Recombinant collagen-ionic liquid composition, and preparation method therefor and use thereof

Abstract

The present invention relates to the technical fields of cosmetics, medical instruments, drugs, and pharmaceutical instruments. Provided are a recombinant collagen-ionic liquid composition, and a preparation method therefor and the use thereof. The recombinant collagen-ionic liquid composition comprises, in parts by mass, 19.8-79.99 parts of a lysine-citric acid ionic liquid, 20-80 parts of glycerol, and 0.01-0.2 parts of recombinant collagen, wherein the lysine-citric acid ionic liquid is essentially composed of lysine and citric acid, and the molar ratio of lysine to citric acid is (4:1)-(1:2). The recombinant collagen-ionic liquid composition exhibits good solubility, a high transdermal efficiency, low irritation, a short preparation cycle, and a simple process.

Description

Recombinant collagen ionic liquid composition, its preparation method and application

[0001] This application claims priority to Chinese Patent Application No. 202411794366.0, filed on December 9, 2024, entitled "Recombinant Collagen Ionic Liquid Composition and its Preparation Method and Application", the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention relates to the fields of cosmetics, medical devices, pharmaceuticals and medical device technologies, and in particular to a recombinant collagen ionic liquid composition, its preparation method and application. Background Technology

[0003] Hair loss is the phenomenon of hair falling out of the scalp. Physiological hair loss is normal hair loss caused by the body's metabolism; pathological hair loss refers to abnormal or excessive hair loss caused by various factors such as genetics, hormonal changes, medical conditions, and nutritional deficiencies, leading to thinning hair or even baldness. Hair loss not only affects personal self-image but can also have a profound impact on psychological and social aspects. Drug treatment is a common method for improving and treating hair loss due to its convenience, ease of use, and sustained effects. Among them, minoxidil and finasteride have been proven to be effective in improving hair loss, but they have problems such as long treatment cycles, adverse reactions (such as rash, headache, hirsutism, lower limb edema, and high blood pressure), and usage limitations (such as finasteride not being suitable for women). Therefore, it is necessary to develop functional ingredients with high safety and few side effects to promote hair growth to make up for the shortcomings of existing methods.

[0004] Studies have shown that hair loss is mainly caused by the aging of hair follicle stem cells. Type 17 collagen (XVII collagen) has high biocompatibility and good efficacy, and is a key molecule in preventing the aging of hair follicle stem cells (Science, 2016, 351, 6273). It can maintain the dry characteristics of hair follicles and promote hair regeneration. Among them, recombinant collagen can be produced on a large scale and with high purity, effectively avoiding the risk of pathogens, and has broad application prospects in the fields of cosmetics and biomedicine. However, recombinant collagen has a relatively large molecular weight and complex structure, making it difficult to penetrate multiple biological barriers in the body. It is easily metabolized and decomposed by gastric acid, enzymes, and enterohepatic circulation. When used to promote hair growth, more attention should be paid to the effective delivery of type 17 collagen to the target skin area to maximize the effect. Microneedling is a common method to improve the transdermal delivery efficiency of large molecular active ingredients such as proteins and peptides, but it is more destructive to the skin and may cause local tissue damage and pain, while also posing risks of cross-infection and allergic reactions. Ionic liquids possess advantages such as strong dissolving power and excellent transdermal absorption. When combined with active ingredients, they can be directly applied to the skin surface to deliver the active ingredients, increasing targeting and reducing adverse reactions, providing a new approach for efficient collagen delivery and hair growth promotion. However, current ionic liquid formulations may have strong irritant and sensitizing properties, resulting in poor skin compatibility. Therefore, there is an urgent need for a system with high transdermal delivery rate and low skin irritation, ensuring efficient transdermal collagen delivery while minimizing allergic reactions and user discomfort.

[0005] Therefore, it is of great significance to provide a method for preparing recombinant collagen ionic liquid compositions that have good protein solubility, high transdermal efficiency, low skin irritation, short preparation cycle, simple process, and can be continuously produced. Summary of the Invention

[0006] The first objective of this invention is to provide a recombinant collagen ionic liquid composition to solve the above-mentioned technical problems.

