Bicontinuous phase polypeptide compound, preparation method and cosmetics

Abstract

The invention discloses an active peptide compound, a preparation method thereof and a cosmetic. The active peptide compound comprises a phase A and a phase B, the phase A comprises an oily solvent, a lipophilic surfactant and a hydrophilic surfactant I; the phase B comprises oil-soluble polypeptide, a hydrophilic surfactant II, an alcohol solvent and water; wherein the water solubility of the hydrophilic surfactant I is different from that of the hydrophilic surfactant II; wherein the alcohol solvent at least comprises polyhydric alcohol with more than four carbon atoms. The active peptide compound disclosed by the invention is a stable and uniform solution and has excellent enzyme hydrolysis resistance.

Description

Technical Field

[0001] The invention relates to an active peptide complex and a preparation method and cosmetics thereof. Background Art

[0002] Aging is an inevitable natural process as we age. Keeping facial skin smooth and wrinkle-free is the wish of almost everyone. Lips are a very important part of the face. The lip skin not only has no sebaceous glands and sebum membranes, but also has a very fast metabolism rate of the stratum corneum, and serious loss of collagen, which often shows dry, rough, dull and matte lip appearance. Therefore, skin care products that help anti-aging of facial skin and lips have been widely studied, and the types are constantly increasing. Active peptides are one of the commonly used ones.

[0003] Active peptides include water-soluble and oil-soluble ones. Water-soluble ones are usually more easily absorbed by the skin surface and are often used for moisturizing. They can help maintain the moisture balance of the skin, thereby reducing the appearance of fine lines and wrinkles. Oil-soluble peptides, due to their fat-soluble properties, can penetrate deep into the skin and have a greater impact on collagen in the deep layers of the skin. They can stimulate fibroblasts to produce collagen, thereby fundamentally reducing fine lines and wrinkles. Common oil-soluble peptides include palmitoyl tripeptide, palmitoyl tetrapeptide and palmitoyl pentapeptide.

[0004] However, if active peptide products are applied to the face or lips, they will be degraded by proteases in the skin after penetrating the skin, which will cause the active peptide products to fail to exert their efficacy. The existing technology often uses the method of encapsulating active peptides to resist enzymatic hydrolysis in the skin. However, when using liposomes or other encapsulating materials to encapsulate oil-soluble peptide molecules one by one, there is a situation where the active peptides cannot be encapsulated, resulting in the loss of active peptides.

[0005] BiContinuous MicroEmulsion (BCME) is an intermediate transition phase that appears during the mutual transformation of water-in-oil microemulsion and oil-in-water microemulsion. The water phase and the oil phase are both continuous, so it is called "bi" continuous. Compared with droplet-type microemulsion, bicontinuous microemulsion has strong solubilization ability and large interface area. BCME is currently mainly used in the development of makeup removers because it has both hydrophilicity and lipophilicity. There is no report on its use in active peptide products. Summary of the invention

[0006] In view of the above defects of the prior art, the present invention provides an active peptide complex and a preparation method and cosmetics thereof. The oil-soluble polypeptide in the active peptide complex of the present invention is stably present in the solution system, and the solution system can maintain long-term stability and effectively resist degradation by proteases.

[0007] One aspect of the present invention provides an active peptide complex, which includes a phase A and a phase B;

[0008] The phase A comprises an oily solvent, a lipophilic surfactant and a hydrophilic surfactant I;

[0009] The phase B includes an oil-soluble polypeptide, a hydrophilic surfactant II, an alcohol solvent and water;

[0010] Wherein, the water solubility of the hydrophilic surfactant I is different from the water solubility of the hydrophilic surfactant II;

[0011] Wherein, the alcohol solvent at least includes a polyol with more than 4 carbon atoms.

[0012] In a specific embodiment of the present invention, the active peptide complex is a clear uniform solution. The clear solution generally refers to a solution without color under natural light, a transparent solution, and no particles visible to the naked eye. The uniform solution generally refers to a solution without stratification.

[0013] In the present invention, the active peptide complex is preferably a bicontinuous phase structure, and the phase A and the phase B form a bicontinuous phase structure. The bicontinuous phase structure is composed of two mutually separated but mutually intercalated phase regions, both of which are continuous phases and are connected in all directions of space. The bicontinuous phase is formed by layer-by-layer electrostatic self-assembly technology to form two interfacial layers, and the two interfacial layers are formed on the surface of the droplet by electrostatic adsorption or covalent bonding of small molecule surfactants.

