High-transdermal recombinant protein peptide as well as preparation method and application thereof

Collagen is solved by increasing hydrogen bonding with betaine succinate and pyrrolidone carboxylate madine salt in recombinant protein peptides, combining the oil-phase environment of acetylhexapeptide-8 and arginine/lysine polypeptides The problem of insufficient transdermal properties achieves efficient skin absorption and long-lasting moisturizing effects, reducing costs.

CN119074582AInactive Publication Date: 2024-12-06广州博士派生物科技有限公司
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Patent Information

Application Number
CN202411193348.7
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-08-28
Publication Date
2024-12-06
Estimated Expiration
Not applicable · inactive patent

AI Technical Summary

Technical Problem

In terms of transdermal properties, existing recombinant collagen has problems such as difficult to penetrate the skin's stratum corneum and too small molecular weight, resulting in rapid metabolism, and the high cost of genetic engineering technology limits its wide application.

Method used

Betaine succinate and pyrrolidone carboxylate madine salt are used as eutectic solvents to generate through the Brownest acid-base reaction, increasing the number of hydrogen bonds to improve the transdermal properties of collagen, and acetyl hexapeptide- 8. The arginine/lysine polypeptide is used as the oil phase, combined with betaine succinate and matrine pyrrolidone carboxylate as the aqueous phase to form a highly transdermal recombinant protein peptide.

Benefits of technology

Improve the transdermality and absorption utilization of collagen, enhance the interaction with the skin extracellular matrix, reduce competition with water, prolong the residence time of peptides in the skin, improve the skin environment, and reduce external stimulation Effects on the skin.

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Abstract

The invention relates to a high-transdermal recombinant protein peptide as well as a preparation method and application thereof, and belongs to the technical field of protein peptides. The recombinant protein peptide is prepared from the following raw materials in parts by mass: 1 to 4 parts of acetyl hexapeptide-8, 3 to 6 parts of arginine / lysine polypeptide, 20 to 30 parts of succinic acid betaine salt, 10 to 20 parts of pyrrolidone carboxylic acid matrine salt, 5 to 10 parts of grease, 5 to 10 parts of vegetable oil, 1 to 4 parts of emulsifier and 200 to 300 parts of water. The quantity of hydrogen bonds is increased by adding the succinic acid betaine salt and the pyrrolidone carboxylic acid sophocarpidine salt, so that the transdermal property of the collagen can be improved.
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Description

Technical Field

[0001] The present invention relates to the technical field of protein peptides, and in particular to a highly transdermal recombinant protein peptide and a preparation method and application thereof. Background Art

[0002] The peptide mixture between protein and amino acid is formed by the disintegration and rupture of collagen molecular chains through hydrolysis. Its relative molecular mass distribution is wide, generally ranging from several hundred to several thousand. Its absorbability, solubility, and water absorption are better than collagen. The difference between "transdermal absorption" of cosmetics and drugs is reflected in the fact that the functional ingredients of cosmetics are ultimately aimed at accumulating and acting on the skin layer, and do not need to enter the systemic circulation.

[0003] The main drawbacks of recombinant collagen containing peptides in terms of transdermal properties include that its large molecular size makes it difficult to penetrate the stratum corneum of the skin, making it difficult to exert a deep skin care effect. In addition, if the molecular weight is too small, the molecular structure of collagen may be broken down into amino acid fragments, losing its original efficacy and being easily metabolized quickly. The common use of genetic engineering technology to generate collagen with high transdermal properties may face high cost issues. Due to the complex genetic manipulation and production process involved, its synthesis cost is relatively high, which may limit its widespread application. Summary of the invention

[0004] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a highly transdermal recombinant protein peptide and its preparation method and application. The addition of a transdermal penetration enhancer can effectively improve the absorption and utilization of collagen, and the raw materials of the transdermal penetration enhancer are all common ingredients, which are cheap and easily available.

