A natural medicine hair growth agent and preparation method thereof

Abstract

The present invention relates to the technical field of research and development of natural medicine hair growth agents, and discloses a natural medicine hair growth agent and a preparation method. The natural medicine hair growth agent includes an active component and a gel preparation component, wherein the active component is ginsenoside nano-micelles, which are self-assembled by dopamine-functionalized amphiphilic compounds to form nano-micelles and encapsulate ginsenosides inside the nano-micelles. The drug loading of ginsenoside nano-micelles is 3-8%. The preparation method of the natural medicine hair growth agent comprises the following steps: mixing carbomer resin 940 and glycerol, adding an appropriate amount of purified water, and after sufficient swelling, adding propylene glycol, azone, vitamin E and ginsenoside nano-micelles, stirring evenly, adjusting the pH value to 6-7 with triethanolamine, adding purified water, and preparing the natural medicine hair growth agent. The natural medicine hair growth agent prepared by the present invention achieves the beneficial technical effect of significantly promoting hair growth.

Description

Technical Field

[0001] The present invention relates to the technical field of research and development of natural medicine hair growth enhancers, and in particular to a natural medicine hair growth enhancer and a preparation method thereof. Background Art

[0002] Hair loss is a common clinical hair disease, which can be divided into alopecia areata, seborrheic alopecia, chemotherapy-induced alopecia, senile alopecia, chronic telogen effluvium, post-illness alopecia, etc. The drugs for treating hair loss are mainly divided into the following categories: (1) biological response modifiers: including retinoic acid, fibroblast growth factor, placenta extract and embryo extract; (2) immunomodulators: including tacrolimus, adrenocortical hormone, cyclosporine, anthocyanin; (3) vasodilators: such as pilocarpine, carbomer, cyclic adenosine monophosphate, lecithin; (4) local irritant hair growth drugs: such as aloe vera, ginger juice, chili oleoresin garlic juice, blister beetle tincture; (5) anti-androgen drugs: such as finasteride, estramide, spironolactone, estrogen; (6) potassium channel openers: such as minoxidil, diazoxide; (7) traditional Chinese medicine and others.

[0003] The chemical drugs currently used in clinical treatment of hair loss have side effects of varying degrees and the disadvantage of easy recurrence after discontinuation of the drugs. People have gradually begun to turn their attention to the research of natural drugs.

[0004] Studies have found that ginseng extract has a significant effect in promoting hair growth, and its mechanism of action is related to dilating skin capillaries and improving local microcirculation. Summary of the Invention

[0005] The present invention provides a natural medicinal hair growth agent, which uses total ginsenosides extracted from artificially cultivated ginseng powder as the active component of the hair growth agent, and utilizes independently developed dopamine-functionalized amphiphilic compounds as drug carriers. The dopamine-functionalized amphiphilic compounds encapsulate the total ginsenosides and form nano-micelles through self-assembly. This technical arrangement can promote the efficacy of the total ginsenosides and enhance the hair growth efficacy.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions:

[0007] A natural medicinal hair growth agent comprises an active component and a gel preparation component. The active component is ginsenoside nano-micelles, which are prepared by self-assembly of dopamine-functionalized amphiphilic compounds to form nano-micelles and encapsulating ginsenosides inside the nano-micelles. The drug loading capacity of ginsenosides, a hair growth agent, in the ginsenoside nano-micelles is 3-8%.

[0008] Preferably, the preparation method of the dopamine functionalized amphiphilic compound is:

[0009] Step 1: 1 molar equivalent of the carboxyl functional group on citric acid reacts with 3 molar equivalents of thionyl chloride in the presence of pyridine to prepare citric acid chloride;

[0010] Step 2: Based on the nucleophilic substitution reaction mechanism, 1 molar equivalent of citric acid chloride and 3 molar equivalents of octadecanol undergo esterification reaction to prepare citrate;

[0011] Step 3: Based on the nucleophilic addition-elimination reaction mechanism, 1 molar equivalent of hexaethylene glycol and 2 molar equivalents of succinic anhydride undergo esterification reaction to prepare terminal carboxyl polyethylene glycol;

[0012] Step 4: 1 molar equivalent of terminal carboxyl-containing polyethylene glycol and 2 molar equivalents of thionyl chloride are reacted to convert the carboxyl group into an acyl chloride group to prepare polyethylene glycol dichloride;

[0013] Step 5: 1 molar equivalent of polyethylene glycol dichloride is first reacted with 1 molar equivalent of citrate to undergo an esterification reaction based on a nucleophilic substitution reaction mechanism, and then reacted with 1 molar equivalent of dopamine hydrochloride to undergo an amidation reaction based on a nucleophilic substitution reaction mechanism to prepare a dopamine functionalized amphiphilic compound.

[0014] Preferably, the extraction method of total ginsenosides is as follows: artificially cultivated ginseng powder is sieved, the raw material powder is weighed, a low eutectic solvent containing water is added, the powder is placed in a centrifuge tube and fully mixed, ultrasonic extraction is performed, anhydrous ethanol is added and centrifuged, the supernatant is taken, concentrated under reduced pressure, allowed to stand, and filtered through a microporous membrane to obtain total ginsenosides.

[0015] Preferably, the deep eutectic solvent uses choline chloride as a hydrogen bond donor, and is prepared by mixing choline chloride with any one of 1,4-butanediol, urea, glycerol, ethylene glycol, citric acid, and 1-2-propylene glycol in a volume ratio of 1:1.

[0016] Preferably, the water content of the aqueous deep eutectic solvent is 35-50%.