[0014] In a specific embodiment of the present invention, a bicontinuous phase structure is formed by combining the oily solvent, alcohol solvent and surfactants in each phase of the present invention, and the oil-soluble polypeptide is contained in the continuous phase. Experimental verification has found that this bicontinuous phase structure is not only highly stable, but also can protect the oil-soluble polypeptide and effectively prevent the degradation of proteases.

[0015] In the present invention, those skilled in the art can know that the phase A is generally referred to as an oil phase based on the components of the phase A. Similarly, those skilled in the art can know that the phase B is generally referred to as a water phase based on the components of the phase B.

[0016] In the present invention, the ratio of the total mass of the phase A to the total mass of the phase B is preferably (3.5-6):1, more preferably (3.5-5.5):1, for example 3.78:1, 4.15:1 or 5.27:1.

[0017] In the present invention, the ratio of the mass of the oily solvent to the total mass of "the alcohol solvent and the water" is preferably (1.5-3):1, more preferably (2-2.5):1, for example 2.2:1.

[0018] In the present invention, the water solubility of the hydrophilic surfactant II is preferably greater than the water solubility of the hydrophilic surfactant I. The water solubility may be the meaning commonly understood in the art, and generally refers to the solubility of the hydrophilic surfactant I or the hydrophilic surfactant II in water. For the hydrophilic surfactant of the present invention, the water solubility represents the numerical value of the HLB value, and the higher the numerical value, the higher the water solubility. Preferably, the HLB value of the hydrophilic surfactant II is 4-6 greater than the HLB value of the hydrophilic surfactant I, for example, 5.

[0019] In the present invention, the oily solvent may be conventional in the art, preferably isoparaffin. In the present invention, the oily solvent is usually liquid at room temperature. The number of carbon atoms in the isoparaffin is preferably 9-19, more preferably 14-18, for example 16. In a specific embodiment of the present invention, the oily solvent is isohexadecane.

[0020] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the oily solvent is preferably 35-55%, more preferably 40-50%, for example 41%, 42%, 42.5%, 43%, 44%, 45% or 46%.

[0021] In the present invention, the HLB value of the lipophilic surfactant is preferably below 7, such as 6, 5, 4.7 and 4.

[0022] In the present invention, the lipophilic surfactant is preferably a polyglyceryl surfactant, preferably polyglyceryl-2 isostearate. Those skilled in the art know that the HLB value of the polyglyceryl-2 isostearate is about 4.7.

[0023] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the lipophilic surfactant is preferably 10-25%, more preferably 15-20%, for example 17%.

[0024] In the present invention, the HLB value of the hydrophilic surfactant I is preferably 8-15, such as 9, 10, 11, 11.5, 12 or 13.

[0025] In the present invention, the hydrophilic surfactant I is preferably a sorbitol polyether surfactant, preferably sorbitol polyether-30 tetraoleate. Those skilled in the art know that the HLB value of the sorbitol polyether-30 tetraoleate is 11.5.

[0026] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the hydrophilic surfactant I is preferably 10-30%, more preferably 18-23%, such as 21% or 21.2%.

[0027] In the present invention, the mass ratio of the hydrophilic surfactant I to the oily solvent is preferably (0.4-0.6):1, more preferably (0.45-0.55), for example 0.46:1, 0.5:1 or 0.51:1.

[0028] In the present invention, the mass ratio of the lipophilic surfactant to the oily solvent is preferably (0.3-0.5):1, more preferably (0.35-0.45):1, such as 0.37:1, 0.4:1 or 0.41:1.

[0029] In the present invention, the oil-soluble polypeptide may be a conventional oil-soluble bioactive polypeptide, including but not limited to palmitoyl polypeptides, such as palmitoyl tripeptide and / or palmitoyl pentapeptide. Specifically, for example, one or more of palmitoyl tripeptide-1, palmitoyl pentapeptide-4, palmitoyl pentapeptide-5, palmitoyl tripeptide-8 and palmitoyl tetrapeptide-7. In a specific embodiment of the present invention, the palmitoyl tripeptide is palmitoyl tripeptide-1. In a specific embodiment of the present invention, the palmitoyl pentapeptide is palmitoyl pentapeptide-4.

