Anti-hair loss care ingredient, preparation method thereof and shampoo

Abstract

The present invention discloses an anti-hair loss care component and a preparation method thereof and a shampoo, wherein the anti-hair loss care component is an ionic salt formed by R-Lys-Gly-His-Lys-NH2 and oleanolic acid; wherein R is a palmitoyl or myristoyl group; and it has high temperature storage stability, transdermal permeability and a proliferation promoting effect of HDPCs in an aqueous solution environment, thereby promoting anti-hair loss and hair growth. The present invention prepares the ionic salt by atomization mixing, and has the characteristics of high product purity, high reaction efficiency and simple process. The present invention also provides a shampoo containing the above-mentioned anti-hair loss care component, which has a suitable viscosity and pH value.

Description

Technical Field

[0001] The invention belongs to the technical field of daily chemicals, and particularly relates to an anti-hair loss care component and a preparation method thereof and a shampoo. Background Art

[0002] Human hair has multiple functions such as defense, maintaining body temperature and decoration. In recent years, with the increasingly fierce social competition, people's mental stress, the deteriorating environment and the popularity of hair dyeing and perming, the incidence of hair loss has been on the rise, and the trend of younger people is becoming more and more obvious. Hair loss has become a common disease in dermatology, seriously affecting the normal life of patients.

[0003] The public's demand for "anti-hair loss and hair growth" is increasing, and the hair care products they buy are concentrated on those with "anti-hair loss and hair growth" functions. For those with severe hair loss or long-term hair growth, nutrient solution should be applied to the scalp in time to supplement the nutrients needed for scalp cell growth and hair growth, promote the rapid division of hair follicle cell metabolism, prolong the tolerance period of hair follicle functional degradation after hair loss, promote hair growth, relieve hair loss and promote hair growth. The anti-hair loss market demand is becoming more and more potential.

[0004] As a natural bioactive substance, functional peptides have a variety of beneficial effects, such as strengthening hair, promoting scalp blood circulation, antibacterial / antibacterial, maintaining scalp water and oil balance, anti-photoaging, promoting hair growth, maintaining melanin, etc., so their application in hair care products has attracted much attention. Acetyl tetrapeptide-3 is a functional peptide that promotes hair growth. It can accelerate the formation of extracellular matrix (ECM) proteins, such as adhesion proteins, collagen III and VI I, etc., thereby effectively improving the structure of hair follicles and increasing the stability of hair anchoring. Acetyl tetrapeptide-3 cannot directly reduce DHT, but it can enhance the resistance of hair follicles to DHT. It can stimulate the hair papilla and accelerate the synthesis of ECM proteins, increase the volume of hair follicles; repair the epidermis-dermis junction (DEJ), promote the fixation of hair in the hair follicles, and stimulate hair growth; it can also effectively reduce the hair loss caused by aging, making the hair thicker, natural, smooth and tight. However, the transport of acetyl tetrapeptide-3 on biological membranes is very poor, mainly due to the enzymatic reaction or chemical degradation of the polypeptide and the insufficient stability caused by excessive hydrophilicity, making it difficult to be absorbed and utilized through the stratum corneum of the skin.

[0005] Based on the above technical status, the present invention is proposed. Summary of the invention

[0006] The purpose of the invention is to provide an anti-hair loss care ingredient and a preparation method thereof and a shampoo. The anti-hair loss care ingredient has good skin permeability and storage stability, and can promote the synthesis of collagen III, which is beneficial to anchoring hair and reducing hair loss.

[0007] The present invention adopts the following technical solutions:

[0008] In a first aspect, the present invention provides an anti-hair loss care ingredient, which is an ionic salt formed by R-Lys-Gly-His-Lys-NH2 and oleanolic acid; wherein R is palmitoyl or myristoyl, and Lys, Gly, and His are lysine, glycine, and histidine, respectively. In detail, the ionic salt has the following chemical structure:

[0009]

[0010] In some embodiments of the present invention, the preparation method of R-Lys-Gly-His-Lys-NH2 comprises the following steps:

[0011] (1) Preparation of R-Lys(Boc)-OH

[0012] H-Lys(Boc)-Otbu·HCl and fatty acid chloride are mixed and dissolved in a solvent, and an activator is added to perform an acylation reaction; and R-Lys(Boc)-OH is obtained after a first purification and a first deprotection.

[0013] The fatty acid chloride includes palmitic acid chloride or myristoyl chloride.

[0014] (2) Preparation of R-Lys(Boc)-Gly-OH

[0015] R-Lys(Boc)-OH and H-Gly-Otbu·HCl are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to carry out an acylation reaction; and R-Lys(Boc)-Gly-OH is obtained after a first purification and a first deprotection.

[0016] (3) Preparation of R-Lys(Boc)-Gly-His(1-Trt)-OH

[0017] R-Lys(Boc)-Gly-OH and H-His(1-Trt)-Otbu·HCl are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to carry out an acylation reaction; after a first purification and a first deprotection, R-Lys(Boc)-Gly-His(1-Trt)-OH is obtained.

[0018] (4) Preparation of R-Lys(Boc)-Gly-His-Lys(Boc)-OBn

[0019] R-Lys(Boc)-Gly-His(1-Trt)-OH and H-Lys(TFA)-OBn are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to carry out an acylation reaction; after a second purification, R-Lys(Boc)-Gly-His-Lys(Boc)-OBn is obtained.

[0020] (5) Preparation of R-Lys-Gly-His-Lys-NH2

[0021] R-Lys(Boc)-Gly-His-Lys(TFA)-OBn was subjected to a second deprotection to obtain R-Lys-Gly-His-Lys-NH2.

[0022] In some embodiments of the present invention, the solvent is N,N-dimethylformamide (DMF), dichloromethane (DCM) or acetonitrile.

[0023] In some embodiments of the present invention, the activating agent is N,N-diisopropylethylamine (DIEA) or N-methylmorpholine (NMM).

[0024] In some embodiments of the present invention, the condensing agent is at least one of O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU), O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU) and 1-hydroxybenzotriazole (HOBT).

[0025] In some embodiments of the present invention, the reaction temperature of the acylation reaction is 25 to 30° C., and the reaction time is 15 to 40 min.

[0026] In some embodiments of the present invention, the first purification comprises the following steps: adding 10 times the volume of water for sedimentation, after solid-liquid separation, dissolving the solid with ethyl acetate, then washing with saturated sodium bicarbonate solution, citric acid solution, and saturated sodium chloride solution in sequence, then taking the organic phase and adding anhydrous magnesium sulfate for drying, and drying after solid-liquid separation to obtain the product before deprotection.

