CN116687786A - A kind of supramolecular myristoyl pentapeptide-4 and its preparation method and application - Google Patents

Abstract

The invention discloses a supermolecule myristoyl pentapeptide-4 and a preparation method and application thereof, wherein the method comprises the following steps: placing the L-carnitine taurine ionic liquid in a water bath under an inert atmosphere, and adding myristoyl pentapeptide-4 into the L-carnitine taurine ionic liquid to obtain a mixed solution; and (3) carrying out ultrasonic stirring, homogenizing and dialysis on the mixed solution to obtain the supermolecule myristoyl pentapeptide-4. The invention adopts the L-carnitine taurine ionic liquid as a carrier, combines with myristoyl pentapeptide-4 to carry out supermolecular modification to obtain the supermolecular myristoyl pentapeptide-4, which not only can improve the permeability of skin, but also can ensure that the effects of the myristoyl pentapeptide-4 on repairing, breaking prevention and skin nourishing of the hair can be further exerted on the basis of the original effects of protecting the hair and the skin of the L-carnitine and the taurine, thereby greatly improving the bioavailability and enhancing the application effect.

Description

A kind of supramolecular myristoyl pentapeptide-4 and its preparation method and application

technical field

The invention relates to the technical field of cosmetic compounds, in particular to a supramolecular myristoyl pentapeptide-4 and its preparation method and application.

Background technique

Myristoyl Pentapeptide-4 is a compound polypeptide that can effectively stimulate the synthesis of hair keratin by activating keratin gene, so as to promote eyelash growth and make hair thicker and tougher. Clinical trials have shown that using a care product containing 10% eyelash peptide solution, applied to the eyelashes once a day, after six weeks, the eyelashes will grow and thicken by 71%. In addition, Myristoyl Pentapeptide-4 also has the effect of nourishing the skin. Myristoyl pentapeptide-4 is a long-chain fatty acyl myristic acid connected to pentapeptide-4, which can prevent peptide degradation, change the hydrophilic-lipophilic balance of peptide compounds, improve the surface activity of peptides, and help Because of the emulsification effect, but its permeability becomes poor, and more peptides stay on the skin surface, so it is urgent to use ionic liquids with penetration-promoting ability to form supramolecules with myristoyl pentapeptide-4 to increase its permeability and make it Fully functioning.

Therefore, the prior art still needs to be improved and developed.

Contents of the invention

In view of the above-mentioned deficiencies in the prior art, the object of the present invention is to provide a supramolecular myristoyl pentapeptide-4 and its preparation method and application, aiming at solving the problem of myristoyl pentapeptide-4 transdermal penetration efficiency in the prior art low problem.

The technical scheme that the present invention adopts for solving the problems of the technologies described above is as follows:

A preparation method of supramolecular myristoyl pentapeptide-4, comprising the steps of:

Under an inert atmosphere, the L-carnitine taurine ionic liquid was placed in a water bath at a preset temperature, and myristoyl pentapeptide-4 was added to the L-carnitine taurine ionic liquid to obtain a mixed solution. The mixed solution was ultrasonically stirred, homogenized and dialyzed to obtain the supramolecular myristoyl pentapeptide-4.

The preparation method of the supramolecular myristoyl pentapeptide-4, wherein the mass ratio of the L-carnitine taurine ionic liquid to the myristoyl pentapeptide-4 is (5:1)~(1 :5).

The preparation method of supramolecular myristoyl pentapeptide-4, wherein the inert gas is nitrogen or argon.

The preparation method of supramolecular myristoyl pentapeptide-4, wherein, the preset temperature is 25-35°C.

The preparation method of supramolecular myristoyl pentapeptide-4, wherein, the stirring speed of the stirring is 500-700 rad/min, and the stirring time is 16-24 hours.

The preparation method of the supramolecular myristoyl pentapeptide-4, wherein the frequency of the ultrasound is 20-40kHz, the power of the ultrasound is 800-2000W, the time of the ultrasound is 4-12h, and the intermittent time For every interval of 1~5s, ultrasound 2~10s.

The preparation method of described supramolecular myristoyl pentapeptide-4, wherein, the homogeneous pressure is 10 ~ 80MPa, the homogeneous flow is 30 ~ 60 L/h, and the homogeneous number of times is 1~3 times.

The preparation method of the supramolecular myristoyl pentapeptide-4, wherein, the dialysis adopts a cellulose dialysis bag, the molecular weight of the cellulose dialysis bag is 1000, the time of dialysis is 2~6h, and the number of dialysis is 1 ~3 times.

A supramolecular myristoyl pentapeptide-4, which is prepared by the preparation method as described in the above scheme of the present invention.

