effect

[0132] 90 people with hair loss were randomly divided into three groups, namely a blank group, a comparative example group 2, and an example group 2. The hair growth effects of each group were compared after using different hair growth liquids for 1, 2, 3, and 6 months.

[0133] Table 9: Hair growth effect

[0134] Grouping 1 month 2 months 3 months 6 months Blank Group No significant effect No significant effect No significant effect No significant effect Comparative Example 2 No significant effect Ⅰ Ⅱ Ⅲ Example 2 Group Ⅰ Ⅱ Ⅲ Ⅳ

[0135] The experimental results in Table 9 show that the comparative example 2 group can promote hair growth to a certain extent, among which the example 2 group has the best effect. Compared with the blank group and the comparative example 2 group, the example 2 group effectively promotes hair growth. The numbers Ⅰ, Ⅱ, Ⅲ, and Ⅳ in the above table represent the hair growth effect, and the larger the number, the better the effect.

[0136] Example 3

[0137] Biotin tripeptide anti-hair loss efficacy test (human hair papilla cell gene expression detection)

[0138] (1) Experimental methods

[0139] The experiment was designed according to the "Evaluation Standards for Cosmetic Efficacy Claims" and other standards, and the anti-hair loss efficacy of the samples was verified through sample groups, blank controls, negative controls and positive controls. After human hair papilla cells were inoculated in 96-well plates, they were given different treatments, without adding sample solutions or adding sample solutions of different concentrations. After incubation for a period of time, the cell growth and the gene expression of collagen IV, laminin 5, 5α reductase, and transcriptional growth factor-β2 in the cells were detected.

[0140] (2) Correlation between experimental indicators and firming effects

[0141] Increase rate (%) = (AB) / B*100%

[0142] Inhibition rate (%) = (CA) / C*100%

[0143] A: Detection value of sample solution;

[0144] B: Detection value of blank control group solution;

[0145] C: Detection value of negative control group (1 μM DHT);

[0146] The results of this experiment show that the product improves cell viability, promotes the production of collagen IV and laminin, and inhibits the expression of 5α-reductase, androgen receptor, and transcriptional growth factor-β2 genes. If the test sample promotes the upregulation of collagen IV and laminin compared with the model blank control, the expression of 5α-reductase, androgen receptor, and transcriptional growth factor-β2 genes is inhibited, and the improvement of the test product is significantly different from that of the model blank control, it means that the test sample has anti-hair loss effect. The significant difference is statistically analyzed by SPSS software, and when the significance factor P<0.05, it is considered to be significantly different.

[0147] (3) Experimental results

[0148] ① Under normal culture conditions, the growth of human dermal papilla cells is shown in Table 10. Figure 1 Compared with the blank group, the activity of hair papilla cells in the 0.1%, 0.01%, 0.0001% and 0.00001% biotin tripeptide-1 raw material groups increased significantly, with the upregulation rates of 13.08%, 12.15%, 12.49% and 12.55%.

[0149] ② Under normal culture conditions, the test substances affect the expression of collagen Ⅳ gene in human hair papilla cells as shown in Table 11. Figure 2 and Figure 3 Compared with the blank control, the expression of collagen Ⅳ gene in the 0.1%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups was significantly increased, with the up-regulation rates being 73.81%, 57.56% and 42.21%.

[0150] ③ Under normal culture conditions, the test substances affect the expression of laminin 5 gene in human hair papilla cells as shown in Table 12. Figure 4 and Figure 5 Compared with the blank control, the expression of laminin 5 gene in the 0.1%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups was significantly increased, with the up-regulation rates being 77.74%, 57.54 and 42.32.

[0151] ④ The inhibition rate of samples on 5α-reductase is shown in Table 13 and Figure 6 As shown, the 5α-reductase inhibition rates of the 1%, 0.1% and 0.01% biotin tripeptide-1 raw material groups were 50.989%, 30.593% and 17.066%, respectively. The 5α-reductase inhibition rate IC 50 It is 0.456%.

[0152] ⑤ Under DHT stimulation, the test substance's expression level and inhibition rate of androgen receptor (AR) gene in human hair papilla cells are shown in Table 14. Figure 7 and Figure 8 Compared with the negative control, the androgen receptor (AR) gene expression levels in the 0.01%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups were significantly decreased, with inhibition rates of 22.47%, 18.54% and 13.48%.

[0153] ⑥ Under DHT stimulation, the test substances have an effect on the gene expression and inhibition rate of 5α-reductase 2 (SRD5A2) in human hair papilla cells. See Table 15. Fig. 9 and Fig.10 Compared with the negative control, the 5α-reductase 2 (SRD5A2) gene expression levels in the 0.01%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups were significantly decreased, with inhibition rates of 39.47%, 32.02% and 27.63%.