[0030] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the oil-soluble polypeptide may be less than 1% but not 0%, 0.005-0.02%, for example 0.006%, 0.01%, 0.012%, 0.018% or 0.02%. In a specific embodiment of the present invention, the content of palmitoyl tripeptide-1 is 0.012%, and the content of palmitoyl pentapeptide-5 is 0.006%.

[0031] In the present invention, the HLB value of the hydrophilic surfactant II is preferably greater than 12, preferably 15-18, such as 16.5.

[0032] In the present invention, the hydrophilic surfactant II is preferably a polysorbate, such as polysorbate-20. Those skilled in the art know that the HLB value of polysorbate-20 is 16.5.

[0033] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the hydrophilic surfactant II may be 0.1-2.0%, preferably 0.5% or 1%.

[0034] In the present invention, the alcohol solvent preferably includes a polyol having a carbon number of 4 to 6. The polyol is preferably a diol, such as one or more of 1,2-butanediol, 1,3-butanediol and 1,2-pentanediol.

[0035] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the alcohol solvent is preferably 1-10%, more preferably 3-8%, for example 3%, 3.42%, 4%, 5%, 6%, 6.88%, 7% or 8%.

[0036] In the present invention, based on the mass content of the active peptide complex as 100%, the content of the polyol is preferably 1.5-8%, such as 1.56%; more preferably 3-8%, such as 3%, 3.13%, 4%, 5%, 6%, 6.88% or 7%.

[0037] In the present invention, based on the mass content of the active peptide complex as 100%, the water content is preferably 10-20%, preferably 10-15%, such as 12% or 13%.

[0038] In a preferred embodiment of the present invention, the alcohol solvent may further include glycerol. In a specific embodiment of the present invention, based on the mass content of the active peptide complex as 100%, the content of the glycerol is 1-5%, such as 2%, 3% or 4%.

[0039] In the present invention, the mass ratio of the hydrophilic surfactant II to the oil-soluble polypeptide is preferably (20-130):1, more preferably (25-120):1, such as 27.78:1 or 111.11:1.

[0040] In the present invention, the mass ratio of the alcohol solvent to the oil-soluble polypeptide is preferably (150-400):1, more preferably (180-390):1, such as 190.11:1 or 382.22:1.

[0041] In the present invention, the mass ratio of the water to the oil-soluble polypeptide is preferably (500-1000):1, more preferably (600-900):1, such as 666.67:1, 667.78:1 or 858.89:1.

[0042] In the present invention, the formation of a bicontinuous phase is relatively dependent on the interfacial curvature of the surfactant framework. It is particularly important to select a suitable surfactant and ratio. The addition of different oils and different oil-water ratios will affect the interfacial curvature of the surfactant combination. In particular, the addition of oil-soluble polypeptides poses new challenges to the formation of a bicontinuous phase structure. The present invention forms a uniform and stable clear solution by controlling the type and content of surfactants in the oil phase and the water phase, combined with the coordination of the solvent system, so that the oil-soluble polypeptides are stably present in the entire system, which is equivalent to a protective effect, and can effectively resist the hydrolysis of enzymes in the skin.

[0043] Another aspect of the present invention provides a method for preparing an active peptide complex, wherein the phase A and the phase B are mixed until a uniform and clear solution is formed.

[0044] In a specific embodiment of the present invention, in order to obtain the active peptide complex, the two phases need to be prepared separately, and one phase is added to the other phase in batches or slowly to form a bicontinuous phase structure. The mixing is preferably to add the B phase slowly or in batches to the A phase, or to add the A phase slowly or in batches to the B phase. When the B phase is added to the A phase, a W / O spherical microemulsion is formed due to the small amount of water. The B phase is continuously added dropwise, the water-oil ratio changes, and the system slowly forms a bicontinuous phase.

[0045] In the present invention, the mixing preferably also includes stirring to make the system reach a uniform state.

[0046] In the present invention, the duration of the mixing is preferably more than 10 min, such as 15 min, 20 min or 30 min.

[0047] In the present invention, the homogeneous and clear solution generally refers to a solution without stratification and without particles visible to the naked eye.

[0048] Another aspect of the present invention provides an active peptide complex, which is prepared by the above preparation method.

[0049] Another aspect of the present invention provides a cosmetic comprising the above active peptide complex.