An application of supramolecular myristoyl pentapeptide-4 as described in the above scheme of the present invention in the preparation of cosmetics.

Beneficial effects: the invention discloses a supramolecular myristoyl pentapeptide-4 and its preparation method and application. In order to solve the problem of poor permeability of polypeptides, the invention uses L-carnitine taurine ionic liquid as a carrier, and Acyl pentapeptide-4 is combined for supramolecular modification to obtain supramolecular myristoyl pentapeptide-4. After forming a supramolecular, the permeability of myristoyl pentapeptide-4 is improved, so as to better exert myristoyl pentapeptide Efficacy of peptide-4. Myristoyl pentapeptide-4 is a long-chain fatty acyl myristic acid connected to pentapeptide-4. Although it changes the hydrophilic-lipophilic balance of the peptide compound and improves the surface activity of the peptide, its permeability becomes poor. , Peptides stay more on the skin surface. L-carnitine taurine ionic liquid is combined with myristoyl pentapeptide-4 for supramolecular modification, the amino groups in L-carnitine and the hydroxyl groups in taurine attract each other, and form L-carnitine taurine through ionic bonds The sulfonic acid ionic liquid, the amino group in the ionic liquid and the carboxyl group in myristyl pentapeptide-4 are attracted to each other to generate hydrogen offset to form supramolecular myristoyl pentapeptide-4. L-carnitine taurine ionic liquids enhance transdermal transcellular and decellularized transport, bypass the barrier of the stratum corneum (SC), disrupt cell integrity, and act by opening tight junctions within the SC, primarily by enhancing muscle The intracellular fluidization of myristoyl pentapeptide-4 promotes paracellular transport, thereby enhancing the ability of myristoyl pentapeptide-4 to permeate the skin. Therefore, the supramolecular myristoyl pentapeptide-4 prepared by the method of the present invention can improve the permeability of the skin, so that it can further exert the effect of nutmeg on the basis of the original hair care and skin nourishing effects of L-carnitine and taurine. Acyl pentapeptide-4 has the effect of repairing, preventing breakage and nourishing the skin, which greatly improves its bioavailability and enhances the application effect.

Description of drawings

Fig. 1 is a flow chart of a preferred embodiment of the preparation method of supramolecular myristoyl pentapeptide-4 provided by the present invention.

Fig. 2 is the H NMR spectrum of L-carnitine taurine ionic liquid in Example 1 of the present invention.

Fig. 3 is the two-dimensional NMR NOESY spectrum of supramolecular myristoyl pentapeptide-4 in Example 1 of the present invention.

Fig. 4 is the transdermal penetration statistics of the samples of the embodiment of the present invention at different time points.

Fig. 5 is the cuticle test result of Example 1 of the present invention.

Fig. 6 is a comparative graphic analysis diagram of the dry combing property of the hair tress after using the test sample and the control sample.

Fig. 7 is a graphical analysis diagram of the comparison of the breaking load of the hair bundle after using the test sample and the control sample.

Detailed ways

In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only It is a part of embodiments of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts belong to the protection scope of the present invention.

Those skilled in the art can understand that, unless otherwise defined, all terms (including technical terms and scientific terms) used herein have the same meaning as commonly understood by those of ordinary skill in the art to which this invention belongs. It should also be understood that terms, such as those defined in commonly used dictionaries, should be understood to have meanings consistent with their meaning in the context of the prior art, and unless specifically defined as herein, are not intended to be idealized or overly Formal meaning to explain.

Myristoyl pentapeptide-4 is a long-chain fatty acyl myristic acid connected to pentapeptide-4, which can prevent peptide degradation, change the hydrophilic-lipophilic balance of peptide compounds, improve the surface activity of peptides, and help Emulsification, but its permeability becomes poor, and more polypeptides stay on the skin surface. Therefore, it is urgent to use ionic liquids with penetration-promoting ability to form supramolecules with myristoyl pentapeptide-4 to solve the problem of poor permeability of polypeptides.

Based on this, the present invention provides a kind of preparation method of supramolecular myristoyl pentapeptide-4, see Fig. 1, it comprises steps:

S10. Under an inert atmosphere, place the L-carnitine taurine ionic liquid in a water bath at a preset temperature, and add myristoyl pentapeptide-4 to the L-carnitine taurine ionic liquid to obtain a mixed solution;

S20. Perform ultrasonic stirring, homogenization, and dialysis on the mixed solution to obtain the supramolecular myristoyl pentapeptide-4.