[0027] In some embodiments of the present invention, the second purification comprises the following steps: adding a saturated sodium bicarbonate solution after concentrating the reaction solution, separating the solid and the liquid after pulping, drying the solid and re-dissolving it with methanol, adding methyl tert-butyl ether dropwise, gradually causing precipitation, standing in an ice bath for 24 hours, separating the solid and the liquid, and drying the solid to obtain the product.

[0028] In some embodiments of the present invention, the first deprotection comprises the following steps: dispersing the product before deprotection in a TFA solution, stirring the reaction, concentrating until the volume no longer decreases, then adding chilled anhydrous ether for precipitation, and obtaining the product after centrifugation, washing, and freeze-drying.

[0029] In some embodiments of the present invention, the second deprotection comprises the following steps: dispersing R-Lys(Boc)-Gly-His-Lys(TFA)-OBn in aqueous ammonia, stirring the reaction at 25-30°C, concentrating the reaction solution, adding TFA solution for dilution, stirring the reaction, concentrating the reaction solution until the volume no longer decreases, adding chilled anhydrous ether for precipitation, and obtaining the product after centrifugation, washing, and freeze-drying.

[0030] In a second aspect, the present invention provides a method for preparing the above-mentioned anti-hair loss care ingredient, comprising the following steps:

[0031] Dissolving oleanolic acid and R-Lys-Gly-His-Lys-NH2 in an alcohol solution respectively to obtain an oleanolic acid solution and a polypeptide solution;

[0032] The oleanolic acid solution and the polypeptide solution are respectively atomized and injected into the reaction vessel cavity for mixing, and stirred for reaction;

[0033] The reaction liquid in the reaction kettle is collected and dried to obtain the ion salt.

[0034] In some embodiments of the present invention, the alcohol solution is methanol or ethanol;

[0035] In some embodiments of the present invention, the concentration of the oleanolic acid solution is 0.5-2%, and the concentration of the polypeptide solution is 1%-5%;

[0036] In some embodiments of the present invention, the molar ratio of the oleanolic acid to the R-Lys-Gly-His-Lys-NH2 is 1 to 1.2:1;

[0037] In some embodiments of the present invention, the atomization is performed using an atomizing gun, and the pressure of the atomizing gun is 0.1 to 5 MPa;

[0038] In some embodiments of the present invention, the atomized liquid flow rate is 0.8 to 1 L / h;

[0039] In some embodiments of the present invention, the stirring reaction is carried out under an inert atmosphere;

[0040] In some embodiments of the present invention, the stirring reaction refers to stirring the reaction liquid condensed at the bottom of the reactor, and the stirring speed is 800-1200 rpm.

[0041] In a third aspect, the present invention provides a shampoo comprising the following components, calculated by mass percentage:

[0042] 10% to 20% surfactant, 0.1% to 1% hair conditioning agent, 0.003% to 0.03% anti-hair loss care ingredient, 0.05% to 0.1% plant extract, 0.1% to 0.8% moisturizer, 0.05% to 0.1% pH adjuster, 1% to 3% preservative, 0.05% to 0.2% chelating agent, 1% to 2% emollient, 0.2% to 0.6% viscosity regulator, and the balance is water.

[0043] In some embodiments of the present invention, a shampoo comprises the following components, calculated by mass percentage:

[0044] 10% to 20% surfactant, 0.1% to 1% hair conditioning agent, 0.003% to 0.03% anti-hair loss care ingredient, 0.05% to 0.1% plant extract, 0.1% to 0.8% moisturizer, 0.05% to 0.1% pH adjuster, 1% to 3% preservative, 0.05% to 0.2% chelating agent, 1% to 2% emollient, 0.2% to 0.6% viscosity regulator, 0.01% to 0.5% scalp care agent, and the balance is water.

[0045] In some embodiments of the present invention, a shampoo comprises the following components, calculated by mass percentage:

[0046] Surfactant 10% to 20%, hair conditioner 0.1% to 1%, anti-hair loss care ingredient 0.003% to 0.03%, plant extract 0.05% to 0.1%, moisturizer 0.1% to 0.8%, pH adjuster 0.05% to 0.1%, preservative 1% to 3%, chelating agent 0.05% to 0.2%, emollient 1% to 2%, viscosity regulator 0.2% to 0.6%, scalp care agent 0.01% to 0.5%, appearance improver 1% to 1.5%, fragrance 0.1% to 1%, and the balance is water.

[0047] In some embodiments of the present invention, the surfactant is selected from at least one of ammonium lauryl sulfate, sodium laureth sulfate, sodium lauroyl sarcosinate, potassium cocoyl glycinate, cocamidopropyl betaine, potassium lauryl phosphate, capryl / decyl glucoside, cocamide DEA and sodium laurylamphoacetate.

[0048] In some embodiments of the present invention, the hair conditioning agent is selected from at least one of guar hydroxypropyltrimonium chloride, stearamidopropyl dimethylamine lactate, polyquaternium-10, polyquaternium-22, polyquaternium-73, laureth-25, tripeptide-1 copper, biomimetic KP peptide and glutathione.

[0049] In some embodiments of the present invention, the scalp care agent is selected from at least one of palmitoyl hexapeptide-21, menthol, caffeine, palmitoyl tripeptide-37, zinc pyrithione, octopirox olamine, and climbazole.

[0050] In some embodiments of the present invention, the plant or plant part in the plant extract is selected from at least one of Platycladus orientalis leaves, Polygonum multiflorum, ginger root, lavender, ginseng, Swertia japonica, Isatis indigotica leaves, Pandanus odoratus leaves, Centella asiatica and Artemisia argyi.

[0051] In some embodiments of the present invention, the humectant is at least one of glycerin, butylene glycol, dipropylene glycol, propylene glycol and pentylene glycol.

[0052] In some embodiments of the present invention, the pH adjuster is selected from at least one of citric acid, sodium hydroxide and triethanolamine.

[0053] In some embodiments of the present invention, the preservative is selected from at least one of sodium benzoate, phenoxyethanol, methylpropylene glycol, methylchloroisothiazolinone, methylisothiazolinone, parabens and parabens.

[0054] In some embodiments of the invention, the chelating agent is disodium EDTA.

[0055] In some embodiments of the present invention, the emollient is selected from at least one of dimethicone and its derivatives and triisostearin.

[0056] In some embodiments of the present invention, the viscosity modifier is sodium chloride.

[0057] In some embodiments of the present invention, the appearance improving agent is selected from at least one of ethylene glycol distearate and ethylene glycol stearate.