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] In the first aspect, the present invention provides a highly transdermal recombinant protein peptide, comprising the following raw materials in parts by weight: 1 to 4 parts of acetyl hexapeptide-8, 3 to 6 parts of arginine / lysine polypeptide, 20 to 30 parts of succinic acid betaine salt, 10 to 20 parts of pyrrolidone carboxylic acid matrine salt, 5 to 10 parts of fats and oils, 5 to 10 parts of vegetable oils, 1 to 4 parts of emulsifiers, and 200 to 300 parts of water; the pyrrolidone carboxylic acid matrine salt is generated by a Bronsted acid-base reaction of pyrrolidone carboxylic acid and matrine; the succinic acid betaine salt is generated by a Bronsted acid-base reaction of succinic acid and betaine.

[0007] Both succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt are deep eutectic solvents (DES) generated by Bronsted acid-base reaction of corresponding acids and bases. Bronsted acid-base reaction is a chemical reaction based on proton transfer, in which the acid is a proton (H +) donors, and bases are proton acceptors. This reaction can increase the number of hydrogen bonds because the hydrogen bonding ability of molecules or ions is increased during the formation and transformation of Brønsted acid-base pairs.

[0008] Betaine is used as a hydrogen bond acceptor (HBA) and succinic acid is used as a hydrogen bond donor (HB) to generate succinic acid betaine salt; similarly, matrine is used as a hydrogen bond acceptor (HBA) and pyrrolidone carboxylic acid is used as a hydrogen bond donor (HB) to generate pyrrolidone carboxylic acid matrine salt, so succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt contain a large amount of hydrogen bonds, which have stronger intermolecular forces than unreacted acids and bases, and are more likely to form associations with the skin. The present invention helps to improve the transdermal properties of collagen by adding succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt to increase the number of hydrogen bonds, because this can enhance the interaction between collagen and the extracellular matrix of the skin. Increasing protein-ligand binding affinity through hydrogen bond pairing can reduce competition with water, thereby enhancing receptor-ligand interaction.

[0009] Pyrrolidone carboxylic acid, the raw material of pyrrolidone carboxylic acid matrine salt, is a common transdermal penetration enhancer that can preferentially interact with skin barrier lipids and reduce the overall chain order without causing lipid extraction, thereby improving transdermal efficiency. Matrine has multiple pharmacological activities, including anti-inflammatory and antioxidant effects, which help reduce oxidized low-density lipoproteins and advanced glycation end products, thereby helping to improve the skin environment and create favorable conditions for transdermal absorption of collagen.

[0010] As a commonly used solvent ingredient, succinic acid helps other active ingredients to disperse and penetrate better, improves the stability and efficacy of the product, and also has an excellent moisturizing and water-locking effect, can effectively absorb and retain moisture in the air, and provide a lasting moisturizing effect for the skin. Betaine has an excellent moisturizing effect, can absorb and retain moisture, enhance the skin's hydration capacity, and maintain the skin's moisturizing state for a long time. It can also improve the pH value of the skin surface, enhance the skin's resistance, reduce the impact of external stimuli on the skin, and reduce skin sensitivity, redness, and dryness and itching.

[0011] Specifically, the preparation method of the pyrrolidone carboxylic acid matrine salt comprises the following steps:

[0012] Pyrrolidone carboxylic acid and matrine are mixed in an aqueous solution, reacted at 85-95° C. for 7-10 hours, and refluxed after the reaction to obtain the pyrrolidone carboxylic acid matrine salt. The specific preparation process is as follows:

[0013]

[0014] Preferably, the mass ratio of pyrrolidone carboxylic acid to matrine is (1.1-1.5):1.

[0015] Specifically, the preparation method of the succinic acid betaine salt comprises the following steps:

[0016] Succinic acid and betaine are mixed in an aqueous solution, reacted at 30-40° C. for 7-9 hours, and the product is taken out, washed, and dried to obtain the succinic acid betaine salt. The specific preparation process is as follows:

[0017]

[0018] More preferably, the mass ratio of succinic acid to betaine is 1:(1.2-1.5).

[0019] Preferably, the emulsifier is at least one of wax alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20, and steareth-20.

[0020] Preferably, the vegetable oil is at least one of olive oil and jojoba oil.