Specifically, myristoyl pentapeptide-4 can stimulate hair keratin synthesis by activating keratin genes, thereby promoting eyelash growth, making hair thicker and tougher, and also has the effect of nourishing the skin; L-carnitine and taurine are also often used Used in hair care and nourishing products, in which L-carnitine can enhance cell energy, up-regulate the expression of the main components of extracellular matrix, and increase skin tension and elasticity, so it is often used in hair care and skin care, while taurine can increase IGF The production of -1 growth factor, which can act on the human hair cycle, thereby prolonging the growth period and producing thick and strong hair, so taurine has the functions of repairing damaged hair, increasing the production of hair growth factors and promoting hair growth ability.

Myristoyl pentapeptide-4 is a long-chain fatty acyl myristic acid connected to pentapeptide-4. Although it changes the hydrophilic-lipophilic balance of the peptide compound and improves the surface activity of the peptide, its permeability becomes poor. , Peptides stay more on the skin surface. After L-carnitine taurine ionic liquid is combined with myristoyl pentapeptide-4 for supramolecular modification to form supramolecules, under the action of L-carnitine taurine ionic liquid, the tight junction in the stratum corneum is opened, thereby promoting The paracellular transport of myristoyl pentapeptide-4 can enhance the transdermal penetration of myristoyl pentapeptide-4. Therefore, the supramolecular myristoyl pentapeptide-4 prepared by the method of the present invention can improve the permeability of the skin, so that it can further exert the effect of nutmeg on the basis of the original hair care and skin nourishing effects of L-carnitine and taurine. Acyl pentapeptide-4 has the effect of repairing, preventing breakage and nourishing the skin, which greatly improves its bioavailability and enhances the application effect.

Optionally, the mass ratio of the L-carnitine taurine ionic liquid to the myristoyl pentapeptide-4 is (5:1) to (1:5), and the L-carnitine taurine ion The mass ratio of the liquid and the myristoyl pentapeptide-4 is controlled within this range, which can make synergistic effect between the L-carnitine taurine ionic liquid and the myristoyl pentapeptide-4. Hair and skin nourishing effect, as well as hair repairing and anti-breakage effect are the best.

Optionally, the inert gas is nitrogen or argon, which can prevent the generation of by-products.

Optionally, the preset temperature is 25~35°C; the stirring speed is 500~700rad/min, and the stirring time is 16~24h; the ultrasonic frequency is 20~40kHz, and the ultrasonic power is 800 ~2000W, ultrasonic time is 4~12h, intermittent time is 1~5s every interval, ultrasonic 2~10s. Under the above conditions, the reaction between L-carnitine taurine ionic liquid and myristoyl pentapeptide-4 is more complete, and the supramolecular myristoyl pentapeptide-4 can be synthesized through the reaction.

Optionally, the homogeneous pressure is 10-80MPa, the homogeneous flow rate is 30-60 L/h, and the number of homogenization is 1-3 times; the dialysis adopts a cellulose dialysis bag, and the cellulose The molecular weight of the dialysis bag is 1000, the dialysis time is 2~6h, and the dialysis frequency is 1~3 times. The reaction rate can be increased and the yield of supramolecular myristoyl pentapeptide-4 can be increased by homogeneous treatment under the above conditions, and the separation and purification of the product can be realized by performing dialysis treatment under the above conditions, supramolecular myristoyl pentapeptide-4 The molecular weight of myristoyl pentapeptide-4, L-carnitine, and taurine are all less than 1000, so the substances that do not form supramolecular myristoyl pentapeptide-4 can be dialyzed to the outside of the dialysis bag, while in Only the supramolecular myristoyl pentapeptide-4 is left inside the dialysis bag, so that the supramolecular myristoyl pentapeptide-4 can reach a higher purity, and then the supermolecular myristoyl pentapeptide-4 can be used to the greatest extent in hair care and hair care. Benefits in skin nourishment.

The present invention also provides a supramolecular myristoyl pentapeptide-4, which is prepared by the preparation method described in the above scheme of the present invention.

The present invention also provides an application of supramolecular myristoyl pentapeptide-4 as described in the above scheme of the present invention in the preparation of cosmetics such as water, milk, essence, ointment, cream, and aqueous solution.

The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the drawings in the embodiments of the present invention. Apparently, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments, and are only intended to illustrate the present invention but not to limit the present invention. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without creative efforts fall within the protection scope of the present invention.