[0154] ⑦ Under DHT stimulation, the test substance's expression level and inhibition rate of transcriptional growth factor-β2 (TGF-β2) gene in human hair papilla cells are shown in Table 16. Fig.11 and Fig.12 Compared with the negative control, the expression of transcriptional growth factor-β2 (TGF-β2) gene in the 0.01% and 0.001% biotin tripeptide-1 raw material groups was significantly decreased, with inhibition rates of 21.35% and 12.92%.

[0155] Table 10: Activity and upregulation rate of human dermal papilla cells

[0156]

[0157] “*” indicates significant difference compared with the blank control group, “*”: p<0.05.

[0158] Table 11: Collagen Ⅳ gene expression in human hair papilla cells

[0159]

[0160] “*” indicates significant difference compared with the blank control group, “**”: p<0.001, “***”: p<0.001.

[0161] Table 12: Expression of laminin 5 gene in human hair papilla cells

[0162]

[0163] “*” indicates significant difference compared with the blank control group, “****”: p<0.0001, “***”: p<0.001.

[0164] Table 13: 5α-reductase inhibition rate statistics

[0165]

[0166]

[0167] Table 14: Androgen receptor (AR) gene expression in human hair papilla cells

[0168]

[0169] “*” indicates significant difference compared with the blank control group, “*”: p<0.05, “**”: p<0.01.

[0170] Table 15: Human hair papilla cell 5α reductase 2 (SRD5A2) gene expression

[0171]

[0172] “*” indicates significant difference compared with the blank control group, “**”: p<0.01, “***”: p<0.001, “****”: p<0.0001.

[0173] Table 16: Expression of human hair papilla cell transcriptional growth factor-β2 (TGF-β2) gene

[0174]

[0175]

[0176] “*” indicates significant difference compared with the blank control group, “*”: p<0.05, “***”: p<0.001.

[0177] (4) Experimental conclusion

[0178] ①Compared with the blank control, the activity of hair papilla cells in the 0.1%, 0.01%, 0.0001% and 0.00001% biotin tripeptide-1 sample groups increased significantly, with the up-regulation rates of 13.08%, 12.15%, 12.49% and 12.55%, respectively, indicating that biotin tripeptide-1 has the ability to promote the proliferation of human papilla cells, and the expression levels of collagen IV gene and laminin 5 in the 0.01%, 0.001% and 0.0001% biotin tripeptide-1 sample groups were significantly increased, with the up-regulation rates of collagen IV gene expression being 73.81%, 57.56% and 42.21%, and the up-regulation rates of laminin 5 gene expression being 77.74%, 57.54% and 42.32%, respectively, indicating that biotin tripeptide-1 has the ability to promote the expression of collagen IV gene and laminin 5 gene in hair papilla cells.

[0179] ② The 5α-reductase inhibition rates of the 1%, 0.1% and 0.01% biotin tripeptide-1 raw material groups were 50.989%, 30.593% and 17.066%, respectively. The 5α-reductase IC 50 Compared with the negative control, the androgen receptor (AR) gene expression in the 0.01%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups decreased significantly, with inhibition rates of 22.47%, 18.54% and 13.48%, respectively, indicating that the raw material has the ability to inhibit the androgen receptor (AR) gene expression in dermal papilla cells stimulated by dihydrotestosterone, and compared with the negative control, the 5α reductase (SRD5A2) gene expression in the 0.01%, 0.001% and 0.0001% biotin tripeptide-1 raw material groups increased significantly. The inhibition rates were 39.47%, 32.02% and 27.63%, indicating that the biotin tripeptide-1 raw material has the ability to inhibit the expression of 5α reductase (SRD5A2) gene in hair papilla cells stimulated by dihydrotestosterone. The expression of transcription growth factor-β2 (TGF-β2) gene in the 0.01% and 0.001% biotin tripeptide-1 raw material groups decreased significantly, with inhibition rates of 21.35% and 12.92%, indicating that the raw material has the ability to inhibit the expression of transcription growth factor-β2 (TGF-β2) gene in hair papilla cells stimulated by dihydrotestosterone. According to the experimental basis and the anti-hair loss mechanism, the above results can be used as one of the evidences to support the claim of the anti-hair loss effect of biotin tripeptide-1 raw material.

[0180] Example 4

[0181] Biotin tripeptide-1 (soothing effect test)

[0182] (1) Experimental methods

[0183] The experiment was designed according to the standard of "T / SHRH 034-2021 Cosmetic Soothing Efficacy Test-In Vitro TNF-α Inflammatory Factor Content Determination of Lipopolysaccharide-Induced Macrophage Inflammatory Cell Model Test Method", and the soothing effect of the product was verified through sample groups, blank controls, negative controls and positive controls. After macrophages were inoculated into 96-well plates and cultured overnight, they were given different treatments, stimulated without adding sample solutions, and incubated for a period of time with sample solutions of different concentrations. The TNF-α content in different samples was detected by TNF-α enzyme-linked immunosorbent assay kit, and finally the absorbance value of each sample well was measured at 450nm using an ELISA instrument.