[0021] Preferably, the oil is at least one of octyldodecyl myristate, avocado butter, and caprylic / capric triglyceride;

[0022] Preferably, the oil is a composition of octyldodecyl myristate, avocado butter, and caprylic / capric triglyceride in a mass ratio of (12-15):(3-6):1.

[0023] In a second aspect, the present invention provides a method for preparing the highly transdermal recombinant protein peptide, comprising the following steps:

[0024] S1: mixing oil, vegetable oil, emulsifier, acetyl hexapeptide-8, and arginine / lysine polypeptide to obtain an oil phase; mixing the betaine succinate salt, pyrrolidone carboxylic acid matrine salt, and water to obtain an aqueous phase;

[0025] S2: stirring and mixing the oil phase and the water phase to obtain the highly transdermal recombinant protein peptide.

[0026] The present invention uses acetyl hexapeptide-8 and arginine / lysine polypeptide as the oil phase, and the oil phase environment increases the lipophilicity of these polypeptides, thereby helping them to penetrate the lipid bilayer of the stratum corneum of the skin. The oil phase environment can also provide a more stable environment for the polypeptides, protecting them from the influence of the external environment (such as moisture and oxygen), thereby maintaining their structure and biological activity. The oil phase as a carrier can achieve the sustained release of the polypeptide, reduce its rapid evaporation or degradation on the skin surface, and thus increase the time window for transdermal absorption.

[0027] Penetration enhancers such as betaine succinate and matrine pyrrolidone carboxylic acid can increase hydrophilicity in the aqueous phase, and this balance helps the permeability of peptides in the skin. By adding penetration enhancers to the aqueous phase, the lipid arrangement of the stratum corneum can be disturbed, increasing its fluidity, thereby reducing the diffusion resistance of the drug.

[0028] Preferably, in a third aspect, the present invention provides use of the highly transdermal recombinant protein peptide in the preparation of cosmetics.

[0029] Compared with the prior art, the present invention has the following beneficial effects:

[0030] (1) The highly transdermal recombinant protein peptide of the present invention is mainly improved in transdermal property by adding betaine succinate and matrine pyrrolidone carboxylate. Betaine succinate and matrine pyrrolidone carboxylate are both low eutectic solvents prepared from hydrogen bond donors and hydrogen bond acceptors, which contain a large number of hydrogen bonds and have stronger intermolecular forces than unreacted acids and bases. They are more likely to form associations with the skin, which helps to improve the transdermal property of collagen because it can enhance the interaction between collagen and the extracellular matrix of the skin, improve the protein-ligand binding affinity through hydrogen bond pairing, and reduce competition with water, thereby enhancing the receptor-ligand interaction.

[0031] (2) The preparation method of the recombinant protein peptide of the present invention is to use acetyl hexapeptide-8 and arginine / lysine polypeptide as the oil phase. The oil phase environment will increase the lipophilicity of these polypeptides, thereby helping them to penetrate the lipid bilayer of the stratum corneum of the skin, while penetration enhancers such as betaine succinate and matrine pyrrolidone carboxylic acid salt can increase the hydrophilicity in the aqueous phase. This balance helps the permeability of the polypeptide in the skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is the nuclear magnetic resonance spectrum of betaine succinate;

[0033] Figure 2 This is the nuclear magnetic resonance spectrum of pyrrolidone carboxylic acid matrine salt. DETAILED DESCRIPTION

[0034] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0035] The sources of the reagents and products used in the following examples and comparative examples are as follows:

[0036] Acetyl hexapeptide-8: The manufacturer is Jiangsu Qianzhusong Biotechnology Co., Ltd., the brand number is QS02074;

[0037] Arginine / lysine peptide: the manufacturer is Jiangsu Qianzhusong Biotechnology Co., Ltd., brand number is QS02094;

[0038] Succinic acid: The manufacturer is Shanghai Yien Chemical Technology Co., Ltd., the brand is R014935, the purity is AR, 99.5%;

[0039] Betaine: The manufacturer is Shanghai Yien Chemical Technology Co., Ltd., brand number 1079620, purity 98%;

[0040] Pyrrolidone carboxylic acid: The manufacturer is Shanghai Yien Chemical Technology Co., Ltd., the brand is R010948, the purity is 98%;

[0041] Matrine: The manufacturer is Shanghai MacLean Biochemical Technology Co., Ltd., the brand is M813524, the purity is 98%;

[0042] Artificial membrane: Strat-M TM Skin-specific membrane, manufactured by Merck Millipore Corporation of the United States;

[0043] Hydroxyproline (Hyp) standard: manufacturer is Sigma-Aldrich (Shanghai) Trading Co., Ltd.