Example 1

Under the action of nitrogen, 3 g of L-carnitine taurine ionic liquid was placed in a water bath at 25° C., and 1 g of myristoyl pentapeptide-4 was added to the L-carnitine taurine ionic liquid to obtain a mixed solution; The mixed solution is ultrasonically stirred and homogenized, wherein the stirring rate is 700rad/min, the stirring time is 18h, the ultrasonic frequency is 30kHz, the ultrasonic power is 1000W, the ultrasonic time is 6h, the intermittent time is ultrasonic 5s every 2s, and the homogenization pressure It is 50MPa, the flow rate of homogenization is 40 L/h, and the number of homogenization is 3 times. After 18 hours of reaction, a cellulose dialysis bag with a molecular weight of 1000 was used for dialysis, the dialysis time was 6 hours, and the number of dialysis was 3 times, so as to obtain supramolecular myristoyl pentapeptide-4.

The L-carnitine taurine ionic liquid in Example 1 was characterized by one-dimensional hydrogen nuclear magnetic resonance (1H-NMR), and _D2O was selected as the test solvent in the experiment. The results are shown in Figure 2, and the data are as follows: H1 NMR ( 700 MHz, D ₂ O) δ 4.86 –4.81 (m, 1H), 3.69 (dd, J = 8.8, 4.2 Hz, 4H), 3.52 (dd, J = 8.9, 4.3 Hz, 2H),3.51 – 3.48 (m , 9H), 2.70 (qd, J =15.4, 6.7 Hz, 2H). The H NMR spectrum shows that L-carnitine and taurine exist in a molecular ratio of 1:1 in the L-carnitine taurine ionic liquid.

The supramolecular myristoyl pentapeptide-4 prepared in Example 1 was characterized by two-dimensional NMR (NOESY spectrum), and DMSO was selected as the test solvent in the experiment. Figure 3 is the two-dimensional NMR NOESY spectrum of supramolecular myristoyl pentapeptide-4. It can be clearly seen that L-carnitine taurine ionic liquid and myristoyl pentapeptide-4 are in (H1 3.2 ppm, H2 2.1 ppm) and (H1 2.1 ppm, H2 3.2 ppm) have relevant points. The correlation point (cross peak) of the NOESY spectrum means that the protons of the two groups are close to each other in space, indicating that there is an interaction between L-carnitine taurine ionic liquid and myristoyl pentapeptide-4, and there is a hydrogen bond. That is, the supramolecular myristoyl pentapeptide-4 is formed.

Comparative example 1

A supramolecular myristoyl pentapeptide-4 (2) is provided, which is different from the preparation process in Example 1 in that the mass of the L-carnitine taurine ionic liquid is 5 g.

Comparative example 2

A supramolecular myristoyl pentapeptide-4 (3) is provided. The difference from the preparation process in Example 1 is that the mass of L-carnitine taurine ionic liquid is 1 g, and the mass of myristoyl pentapeptide-4 is 5g.

Comparative example 3

A supramolecular myristoyl pentapeptide-4 (4) is provided. The difference from the preparation process in Example 1 is that the mass of L-carnitine taurine ionic liquid is 7 g, and the mass of myristoyl pentapeptide-4 is 1g.

Comparative example 4

A supramolecular myristoyl pentapeptide-4 (5) is provided. The difference from the preparation process in Example 1 is that the mass of L-carnitine taurine ionic liquid is 1 g, and the mass of myristoyl pentapeptide-4 is 7g.

test case 1

Prepare 4% supramolecular myristoyl pentapeptide-4 solution and 1% myristoyl pentapeptide-4 solution. -4 experimental group and supramolecular myristoyl pentapeptide-4 control group, the above solution was tested for transdermal effect, the specific test method is:

I. Use the back skin of suckling pigs, carefully peel off the subcutaneous fat layer and connective tissue, rinse with normal saline, and place in normal saline for later use.

II. The Franz cell method was used to conduct transdermal experiments. The exposed skin area in the diffusion cell in the Franz diffusion device was 1.13 cm ² , and the volume of the receptor chamber was 15 mL.

III. Take 1mL of the experimental group and control group prepared above, respectively, and place it on the exposed skin surface in the diffusion cell as the drug solution to be tested, add 15mL of physiological saline receiving solution into the receiving cell, and place it in a constant temperature water bath at 37±1°C , the stirring speed is 300rad/min.

IV. Subcutaneous sample collection: Take 1mL of the receiving solution at 2, 4, 8, 16, and 24 hours, add 1mL of the receiving solution to the receiving chamber immediately after sampling, and collect the sample at 24 hours.

V. After filtering through a 0.22 μm microporous membrane, it is detected by high performance liquid chromatography (HPLC).

The calculation formula of permeation per unit volume is as formula (1):

(1)

In the formula: P: penetration per unit volume; V: receiving fluid volume in the receiving chamber, 15 mL; V ₀ : volume of each sampling, 1.0 mL; Ci: drug concentration in the receiving fluid from the 1st to n-1 sampling ; Cn: sample concentration measured at the nth sampling point.