[0007] A second objective of this invention is to provide a method for preparing the above-mentioned recombinant collagen ionic liquid composition.

[0008] A third objective of this invention is to provide the application of the above-mentioned recombinant collagen ionic liquid composition in promoting hair follicle repair and hair growth.

[0009] To achieve the above objectives, the following technical solution is adopted:

[0010] In a first aspect, the present invention provides a recombinant collagen ionic liquid composition, comprising, by mass parts, 19.8-79.99 parts of lysine citrate ionic liquid, 20-80 parts of glycerol and 0.01-0.2 parts of recombinant collagen;

[0011] The lysine-citric acid ionic liquid is mainly composed of lysine and citric acid, and the molar ratio of lysine to citric acid is (4:1)-(1:2).

[0012] As a further technical solution, by mass fraction, it includes 29.85-49.95 parts of lysine citrate ionic liquid, 50-70 parts of glycerol, and 0.05-0.15 parts of recombinant collagen.

[0013] As a further technical solution, the preparation method of the lysine citric acid ionic liquid includes: mixing lysine, citric acid and water to react, removing water after the reaction is completed, and preparing the lysine citric acid ionic liquid.

[0014] As a further technical solution, the reaction temperature is 25-100℃;

[0015] The reaction time is 12-24 hours.

[0016] As a further technical solution, the method of removing moisture includes vacuum distillation.

[0017] As a further technical solution, the recombinant collagen includes type XVII recombinant collagen.

[0018] As a further technical solution, it also includes 0-30 parts of water by weight.

[0019] Secondly, the present invention provides a method for preparing the above-mentioned recombinant collagen ionic liquid composition, comprising: mixing the various components in the prescribed amounts to prepare the recombinant collagen ionic liquid composition.

[0020] As a further technical solution, the components other than recombinant collagen are mixed first, and then recombinant collagen is added and mixed again.

[0021] Thirdly, the present invention provides the application of the above-mentioned recombinant collagen ionic liquid composition in promoting hair follicle repair and hair growth.

[0022] Fourthly, the present invention provides a method for promoting hair follicle repair, comprising administering the recombinant collagen ionic liquid composition and / or the recombinant collagen ionic liquid composition prepared by the preparation method.

[0023] In some implementations, the method of administration includes one or more of oral, injectable, or topical administration.

[0024] Fifthly, the present invention provides a method for promoting hair growth, comprising administering the recombinant collagen ionic liquid composition and / or the recombinant collagen ionic liquid composition prepared by the preparation method.

[0025] In some implementations, the method of administration includes one or more of oral, injectable, or topical administration.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The recombinant collagen ionic liquid composition provided by this invention mainly consists of a specific ratio of lysine citrate ionic liquid, glycerin, and recombinant collagen. The lysine citrate ionic liquid is a purely natural product with good biocompatibility and safety, and features good skin penetration, non-irritation, and convenient administration. This composition can effectively reduce allergic and irritant reactions in users; it contains hair growth-promoting active ingredients, is easy to use, and can be directly applied to the scalp area for administration, exhibiting strong targeting and high hair regrowth efficiency.

[0028] The method for preparing the recombinant collagen ionic liquid composition provided by this invention has a short preparation cycle, simple process, can be continuously produced, and has low cost. Attached Figure Description

[0029] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0030] Figure 1 shows the 1H NMR spectrum of the lysine citrate ionic liquid;

[0031] Figure 2 shows the 1H NMR spectrum of arginine octanoic acid ionic liquid;

[0032] Figure 3 shows the 1H NMR spectrum of proline citrate ionic liquid;

[0033] Figure 4 shows the lysine citrate ionic liquid;

[0034] Figure 5 shows the recombinant collagen ionic liquid composition;

[0035] Figure 6 shows the hair growth experiment in mice;