[0184] (2) Correlation between experimental indicators and moisturizing efficacy

[0185] Inhibition rate (%) = (AB) / A*100%

[0186] A: OD value of negative control group solution;

[0187] B: OD values ​​of LPS+sample groups with different concentrations;

[0188] The results of this experiment are to characterize the inhibition of TNF-α production by biotin tripeptide-1. If the expression of TNF-α in the test sample is decreased compared with the model control, and there is a significant difference between the test product and the model control, it means that the test sample has soothing ability. The significant difference is statistically analyzed by SPSS software. When the significance factor P<0.05, it is considered to be significantly different.

[0189] (3) Experimental results

[0190] Under LPS stimulation culture conditions, the content and inhibition rate of the test substances on the secretion of TNF-α inflammatory factors by macrophages are shown in Table 17. Fig.13 and Fig.14 Compared with the negative control group, the TNF-α inflammatory factor content in the 0.1% and 0.01% sample groups was significantly inhibited, with inhibition rates of 33.684% and 22.233% respectively.

[0191] Table 17: TNF-α content and inhibition rate in macrophages

[0192]

[0193] “*” indicates significant difference compared with the negative control group (LPS group), “**”: p<0.01, and “***”: p<0.0001.

[0194] (4) Experimental conclusion

[0195] Compared with the negative control group, the 0.1% and 0.01% sample groups showed significant inhibition of TNF-α inflammatory factor content, with inhibition rates of 33.684% and 22.233%, indicating that biotin tripeptide-1 has the ability to inhibit the secretion of TNF-α inflammatory factors. Based on the test basis and the skin irritation mechanism, this result can be used as one of the evidences to support the soothing effect claim of biotin tripeptide-1.

[0196] Example 5

[0197] (1) Experimental methods

[0198] The experiment was designed according to the "Specifications for the Evaluation of Cosmetic Efficacy Claims" and other standards. The anti-hair loss efficacy of different raw material samples was verified by testing sample groups with different activities and blank controls. After human hair papilla cells were inoculated in a 96-well plate, they were given different treatments, without adding sample solution, adding sample solutions of different concentrations, and after incubation for a period of time, the expression of collagen IV in the cells was detected.

[0199] (2) Correlation between experimental indicators and firming and anti-hair loss effects

[0200] Increase rate (%) = (AB) / B*100%

[0201] A: Detection value of sample solution;

[0202] B: Detection value of blank control group solution;

[0203] The experimental results show that the sample raw materials can promote the production of collagen IV in human hair papilla cells, and the improvement of the test product is significantly different from that of the model blank control, indicating that the test sample has anti-hair loss effect. The significant difference was statistically analyzed by SPSS software, and when the significance factor P<0.05, it was considered to be significantly different.

[0204] (3) Experimental results

[0205] Under normal culture conditions, the expression levels of collagen Ⅳ gene in human hair papilla cells from different sample groups are shown in Table 18. Fig.15 Compared with the blank control group, the expression of collagen Ⅳ gene in the biotin tripeptide-1 raw material group, Platycladus orientalis leaf extract and tetrahydromethylpyrimidine carboxylic acid group was increased, and the up-regulated expression of collagen Ⅳ in the sample group containing the three active ingredients was higher, ranging from 87.8% to 91.36%.

[0206] Table 18: Collagen Ⅳ gene expression in human hair papilla cells

[0207]

[0208]

[0209] “*” indicates significant difference compared with the blank control group, “***”: p<0.001, “****”: p<0.0001.

[0210] Example 6

[0211] (1) Experimental methods

[0212] The experiment was designed according to the "Specifications for the Evaluation of Cosmetic Efficacy Claims" and other standards. The anti-hair loss efficacy of different raw material samples was verified by testing sample groups with different activities and blank controls. After human hair papilla cells were inoculated in a 96-well plate, they were given different treatments, without adding sample solution or adding sample solutions of different concentrations. After incubation for a period of time, the expression of the laminin 5 gene in the cells was detected.

[0213] (2) Correlation between experimental indicators and anti-hair loss efficacy

[0214] Increase rate (%) = (AB) / B*100%

[0215] A: Detection value of sample solution;

[0216] B: Detection value of blank control group solution;

[0217] The experimental results show that the sample raw materials can promote the production of laminin 5 in human hair papilla cells, and the improvement of the test product is significantly different from that of the model blank control, indicating that the test sample has anti-hair loss effect. The significant difference was statistically analyzed by SPSS software, and when the significance factor P<0.05, it was considered to be significantly different.