The results are shown in Figure 4. After 24 hours of permeation through the skin, based on the content of myristoyl pentapeptide-4, the supramolecular myristoyl pentapeptide-4 experimental group and the supramolecular myristoyl pentapeptide-4 control group The volume permeation volume was 0.18 and 0.07 μg/mL respectively, and the permeation volume per unit volume of myristoyl pentapeptide-4 in the supramolecular myristoyl pentapeptide-4 experimental group was 2.57 times that of the supramolecular myristoyl pentapeptide-4 control group , the results showed that supramolecular myristoyl pentapeptide-4 has a better permeation ability than myristoyl pentapeptide-4, indicating that L-carnitine taurine ionic liquid has a permeation-promoting effect on myristoyl pentapeptide-4.

Supramolecular myristoyl pentapeptide-4 (2), supramolecular myristoyl pentapeptide-4 (3), supramolecular myristoyl pentapeptide-4 (4), supramolecular myristoyl pentapeptide-4 (4), supramolecular Myristoyl pentapeptide-4 (5) was tested for transdermal effect according to the above method, and compared with the supramolecular myristoyl pentapeptide-4 prepared in Example 1, the test results are shown in Table 1:

Table 1 Penetration effect statistics

As shown in Table 1, the permeation per unit volume of supramolecular myristoyl pentapeptide-4 and supramolecular myristoyl pentapeptide-4 (2)~(5) were 0.18, 0.16, 0.14, 0.08, 0.07 μg/ mL, when the mass ratio of L-carnitine taurine ionic liquid to myristoyl pentapeptide-4 is within (5:1)~(1:5), the penetration per unit volume is higher, and the mass ratio is (5:1 )~(1:5) The permeation per unit volume is low. Therefore, the mass ratio of (5:1)~(1:5) to prepare supramolecular myristoyl pentapeptide-4 can effectively improve the transdermal penetration of myristoyl pentapeptide-4.

test case 2

Prepare 4% supramolecular myristoyl pentapeptide-4 solution and 1% myristoyl pentapeptide-4 solution, both of which have the same content of myristoyl pentapeptide-4. According to [Group Standard T/SHFCA Cosmetics Stability Guidelines], under different temperature conditions of freezing (-20°C), cold storage (5°C), high temperature (45°C), light, and cold and hot cycle conditions, the L-carnitine cattle were investigated. The effect of sulfonic acid ionic liquid on improving the stability of myristoyl pentapeptide-4, the results are shown in Table 2: Compared with myristoyl pentapeptide-4, the supramolecular myristoyl pentapeptide-4 has a longer half-life, better physicochemical The nature is more stable.

Table 2 Statistics of stability results of myristoyl pentapeptide-4 and supramolecular myristoyl pentapeptide-4

Test case 3

Prepare 4% supramolecular myristoyl pentapeptide-4 solution and 1% myristoyl pentapeptide-4 solution. The -4 experimental group and the supramolecular myristoyl pentapeptide-4 control group were subjected to closed patch tests on human skin to verify the safety of the samples. According to [Safety Technical Specifications for Cosmetics 2015 Edition], select qualified spot test equipment, use the closed patch test method, place 0.020 g~0.025 g of the test substance in the spot test equipment, and apply hypoallergenic tape on the subject. On the curved side of the forearm of the test subject, the test substance was removed after 24 hours, and the skin reaction was observed at 0.5, 24, and 48 hours after removal, and the results were recorded according to the skin reaction grading standard in the "Safety and Technical Specifications for Cosmetics" (2015 Edition) in Table 3 , to detect potential adverse reactions of cosmetic products on human skin. The results are shown in Table 4: the results of the human skin closed patch test of the supramolecular myristoyl pentapeptide-4 control group and the supramolecular myristoyl pentapeptide-4 experimental group showed that 0 cases of adverse reactions occurred in 31 people. Explain that the sample is safe and non-irritating.

Table 3 Grading standard of skin reaction in skin-closed patch test

Table 4 Summary of patch test results of cosmetics on human skin

Test case 4

Prepare 4% supramolecular myristoyl pentapeptide-4 solution and 1% myristoyl pentapeptide-4 solution. The -4 experimental group and the supramolecular myristoyl pentapeptide-4 control group were subjected to closed patch tests on human skin to verify the safety of the samples. According to [Safety and Technical Specifications for Cosmetics (2015 Edition) Chapter 6 Toxicological Test Methods: 4 Skin Irritation/Corrosion Test], about 24 hours before the test, the hair on both sides of the back and spine of the test animal was shaved without damaging the epidermis. The left and right sides are about 3cm×3cm each. Take 0.5mL sample and smear it on the left shaved skin with an area of 2.5cm×2.5cm, and the other side skin as a control. Apply once a day for 14 days. From the next day, shave the hair before each application, remove the residual test substance with warm water, and observe the local skin reaction 1 hour later and score it. The results are shown in Table 5 and Table 6: myristoyl pentapeptide-4 solution and supramolecular myristoyl pentapeptide-4 are 0 to Hartley guinea pig multiple skin irritation tests every day. "Technical Specifications" (2015 Edition) skin irritation test classification of skin irritation intensity, is non-irritating.