[0036] Figure 7 shows the before-and-after comparison of the subjects in Test Example 3 using the recombinant collagen ionic liquid composition;

[0037] Figure 8 shows the before-and-after comparison of the subjects in Test Example 4 using the recombinant collagen ionic liquid composition. Detailed Implementation

[0038] This invention discloses a recombinant collagen ionic liquid composition, its preparation method, and its applications. The embodiments and examples of this invention will be described in detail below. However, those skilled in the art will understand that the following embodiments and examples are for illustrative purposes only and should not be considered as limiting the scope of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without inventive effort are within the scope of protection of this invention. Unless otherwise specified, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0039] In a first aspect, the present invention provides a recombinant collagen ionic liquid composition, mainly composed of lysine citrate ionic liquid, glycerol and recombinant collagen. The mass fraction of lysine citrate ionic liquid can be, for example, but not limited to, 19.8 parts, 40 parts, 60 parts or 79.99 parts.

[0040] The recombinant collagen ionic liquid composition preferably uses glycerol as a solubilizer to improve the dissolution rate of collagen, optimize the color of the composition, and reduce the viscosity of the composition. The mass fraction of glycerol can be, for example, but not limited to, 20 parts, 40 parts, 60 parts, or 80 parts.

[0041] The mass fractions of recombinant collagen can be, for example, but not limited to, 0.01 parts, 0.05 parts, 0.1 parts, 0.15 parts, or 0.2 parts;

[0042] The lysine-citric acid ionic liquid is mainly composed of lysine and citric acid, and the molar ratio of lysine to citric acid can be, for example, but not limited to, 4:1, 3:2, 2:3 or 1:2.

[0043] The recombinant collagen ionic liquid composition provided by this invention can effectively reduce allergic and irritant reactions in users, promote the absorption of recombinant collagen by the scalp, and has a good effect on promoting hair follicle growth and hair growth. In some optional embodiments, by weight, it includes 29.85-49.95 parts of lysine citrate ionic liquid, 50-70 parts of glycerin, and 0.05-0.15 parts of recombinant collagen.

[0044] In some optional embodiments, the preparation method of the lysine citric acid ionic liquid includes: mixing lysine, citric acid and water and reacting them, removing the water after the reaction is completed, and preparing the lysine citric acid ionic liquid.

[0045] The preparation method of this lysine citrate ionic liquid is simple, convenient, and low in cost.

[0046] In some alternative embodiments, the reaction temperature may be, for example, but not limited to, 25°C, 50°C, 75°C, or 100°C;

[0047] The reaction time can be, for example, but is not limited to, 12h, 18h or 24h.

[0048] In some alternative implementations, the method of removing moisture includes, but is not limited to, vacuum distillation, or other methods of removing moisture known to those skilled in the art.

[0049] In some alternative embodiments, the recombinant collagen includes type XVII recombinant collagen.

[0050] In some alternative implementations, the water is also included in parts by weight, ranging from 0 to 30 parts, for example, but not limited to 0, 5, 10, 20, 25, or 30 parts.

[0051] Secondly, the present invention provides a method for preparing the above-mentioned recombinant collagen ionic liquid composition, comprising: mixing the various components in the prescribed amounts to prepare the recombinant collagen ionic liquid composition.

[0052] This preparation method has a short cycle, simple process, can be continuously produced, and has low cost.

[0053] To ensure uniform mixing of raw materials and the solubility and stability of collagen in the composition, in some optional embodiments, the components other than recombinant collagen are mixed first, and then the recombinant collagen is added and mixed.

[0054] Thirdly, the present invention provides the application of the above-mentioned recombinant collagen ionic liquid composition in promoting hair follicle repair and hair growth.

[0055] The recombinant collagen ionic liquid composition provided by this invention can effectively reduce allergic and irritant reactions in users, promote the scalp absorption of recombinant collagen, and has a good effect on promoting hair follicle growth and hair growth.

[0056] Fourthly, the present invention provides a method for promoting hair follicle repair, comprising administering the recombinant collagen ionic liquid composition and / or the recombinant collagen ionic liquid composition prepared by the preparation method.

