Acid dissolution method of palmitoyl peptide and application of palmitoyl peptide in transparent aqueous skin care product

Abstract

The invention relates to the technical field of cosmetic active ingredients, in particular to a palmitoyl peptide acid dissolution method and application of the palmitoyl peptide acid dissolution method in a transparent aqueous skin care product, and the palmitoyl peptide acid dissolution method comprises the following steps: S1, adding palmitoyl peptide powder into an acid aqueous solution with the pH value of less than or equal to 4.0, and stirring to dissolve until the palmitoyl peptide powder is completely transparent to obtain a first solution; and S2, adding an alkaline regulator into the first solution, and raising the pH value to 4.0-4.5 to obtain the palmitoyl peptide acidic concentrated solution. The reversible dissolution characteristic of palmitoyl peptide under the acidic condition is never disclosed in the prior art, stable existence of the palmitoyl peptide under the physiological pH is never realized by a strategy of first acid dissolution and then callback, and the method overcomes the technical prejudice existing in the field for a long time, and hydrophobic peptide cannot be stabilized in a transparent aqueous system.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of cosmetic active ingredients, in particular to a palmitoyl peptide acidic dissolution method and its application in transparent lotion skin care products. BACKGROUND

[0002] Palmitoyl peptides (such as palmitoyl pentapeptide-4, palmitoyl tripeptide-5, etc.) are widely used in skin care products due to their excellent anti-wrinkle and collagen production promotion effects. However, the palmitoyl long chain in its molecular structure leads to extremely low water and oil solubility. In the prior art:

[0003] Cream emulsion system: can only be added by dispersion suspension method, the appearance is milky white, the peptide exists in the form of solid particles, resulting in low skin absorption rate and insufficient bioavailability.

[0004] Transparent system (skin care water, serum, freeze-dried powder): precipitates immediately after addition, and cannot realize a transparent and stable system.

[0005] The prior art uses methods such as liposome wrapping and organic solvent solubilization, but there are risks of toxicity, high cost and destruction of system transparency. There is no solution to achieve high-concentration dissolution in conventional skin care products with pH 4.5-7.0. SUMMARY

[0006] The purpose of the present application is to provide a palmitoyl peptide acidic dissolution method and its application in transparent lotion skin care products, solving the problem that there is no solution to achieve high-concentration dissolution in conventional skin care products with pH 4.5-7.0 in the prior art.

[0007] To solve the above technical problems, the first technical solution adopted by the present application is:

[0008] A palmitoyl peptide acidic dissolution method, comprising the following steps: step S1, adding palmitoyl peptide powder to an acidic aqueous solution with pH≤4.0, stirring and dissolving until completely transparent to obtain a first solution; step S2, adding an alkaline adjusting agent to the first solution to increase the pH to 4.0-4.5 to obtain a palmitoyl peptide acidic concentrate.

[0009] Further technical solutions are that the stirring condition in step S1 is at room temperature, and the stirring rate is 300-1000 r / min.

[0010] Further technical solutions are that the acidic aqueous solution in step S1 is one or more of an acetic acid aqueous solution, a hydrochloric acid aqueous solution, a citric acid aqueous solution, and a lactic acid aqueous solution.

[0011] Further technical solutions are that the pH of the acidic aqueous solution in step S1 is 2.0-3.5.

[0012] Further, the step S2 is stirring when the alkaline regulator is added, and the stirring rate is 300-1000 r / min.

[0013] Further, the alkaline regulator is one or more of sodium hydroxide solution, triethanolamine and arginine.

[0014] Further, the concentration of the peptide in the first solution in the step S1 is 10-1000 ppm.

[0015] Further, the palmitoyl peptide is one or more of palmitoyl pentapeptide-4, palmitoyl tripeptide-5, palmitoyl hexapeptide-12 and palmitoyl tripeptide-38.

[0016] The second technical solution adopted by the present application is:

[0017] The application of a palmitoyl peptide acidic concentrate in a transparent water-based skin care product, characterized in that the palmitoyl peptide acidic concentrate obtained by the palmitoyl peptide acidic dissolving method in any one of claims 1-8 is added to the transparent skin care product base at 0.1-20 wt%.

[0018] Further, the transparent skin care product base is one of cosmetic water, essence, freeze-dried powder mother liquor and shampoo.

[0019] Compared with the prior art, the present application has the following advantages: 1. Breakthrough in solubility limit, achieve 500 ppm level solubility under the condition of pH 4.5, more than 50 times higher than the traditional method; 2. Maintain transparency, the final product transmittance > 90%, solve the problem of precipitation; 3. Improve bioavailability, molecular state peptide is more easily absorbed by the skin, and the efficacy is greatly improved; 4. Strong process compatibility, can be directly added to the existing transparent product production line; 5. The reversible solubility characteristics of palmitoyl peptide under acidic conditions have never been disclosed in the prior art, and the method of realizing its stable existence under physiological pH by adjusting the pH after acid dissolution has never been proposed, which overcomes the long-standing technical bias in the field that hydrophobic peptides cannot be stable in transparent aqueous systems. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical scheme and advantages of the present application more clear, the present application will be further described in detail below with examples. It should be understood that the specific examples described herein are only used to explain the present application, and are not used to limit the present application.