[0050] In the present invention, the cosmetics may have the meaning commonly understood in the art, and generally refer to daily chemical industrial products that are applied to the human body surface such as skin, hair, nails, lips, etc. by rubbing, spraying or other similar methods for the purpose of cleaning, protecting, beautifying and modifying. The cosmetics of the present invention include the color cosmetics and / or skin care products commonly referred to in the art.

[0051] In the present invention, the cosmetics preferably include lip cosmetics and / or facial cosmetics.

[0052] Positive improvement effect: The present invention controls the types of surfactants and solvents in the oil phase and the water phase, so that the oil-soluble polypeptide is well dissolved in the solution system, forming a uniform and stable clear solution, and the oil-soluble polypeptide has excellent anti-enzymatic effect.

[0053] The concept, specific structure and technical effects of the present invention will be further described below in conjunction with the accompanying drawings to fully understand the purpose, characteristics and effects of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0054] Figure 1This is a picture of the active peptide complex prepared in Example 1 under a transmission electron microscope (TEM). Figure 1 A is the picture at 0.5μm magnification. Figure 1 B is the picture at a magnification of 200nm. Figure 1 C is a picture at a magnification of 100nm.

[0055] Figure 2 This is a curve showing the change of the content of palmitoyl pentapeptide-4 in the active peptide complex with enzymatic hydrolysis time.

[0056] Figure 3 This is a curve showing the change of the content of palmitoyl tripeptide-1 in the active peptide complex with enzymatic hydrolysis time. DETAILED DESCRIPTION

[0057] In order to make the technical means, creative features, objectives and effects of the invention easier to understand, the invention is further described below with reference to specific diagrams. However, the invention is not limited to the following implementation cases.

[0058] Herein, the term "HLB" is well known to those skilled in the art and indicates the hydrophile-lipophile balance (HLB) of a surfactant. The HLB or hydrophile-lipophile balance of one or more surfactants used in the present invention can be determined via the Griffin method or the Davis method. The higher the HLB value, the greater the solubility in water; and conversely, the lower the HLB value, the greater the affinity of the surfactant for oil.

[0059] The sources of raw materials, reagents and instruments used in the following examples and comparative examples are as follows:

[0060] Electronic balance: manufacturer: Sartorius;

[0061] High performance liquid chromatograph: manufacturer: Thermo Fisher, model: U3000;

[0062] Chromatographic column: Manufacturer: Yuexu, Model: LP-C18 4.6*150mm,5um;

[0063] Trifluoroacetic acid: Aladdin, HPLC grade;

[0064] Acetonitrile: Shanghai Xingke High Purity Solvent Co., Ltd., HPLC grade;

[0065] Methanol: Shanghai Xingke High Purity Solvent Co., Ltd., HPLC grade;

[0066] Water: Guangzhou Watsons Food and Beverage Co., Ltd., distilled water;

[0067] Protease OK200: Wuhan Xinhuayang Biotechnology Co., Ltd.;

[0068] Palmitoyl tripeptide-1: Shenzhen Vicky Technology Co., Ltd., mass content 78.47%;

[0069] Palmitoyl Pentapeptide-4: Shenzhen Vicky Technology Co., Ltd., mass content 95.09%.

[0070] Isohexadecane: CAS No.: 60908-77-2;

[0071] Polysorbate 20: CAS number: 9005-64-5.

[0072] Property stability test: The active peptide complexes prepared in Examples 1-6 and Comparative Examples 1-4 were sealed and left to stand for a certain period of time at 10-30°C under natural light, and the clarity, uniformity and transparency of the active peptide complexes were observed, and the solution properties and standing time were recorded. Among them, clarity means that no visible precipitation or agglomerates are formed, and uniformity means that the solution system does not have stratification.

[0073] Examples 1-5

[0074] The preparation method of the active peptide complex is as follows:

[0075] Prepare phase A: weigh the oily solvent and sorbitan polyether-30 tetraoleate of phase A of Examples 1-5 according to Table 1-5, stir and mix evenly, slowly add polyglyceryl-2 isostearate, stir and mix until the solution is clear, and set aside;

[0076] Prepare phase B: According to Table 1-5, weigh palmitoyl tripeptide-1 powder and palmitoyl pentapeptide-4 powder of phase B of Examples 1-5, add polysorbate-20 and a small amount of water, and stir ultrasonically to dissolve; then add alcohol solvent and remaining water to phase B and stir evenly;

[0077] Mixing phase I: While stirring phase A, slowly add phase B in portions, keep mixing phase I transparent, and stir until the solution is clear. Continue stirring for 15-20 minutes to obtain the active peptide complex.