[0044] Unless otherwise specified, other materials, reagents, etc. used in the examples and comparative examples can be obtained from commercial sources.

[0045] Example 1

[0046] A highly transdermal recombinant protein peptide, comprising the following raw materials in parts by mass: 2 parts of acetyl hexapeptide-8, 5 parts of arginine / lysine polypeptide, 25 parts of succinic acid betaine salt, 15 parts of pyrrolidone carboxylic acid matrine salt, 8 parts of fat, 7 parts of vegetable oil, 3 parts of emulsifier, and 245 parts of water; wherein the emulsifier is a composition of glyceryl stearate, PEG-75 stearate, and cetyl alcohol polyether-20 in a mass ratio of 1:1:1. The vegetable oil is a composition of olive oil and jojoba oil in a mass ratio of 1::1. The oil is a composition of octyldodecyl myristate, avocado tree butter, and caprylic / capric triglyceride in a mass ratio of 13:5:1;

[0047] Wherein, the preparation method of pyrrolidone carboxylic acid matrine salt comprises the following steps:

[0048] Pyrrolidone carboxylic acid and matrine in a mass ratio of 1.2:1 were mixed in an aqueous solution, reacted at 90°C for 8 hours, and refluxed after the reaction. The obtained product was tested by nuclear magnetic resonance (NMR) spectroscopy. Figure 1 As shown, it was compared with pyrrolidone carboxylic acid and matrine respectively, and the product was determined to be pyrrolidone carboxylic acid matrine salt.

[0049] The preparation method of the succinic acid betaine salt comprises the following steps:

[0050] Succinic acid and betaine in a mass ratio of 1:1.3 were mixed in an aqueous solution and reacted at 35°C for 8 hours. The product was taken out, washed, and dried. The obtained product was tested by nuclear magnetic resonance (NMR) spectroscopy. Figure 2 As shown, it was compared with succinic acid and betaine respectively, and the product was determined to be succinic acid betaine salt.

[0051] The method for preparing the highly transdermal recombinant protein peptide comprises the following steps:

[0052] S1, mixing fat, vegetable oil, emulsifier, acetyl hexapeptide-8, and arginine / lysine polypeptide to obtain an oil phase; mixing the succinic acid betaine salt, pyrrolidone carboxylic acid matrine salt and water to obtain an aqueous phase;

[0053] S2. Stirring and mixing the oil phase and the water phase to obtain the highly transdermal recombinant protein peptide, wherein the stirring and mixing temperature is 55° C., the stirring and mixing speed is 2500 rpm / min, and the stirring and mixing time is 6 min.

[0054] Example 2

[0055] A highly transdermal recombinant protein peptide comprises the following raw materials in parts by weight: 1 part of acetyl hexapeptide-8, 3 parts of arginine / lysine polypeptide, 20 parts of succinic acid betaine salt, 10 parts of pyrrolidone carboxylic acid matrine salt, 5 parts of fat, 5 parts of vegetable oil, 1 part of emulsifier and 200 parts of water; wherein the emulsifier is steareth-20. The vegetable oil is jojoba oil. The fat is avocado tree fat.

[0056] Wherein, the preparation method of pyrrolidone carboxylic acid matrine salt comprises the following steps:

[0057] Pyrrolidone carboxylic acid and matrine are mixed in an aqueous solution, reacted at 85° C. for 10 hours, and refluxed after the reaction to obtain the pyrrolidone carboxylic acid matrine salt, wherein the mass ratio of the pyrrolidone carboxylic acid to matrine is 1.1:1.