[0057] In some implementations, the method of administration includes one or more of oral, injectable, or topical administration.

[0058] Fifthly, the present invention provides a method for promoting hair growth, comprising administering the recombinant collagen ionic liquid composition and / or the recombinant collagen ionic liquid composition prepared by the preparation method.

[0059] In some implementations, the method of administration includes one or more of oral, injectable, or topical administration.

[0060] The present invention will be further illustrated below with specific embodiments and comparative examples. However, it should be understood that these embodiments are merely for the purpose of more detailed illustration and should not be construed as limiting the present invention in any way.

[0061] Example 1

[0062] This embodiment provides an amino acid ionic liquid, which is mainly prepared through the following steps:

[0063] Under a nitrogen atmosphere, 0.4 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0064] Dissolve 0.1 mol of citric acid in 50 mL of deionized water, add it dropwise to the reaction vessel and mix well. Stir magnetically at 80 °C for 12 hours.

[0065] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (4:1).

[0066] Example 2

[0067] This embodiment provides an amino acid-based ionic liquid, which is mainly prepared through the following steps:

[0068] Under a nitrogen atmosphere, 0.3 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0069] Dissolve 0.1 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 80 °C for 12 hours.

[0070] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (3:1).

[0071] Example 3

[0072] This embodiment provides an amino acid-based ionic liquid, which is mainly prepared through the following steps:

[0073] Under a nitrogen atmosphere, 0.2 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0074] Dissolve 0.1 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 80 °C for 12 hours.

[0075] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (2:1).

[0076] Example 4

[0077] This embodiment provides an amino acid-based ionic liquid, which is mainly prepared through the following steps:

[0078] Under a nitrogen atmosphere, 0.1 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0079] Dissolve 0.1 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 80 °C for 12 hours.

[0080] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (1:1).

[0081] Example 5

[0082] This embodiment provides an amino acid-based ionic liquid, which is mainly prepared through the following steps:

[0083] Under a nitrogen atmosphere, 0.1 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0084] Dissolve 0.15 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 25 °C for 24 hours.

[0085] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (1:1.5).

[0086] Example 6

[0087] This embodiment provides an amino acid-based ionic liquid, which is mainly prepared through the following steps:

[0088] Under a nitrogen atmosphere, 0.1 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0089] Dissolve 0.2 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 100 °C for 18 hours.

[0090] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (1:2).

[0091] Experiments were conducted to verify the amino acid ionic liquids prepared above. The results showed that ionic liquids were successfully prepared in Examples 1-6. The experimental results of Example 3 are as follows:

[0092] The appearance of the ionic liquid is shown in Figure 4, and its 1H NMR spectrum is shown in Figure 1. The lysine citrate ionic liquid... 1 ¹H NMR spectroscopy revealed signals corresponding to the methylene group at 1.95–1.43 ppm (m, -CH₂), 3.029 ppm (m, -CH₂), and 3.756 ppm (m, -CH₂), and a signal corresponding to the amino group at 7.46 ppm (s, -NH₂), representing the L-lysine fragment. Signals corresponding to the methylene group at 2.757 ppm (q, -CH₂) and 2.662 ppm (q, -CH₂) were observed, indicating citric acid-related fragments. A chemical shift change of 8.51 ppm (s, -COOH) in the carboxyl group of citric acid confirmed the successful synthesis of [L-Lys][CA]. These results indicate the successful preparation of the [L-Lys][CA] ionic liquid.

[0093] Comparative Example 1

[0094] An arginine-octanoic acid ionic liquid (NMR spectrum shown in Figure 2) differs from Example 2 in that lysine is replaced with arginine and citric acid is replaced with octanoic acid.

[0095] Comparative Example 2

[0096] A proline citrate ionic liquid (NMR spectrum shown in Figure 3) differs from Example 2 in that lysine is replaced with proline.