Table 5 Results of multiple skin irritation tests of myristoyl pentapeptide-4 solution

Table 6 Multiple skin irritation test results of supramolecular myristoyl pentapeptide-4

Test case 5

Prepare 4% supramolecular myristoyl pentapeptide-4 solution and 1% myristoyl pentapeptide-4 solution. -4 sample group and supramolecular myristoyl pentapeptide-4 control group were tested for hair repair and breakage prevention efficacy.

1. Repair damaged hair scales

According to the laboratory method, observe the condition of the hair bundle hair scales before and after using the supramolecular myristoyl pentapeptide-4 sample group and the supramolecular myristoyl pentapeptide-4 control group through electron microscope shooting technology, before and after comparison, parallel comparison, and evaluate the samples The effect of repairing hair cuticles.

The results are shown in Figure 5: before treatment, the cuticles of the hair bundles had a relatively large opening and closing degree, and the cuticles fell off; Larger hair cuticles have shedding; after treatment with the supramolecular myristoyl pentapeptide-4 sample group, the degree of opening and closing of the hair bundle hair cuticles is reduced, and the hair cuticles do not fall off. The condition of hair cuticles treated by the supramolecular myristoyl pentapeptide-4 sample group is better than that of the supramolecular myristoyl pentapeptide-4 control group, indicating that supramolecular myristoyl pentapeptide-4 has repairing properties. The efficacy of damaged hair cuticles, and the effect is better than myristoyl pentapeptide-4.

2. Improve hair dry combing effect

According to the laboratory method, single-center experiment, through the dry comb test of the hair strands treated with supramolecular myristoyl pentapeptide-4 sample group and supramolecular myristoyl pentapeptide-4 control group, parallel control, evaluation The samples were tested to improve the dry combing efficacy of the tresses.

The results are shown in Table 7 and Figure 6: after the supramolecular myristoyl pentapeptide-4 sample group treatment, the dry combing power of hair strands decreased by 24.7%, which was significantly lower than that of the supramolecular myristoyl pentapeptide-4 control group. Beam stem combing function. The smaller the combing work, the better the dry combing effect of the hair bundle, that is, the supramolecular myristoyl pentapeptide-4 can significantly improve the dry combing property of the hair, and the effect is better than that of myristoyl pentapeptide-4.

Table 7 Combing test results

Note: "ns" indicates p>0.05; "*" indicates p≤0.05; "**" indicates 0.001≤p<0.01; "***" indicates p<0.001.

3. Prevent hair loss

According to the laboratory method, by measuring the breaking strength of the hair after using the supramolecular myristoyl pentapeptide-4 sample group and the supramolecular myristoyl pentapeptide-4 control group, parallel comparisons are made to evaluate the efficacy of the product in improving hair toughness. The results are shown in Table 8 and Figure 7: after the treatment of the supramolecular myristoyl pentapeptide-4 sample group, the breaking load of a single hair increased by 36.45%, which was significantly higher than that of the supramolecular myristoyl pentapeptide-4 control group. breaking load. The greater the breaking load, the better the anti-hair breakage effect of the test sample, that is, the supramolecular myristoyl pentapeptide-4 has the effect of preventing hair breakage, and the effect is better than that of myristoyl pentapeptide-4.

Table 8 Descriptive statistics of breaking load test results (unit: gmf)

Note: "ns" indicates p>0.05; "*" indicates p≤0.05; "**" indicates 0.001≤p<0.01; "***" indicates p<0.001.

According to the data analysis of the effect of repairing damaged hair scales, improving hair dry combability and preventing hair breakage, myristoyl pentapeptide-4 is a supramolecular myristoyl pentapeptide obtained by supramolecular modification of L-carnitine taurine ionic liquid Acyl pentapeptide-4 is better than myristoyl pentapeptide-4 in repairing and preventing hair breakage. The effect of play.

Test case 6

The supramolecular myristoyl pentapeptide-4, the mixture of myristoyl pentapeptide-4 and imidazolium ionic liquid and myristoyl pentapeptide-4 were made into essences with contents of 4%, 1% and 4% respectively, three The contents of myristoyl pentapeptide-4 were the same, and they were used as supramolecular myristoyl pentapeptide-4 sample group, supramolecular myristoyl pentapeptide-4 control group (1) and supramolecular myristoyl pentapeptide-4 4 The control group (2) was tested for nourishing efficacy.