[0058] The preparation method of the succinic acid betaine salt comprises the following steps:

[0059] Succinic acid and betaine are mixed in an aqueous solution, reacted at 30° C. for 9 hours, and the product is taken out, washed, and dried to obtain the succinic acid betaine salt, wherein the mass ratio of succinic acid to betaine is 1:1.2.

[0060] The method for preparing the highly transdermal recombinant protein peptide comprises the following steps:

[0061] S1, mixing fat, vegetable oil, emulsifier, acetyl hexapeptide-8, and arginine / lysine polypeptide to obtain an oil phase; mixing the succinic acid betaine salt, pyrrolidone carboxylic acid matrine salt and water to obtain an aqueous phase;

[0062] S2. Stirring and mixing the oil phase and the water phase to obtain the highly transdermal recombinant protein peptide, wherein the stirring and mixing temperature is 50° C., the stirring and mixing speed is 2000 rpm / min, and the stirring and mixing time is 10 min.

[0063] Example 3

[0064] A highly transdermal recombinant protein peptide comprises the following raw materials in parts by weight: 4 parts of acetyl hexapeptide-8, 6 parts of arginine / lysine polypeptide, 30 parts of succinic acid betaine salt, 20 parts of pyrrolidone carboxylic acid matrine salt, 10 parts of fat, 10 parts of vegetable oil, 4 parts of emulsifier, and 300 parts of water; wherein the emulsifier is PEG-75 stearate. The vegetable oil is olive oil. The fat is octyldodecyl myristate and caprylic / capric triglyceride in a mass ratio of 1:1.

[0065] Wherein, the preparation method of pyrrolidone carboxylic acid matrine salt comprises the following steps:

[0066] Pyrrolidone carboxylic acid and matrine are mixed in an aqueous solution, reacted at 95° C. for 7 hours, and refluxed after the reaction to obtain the pyrrolidone carboxylic acid matrine salt, wherein the mass ratio of the pyrrolidone carboxylic acid to matrine is 1.5:1.

[0067] The preparation method of the succinic acid betaine salt comprises the following steps:

[0068] Succinic acid and betaine are mixed in an aqueous solution, reacted at 40° C. for 7 hours, and the product is taken out, washed, and dried to obtain the succinic acid betaine salt, wherein the mass ratio of succinic acid to betaine is 1:1.5.

[0069] The method for preparing the highly transdermal recombinant protein peptide comprises the following steps:

[0070] S1, mixing fat, vegetable oil, emulsifier, acetyl hexapeptide-8, and arginine / lysine polypeptide to obtain an oil phase; mixing the succinic acid betaine salt, pyrrolidone carboxylic acid matrine salt and water to obtain an aqueous phase;

[0071] S2. Stirring and mixing the oil phase and the water phase to obtain the highly transdermal recombinant protein peptide, wherein the stirring and mixing temperature is 60° C., the stirring and mixing speed is 2000 rpm / min, and the stirring and mixing time is 5 min.

[0072] Example 4

[0073] The difference between Example 4 and Example 1 is that Example 4 adds 20 parts of betaine succinate and 20 parts of matrine pyrrolidonecarboxylate.

[0074] Example 5

[0075] The difference between Example 5 and Example 1 is that: Example 5 adds 27 parts of betaine succinate and 13 parts of matrine pyrrolidonecarboxylate.

[0076] Comparative Example 1

[0077] The difference between Comparative Example 1 and Example 1 is that no succinic acid betaine salt is added in Comparative Example 1.

[0078] Comparative Example 2

[0079] The difference between Comparative Example 2 and Example 1 is that: in Comparative Example 2, no succinic acid betaine salt is added, and only equal amounts of succinic acid and betaine are added.

[0080] Comparative Example 3

[0081] The difference between Comparative Example 3 and Example 1 is that: Comparative Example 3 does not add betaine succinate salt, but only adds matrine succinate salt, and its preparation method is similar to that of betaine succinate salt, except that betaine is replaced by matrine.

[0082] Comparative Example 4

[0083] The difference between Comparative Example 4 and Example 1 is that: Comparative Example 4 does not add pyrrolidone carboxylic acid matrine salt.