[0058] In some embodiments of the present invention, a shampoo comprises the following components, calculated by mass percentage: 1.5% to 2% of cocamide MEA, 10% to 18% of sodium laureth sulfate, 0.1% to 1% of ammonium lauryl sulfate, 1.8% to 2.1% of cocamidopropyl betaine, 0.3% to 0.5% of stearamidopropyl dimethylamine lactate, 0.1% to 0.2% of guar hydroxypropyltrimethylammonium chloride, 0.3% to 0.5% of polyquaternium-10, 0.0004% to 0.001% of tripeptide-1 copper, 0.003% to 0.03% of anti-hair loss care ingredients, 0.03% to 0.04% of Platycladus orientalis leaf extract, 0.03% to 0.04% of Polygonum multiflorum extract, 0.01% to 0.02% of ginger root extract, and 0.06% to 0.1% of lavender extract. .001%~0.005%, propylene glycol 0.08%~0.12%, glycerin 0.3%~0.5%, citric acid 0.06%~0.08%, methylpropanediol 1%~1.5%, phenoxyethanol 0.4%~0.7%, sodium benzoate 0.2%~0.4%, disodium EDTA 0.05%~0.2%, menthol 0.2%~0.4%, polydimethylsiloxane 1%~2%, triisostearin 0.4%~0.5%, ethylene glycol distearate 0.7%~0.8%, ethylene glycol stearate 0.7%~0.8%, sodium chloride 0.3%~0.6%, flavor 0.5%~0.8%, and the balance is water.

[0059] Beneficial effects:

[0060] The present invention provides an anti-hair loss care component, which is an ionic salt prepared from hydrophobically modified tetrapeptide-3 and oleanolic acid; the hydrophobically modified tetrapeptide-3 (R-Lys-Gly-His-Lys-NH2) has better high-temperature storage stability and higher transdermal properties in an aqueous solution environment than acetyl tetrapeptide-3, can promote the synthesis of collagen III, is conducive to anchoring hair, and reduces hair loss. The hydrophobically modified tetrapeptide-3 is further prepared with oleanolic acid to obtain an ionic salt, and its high-temperature storage stability, transdermal properties, and HDPCs proliferation promotion effect are further improved.

[0061] The present invention provides a method for preparing the ionic salt, which innovatively uses an atomization mixing method to mix the organic base and the organic acid, so that the ionic salt obtained by the reaction has a better purity, and the reaction is efficient and simple.

[0062] The present invention also provides a shampoo having suitable adhesion and pH value. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] Figure 1 This is the HPLC chromatogram of palmitoyl tetrapeptide-3 prepared in Example 1.

[0064] Figure 2This is the HPLC chromatogram of myristoyl tetrapeptide-3 prepared in Example 2.

[0065] Figure 3 This is the mass spectrum of palmitoyl tetrapeptide-3 prepared in Example 1.

[0066] Figure 4 This is the mass spectrum of myristoyl tetrapeptide-3 prepared in Example 2.

[0067] Figure 5 This is the mass spectrum of the ionic salt prepared in Example 3.

[0068] Figure 6 This is the mass spectrum of the ionic salt prepared in Comparative Example 1.

[0069] Figure 7 This is a photo of the hair growth condition in the hair-depleting area on the back of the mouse in Test Example 6. DETAILED DESCRIPTION

[0070] The present invention is further described in detail below in conjunction with specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0071] The manufacturers of some raw materials in the following examples are shown in Table 1.

[0072] Table 1

[0073]

[0074] The invention provides an anti-hair loss care component, which is an ion salt formed by R-Lys-Gly-His-Lys-NH2 and oleanolic acid; wherein R is a palmitoyl group or a myristoyl group, and Lys, Gly and His are lysine, glycine and histidine respectively.

[0075] In some embodiments of the present invention, the above ionic salt has the following chemical structure:

[0076]

[0077] When R is C 15 H 21 CO (palmitoyl), R-Lys-Gly-His-Lys-NH2 is palmitoyl tetrapeptide-3; when R is C 13 H 27CO (myristoyl), R-Lys-Gly-His-Lys-NH2 is myristoyl tetrapeptide-3; R-Lys-Gly-His-Lys-NH2 has good skin permeability and storage stability, and can promote the synthesis of collagen III, which is beneficial to anchor hair and reduce hair loss.

[0078] Oleanolic acid can inhibit apoptosis of cells in hair follicles to a certain extent, and promote hair growth by prolonging the growth phase of hair follicles and delaying their entry into the regression phase. It can also promote the synthesis and secretion of vascular endothelial growth factor by hair follicle cells, further enhancing the blood supply to the scalp and providing sufficient nutrition for hair follicles, thereby achieving the effect of promoting hair growth.

[0079] The present invention combines palmitoyl tetrapeptide-3 or myristoyl tetrapeptide-3 with oleanolic acid to form an ionic salt. The ionic salt has a better ability to promote the synthesis of collagen III, and its transdermal permeability and storage stability are also improved compared with palmitoyl tetrapeptide-3 or myristoyl tetrapeptide-3. It can also promote the proliferation of human hair papilla cells HDPCs, thereby promoting hair growth.

[0080] In some embodiments of the present invention, the method for preparing the anti-hair loss care ingredient comprises the following steps:

[0081] Dissolving oleanolic acid and R-Lys-Gly-His-Lys-NH2 in an alcohol solution respectively to obtain an oleanolic acid solution and a polypeptide solution;

[0082] The oleanolic acid solution and the polypeptide solution are respectively atomized and injected into the reaction vessel cavity for mixing, and stirred for reaction;

[0083] The reaction liquid in the reaction kettle is collected and dried to obtain the anti-hair loss care component.

[0084] The present invention creatively uses an atomization mixing method to react an organic acid (oleanolic acid) and an organic base (polypeptide) to obtain an ionic salt. The atomization mixing method greatly improves the contact between the organic acid and the organic base at the ionic level, improves the reaction rate and uniformity, and obtains an ionic salt of the polypeptide and oleanolic acid.

[0085] In some embodiments of the present invention, the alcohol solution is methanol or ethanol.

[0086] In some embodiments of the present invention, the concentration of the oleanolic acid solution is 0.5-2%, and the concentration of the polypeptide solution is 1%-5%. The concentration of the oleanolic acid solution of the present invention is lower than that of the polypeptide solution because R-Lys-Gly-His-Lys-NH2 has multiple basic groups, and imidazole has a higher reaction activity due to conjugation. Therefore, when the concentration of the acidic group is low, the acidic group is preferentially neutralized with the basic group of imidazole to form a salt, thereby forming an ionic salt with a relatively simple composition.

[0087] In some embodiments of the present invention, the molar ratio of the oleanolic acid to the R-Lys-Gly-His-Lys-NH2 is 1 to 1.2:1.

[0088] In some embodiments of the present invention, the atomization is performed using an atomizing gun, and the pressure of the atomizing gun is 0.1-5 MPa; the atomization pressure can affect the diameter of the atomized droplets, and the greater the atomization pressure, the smaller the droplet diameter.