[0078] Table 1 Active peptide complex formula of Example 1

[0079]

[0080] Table 2 Active peptide complex formula of Example 2

[0081]

[0082]

[0083] Table 3 Active peptide complex formula of Example 3

[0084]

[0085] Table 4 Active peptide complex formulation of Example 4

[0086]

[0087] Table 5 Active peptide complex formulation of Example 5

[0088]

[0089] Example 6

[0090] The formula of the active peptide complex is the same as that of Example 1. The preparation method of Example 6 is different from that of Example 1 in that:

[0091] Mixing phase I: phase B, slowly add phase A under stirring, phase A is white milky when first added to phase B, and as phase A is continuously added, the solution system gradually becomes clear, and the obtained mixed phase I is the active peptide complex. The other steps are the same as in Example 1. The property stability of Example 6 is equivalent to that of Example 1.

[0092] Embodiment 7-8

[0093] The preparation method is the same as that of Example 2, and the formulations are shown in Tables 6 and 7 below.

[0094] Table 6 Active peptide complex formulation of Example 7

[0095]

[0096] Table 7 Active peptide complex formulation of Example 8

[0097]

[0098] Comparative Example 1

[0099] The preparation method of the active peptide complex is the same as that of Example 1, and the formula is shown in Table 8 below.

[0100] Table 8 Active peptide complex formula of comparative example 1

[0101]

[0102] Comparative Examples 2-4

[0103] The preparation method of the active peptide complex is as follows:

[0104] Prepare phase A: weigh the oily solvent and sorbitan polyether-30 tetraoleate according to Tables 9-11, stir and mix evenly, slowly add PEG-20 glyceryl triisostearate, stir and mix until the solution is clear, and set aside;

[0105] Preparation of phase B: According to Tables 9-11, weigh palmitoyl tripeptide-1 powder and palmitoyl pentapeptide-4 powder of phase B of comparative examples 2-4, add polysorbate-20 and a small amount of water, and stir ultrasonically to dissolve; then add alcohol solvent and remaining water to phase B and stir evenly;

[0106] Mixing phase I: While stirring phase A, slowly add phase B in portions, and continue stirring to keep phase I transparent. Continue stirring for 15-20 minutes until the solution is clear.

[0107] Table 9 Active peptide complex formula of comparative example 2

[0108]

[0109] Table 10 Active peptide complex formula of comparative example 3

[0110]

[0111] Table 11 Active peptide complex formula of comparative example 4

[0112]

[0113]

[0114] Effect Example 1 Structural Characterization of Bicontinuous Phase Peptides

[0115] The active peptide complex prepared in Example 1 was tested using a transmission electron microscope (TEM).

[0116] The test method is as follows: take a copper mesh and place it on the self-adhesive backing paper; absorb 30μL of active peptide complex and drop it on the copper mesh, and let it stand for 10 minutes; use filter paper to remove excess active peptide complex on the copper mesh, absorb 30μL of phosphotungstic acid dye and drop it on the copper mesh, and dye it for 2 minutes; use filter paper to remove excess dye on the copper mesh, and place the copper mesh in a ventilated place to dry; observe it under a microscope.

[0117] The test results are as follows Figure 1 As shown, the sample morphology was observed at different magnifications of 0.5 μm, 200 nm, and 100 nm, and the following results were obtained: Figure 1Electron microscope images of A, 1B and 1C. In images 1B and 1C, the large gray blank area is observed to be the negatively stained phosphotungstic acid background; the dark irregular part is the active peptide complex, and the multi-circle edge white part and the dark irregular part form a double continuous phase that is separated from each other and intercalated with each other.

[0118] Effect Example 2 Anti-enzymatic test

[0119] 1) High performance liquid chromatography is used to test the content of oil-soluble polypeptides in the solution after the test sample and the protease are mixed.

[0120] Chromatographic conditions: Determined by reference to high performance liquid chromatography (General Rules 0512 of the 2020 edition of the Chinese Pharmacopoeia).