[0097] Comparative Example 3

[0098] An amino acid-based ionic liquid, differing from Example 2 in that citric acid is replaced with butyric acid.

[0099] Example 7

[0100] A recombinant collagen ionic liquid composition is prepared mainly through the following steps:

[0101] Water, glycerol and the amino acid ionic liquid prepared in Example 1 were mixed evenly to obtain a mixed solution. Then, type XVII recombinant collagen was dissolved in the mixed solution and stirred at 30°C for 10 hours to obtain a recombinant collagen ionic liquid composition.

[0102] The mass ratio of water, glycerol, amino acid ionic liquid and type XVII recombinant collagen is 10:70:20:0.1.

[0103] Example 8

[0104] A recombinant collagen ionic liquid composition is prepared mainly through the following steps:

[0105] Water, glycerol and the amino acid ionic liquid prepared in Example 2 were mixed evenly to obtain a mixed solution. Then, type XVII recombinant collagen was dissolved in the mixed solution and stirred at 30°C for 10 hours to obtain a recombinant collagen ionic liquid composition.

[0106] The mass ratio of water, glycerol, amino acid ionic liquid and type XVII recombinant collagen is 5:60:35:0.1.

[0107] Example 9

[0108] A recombinant collagen ionic liquid composition is prepared mainly through the following steps:

[0109] Water, glycerol and the amino acid ionic liquid prepared in Example 3 were mixed evenly to obtain a mixed solution. Then, type XVII recombinant collagen was dissolved in the mixed solution and stirred at 30°C for 10 hours to obtain a recombinant collagen ionic liquid composition.

[0110] The mass ratio of water, glycerol, amino acid ionic liquid and type XVII recombinant collagen is 30:50:19.8:0.2.

[0111] Example 10

[0112] A recombinant collagen ionic liquid composition is prepared mainly through the following steps:

[0113] Glycerol was mixed with the amino acid ionic liquid prepared in Example 2 to obtain a mixed solution. Then, type XVII recombinant collagen was dissolved in the mixed solution and stirred at 30°C for 10 hours to obtain a recombinant collagen ionic liquid composition.

[0114] The mass ratio of glycerol, amino acid ionic liquid and type XVII recombinant collagen is 20:79.99:0.01.

[0115] Example 11

[0116] A recombinant collagen ionic liquid composition is prepared mainly through the following steps:

[0117] Glycerol was mixed with the amino acid ionic liquid prepared in Example 3 to obtain a mixed solution. Then, type XVII recombinant collagen was dissolved in the mixed solution and stirred at 30°C for 10 hours to obtain a recombinant collagen ionic liquid composition.

[0118] The mass ratio of glycerol, amino acid ionic liquid and type XVII recombinant collagen is 80:19.9:0.1.

[0119] Comparative Example 4

[0120] The difference from Example 8 is that the amino acid ionic liquid of Comparative Example 1 is used.

[0121] Comparative Example 5

[0122] The difference from Example 8 is that the amino acid ionic liquid of Comparative Example 2 is used.

[0123] Comparative Example 6

[0124] The difference from Example 8 is that the amino acid ionic liquid of Comparative Example 3 is used.

[0125] Comparative Example 7

[0126] The difference from Example 8 lies in the use of a different amino acid ionic liquid, which is prepared as follows:

[0127] Under a nitrogen atmosphere, 0.1 mol of lysine was added to a round-bottom flask, followed by 50 mL of deionized water. The mixture was stirred thoroughly at 800 rpm.

[0128] Dissolve 0.4 mol of citric acid in 50 mL of deionized water, then add it dropwise to the reaction vessel and mix well. Stir the mixture magnetically at 100 °C for 18 hours.

[0129] After the reaction was complete, most of the water was removed by rotary evaporation at 70°C, and then the residual water was removed by drying in a vacuum oven at 60°C for 48 hours to obtain lysine citrate ionic liquid (1:4).