[0089] In some embodiments of the present invention, the flow rate of the atomized liquid is 0.8 to 1 L / h.

[0090] In some embodiments of the present invention, the stirring reaction is carried out under an inert atmosphere;

[0091] In some embodiments of the present invention, the stirring reaction refers to stirring the reaction liquid condensed at the bottom of the reactor, and the stirring speed is 800-1200 rpm.

[0092] The solution of the present invention will be discussed below in conjunction with specific implementation methods:

[0093] Example 1

[0094] Preparation of palmitoyl tetrapeptide-3, which has the following chemical molecular structure:

[0095]

[0096] The preparation method of palmitoyl tetrapeptide-3 comprises the following steps:

[0097] (1) Preparation of C 15 H 31 CO-Lys(Boc)-OH

[0098] H-Lys(Boc)-Otbu·HCl, palmitoyl chloride and DIEA were weighed and dissolved in DMF according to a molar ratio of 1:1:1, and stirred at 25°C for 30 minutes under nitrogen protection. 10 times the volume of water was added for precipitation. After suction filtration, the solid was dissolved in ethyl acetate, and then washed twice with saturated sodium bicarbonate solution, 10wt% citric acid aqueous solution and saturated sodium chloride solution in sequence. The organic phase was dried with anhydrous magnesium sulfate, filtered and vacuum dried at 50°C to obtain the pre-deprotection product C. 15 H 31 CO-Lys(Boc)-Otbu; the product before deprotection was dispersed in a 90 wt% TFA aqueous solution, placed in a -5°C ice bath and stirred for reaction for 3 h, the reaction solution was concentrated until the volume no longer decreased, and then 10 times the volume of frozen anhydrous ether was added for precipitation. The solid obtained after centrifugation was freeze-dried to obtain product C 15 H 31 CO-Lys(Boc)-OH.

[0099] (2) Preparation of C 15 H 31 CO-Lys(Boc)-Gly-OH

[0100] Weigh C in a molar ratio of 1:1:1:1:2 15 H 31 CO-Lys(Boc)-OH, H-Gly-Otbu·HCl, HOBT, HBTU, NMM, first C 15 H 31 CO-Lys(Boc)-OH, H-Gly-Otbu·HCl, and HOBT were stirred and dissolved in DMF at a solid-liquid ratio of 3mL:1g, and then HBTU was added and stirred to dissolve, and then NMM was added dropwise in an ice bath at 0°C. After the addition was complete, the mixture was stirred and reacted at 25°C. After the reaction was completed as detected by HPLC, 10 times the volume of water was added for precipitation. After filtration, the solid was dissolved in ethyl acetate, and then washed twice with a saturated sodium bicarbonate solution, a 10wt% citric acid aqueous solution, and a saturated sodium chloride solution in sequence. The organic phase was dried with anhydrous magnesium sulfate, filtered, and dried in vacuo at 50°C to obtain the deprotection pre-product C. 15 H 31 CO-Lys(Boc)-Gly-Otbu; the product before deprotection was dispersed in a 90 wt% TFA aqueous solution, placed in a -5°C ice bath and stirred for reaction for 3 h, the reaction solution was concentrated until the volume no longer decreased, and then 10 times the volume of frozen anhydrous ether was added for precipitation. The solid obtained after centrifugation was freeze-dried to obtain product C 15 H 31 CO-Lys(Boc)-Gly-OH.

[0101] (3) Preparation of C 15 H 31 CO-Lys(Boc)-Gly-His(1-Trt)-OH

[0102] C 15 H 31 CO-Lys(Boc)-Gly-OH instead of C 15 H 31 CO-Lys(Boc)-OH, H-His(1-Trt)-Otbu·HCl was used instead of H-Gly-Otbu·HCl, and the method of step (2) was repeated to prepare C 15 H 31 CO-Lys(Boc)-Gly-His(1-Trt)-OH.

[0103] (4) Preparation of C 15 H 31 CO-Lys(Boc)-Gly-His-Lys(Boc)-OBn

[0104] Weigh C in a molar ratio of 1:1:1:1:2 15 H 31 CO-Lys(Boc)-Gly-His(1-Trt)-OH, H-Lys(TFA)-OBn, HOBT, HBTU, NMM, firstly C 15 H 31 CO-Lys(Boc)-Gly-His(1-Trt)-OH, H-Lys(TFA)-OBn, and HOBT were stirred and dissolved in acetonitrile at a solid-liquid ratio of 1g:3mL, and then HBTU was added and stirred to dissolve, and then NMM was added dropwise in an ice bath at 0°C. After the addition was complete, the mixture was stirred and reacted at 25°C. After the reaction was completed as detected by HPLC, the reaction solution was concentrated and a saturated sodium bicarbonate solution was added. After beating for 3 hours, the solid-liquid separation was performed, and the filter residue was dried at 50°C and redissolved in methanol. Methyl tert-butyl ether was added dropwise, and a precipitate gradually appeared. The mixture was then placed in an ice bath and allowed to stand for 24 hours to allow the precipitation to be complete. After solid-liquid separation, the filter residue was dried to obtain product C. 15 H 31 CO-Lys(Boc)-Gly-His-Lys(Boc)-OBn.

[0105] (5) Preparation of C 15 H 31 CO-Lys-Gly-His-Lys-NH2

[0106] C 15 H 31CO-Lys(Boc)-Gly-His-Lys(TFA)-OBn was dispersed in saturated ammonia water at a solid-liquid ratio of 1g:2mL, and stirred at 30°C for reaction. After the reaction was completed by HPLC, the reaction solution was concentrated, and a 90wt% TFA aqueous solution was added for dilution. After the reaction was continued for 3 hours with stirring, the reaction solution was concentrated until the volume did not decrease, and then frozen anhydrous ether was added for precipitation. After centrifugation, the bottom precipitate was washed with pure water and freeze-dried to obtain product C. 15 H 31 CO-Lys-Gly-His-Lys-NH2.

[0107] Example 1 prepared C 15 H 31 The HPLC and mass spectrometry of CO-Lys-Gly-His-Lys-NH2 are shown in the attached Figure 1 and 3 shown.

[0108] The test conditions of HPLC were as follows: the mobile phase was 0.1% trifluoroacetic acid-water; the chromatographic column was a silica gel alkyl bonded phase C18 column (4.6mm×300mm), a binary mobile phase gradient elution system was used, and gradient elution was performed, the content of the mobile phase in the eluent increased linearly from 0% to 80%, and the flow rate was 1mL / min. The test conditions of mass spectrometry were as follows: ion source: ESI, sheath gas flow rate: 20psi, auxiliary gas flow rate: 8psi, sweep gas flow rate: 5psi, spray voltage: 4.5KV, capillary temperature: 275℃, capillary voltage: 35V, and sleeve lens voltage: 110V.