[0121] Octadecylsilane bonded silica gel was used as the filler (column length 150 mm, inner diameter 4.6 mm, particle size 5 μm); 0.1% trifluoroacetic acid in water was used as mobile phase A, 0.1% trifluoroacetic acid in acetonitrile was used as mobile phase B, and gradient elution was performed as shown in the following table; column temperature was 35°C; flow rate was 1.0 mL per minute; detection wavelength was 215 nm; injection volume was 10 μL. Elution conditions are shown in Table 12:

[0122] Table 12

[0123] Time (min) A％ B％ 0 60 40 15 25 75 20 25 75 21 60 40

[0124] 2) Solution preparation

[0125] Palmitoyl pentapeptide-4 reference substance stock solution: Take an appropriate amount of palmitoyl pentapeptide-4 reference substance, accurately weigh it, place it in a volumetric bottle, add methanol to make a solution containing approximately 1 mg of palmitoyl pentapeptide-4 per 1 mL, shake well, and obtain.

[0126] Palmitoyl tripeptide-1 reference substance stock solution: Take an appropriate amount of palmitoyl tripeptide-1 reference substance, accurately weigh it, place it in a volumetric bottle, add methanol to make a solution containing approximately 1 mg of palmitoyl tripeptide-1 per 1 mL, shake well, and obtain.

[0127] Reference solution: Accurately measure the reference stock solution of palmitoyl pentapeptide-4 and the reference stock solution of palmitoyl tripeptide-1, place them in the same volumetric flask, add water to make a solution containing approximately 0.06 mg of palmitoyl pentapeptide-4 and 0.12 mg of palmitoyl tripeptide-1 per 1 mL, shake well, and you have it.

[0128] Test solution: Take the active peptide complex test sample prepared in Example 1 and filter it through a 0.22 μm membrane to obtain the solution.

[0129] Reference substance enzymatic hydrolysis solution: Take 10 mL of reference substance solution, add 0.1 mL of protease OK200, shake well, and obtain.

[0130] Test sample enzymatic hydrolysis solution: Take 10 mL of the test sample solution, add 0.1 mL of protease OK200, shake well, and obtain.

[0131] 3) Determination method: Accurately pipette 10 μL of reference solution, test solution, reference enzymatic hydrolyzate solution and test enzymatic hydrolyzate solution respectively, inject into liquid chromatograph (one injection of reference enzymatic hydrolyzate solution and test enzymatic hydrolyzate solution every 1 hour, and observe for 6 hours), and record the chromatogram.

[0132] 4) Test results

[0133] The reference solution was tested for the contents of palmitoyl pentapeptide-4 and palmitoyl tripeptide-1 using high performance liquid chromatography. The test results are shown in Table 13 below.

[0134] Table 13

[0135]

[0136] The HPLC test results of the test solution, reference sample hydrolyzate solution and test sample hydrolyzate solution are shown in Table 14 below.

[0137] Table 14

[0138]

[0139]

[0140] like Figure 2 The figure shows the changes of palmitoyl pentapeptide-4 in the enzymatic hydrolysis solution of the reference substance and the test substance as the enzymatic hydrolysis time increases. Figure 3 The figure shows the change of palmitoyl tripeptide-1 in the reference enzymatic solution and the test enzymatic solution with the enzymatic hydrolysis time. As can be seen from the figure, within 6 hours, the content of palmitoyl pentapeptide-4 and palmitoyl tripeptide-1 in the reference enzymatic solution decreased significantly; the content of palmitoyl pentapeptide-4 and palmitoyl tripeptide-1 in the test enzymatic solution remained almost unchanged, indicating that the active peptide complex prepared by the present invention enables the oil-soluble polypeptide to effectively resist the hydrolysis of proteases. On the other hand, according to the content detection results of Table 14, the content of palmitoyl pentapeptide-4 and palmitoyl tripeptide-1 in the test solution is basically consistent with the content when the raw materials are added, which also reflects that the polypeptide in the active peptide complex prepared by the formula of the present invention can be basically completely dissolved in the solution system.

[0141] It can be seen from the above embodiments and comparative examples that the present invention, through the coordination of the types and contents of surfactants and solvents in phases A and B, enables the components in the active peptide complex to form a uniform and clear solution after mixing, indicating that the oil-soluble polypeptide can be dissolved in the dual-continuous phase system, so that the oil-soluble polypeptide can resist hydrolysis by proteases, and can fully exert the efficacy of the polypeptide when used on the skin surface, such as the role of palmitoyl polypeptide in promoting collagen regeneration.