[0130] Test Example 1

[0131] The effect of the recombinant collagen ionic liquid composition prepared in this invention on promoting hair growth in mice was evaluated. Female C57BL / 6J mice (6-8 weeks old, 18-20g) were selected. Hair on the back was trimmed short with electric clippers. A suitable amount of depilatory cream was evenly applied to the trimmed area to remove residual hair. The area was washed with warm water and dried. The area covered was approximately 3cm × 2cm. The mice were considered clean when the skin on the back was smooth, without any breaks or residual hair. The depilated area and surrounding area were then disinfected with 75% ethanol. Mice with pink skin and telogen effluvium were selected to establish a mouse alopecia model. The next day, the mice were randomly divided into groups of 3: a control group (administered saline), a collagen group (recombinant collagen concentration consistent with Example 8), Example 7-11 groups, and Comparative Examples 4-6 groups. 。 The appearance of the products from Examples 8, 4, 5, and 6 is shown in Figure 5. The drugs were applied to the hair-removed areas on the backs of mice in each group once daily at a dose of 0.5 mL, covering the hair-removed area, for 14 consecutive days. Hair changes in the mice were observed from day 1 to day 21.

[0132] Seven days after administration, the backs of mice in the blank control group remained pink, indicating that the hair follicles were in the resting phase. The backs of mice in the collagen group and the Example 10 group (which had the lowest content of recombinant collagen in the composition) showed a small amount of light gray, indicating that collagen could promote the entry of hair from the resting phase into the growth phase, with a small amount of hair follicle growth. The Example 7, 8, 9, and 11 groups and the Comparative Examples 4-6 groups showed varying degrees of hair follicle growth. Among them, the Comparative Example 6 group had fewer hair follicles in the growth phase. There was no significant difference between the Example 7, 8, and 11 groups and the Comparative Examples 4 and 5 groups. The light gray area on the backs of mice in the Example 9 group was larger and more uniform, mainly due to the higher content of recombinant protein in this composition. After 12 days of drug administration, the skin on the backs of mice in the control group, collagen group, and Example 10 group appeared light gray to gray, with short hair growing in some areas. Among these, the collagen group, Example 10 group, and Comparative Example 6 group were superior to the control group. Examples 7, 8, 9, and 11 groups and Comparative Examples 4 and 5 groups showed better hair growth, with mice appearing dark gray to black. Example 9 group showed the best hair growth. Examples 7, 8, and 11 groups showed no significant difference in hair growth, but were superior to Comparative Examples 4 and 5. Comparative Examples 4 and 5 groups showed no significant difference in hair growth, but were superior to the control group and collagen group. After 14 days of drug administration, the hair of mice in the control group and collagen group was shorter and had not fully recovered to pre-hair loss levels. The hair of some mice in Example 10 group and Comparative Example 6 group returned to normal levels. The hair of mice in Examples 7, 8, 9, and 11 groups and Comparative Examples 4 and 5 groups all returned to normal levels, appearing as dark gray. After discontinuing the drug administration, the mice were observed again. It was found that some mice in the comparative groups 5 and 6 began to lose hair, with sparse hair on their backs, while mice in the examples 7-11 and the comparative group 4 did not experience hair loss. These results indicate that ionic liquids can promote hair growth in mice, but their composition affects the hair growth effect and its persistence. The ionic liquid composition described in this invention (examples 7-11) has a better hair growth promoting effect.

[0133] Test Example 2

[0134] The hair growth-promoting effect of the recombinant collagen ionic liquid composition prepared in this invention was evaluated. Eighty volunteers with hair loss problems, aged 25-55 years, were selected and divided into four groups of 20 each. Each group used the compositions of Comparative Example 4 and Examples 8, 9, and 11 (the pH of Comparative Examples 5 and 7 did not meet the requirements for skin care products (≥pH 4.5) and could not be used in human experiments; the composition of Comparative Example 6 had a strong odor, causing nausea and other reactions in the subjects, and the subjects were unwilling to try it). The compositions were applied once a day for 14 days or more, evenly covering the test area and left on for 15-30 minutes. The results and user experience were evaluated.