[0109] From the attached Figure 1 It can be seen from the above that the palmitoyl tetrapeptide-3 prepared by the present invention has a high purity of more than 95%. Figure 3 It can be seen that the mass-to-charge ratio m / z of the pure palmitoyl tetrapeptide-3 prepared by the present invention is 706.54.

[0110] Example 2

[0111] Preparation of myristoyl tetrapeptide-3, having the following chemical molecular structure:

[0112]

[0113] The method for preparing myristoyl tetrapeptide-3 is different from that of Example 1 in that myristoyl chloride is used instead of palmitoyl chloride.

[0114] Example 2 prepared C 13 H 27 The HPLC and mass spectrometry of CO-Lys-Gly-His-Lys-NH2 are shown in the attached Figure 2 and4 shown.

[0115] From the attached Figure 2 It can be seen that the purity of the myristoyl tetrapeptide-3 prepared by the present invention is high, reaching more than 95%; Figure 4 It can be seen that the mass-to-charge ratio m / z of the pure myristoyl tetrapeptide-3 prepared by the present invention is 678.49.

[0116] Example 3

[0117] Oleanolic acid and C 15 H 31 CO-Lys-Gly-His-Lys-NH2 was dissolved in methanol to obtain a 0.5 wt% oleanolic acid solution and a 1 wt% polypeptide solution;

[0118] The inner cavity of the reactor was replaced with nitrogen, and then the oleanolic acid solution and the polypeptide solution were placed in the liquid storage tank of the atomizer gun, and injected into the reactor cavity for mixing after atomization. After liquid began to condense at the bottom of the reactor, stirring was started for reaction. After all the solutions were mixed, stirring was continued for 1 hour, and the reaction liquid in the reactor was collected, concentrated and dried to obtain the ion salt.

[0119] Oleanolic acid and the C 15 H 31 The molar ratio of CO-Lys-Gly-His-Lys-NH2 was 1.05:1. The pressure of the atomizing gun was 0.1 MPa, the flow rate of the atomized liquid was 0.8 L / h, and the stirring speed was 1200 rpm.

[0120] The mass spectrum of the ionic salt prepared in Example 3 is shown in Appendix 5.

[0121] From the attached Figure 5 The largest peak is the molecular ion peak (m / z=1162.87), which corresponds to the ionic salt, indicating that the ionic salt was successfully synthesized; in addition, the cation peak (706.58) and the anion peak (457.54) are also observed. Through calculation, the structure is as follows:

[0122]

[0123] Example 4

[0124] Oleanolic acid and C 13 H 27 CO-Lys-Gly-His-Lys-NH2 was dissolved in ethanol to obtain a 2 wt% oleanolic acid solution and a 5 wt% polypeptide solution;

[0125] The inner cavity of the reactor was replaced with nitrogen, and then the oleanolic acid solution and the polypeptide solution were placed in the liquid storage tank of the atomizer gun, and injected into the reactor cavity for mixing after atomization. After liquid began to condense at the bottom of the reactor, stirring was started for reaction. After all the solutions were mixed, stirring was continued for 1 hour, and the reaction liquid in the reactor was collected, concentrated and dried to obtain the ion salt.

[0126] Oleanolic acid and the C 13 H 27 The molar ratio of CO-Lys-Gly-His-Lys-NH2 was 1.1:1. The pressure of the atomizing gun was 5 MPa, the flow rate of the atomized liquid was 1 L / h, and the stirring speed was 800 rpm.

[0127] Test Example 1 Storage Stability

[0128] In order to evaluate the storage stability of R-Lys-Gly-His-Lys-NH2 and ionic salts, the test samples were prepared according to the following formula: cocamide MEA 2%, sodium laureth sulfate 10%, ammonium lauryl sulfate 0.5%, cocamidopropyl betaine 2%, sample (Examples 1 to 4, acetyl tetrapeptide-3, oleanolic acid) 3%, and the balance was water; blank means that no sample was added to the test sample; the test sample was placed at -5°C, 25°C, and 40°C, and the appearance of the test sample was observed after 90 days to observe whether flocs / precipitates, gels, stratification, etc. appeared. The test results are shown in Table 2.

[0129] Table 2

[0130]

[0131]

[0132] As can be seen from Table 2, Examples 1 and 2 respectively use palmitoyl and myristoyl modified tetrapeptide-3, which have better high temperature stability than acetyl tetrapeptide-3. The reason is that the hydrophobicity of Examples 1 and 2 is enhanced, making the molecular structure similar to that of a surfactant, which has an enhancing effect on the stability of the emulsion system, but the low temperature stability of the three is poor because the polypeptide crystallizes and flocculates at low temperatures. In addition, the storage stability of Examples 3 and 4 is further improved relative to Examples 1 and 2. The reason is that after the polypeptide and the organic acid form an ionic salt, the water solubility of the two is enhanced due to polarization, and the stability in the aqueous solution is greatly improved, which reduces the dependence on the surfactant, so that it does not precipitate due to demulsification at low or high temperatures.

[0133] Test Example 2 Skin Irritation

[0134] The patch test method was used to evaluate the skin irritation of the samples to be tested. The human test was conducted with adults aged 25 to 50 years old, 10 people for each sample. The samples to be tested were the same as those in [Test Example 1]. The application location was the curved side of the forearm, and the application time was 24 hours. The skin reaction was observed after removal, and the results were recorded according to the skin reaction grading standard in the "Safety Technical Specifications for Cosmetics" (2015 Edition). The results are shown in Table 3.

[0135] Table 3

[0136]

[0137]

[0138] The table shows the number of people who developed corresponding symptoms. From the results, it can be seen that Examples 1 to 4 are not irritating to the skin at a concentration of less than 3%.

[0139] Test Example 3: Transdermal

[0140] The permeability of the samples was evaluated by in vitro experiments. The specific method is as follows: the intact hairless mouse skin was installed in a Franz diffusion cell, with the epidermis side facing the donor chamber, the receptor chamber containing HEPES buffer (10mM, pH7.4) containing PMSF and PNT at concentrations of 5mM and 1mM, and the donor chamber was the same sample to be tested as in [Test Example 1]. After 24 hours, the skin was removed from the diffusion cell and washed with 1ml of distilled water (repeated 4 times) to remove the donor solution remaining on the skin surface. Use lint-free absorbent wipes to dry the skin. Separate the stratum corneum, epidermis, and dermis, and mince each of them and continuously shake with 1ml of methanol to extract the peptides distributed in each skin layer. After 24 hours of extraction, the sample was centrifuged and the supernatant was analyzed by LC-MS / MS. The experimental results were used to evaluate the amount of peptides retained in the skin layer. The results are listed in Table 4.