[0084] Comparative Example 5

[0085] The difference between Comparative Example 5 and Example 1 is that: in Comparative Example 5, pyrrolidone carboxylic acid matrine salt is not added, and only equal amounts of pyrrolidone carboxylic acid and matrine are added.

[0086] Comparative Example 6

[0087] The difference between Comparative Example 6 and Example 1 is that: Comparative Example 6 does not add pyrrolidone carboxylic acid matrine salt, but only adds an equal amount of pyrrolidone carboxylic acid betaine salt, and its preparation method is similar to that of pyrrolidone carboxylic acid matrine salt, except that matrine is replaced by betaine.

[0088] Comparative Example 7

[0089] The difference between Comparative Example 7 and Example 1 is that: Comparative Example 7 does not add fats, vegetable oils and emulsifiers, that is, no oil phase components are set, and acetyl hexapeptide-8 and arginine / lysine polypeptide are directly mixed with other components to prepare an aqueous phase solution.

[0090] Performance Testing

[0091] Transdermal test method

[0092] The artificial membrane is directly fixed between the sample pool and the receiving pool. The sample pool contains 10% collagen peptide saline solution, and saline is used as a blank control. The receiving pool is filled with saline to a capacity of 17 mL, and constant stirring and constant temperature are maintained. The water bath temperature is 37±0.5℃ and the speed is 300r / min. 1 mL of sample is taken at 4, 8, and 24 hours, and an equal amount of saline is added at the same time. The mass concentration of Hyp in the extracted liquid is determined, and the cumulative permeation amount per unit area (Qn) and the transdermal rate constant (J) are calculated according to the following formula:

[0093]

[0094] Where: C n ——Hyp mass concentration measured at the nth sampling point, μg / mL;

[0095] C i ——Hyp mass concentration measured at the i-th sampling point, μg / mL;

[0096] 10——Conversion coefficient of Hyp and collagen peptide;

[0097] V——the capacity of the receiving pool, which is 17mL;

[0098] V0——the volume taken at each time point, 1 mL;

[0099] A——penetration area, 1.54cm 2 ;

[0100]

[0101] Cumulative transmission Q n Linear regression is performed on time t, and the slope of the resulting equation is the transdermal rate constant J, in units of μg / cm 2 / h.

[0102] Table 1 Cumulative permeation amount and transdermal rate constant data of samples in each group

[0103]

[0104] As shown in Table 1, when the peptide content is the same, the skin permeation rates of Comparative Examples 1 and 4 are significantly reduced when no succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt are added, respectively, indicating that succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt are important factors affecting the transdermal peptide.

[0105] Comparative Example 2 does not add succinic acid betaine salt, but only adds equal amounts of succinic acid and betaine, and its transdermal effect is also reduced. This is because although succinic acid and betaine can play a penetration effect, since a large number of hydrogen bonds are not generated through reaction, its transdermal effect is significantly reduced. Comparative Example 3 is succinic acid matrine salt. Although succinic acid and matrine can also undergo Bronsted acid-base reaction to generate succinic acid matrine salt, it can be seen from the data that its transdermal property is also lower than that of Example 1, indicating that the succinic acid betaine salt generated by succinic acid and betaine has a synergistic effect with pyrrolidone carboxylic acid matrine salt, which can significantly promote the transdermal absorption performance of the product.

[0106] Similarly, in Comparative Example 5, pyrrolidone carboxylic acid matrine salt is not added, and only an equal amount of pyrrolidone carboxylic acid and matrine are added. Pyrrolidone carboxylic acid is a common transdermal penetration enhancer, but its transdermal effect is still not as good as that of pyrrolidone carboxylic acid matrine salt, indicating that a large number of hydrogen bonds generated by the Bronsted acid-base reaction can significantly promote its transdermal effect. Comparative Example 6 does not add pyrrolidone carboxylic acid matrine salt, and only an equal amount of pyrrolidone carboxylic acid betaine salt is added, but its transdermal rate is reduced, indicating that the transdermal effect of pyrrolidone carboxylic acid matrine salt is better than that of pyrrolidone carboxylic acid betaine salt, and it has a synergistic effect with succinic acid betaine salt, which can significantly promote the transdermal absorption performance of the product.