31 subjects in each group used supramolecular myristoyl pentapeptide-4 sample group, supramolecular myristoyl pentapeptide-4 control group (1) and supramolecular myristoyl pentapeptide-4 control group for 4 consecutive weeks After group (2), skin water content, skin gloss and skin roughness Ra value were measured at 0 weeks, 2 weeks and 4 weeks before using the samples to evaluate the nourishing effect of the samples.

1. Skin moisture content test

The statistical analysis results of the skin moisture content of the sample group and the control group are shown in Table 9.

Table 9 Statistical analysis results of skin water content before and after use in the experimental group and control group

Note: "n.s." means no statistical difference, P≥0.05; 0.01<P<0.05 means significant difference ("*" means); P <0.01 means extremely significant difference ("**" means).

After 2 weeks and 4 weeks of continuous use of the supramolecular myristoyl pentapeptide-4 sample group, compared with 0 weeks, the skin moisture content of the subjects increased by 30.56% and 36.33%, respectively, and the results were significantly different; Molecular myristoyl pentapeptide-4 control group (1) After 2 weeks and 4 weeks, compared with 0 weeks, the skin moisture content of the subjects increased by 22.26% and 28.28% respectively, and the results were significantly different; continuous use of super Molecular myristoyl pentapeptide-4 control group (2) After 2 weeks and 4 weeks, compared with 0 weeks, the skin moisture content of the subjects increased by 25.34% and 32.27%, respectively, and the results were significantly different. It shows that the supramolecular myristoyl pentapeptide-4 can significantly increase the water content of the skin, and the effect is better than that of myristoyl pentapeptide-4, and it is also better than the delivery effect of other ionic liquids on myristoyl pentapeptide-4.

2. Skin gloss test

The statistical analysis results of the skin gloss of supramolecular myristoyl pentapeptide-4 sample group, supramolecular myristoyl pentapeptide-4 control group (1) and supramolecular myristoyl pentapeptide-4 control group (2) are shown in the table 10 shown.

Table 10 Statistical analysis results of skin gloss before and after use in the experimental group and control group

Note: "n.s." means no statistical difference, P≥0.05; 0.01<P<0.05 means significant difference ("*" means); P <0.01 means extremely significant difference ("**" means).

After 2 weeks and 4 weeks of continuous use of the supramolecular myristoyl pentapeptide-4 sample group, compared with 0 weeks, the skin gloss of the subjects increased by 14.02% and 28.28% respectively, and the results were significantly different; Molecular myristoyl pentapeptide-4 control group (1) After 2 weeks and 4 weeks, compared with 0 weeks, the skin gloss of the subjects increased by 12.06% and 19.65% respectively, and the results were significantly different; continuous use of super Molecular myristoyl pentapeptide-4 control group (2) After 2 weeks and 4 weeks, compared with 0 weeks, the skin gloss of the subjects increased by 12.67% and 22.51%, respectively, and the results were significantly different. It shows that supramolecular myristoyl pentapeptide-4 can significantly improve skin gloss, and the effect is better than that of myristoyl pentapeptide-4, and it is also better than the delivery effect of other ionic liquids on myristoyl pentapeptide-4.

3. Skin roughness Ra value test

Statistical analysis results of skin roughness Ra value of supramolecular myristoyl pentapeptide-4 sample group, supramolecular myristoyl pentapeptide-4 control group (1) and supramolecular myristoyl pentapeptide-4 control group (2) As shown in Table 11.

Table 11 Statistical analysis results of skin roughness Ra value before and after use in the experimental group and control group

Note: "n.s." means no statistical difference, P≥0.05; 0.01<P<0.05 means significant difference ("*" means); P <0.01 means extremely significant difference ("**" means).

After 2 weeks and 4 weeks of continuous use of the supramolecular myristoyl pentapeptide-4 sample group, compared with 0 weeks, the skin roughness Ra value of the subjects was reduced by 10.59% and 17.48%, respectively, and the results were significantly different; continuous After using the supramolecular myristoyl pentapeptide-4 control group (1) for 2 weeks and 4 weeks, compared with 0 weeks, the skin roughness Ra value of the subjects was reduced by 7.69% and 12.37%, respectively, and the results were significantly different ; Continuous use of the supramolecular myristoyl pentapeptide-4 control group (2) after 2 weeks and 4 weeks, compared with 0 weeks, the Ra value of the skin roughness of the subjects was reduced by 8.45% and 13.68%, and the results were significant sexual difference. It shows that supramolecular myristoyl pentapeptide-4 can significantly improve skin roughness, and the effect is better than that of myristoyl pentapeptide-4, and it is also better than the delivery effect of other ionic liquids on myristoyl pentapeptide-4.