[0141] Table 4

[0142]

[0143] As shown in Table 4, acetyl tetrapeptide-3 can stay in the stratum corneum, but it is very difficult to penetrate, and the content in the epidermis and dermis is extremely low. The transdermal properties of Example 1 and Example 2 after hydrophobic modification are greatly improved, and the transdermal properties after salt formation with oleanolic acid are further enhanced.

[0144] Test Example 4 Promoting the proliferation of human dermal papilla cells HDPCs

[0145] The CCK-8 method was used to evaluate the promoting effect of the samples on the proliferation of human hair papilla cells HDPCs. The specific steps are as follows: 100 μL of fresh culture medium containing the sample was added to a 96-well cell plate filled with HDPCs to obtain the test group, and the concentration of the sample was 1 μM, 5 μM, and 25 μM; the new culture medium without the sample was used as the control group, and at least 3 replicates were added to each group. The cells were incubated at 37°C for 48 hours, and the cell activity of HDPCs was detected by the CCK-8 method. The cell survival rate of the control group was 100%, and the cell survival rate of the test group relative to the control group was listed in Table 5. The culture medium was DMEM high-glucose medium (containing 20% ​​FBS and 1% P / S).

[0146] Table 5

[0147]

[0148]

[0149] From the data in Table 5, it can be seen that Examples 1 and 2 have similar effects on promoting the proliferation of HDPCs relative to acetyl tetrapeptide-3; but Examples 3 and 4 have stronger promoting effects on the proliferation of HDPCs relative to the above three. However, when the sample is pure oleanolic acid, it has no effect on the proliferation of HDPCs, and even has a slight inhibitory effect. The possible reason for this is that oleanolic acid is not conducive to cell growth due to its certain acidity; but after forming an ion salt with the polypeptide, it affects the molecular configuration of the polypeptide, thereby also having a certain impact on its performance.

[0150] Test Example 5: Promotion of collagen III expression

[0151] To evaluate the promoting effect of the samples on collagen III expression, HDPCs were plated at 3×10 4 Cells were inoculated into 24-well plates at 1 μM, 10 μM and 100 μM respectively, and the control group without samples was set up in the same way. After incubation for 48 hours, the concentration of collagen III in the cell supernatant was detected, and the results are listed in Table 5.

[0152] Table 5

[0153]

[0154]

[0155] The loss of ECM proteins is considered to be one of the causes of androgenic alopecia. Collagen III, as one of the ECM proteins, is also a key component of the connective tissue of the hair follicles. It is synthesized and secreted by human hair papilla cells throughout the hair cycle to maintain the development and volume of the hair follicles. As can be seen from the data in the table, Examples 1 to 4 and acetyl tetrapeptide-3 have the effect of promoting the expression of collagen III, and the polypeptides after surface hydrophobic modification also play a role in promoting expression, while oleanolic acid does not have this function.

[0156] Test Example 6 Hair Growth Promotion Effect

[0157] The mouse model was used to evaluate the promoting effect of the sample on hair growth. The specific steps are as follows: take female C57BL / 6J mice aged 6 to 8 weeks and 18 to 20g, cut the hair on the back with electric clippers, evenly apply an appropriate amount of 8% sodium sulfide solution on the haircut area to remove the residual hair, wash with warm water and dry after 2 to 3 minutes, and the hair removal area is about 3cm×2cm. The skin on the back of the mouse is smooth, without damage and residual hair. After that, the hair removal area and the surrounding parts are disinfected with 75% ethanol. Mice with pink skin and hair in the resting phase were selected to establish a mouse hair loss model. On the second day of hair removal, the mice were randomly divided into 4 groups, 5 in each group, namely, Example 1 group, Example 3 group, acetyl tetrapeptide-3 group, and blank group; the blank group refers to no medication after modeling, and physiological saline is given. Apply the sample to be tested on the depilated area on the back of the mouse. The sample to be tested is a physiological saline solution containing 1 μM sample, once a day, with a dosage of 0.3 mL, covering the depilated area, and apply it continuously for 14 days. Observe and measure the following indicators of the mouse:

[0158] (1) Observation of hair growth in mice

[0159] The time and condition of mouse skin color changes were recorded and photographed.

[0160] (2) Measurement of mouse hair growth length

[0161] When the hair on the depilated part of the back of the mice was observed to grow again, the hair length of each group of mice was measured every other day until the end of the experiment. According to the five-point method, ten tufts of hair were taken from the depilated part of the back of each group of mice with tweezers (two tufts were taken from each point, and 5 to 10 hairs were plucked from each part), and the hair length was measured with a vernier caliper. The farthest distance between the two ends of the hair was recorded as the hair length, and the average hair length of each group of mice was obtained.

[0162] (3) Measurement of mouse hair weight

[0163] At the end of the experiment, each group of mice was killed, and the hair was cut as close to the mouse skin as possible with electric clippers. The hair of each group of mice was collected, weighed and recorded using an electronic analytical balance, and stored in labeled self-sealing bags. The average hair weight of each group of mice was calculated using a 1:100,000 electronic balance.

[0164] Attached Figure 7 The figure shows the typical hair growth condition in the depilatory area on the back of mice on the 7th day of the experiment. Table 6 shows the mean hair growth length on the 7th, 9th, 11th and 14th days of the mouse experiment, and the mean hair weight of each group of mice on the 14th day.

[0165] Table 6

[0166]

[0167]

[0168] It can be seen from the data in Table 6 that the ionic salt sample of Example 3 has a better effect in promoting hair growth than Example 1 and acetyl tetrapeptide-3. On the one hand, this is because the ionic salt has a higher transdermal property, and on the other hand, the ionic salt has a stronger effect on the proliferation of HDPCs cells and a stronger effect on promoting the expression of collagen III.

[0169] Comparative Example 1

[0170] An ionic salt, the preparation method comprises the following steps:

[0171] Oleanolic acid and C 15 H 31 CO-Lys-Gly-His-Lys-NH2 was dissolved in methanol to obtain a 1wt% oleanolic acid solution and a 1wt% polypeptide solution;

[0172] Under nitrogen protection, the oleanolic acid solution was dripped into the polypeptide solution, stirred at 1500 rpm at room temperature, and the reaction was continued for 8 hours after the dripping was completed. The reaction liquid in the reactor was collected, concentrated and dried to obtain the ion salt.

[0173] The mass spectrum of the ionic salt prepared in Comparative Example 1 is shown in Appendix 6.

[0174] From the attached Figure 6 As can be seen in the figure, no molecular ion peak of the ion salt was observed, only the molecular ion peak of the raw material was observed, indicating that oleanolic acid and C 15 H 31 CO-Lys-Gly-His-Lys-NH2 did not form an ionic salt.