[0218] (3) Experimental results

[0219] Under normal culture conditions, the expression levels of laminin 5 gene in human hair papilla cells from different sample groups are shown in Table 19. Fig.16 Compared with the blank control group, the expression of laminin 5 gene in the biotin tripeptide-1 raw material group, Platycladus orientalis leaf extract and tetrahydromethylpyrimidine carboxylic acid group was increased, and the up-regulation rate of laminin 5 gene in the raw material group containing the three active ingredients was higher, ranging from 88.1% to 93.68%.

[0220] Table 19: Expression of laminin 5 gene in human hair papilla cells

[0221]

[0222]

[0223] “*” indicates significant difference compared with the blank control group, “***”: p<0.001, “****”: p<0.0001.

[0224] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of a compound represented by formula (I) or a stereoisomer or a pharmaceutically acceptable salt thereof in the preparation of a product having the effects of preventing hair loss and / or relieving inflammation, Vx-Xaa1-Xaa2-Xaa3 (I) in, Vx is a vitamin or vitamin derivative containing a carboxyl group, Xaa1 is an aliphatic amino acid, a polar amino acid or a neutral amino acid, Xaa2 is an amino acid containing a heterocyclic ring or a basic amino acid; Xaa3 is an aliphatic amino acid or a basic amino acid; The anti-hair loss care comprises: (1) Increase the number of effective hair follicles; and / or (2) Preventing hair loss; and / or (3) increasing the activity of hair papilla cells; and / or (4) Upregulating the expression of collagen IV gene; and / or (5) Upregulating the expression of laminin 5 gene; and / or (6) inhibiting 5α-reductase; and / or (7) down-regulating androgen receptor gene expression; and / or (8) down-regulating 5α-reductase 2 gene expression; and / or (9) down-regulate the expression of transcriptional growth factor-β2 gene; The relief of inflammation includes inhibiting the secretion of TNF-α inflammatory factor.

2. The use according to claim 1, characterized in that The Vx is vitamin H, the Xaa1 is glycine, the Xaa2 is L-histidine, and the Xaa3 is lysine.

3. The use according to claim 1, characterized in that The compound is biotin tripeptide-1.

4. The use according to claim 1, characterized in that The compound accounts for 0.02 wt% to 0.1 wt% of the net weight of the product.

5. A composition, characterized in that Includes biotin tripeptide-1, Thuja orientalis leaf extract and ectoine.

6. The composition according to claim 5, characterized in that In parts by weight, the biotin tripeptide-1 is 0.02 to 0.1 parts, the Platycladus orientalis leaf extract is 1 to 10 parts, and the tetrahydromethylpyrimidine carboxylic acid is 0.1 to 3 parts.

7. A composition, characterized in that Includes Biotinylated Tripeptide-1, Platycladus Orientalis Leaf Extract, and Sodium Hyaluronate.

8. The composition according to claim 7, characterized in that In parts by weight, the biotin tripeptide-1 is 0.02 to 0.1 parts, the Platycladus orientalis leaf extract is 1 to 10 parts, and the sodium hyaluronate is 0.01 to 0.1 parts.

9. Use of the composition according to any one of claims 5 to 8 in the preparation of a product having the effects of preventing hair loss and protecting hair and / or relieving inflammation; The anti-hair loss care comprises: (1) Increase the number of effective hair follicles; and / or (2) Prevent hair loss; and / or (3) increasing the activity of hair papilla cells; and / or (4) Upregulating the expression of collagen IV gene; and / or (5) Upregulating the expression of laminin 5 gene; and / or (6) inhibiting 5α-reductase; and / or (7) down-regulating androgen receptor gene expression; and / or (8) down-regulating 5α-reductase 2 gene expression; and / or (9) down-regulate the expression of transcriptional growth factor-β2 gene; The relief of inflammation includes inhibiting the secretion of TNF-α inflammatory factor.

10. A product, characterized in that The composition comprises the composition according to any one of claims 5 to 8, and acceptable adjuvants or auxiliary agents.

11. The product according to claim 10, characterized in that include: In the composition according to claim 5 or 6, the biotin tripeptide-1 accounts for 0.02wt% to 0.1wt% of the net weight of the product, the Platycladus orientalis leaf extract accounts for 1.0wt% to 10.0wt% of the net weight of the product, and the tetrahydromethylpyrimidine carboxylic acid accounts for 0.1wt% to 3.0wt% of the net weight of the product; or In the composition as claimed in claim 7 or 8, the biotin tripeptide-1 accounts for 0.02wt% to 0.1wt% of the net weight of the product, the Platycladus orientalis leaf extract accounts for 1.0wt% to 10.0wt% of the net weight of the product, and the sodium hyaluronate accounts for 0.01wt% to 0.1wt% of the net weight of the product.

12. The method for preparing the product according to claim 10 or 11, characterized in that: The method comprises the step of mixing the composition according to any one of claims 5 to 8 with an acceptable auxiliary material or adjuvant.

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