According to the data analysis of skin moisture content, skin glossiness and skin roughness Ra value, myristoyl pentapeptide-4 is the supramolecular myristoyl pentapeptide-4 obtained after supramolecular modification by L-carnitine taurine ionic liquid The degree of nourishment to the skin is better than that of myristoyl pentapeptide-4 and other ionic liquids on the delivery of myristoyl pentapeptide-4, indicating that L-carnitine taurine ionic liquid can effectively promote the effect of myristoyl pentapeptide-4 on The skin nourishing effect is brought into play, and the carnitine taurine ionic liquid has a synergistic effect on myristoyl pentapeptide-4.

In summary, the present invention discloses a supramolecular myristoyl pentapeptide-4 and its preparation method and application, which comprises the steps of: placing the L-carnitine taurine ionic liquid at a preset temperature under an inert atmosphere In a water bath, myristoyl pentapeptide-4 is added to the L-carnitine taurine ionic liquid to obtain a mixed solution, and the mixed solution is ultrasonically stirred, homogenized, and dialyzed to obtain the supramolecular myristate Acyl pentapeptide-4. The present invention adopts L-carnitine taurine ionic liquid as a carrier, combines with myristoyl pentapeptide-4 to carry out supramolecular modification, and obtains supramolecular myristoyl pentapeptide-4, and myristoyl pentapeptide-4 is produced in Pentapeptide-4 is connected with a long-chain fatty acyl myristic acid, which changes the hydrophilic-lipophilic balance of the peptide compound and improves the surface activity of the peptide, but its permeability becomes poor, and more peptides stay on the skin surface . After L-carnitine taurine ionic liquid is combined with myristoyl pentapeptide-4 for supramolecular modification to form supramolecules, under the action of L-carnitine taurine ionic liquid, the tight junction in the stratum corneum is opened, thereby promoting The paracellular transport of myristoyl pentapeptide-4 can enhance the transdermal penetration of myristoyl pentapeptide-4. Therefore, the supramolecular myristoyl pentapeptide-4 prepared by the method of the present invention can improve the permeability of the skin, so that it can further exert the effect of nutmeg on the basis of the original hair care and skin nourishing effects of L-carnitine and taurine. Acyl pentapeptide-4 has the effect of repairing, preventing breakage and nourishing the skin, which greatly improves its bioavailability and enhances the application effect.

Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that it can still be Modifications are made to the technical solutions described in the foregoing embodiments, or equivalent replacements are made to some of the technical features; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims (10)

1. A method for preparing supramolecular myristoyl pentapeptide-4, comprising the steps of:

under inert atmosphere, placing the L-carnitine taurine ionic liquid in a water bath with a preset temperature, and adding myristoyl pentapeptide-4 into the L-carnitine taurine ionic liquid to obtain a mixed solution;

and (3) carrying out ultrasonic stirring, homogenizing and dialysis on the mixed solution to obtain the supermolecule myristoyl pentapeptide-4.

2. The method for preparing the supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the mass ratio of the L-carnitine taurine ionic liquid to the myristoyl pentapeptide-4 is (5:1) - (1:5).

3. The method for producing supramolecular myristoylpentapeptide-4 according to claim 1, wherein the inert gas is nitrogen or argon.

4. The method for preparing supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the preset temperature is 25-35 ℃.

5. The method for preparing supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the stirring speed of stirring is 500-700 rad/min, and the stirring time is 16-24 h.

6. The method for preparing the supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the frequency of the ultrasonic wave is 20-40 khz, the power of the ultrasonic wave is 800-2000 w, the time of the ultrasonic wave is 4-12 h, the intermittent time is 1-5 s every interval, and the ultrasonic wave is 2-10 s.

7. The method for preparing the supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the homogenizing pressure is 10-80 MPa, the homogenizing flow is 30-60L/h, and the homogenizing times are 1-3 times.

8. The method for preparing the supramolecular myristoyl pentapeptide-4 according to claim 1, wherein the dialysis is performed by using a cellulose dialysis bag, the molecular weight of the cellulose dialysis bag is 1000, the dialysis time is 2-6 hours, and the dialysis times are 1-3 times.

9. A supramolecular myristoyl pentapeptide-4 prepared by the preparation method according to any one of claims 1-8.

10. Use of the supramolecular myristoylpentapeptide-4 according to claim 9 for the preparation of cosmetics.