[0135] Table 1

[0136] As can be seen from the test results in Table 1, Examples 8, 9, and 11 of the recombinant collagen ionic liquid compositions provided by this invention significantly promote hair growth, with an effectiveness rate of 80% or higher. Compared with Comparative Example 4, Examples 8, 9, and 11 have superior safety and user experience; the subjects' acceptance rate of the composition's odor was 100%, and no adverse reactions occurred during use.

[0137] Test Example 3

[0138] A 45-year-old male used the recombinant collagen ionic liquid composition from Example 8 seven times a week, applying it to the scalp. It was completely absorbed within 15 minutes without pressing. After 14 consecutive days of use, short hairs began to grow and hair density increased (Figure 7).

[0139] Test Example 4

[0140] A 50-year-old woman used the recombinant collagen ionic liquid composition from Example 8 seven times a week, applying it to her scalp. It was completely absorbed within 15 minutes without pressing. After 60 days of continuous use, her hair loss significantly improved and her hair density significantly increased (Figure 8).

[0141] The results above show that the recombinant collagen ionic liquid composition provided by the present invention has good solubility, high transdermal efficiency, low irritation, short preparation cycle, simple process, and can be continuously produced. The ionic liquid composition and its preparation method are of great significance.

[0142] The recombinant collagen ionic liquid composition, its preparation method, and its applications provided by this invention have been described in detail above. Specific examples have been used to illustrate the principles and implementation methods of this invention. The descriptions of the above embodiments are merely for the purpose of helping to understand the method and core ideas of this invention. It should be noted that those skilled in the art can make various improvements and modifications to this invention without departing from its principles, and these improvements and modifications also fall within the protection scope of the claims of this invention.

Claims

1. A recombinant collagen ionic liquid composition, characterized in that, By weight, it includes 19.8-79.99 parts of lysine citrate ionic liquid, 20-80 parts of glycerol, and 0.01-0.2 parts of recombinant collagen; The lysine-citric acid ionic liquid is mainly composed of lysine and citric acid, and the molar ratio of lysine to citric acid is (4:1)-(1:2).

2. The recombinant collagen ionic liquid composition of claim 1, wherein, By weight, it includes 29.85-49.95 parts of lysine citrate ionic liquid, 50-70 parts of glycerol, and 0.05-0.15 parts of recombinant collagen.

3. The recombinant collagen ionic liquid composition of claim 1, wherein, The preparation method of the lysine citric acid ionic liquid includes: mixing lysine, citric acid and water and reacting them; after the reaction is completed, removing the water to prepare the lysine citric acid ionic liquid.

4. The recombinant collagen ionic liquid composition of claim 3, wherein, The reaction temperature is 25-100℃; The reaction time is 12-24 hours.

5. The recombinant collagen ionic liquid composition of claim 3, wherein, The method of removing moisture includes vacuum distillation.

6. The recombinant collagen ionic liquid composition of claim 1, wherein, The recombinant collagen includes type XVII recombinant collagen.

7. The recombinant collagen ionic liquid composition of claim 1, wherein, It also includes 0-30 parts water by weight.

8. A process for the preparation of the recombinant collagen ionic liquid composition according to any one of claims 1 to 7, characterized in that, include: After mixing the various components in the formula, a recombinant collagen ionic liquid composition is prepared.

9. The preparation method according to claim 8, characterized in that, First, mix all the components except the recombinant collagen, then add the recombinant collagen and mix again.

10. The use of the recombinant collagen ionic liquid composition according to any one of claims 1-7 in promoting hair follicle repair and hair growth.

11. A method of promoting hair follicle repair, characterized in that, This includes the recombinant collagen ionic liquid composition according to any one of claims 1-7 and / or the recombinant collagen ionic liquid composition prepared by the preparation method according to claim 8 or 9.

12. A method of promoting hair growth, characterized by, This includes the recombinant collagen ionic liquid composition according to any one of claims 1-7 and / or the recombinant collagen ionic liquid composition prepared by the preparation method according to claim 8 or 9.

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