[0142] In Comparative Example 1, only glycerol was used as the solvent in the aqueous phase, which made the system unstable. In Comparative Examples 2-4, no surfactant with a specific HLB value was added to the oil phase, and a clear uniform solution could not be formed. The experimental results in the research and development process show that the content of hydrophilic surfactants I, II and lipophilic surfactants, as well as the content of the polyols, have a significant effect on the stability of the solution. In addition, during the research and development process, it was also attempted to replace all the sorbitol polyether-30 tetraoleate in phase A of the embodiment with polyglycerol-2 isostearate, or to replace all polyglycerol-2 isostearate with sorbitol polyether-30 tetraoleate, or to replace polysorbate-20 in phase B with sorbitol polyether-30 tetraoleate. All of the obtained products were white milky substances, and stratification occurred the next day.

[0143] The preferred specific embodiments of the present invention are described in detail above. It should be understood that ordinary technicians in the field can make many modifications and changes based on the concept of the present invention without creative work. Therefore, all technical solutions that can be obtained by technicians in the technical field based on the concept of the present invention through logical analysis, reasoning or limited experiments on the basis of the prior art should be within the scope of protection determined by the claims.

Claims

1. An active peptide complex, characterized in that: It includes phase A and phase B; The phase A comprises an oily solvent, a lipophilic surfactant and a hydrophilic surfactant I; The phase B includes an oil-soluble polypeptide, a hydrophilic surfactant II, an alcohol solvent and water; wherein the water solubility of the hydrophilic surfactant I is different from the water solubility of the hydrophilic surfactant I; Wherein, the alcohol solvent at least includes a polyol with more than 4 carbon atoms.

2. The active peptide complex according to claim 1, characterized in that The active peptide complex is a clear homogeneous solution; And / or, the active peptide complex comprises a dual continuous phase structure; wherein, preferably, the A phase and the B phase are both continuous phases, and the A phase and the B phase are separated from each other and intercalated with each other.

3. The active peptide complex according to claim 1, characterized in that The active peptide complex satisfies one or more of the following conditions: (1) The ratio of the total mass of the A phase to the total mass of the B phase is (3.5-6):1, preferably (3.5-5.5):1, for example, 3.78:1, 4.15:1 or 5.27:1; (2) The ratio of the mass of the oily solvent to the total mass of "the alcohol and the water" is (1.5-3):1, preferably (2-2.5):1, for example 2.2:1; (3) The water solubility of the hydrophilic surfactant II is greater than that of the hydrophilic surfactant I; preferably, the HLB value of the hydrophilic surfactant II is 4-6 greater than the HLB value of the hydrophilic surfactant I.

4. The active peptide complex according to claim 1, characterized in that The A phase satisfies one or more of the following conditions: (1) The oily solvent is an isoparaffin having 9 to 19 carbon atoms; (2) based on the mass percentage of the active peptide complex being 100%, the content of the oily solvent is 35-55%; (3) The HLB value of the lipophilic surfactant is less than 7; (4) Based on the mass percentage of the active peptide complex as 100%, the content of the lipophilic surfactant is 10-25%; (5) The HLB value of the hydrophilic surfactant I is 8-15; (6) Based on the mass percentage of the active peptide complex as 100%, the content of the hydrophilic surfactant I is 10-30%; (7) The mass ratio of the hydrophilic surfactant I to the oily solvent is (0.4-0.6):1; (8) The mass ratio of the lipophilic surfactant to the oily solvent is (0.3-0.5):

1.