[0175] Example 5

[0176] An anti-hair loss shampoo comprises the following components calculated by mass percentage:

[0177] Cocamide MEA 1.6%, sodium laureth sulfate 14%, ammonium lauryl sulfate 0.5%, cocamidopropyl betaine 1.98%, stearamidopropyl dimethylamine lactate 0.45%, guar hydroxypropyltrimonium chloride 0.12%, polyquaternium-10 0.4%, tripeptide-1 copper 0.0006%, anti-hair loss care ingredient (Example 3) 0.012%, Platycladus orientalis leaf extract 0.04%, Polygonum multiflorum extract 0.024%, ginger root extract 0.012%, fumigate Lachnos nucifera extract 0.0015%, propylene glycol 0.102%, glycerin 0.46%, citric acid 0.07%, methylpropanediol 1.22%, phenoxyethanol 0.635%, sodium benzoate 0.315%, disodium EDTA 0.05%, menthol 0.3%, polydimethylsiloxane 1.2%, triisostearin 0.5%, ethylene glycol distearate 0.75%, ethylene glycol stearate 0.75%, sodium chloride 0.54%, fragrance 0.8%, and the balance is water.

[0178] Comparative Example 2

[0179] Cocamide MEA 2%, sodium lauroyl sarcosinate 8%, caprylyl / decyl glucoside 1%, cocamidopropyl betaine 2%, stearamidopropyl dimethylamine lactate 0.2%, guar hydroxypropyltrimonium chloride 0.15%, polyquaternium-22 0.5%, laureth-25 0.1%, palmitoyl tetrapeptide-3 of Example 1 0.03%, Platycladus orientalis leaf extract 0.04%, Polygonum multiflorum extract 0.024%, ginger root extract 0.012%, ginseng extract 0.02%, propylene glycol 0. 102%, glycerin 0.46%, citric acid 0.07%, methylpropanediol 1.22%, phenoxyethanol 0.635%, sodium benzoate 0.315%, disodium EDTA 0.05%, menthol 0.3%, caffeine 0.02%, zinc pyrithione 0.005%, polydimethylsiloxane 1.2%, triisostearin 0.5%, ethylene glycol distearate 0.75%, ethylene glycol stearate 0.75%, sodium chloride 0.54%, flavor 0.8%, the balance is water.

[0180] Example 6

[0181] An anti-hair loss shampoo comprises the following components calculated by mass percentage:

[0182] Cocamide MEA 1.2%, potassium cocoyl glycinate 15%, sodium lauryl amphoacetate 0.6%, cocamidopropyl betaine 2%, guar hydroxypropyltrimonium chloride 0.2%, polyquaternium-10 0.3%, tripeptide-1 copper 0.0005%, glutathione 0.0005%, anti-hair loss care ingredient (Example 4) 0.003%, Platycladus orientalis leaf extract 0.04%, Polygonum multiflorum extract 0.022%, ginger root extract 0.012%, Artemisia argyi Extract 0.01%, Centella asiatica extract 0.015%, butylene glycol 0.2%, glycerin 0.6%, citric acid 0.08%, methylpropanediol 1.3%, phenoxyethanol 0.64%, paraben 0.1%, disodium EDTA 0.1%, menthol 0.2%, palmitoyl tripeptide-37 0.001%, hydroxymethyl octopirox olamine 0.0004%, polydimethylsiloxane 1.4%, sodium chloride 0.6%, and the balance is water.

[0183] Comparative Example 3

[0184] Cocamide MEA 1.6%, sodium laureth sulfate 14%, ammonium lauryl sulfate 0.5%, cocamidopropyl betaine 1.98%, stearamidopropyl dimethylamine lactate 0.45%, guar hydroxypropyltrimonium chloride 0.12%, polyquaternium-10 0.4%, tripeptide-1 copper 0.0006%, Example 2 myristoyl tetrapeptide-3 0.01%, Platycladus orientalis leaf extract 0.04%, Polygonum multiflorum extract 0.024%, ginger root extract 0.012%, lavender extract 0.0015%, propylene glycol 0.102%, glycerin 0.46%, citric acid 0.07%, methylpropanediol 1.22%, phenoxyethanol 0.635%, sodium benzoate 0.315%, disodium EDTA 0.05%, polydimethylsiloxane 1.5%, and the balance is water.

[0185] Test Example 7 Shampoo Viscosity

[0186] The viscometer was used for testing, the measuring temperature was 25±1°C, 3 rotors and 12 speeds were selected, and the samples were defoamed before measurement.

[0187] Test Example 8 pH value of shampoo

[0188] Use a pH meter to test, weigh a certain amount of sample, add water to dilute it into a 10% aqueous solution, stir to fully dissolve the sample, immerse the electrode in the solution, and wait until the reading stabilizes. The read data is the pH value of the sample.

[0189] The results of Test Examples 7 and 8 are listed in Table 7.

[0190] Table 7

[0191]

[0192] It can be seen from Table 7 that the shampoo formula provided by the present invention has suitable viscosity and pH value.

[0193] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. An anti-hair loss care ingredient, characterized in that: The anti-hair loss care ingredient is an ionic salt formed by R-Lys-Gly-His-Lys-NH2 and oleanolic acid; wherein R is palmitoyl or myristoyl, and Lys, Gly, and His are lysine, glycine, and histidine respectively.

2. The anti-hair loss care ingredient according to claim 1, characterized in that The anti-hair loss care ingredient has the following chemical formula:

3. The anti-hair loss care ingredient according to claim 1, characterized in that The preparation method of R-Lys-Gly-His-Lys-NH2 comprises the following steps: (1) Preparation of R-Lys(Boc)-OH H-Lys(Boc)-Otbu·HCl and fatty acid chloride are mixed and dissolved in a solvent, and an activator is added to perform an acylation reaction; after a first purification and a first deprotection, R-Lys(Boc)-OH is obtained; The fatty acid chloride includes palmitic acid chloride or myristic acid chloride; (2) Preparation of R-Lys(Boc)-Gly-OH R-Lys(Boc)-OH and H-Gly-Otbu·HCl are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to perform an acylation reaction; after a first purification and a first deprotection, R-Lys(Boc)-Gly-OH is obtained; (3) Preparation of R-Lys(Boc)-Gly-His(1-Trt)-OH R-Lys(Boc)-Gly-OH and H-His(1-Trt)-Otbu·HCl are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to perform an acylation reaction; after a first purification and a first deprotection, R-Lys(Boc)-Gly-His(1-Trt)-OH is obtained; (4) Preparation of R-Lys(Boc)-Gly-His-Lys(Boc)-OBn R-Lys(Boc)-Gly-His(1-Trt)-OH and H-Lys(TFA)-OBn are mixed and dissolved in a solvent, and a condensing agent and an activating agent are added to carry out an acylation reaction; after a second purification, R-Lys(Boc)-Gly-His-Lys(Boc)-OBn is obtained; (5) Preparation of R-Lys-Gly-His-Lys-NH2 R-Lys(Boc)-Gly-His-Lys(TFA)-OBn was subjected to a second deprotection to obtain R-Lys-Gly-His-Lys-NH2.