[0107] Comparative Example 7 is to directly mix the ingredients, and its transdermal performance is reduced, indicating that the present invention uses acetyl hexapeptide-8 and arginine / lysine polypeptide as oil phase, and the oil phase environment will increase the lipophilicity of these polypeptides, thereby helping them to penetrate the lipid bilayer of the stratum corneum of the skin. The oil phase can achieve the sustained release of the polypeptide as a carrier, reduce its rapid evaporation or degradation on the skin surface, thereby increasing the time window of transdermal absorption. And penetration enhancers such as succinic acid betaine salt and pyrrolidone carboxylic acid matrine salt can increase hydrophilicity in the aqueous phase, and this balance helps the permeability of the polypeptide in the skin. By adding a penetration enhancer in the aqueous phase, the lipid arrangement of the stratum corneum can be disturbed, and its fluidity can be increased, thereby reducing the diffusion resistance of the drug.

[0108] In summary, the recombinant protein peptide of the present invention improves the transdermal property of the composite polypeptide by adding betaine succinate salt and matrine pyrrolidone carboxylic acid salt, and also broadens its application range in cosmetics.

[0109] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A highly transdermal recombinant protein peptide, characterized in that: The invention comprises the following raw materials in parts by weight: 1 to 4 parts of acetyl hexapeptide-8, 3 to 6 parts of arginine / lysine polypeptide, 20 to 30 parts of succinic acid betaine salt, 10 to 20 parts of pyrrolidone carboxylic acid matrine salt, 5 to 10 parts of fat, 5 to 10 parts of vegetable oil, 1 to 4 parts of emulsifier, and 200 to 300 parts of water; The preparation method of the pyrrolidone carboxylic acid matrine salt comprises the following steps: Mixing pyrrolidone carboxylic acid and matrine in an aqueous solution, reacting at 85-95° C. for 7-10 hours, and refluxing after the reaction to obtain the pyrrolidone carboxylic acid matrine salt; The preparation method of the succinic acid betaine salt comprises the following steps: Succinic acid and betaine are mixed in an aqueous solution, reacted at 30-40° C. for 7-9 hours, and the product is taken out, washed, and dried to obtain the succinic acid betaine salt.

2. The highly transdermal recombinant protein peptide according to claim 1, characterized in that: The mass ratio of pyrrolidone carboxylic acid to matrine is (1.1-1.5):

1.

3. The highly transdermal recombinant protein peptide according to claim 1, characterized in that: The mass ratio of succinic acid to betaine is 1:(1.2-1.5).

4. The highly transdermal recombinant protein peptide according to claim 1, characterized in that: The emulsifier is at least one of wax alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20, and steareth-20.

5. The highly transdermal recombinant protein peptide according to claim 1, characterized in that: The vegetable oil is at least one of olive oil and jojoba oil.

6. The highly transdermal recombinant protein peptide according to claim 1, characterized in that: The oil is at least one of octyldodecyl myristate, avocado butter, and caprylic / capric triglyceride; 7. The highly transdermal recombinant protein peptide according to claim 1 or 6, characterized in that: The oil is a composition of octyldodecyl myristate, avocado butter, and caprylic / capric triglyceride in a mass ratio of (12-15):(3-6):

1.

8. The method for preparing a highly transdermal recombinant protein peptide according to any one of claims 1 to 7, characterized in that: The following steps are involved: S1, mixing fat, vegetable oil, emulsifier, acetyl hexapeptide-8, and arginine / lysine polypeptide to obtain an oil phase; mixing the succinic acid betaine salt, pyrrolidone carboxylic acid matrine salt and water to obtain an aqueous phase; S2. Stirring and mixing the oil phase and the water phase to obtain the highly transdermal recombinant protein peptide.

9. The method for preparing a highly transdermal recombinant protein peptide according to claim 8, characterized in that: In the step S2, the stirring and mixing temperature is 50-60°C, the stirring and mixing speed is 2000-3000 rpm / min, and the stirring and mixing time is 5-10 min.

10. Use of the highly transdermal recombinant protein peptide according to any one of claims 1 to 7 in the preparation of cosmetics.

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