[0021] Example 1:

[0022] A palmitoyl peptide acid dissolution method, comprising the following steps, step S1, adding palmitoyl peptide powder into an acidic aqueous solution with pH≤4.0, stirring and dissolving until completely transparent to obtain a first solution; step S2, adding an alkaline adjusting agent to the first solution to increase the pH to 4.0-4.5 to obtain a palmitoyl peptide acid concentrate.

[0023] The stirring condition in the step S1 is normal temperature, and the stirring rate is 300-1000 r / min.

[0024] The acidic aqueous solution in the step S1 is one or more of an aqueous glacial acetic acid solution, an aqueous hydrochloric acid solution, an aqueous citric acid solution, and an aqueous lactic acid solution.

[0025] The pH of the acidic aqueous solution in the step S1 is 2.0-3.5.

[0026] The stirring rate is 300-1000 r / min when the alkaline adjusting agent is added in the step S2.

[0027] The alkaline adjusting agent is one or more of a sodium hydroxide solution, triethanolamine, and arginine.

[0028] The peptide concentration in the first solution in the step S1 is 10-1000 ppm.

[0029] The palmitoyl peptide is one or more of palmitoyl pentapeptide-4, palmitoyl tripeptide-5, palmitoyl hexapeptide-12, and palmitoyl tripeptide-38.

[0030] Dissolution mechanism analysis

[0031] Protonation (physical dissolution dominated)

[0032] Protonation of N-terminal amino group and side chain group:

[0033] In a strong acidic environment (pH≤4.0), the free amino group (-NH2) at the N-terminal of the peptide chain and the basic group (such as the ε-amino group of lysine and the guanidino group of arginine) of the side chain of the palmitoyl peptide will combine with H⁺ to form positively charged ammonium ions (-NH3⁺). This protonation:

[0034] Significantly increases the hydrophilicity of the molecule, and destroys the hydrophobic aggregation effect of the palmitoyl long chain;

[0035] Prevents hydrophobic accumulation between peptide molecules through charge repulsion, and promotes its dispersion and dissolution.

[0036] Stability of amide bond: the amide bond (-CO-NH-) of the palmitoyl peptide does not usually hydrolyze and break in strong acid (higher acid concentration or heating conditions are required), so the dissolution process is mainly physical change.

[0037] Solvation effect of palmitoyl

[0038] The polar environment of a strong acid (such as glacial acetic acid) may aid dissolution by:

[0039] The acid molecules form hydrogen bonds with the carbonyl group (C=O) of the palmitoyl group, temporarily weakening the crystallization tendency of the hydrophobic chain;

[0040] Acidic solutions with high ionic strength reduce the hydrophobic interactions of peptide molecules.

[0041] Reversible protonation (non-covalent change)

[0042] The protonation process is a typical acid-base equilibrium reaction (-NH2 + H⁺ ⇌ -NH3⁺). When the pH is adjusted, H⁺ is released, restoring the neutral amino group. This process is completely reversible and does not destroy the covalent structure of the peptide.

[0043] Assessment of potential side effects

[0044] Risk of amide bond hydrolysis: This may occur under extreme conditions (such as pH < 1.0, high temperature), but the present invention controls the pH to ≥ 2.0 and operates at room temperature, so hydrolysis can be ignored (HPLC verification shows no change in peptide purity before and after dissolution).

[0045] Palmitoyl shedding:

[0046] The amide bond (-CO-NH-) between the palmitoyl group and the peptide chain is stable under acidic conditions and can only be broken by heating with a strong acid (such as 6M HCl). No depalmitoylation product was detected under the conditions of the present invention.

[0047] Experimental verification methods

[0048] To confirm the non-destructive nature of the dissolution process, the following methods were used for verification:

[0049] HPLC-MS analysis:

[0050] The retention time and molecular weight of the palmitoyl peptides before and after dissolution were compared to confirm the absence of degradation products.

[0051] Security assurance of technical solutions

[0052] Stability after pH adjustment:

[0053] When the pH rises, although some amino groups are deprotonated, the counterions (such as acetate) in the system inhibit the aggregation of peptide molecules through charge shielding and maintain the dissolved state.

[0054] Final product safety:

[0055] The final pH value of skin care products (4.5-6.0) is consistent with the physiological environment of the skin, and palmitoyl peptides exist in a molecular state to avoid particle irritation.