4. The anti-hair loss care ingredient according to claim 3, characterized in that The preparation method comprises the following steps: The solvent is N,N-dimethylformamide, dichloromethane or acetonitrile; And / or, the activator is N,N-diisopropylethylamine or N-methylmorpholine; and / or, the condensing agent is at least one of O-benzotriazole-tetramethyluronium hexafluorophosphate, O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroboric acid and 1-hydroxybenzotriazole; And / or, the reaction temperature of the acylation reaction is 25-30° C., and the reaction time is 15-40 min; And / or, the first purification comprises the following steps: adding 10 times the volume of water for sedimentation, after solid-liquid separation, dissolving the solid with ethyl acetate, then washing with saturated sodium bicarbonate solution, citric acid solution, and saturated sodium chloride solution in sequence, then taking the organic phase and adding anhydrous magnesium sulfate for drying, and drying after solid-liquid separation to obtain a product before deprotection; And / or, the second purification comprises the following steps: adding a saturated sodium bicarbonate solution to the reaction solution after concentration, separating the solid from the liquid after pulping, drying the solid and redissolving it with methanol, dropping methyl tert-butyl ether to gradually produce a precipitate, standing in an ice bath for 24 hours, separating the solid from the liquid and drying the solid to obtain a product; And / or, the first deprotection comprises the following steps: dispersing the product before deprotection in a TFA solution, stirring for reaction, concentrating until the volume no longer decreases, then adding frozen anhydrous ether for precipitation, centrifuging, washing, and freeze-drying to obtain a product; And / or, the second deprotection comprises the following steps: dispersing R-Lys(Boc)-Gly-His-Lys(TFA)-OBn in aqueous ammonia, stirring the reaction at 25-30°C, concentrating the reaction solution, adding TFA solution for dilution, stirring the reaction, concentrating the reaction solution until the volume no longer decreases, adding chilled anhydrous ether for precipitation, and obtaining the product after centrifugation, washing, and freeze-drying.

5. The method for preparing the anti-hair loss care ingredient according to any one of claims 1 to 4, characterized in that: The following steps are involved: Dissolving oleanolic acid and R-Lys-Gly-His-Lys-NH2 in an alcohol solution respectively to obtain an oleanolic acid solution and a polypeptide solution; The oleanolic acid solution and the polypeptide solution are respectively atomized and injected into the reaction vessel cavity for mixing, and stirred for reaction; The reaction liquid in the reaction kettle is collected and dried to obtain the anti-hair loss care component.

6. The preparation method according to claim 5, characterized in that: The alcohol solution is methanol or ethanol; And / or, the concentration of the oleanolic acid solution is 0.5-2%, and the concentration of the polypeptide solution is 1%-5%; And / or, the molar ratio of the oleanolic acid to the R-Lys-Gly-His-Lys-NH2 is 1 to 1.2:1; And / or, the atomization adopts an atomizing gun, and the pressure of the atomizing gun is 0.1-5MPa; And / or, the atomized liquid flow rate is 0.8 to 1 L / h; And / or, the stirring reaction is carried out under an inert atmosphere; And / or, the stirring reaction refers to stirring the reaction liquid condensed at the bottom of the reactor, and the stirring speed is 800-1200 rpm.

7. A shampoo, characterized in that: The shampoo comprises the anti-hair loss care ingredient according to any one of claims 1 to 4; the shampoo comprises the following components calculated by mass percentage: Surfactant 10%-20%, hair conditioner 0.1%-1%, anti-hair loss care ingredient 0.003%-0.03%, plant extract 0.05%-0.1%, moisturizer 0.1%-0.8%, pH adjuster 0.05%-0.1%, preservative 1%-3%, chelating agent 0.05%-0.2%, emollient 1%-2%, viscosity regulator 0.2%-0.6%, scalp care agent 0.01%-0.5%, appearance improver 1%-1.5%, fragrance 0%-1%, and the balance is water.

8. A shampoo according to claim 7, characterized in that: The hair conditioning agent is selected from at least one of guar hydroxypropyltrimonium chloride, stearamidopropyl dimethylamine lactate, polyquaternium-10, polyquaternium-22, polyquaternium-73, laureth-25, tripeptide-1 copper, biomimetic KP peptide and glutathione; And / or, the scalp care agent is selected from at least one of palmitoyl hexapeptide-21, menthol, caffeine, palmitoyl tripeptide-37, zinc pyrithione, octopirox olamine and climbazole; And / or, the plant or plant part in the plant extract is at least one selected from Platycladus orientalis leaves, Polygonum multiflorum, ginger root, lavender, ginseng, Swertia japonica, Isatis indigotica leaves, Pandanus odoratus leaves, Centella asiatica and Artemisia argyi; And / or, the appearance improver is selected from at least one of ethylene glycol distearate and ethylene glycol stearate.

9. A shampoo according to claim 7 or 8, characterized in that: Calculated by mass percentage, it includes the following components: cocamide MEA 1.5% to 2%, sodium laureth sulfate 10% to 18%, ammonium lauryl sulfate 0.1% to 1%, cocamidopropyl betaine 1.8% to 2.1%, stearamidopropyl dimethylamine lactate 0.3% to 0.5%, guar hydroxypropyltrimethylammonium chloride 0.1% to 0.2%, polyquaternium-100.3% to 0.5%, tripeptide-1 copper 0.0004% to 0.001%, anti-hair loss care ingredients 0.003% to 0.03%, cypress leaf extract 0.03% to 0.04%, Polygonum multiflorum extract 0.03% to 0.04%, ginger root extract 0.01% to 0.02%, lavender extract 0 .001%~0.005%, propylene glycol 0.08%~0.12%, glycerin 0.3%~0.5%, citric acid 0.06%~0.08%, methylpropanediol 1%~1.5%, phenoxyethanol 0.4%~0.7%, sodium benzoate 0.2%~0.4%, disodium EDTA 0.05%~0.2%, menthol 0.2%~0.4%, polydimethylsiloxane 1%~2%, triisostearin 0.4%~0.5%, ethylene glycol distearate 0.7%~0.8%, ethylene glycol stearate 0.7%~0.8%, sodium chloride 0.3%~0.6%, flavor 0.5%~0.8%, and the balance is water.

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