5. The active peptide complex according to claim 4, characterized in that The A phase satisfies one or more of the following conditions: (1) The oily solvent is an isoparaffin having 14 to 18 carbon atoms, such as isohexadecane; (2) based on the mass percentage of the active peptide complex as 100%, the content of the oily solvent is 40-50%, for example, 41%, 42%, 42.5%, 43%, 44%, 45% or 46%; (3) The HLB value of the lipophilic surfactant is 4-5, for example 4.7; the lipophilic surfactant is preferably a polyglyceryl surfactant, for example polyglyceryl-2 isostearate; (4) Based on the mass percentage of the active peptide complex as 100%, the content of the lipophilic surfactant is 15-20%, for example, 17%; (5) The HLB value of the hydrophilic surfactant I is 11-12, for example, 11.5; the hydrophilic surfactant I is preferably a sorbitan polyether surfactant, for example, sorbitan polyether-30 tetraoleate; (6) Based on the mass percentage of the active peptide complex as 100%, the content of the hydrophilic surfactant I is 18-23%, for example, 21% or 21.2%; (7) The mass ratio of the hydrophilic surfactant I to the oily solvent is (0.45-0.55):1, for example, 0.46:1, 0.5:1 or 0.51:1; (8) The mass ratio of the lipophilic surfactant to the oily solvent is (0.35-0.45):1, for example, 0.37:1, 0.4:1 or 0.41:

1.

6. The active peptide complex according to any one of claims 1 to 5, characterized in that The B phase satisfies one or more of the following conditions: (1) The oil-soluble polypeptide is a palmitoyl polypeptide; (2) based on the mass percentage of the active peptide complex as 100%, the content of the oil-soluble polypeptide is less than 1% but not 0%; (3) The HLB value of the hydrophilic surfactant II is greater than 12; (4) Based on the mass percentage of the active peptide complex as 100%, the content of the hydrophilic surfactant II is 0.1-2.0%; (5) The polyol is a diol, preferably including butanediol and / or pentanediol; (6) Based on the mass percentage of the active peptide complex as 100%, the content of the alcohol solvent is 1-10%; (7) Based on the mass percentage of the active peptide complex as 100%, the content of the polyol is 1.5-8%; (8) Based on the mass percentage of the active peptide complex as 100%, the water content is 10-20%; (9) The alcohol solvent further includes glycerol; (10) The mass ratio of the hydrophilic surfactant II to the oil-soluble polypeptide is (20-130):1; (11) The mass ratio of the alcohol solvent to the oil-soluble polypeptide is (150-400):1; (12) The mass ratio of the water to the oil-soluble polypeptide is (500-1000):

1.

7. The active peptide complex according to claim 6, characterized in that The B phase satisfies one or more of the following conditions: (1) The oil-soluble polypeptide is palmitoyl tripeptide and / or palmitoyl pentapeptide; (2) based on the mass percentage of the active peptide complex as 100%, the content of the oil-soluble polypeptide is 0.005-0.02%, for example, 0.006%, 0.012% or 0.018%; (3) The HLB value of the hydrophilic surfactant II is 15-18, for example, 16.5; the hydrophilic surfactant II is preferably a polysorbate, for example, polysorbate-20; (4) based on the mass percentage of the active peptide complex as 100%, the content of the hydrophilic surfactant II is 0.5-1.0%; (5) The polyol includes one or more of 1,2-pentanediol, 1,2-butanediol and 1,3-butanediol; (6) Based on the mass percentage of the active peptide complex as 100%, the content of the alcohol solvent is 3-8%, for example, 3.42% or 6.88%; (7) Based on the mass percentage of the active peptide complex as 100%, the content of the polyol is 3-8%, for example, 3.13% or 6.88%; (8) Based on the mass percentage of the active peptide complex as 100%, the water content is 10-15%, for example, 12% or 13%; (9) When the alcohol solvent also includes glycerol, the content of the glycerol is 1-5%; (10) The mass ratio of the hydrophilic surfactant II to the oil-soluble polypeptide is (25-120):1, for example, 27.78:1 or 111.11:1; (11) The mass ratio of the alcohol solvent to the oil-soluble polypeptide is (180-390):1, for example, 190.11:1 or 382.22:1; (12) The mass ratio of the water to the oil-soluble polypeptide is (600-900):1, for example, 666.67:1, 667.78:1 or 858.89:

1.

8. A method for preparing an active peptide complex, characterized in that: Mixing the phase A as described in any one of claims 1 to 7 with the phase B; The mixing is preferably performed by slowly or portion-wise adding the phase B to the phase A, or slowly or portion-wise adding the phase A to the phase B.

9. An active peptide complex, characterized in that: The method is prepared according to claim 8.

10. A cosmetic, characterized in that: It comprises the active peptide complex according to any one of claims 1 to 7 and 9; the cosmetic preferably comprises lip cosmetics and / or facial cosmetics.

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