[0056] Conclusion

[0057] The solubilization of palmitoyl peptide in strong acid mainly depends on reversible protonation and solvation effect, without irreversible reactions such as amide bond rupture or palmitoyl group shedding. This characteristic enables it to exist stably in transparent skin care products through the "acidic solubilization-pH adjustment" strategy, and it is a safe and reliable physical solubilization method.

[0058] Example 2:

[0059] Application of a palmitoyl peptide acidic concentrate in a transparent water-based skin care product, characterized in that the palmitoyl peptide acidic concentrate obtained by the palmitoyl peptide acidic solubilization method according to any one of claims 1-8 is added to the transparent skin care product base at 0.1-20 wt%.

[0060] The transparent skin care product base is one of a cosmetic water, an essence, a lyophilized powder mother liquor, and a shampoo.

[0061] Example 3:

[0062] Comparative Example 1:

[0063] Solubilization reagent (two cases): 5%, 10% butanediol aqueous solution.

[0064] Target peptide: palmitoyl pentapeptide-4 (50 ppm).

[0065] Operation: rapid stirring (500-1000 r / min) for 5-10 minutes, homogenization for 1 minute.

[0066] Phenomenon: the system is turbid, and insoluble substances can be seen with the naked eye after standing for a few minutes.

[0067] Conclusion: palmitoyl peptide is difficult to dissolve in this system.

[0068] Comparative Example 2:

[0069] Solubilization reagent (two cases): 0.5%, 2% Tween-20 aqueous solution.

[0070] Target peptide: palmitoyl pentapeptide-4 (50 ppm).

[0071] Operation: rapid stirring (500-1000 r / min) for 5-10 minutes, homogenization for 1 minute.

[0072] Phenomenon: the system is turbid, and insoluble substances can be seen with the naked eye after standing for a few minutes.

[0073] Conclusion: palmitoyl peptide is difficult to dissolve in this system.

[0074] Comparative Example 3:

[0075] Dissolution reagent (one example): (2% Tween-20, 20% butylene glycol) in water.

[0076] Target peptide: Palmitoyl pentapeptide-4 (50 ppm).

[0077] Procedure: Rapid stirring (500-1000 r / min) for 5-10 minutes, homogenization for 1 minute.

[0078] Observation: The system was microemulsified, and a small amount of insoluble substance was observed to precipitate after 24 hours.

[0079] Conclusion: The palmitoyl peptide was partially dissolved in this system, but the solubilizing capacity was limited.

[0080] While the application has been described with reference to numerous exemplary embodiments thereof, it will be understood that various other modifications can be made within the spirit and scope of the application. More particularly, various modifications can be made to the embodiments of the subject combination layout in terms of the constituent components and / or layout thereof, without departing from the scope and spirit of the application. In addition to those modifications already described, other modifications will become apparent to those skilled in the art, which are intended to fall within the scope of the application.

Claims

1. A palmitoyl peptide acidic dissolution method, characterized in that, The method comprises the following steps: step S1, adding palmitoyl peptide powder into an acidic aqueous solution with a pH value of ≤4.0, stirring and dissolving the mixture until the mixture is completely transparent, thereby obtaining a first solution; Step S2, adding an alkaline regulator to the first solution to raise the pH to 4.0-4.5 to obtain a palmitoyl peptide acidic concentrate.

2. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The stirring conditions in step S1 are room temperature and a stirring rate of 300-1000 r / min.

3. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The acidic aqueous solution in step S1 is one or more of glacial acetic acid aqueous solution, hydrochloric acid aqueous solution, citric acid aqueous solution, and lactic acid aqueous solution.

4. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The pH of the acidic aqueous solution in step S1 is 2.0-3.

5.

5. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: When adding the alkaline regulator in step S2, stirring is performed at a stirring rate of 300-1000 r / min.

6. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The alkaline regulator is one or more of sodium hydroxide solution, triethanolamine and arginine.

7. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The peptide concentration in the first solution in step S1 is 10-1000 ppm.

8. A palmitoyl peptide acidic dissolution method according to claim 1, characterized in that: The palmitoyl peptide is one or more of palmitoyl pentapeptide-4, palmitoyl tripeptide-5, palmitoyl hexapeptide-12, and palmitoyl tripeptide-38.

9. Application of a palmitoyl peptide acid concentrate in a transparent aqueous skin care product, characterized in that: The palmitoyl peptide acid concentrate obtained by the palmitoyl peptide acid dissolution method according to any one of claims 1 to 8 is added to a transparent skin care product matrix at a concentration of 0.1-20 wt%.

10. Use of a palmitoyl peptide acid concentrate according to claim 9 in a transparent aqueous skin care product, characterized in that: The transparent skin care product matrix is ​​one of lotion, essence, freeze-dried powder mother solution and shampoo.