[0017] Preferably, the material-liquid ratio of the artificially cultivated ginseng powder to the aqueous deep eutectic solvent is: 15-50 mL of the aqueous deep eutectic solvent is required to be added to 1 g of the artificially cultivated ginseng powder.

[0018] Preferably, the following raw materials are included in parts by weight:

[0019] 2 parts of Carbomer resin 940;

[0020] 10 parts glycerin;

[0021] 20 parts propylene glycol;

[0022] 0.5-1.5 parts of azone;

[0023] 0.01-0.05 parts of vitamin E;

[0024] 1.5-2 parts of ginsenoside nano-micelles;

[0025] Purified water, add to 100 parts.

[0026] A method for preparing a natural medicinal hair growth enhancer comprises the following steps: mixing carbomer resin 940 and glycerin, adding an appropriate amount of purified water, and adding propylene glycol, azone, vitamin E, and ginseng total saponin nano-micelles after sufficient swelling, stirring evenly, adjusting the pH value to 6-7 with triethanolamine, adding purified water, and stirring evenly to prepare the natural medicinal hair growth enhancer.

[0027] Preferably, the ginsenoside nano-micelles are prepared by a thin film dispersion method, which specifically comprises dissolving the ginsenoside extract and the dopamine functionalized amphiphilic compound in anhydrous ethanol, evaporating under reduced pressure, and hydrating the obtained thin film to obtain the ginsenoside nano-micelles.

[0028] The beneficial effects of the present invention are as follows:

[0029] Pyridine catalyzes the chlorination reaction of the carboxyl functional group of citric acid with thionyl chloride to produce citric acid chloride, which then undergoes an esterification reaction with octadecyl alcohol to produce citrate ester;

[0030] After hexaethylene glycol is carboxylated and chlorinated, it is first esterified with citrate and then amidated with dopamine hydrochloride to prepare a dopamine-functionalized amphiphilic compound.

[0031] Ginsenoside nanoparticles are prepared by encapsulating ginsenosides with dopamine-functionalized amphiphilic compounds as active components of natural hair growth drugs and using dopamine-functionalized amphiphilic compounds as drug carriers. Ginsenoside nanoparticles are then prepared together with excipients in the formula of natural hair growth drugs to form a gel-like product. The hair growth effect test results show that the natural hair growth drug prepared by the present invention has achieved the beneficial technical effect of significantly promoting hair growth. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 is the chemical structural formula of the dopamine-functionalized amphiphilic compound. DETAILED DESCRIPTION

[0033] Example 1:

[0034] Synthesis of citric acid chloride: Weigh 5.7 g of citric acid, add 15 mL of tetrahydrofuran, stir at high speed to fully dissolve, purge with nitrogen, add 6.5 mL of thionyl chloride dropwise under ice bath, stir for 0.5 h after the addition is complete, then add 4 mL of pyridine dropwise, stir and react for 1 h, then allow to react at room temperature for 24 h, filter, remove the solvent by rotary evaporation, and dry to obtain citric acid chloride;

[0035] Synthesis of citrate ester: Weigh 5.9 g of citric acid chloride, 19.5 g of octadecanol, and 12 mL of triethylamine, add 50 mL of chloroform, and react with stirring in an ice bath for 1 h. Then, react in a 40°C water bath for 12 h. Filter, remove the solvent by rotary evaporation, and dry to obtain citrate ester.

[0036] Synthesis of terminal carboxylated polyethylene glycol: 12.5 mL of hexaethylene glycol, 10 g of succinic anhydride, and 10 mL of toluene were mixed and heated under reflux for 6 h. Chloroform was added, shaken, allowed to stand, and filtered. The pH of the filtrate was adjusted to 2-3, extracted with chloroform, and the chloroform was removed by rotary evaporation. The precipitate was freeze-precipitated in ether and dried to obtain terminal carboxylated polyethylene glycol.

[0037] Synthesis of polyethylene glycol dichloride: Weigh 19 g of terminal carboxylated polyethylene glycol and 6 mL of thionyl chloride, add 20 mL of toluene, react at 80°C for 24 h, and distill off the unreacted thionyl chloride and toluene under reduced pressure to obtain polyethylene glycol dichloride;

[0038] Preparation of dopamine-functionalized amphiphilic compound: 1.0 g of polyethylene glycol dichloride, 1.8 g of citrate, and 0.5 mL of triethylamine were weighed, 40 mL of N,N-dimethylformamide was added, and the mixture was reacted in an 80°C water bath for 10 h. The mixture was cooled to room temperature, nitrogen was passed through, 0.4 g of dopamine hydrochloride was added, and the mixture was stirred and reacted at room temperature for 8 h. The mixture was filtered, and the mixture was freeze-precipitated in methyl tert-butyl ether. The mixture was washed three times with methyl tert-butyl ether, and freeze-dried to obtain the dopamine-functionalized amphiphilic compound.

[0039] The chemical structure of dopamine functionalized amphiphilic compound is shown in Figure 1 , Its hydrogen spectrum characterization results are as follows:

[0040] 1 H NMR (400MHz, DMSO-d6, δ, ppm): 8.16-8.18 (t, 1H), 7.57 (s, 1H), 6.85 (s, 1H), 6.7 0-6.71(d, 1H), 6.54(s, 1H), 6.46-6.48(d, 1H), 4.25-4.28(t, 4H), 4.09-4.12(t, 2H), 4.02-4.05(t, 4H), 3.65-3.70(m, 20H), 3.24-3.28(m, 4H), 3.00-3.04(d, 2H ), 2.50-2.68(m, 10H), 1.64-1.69(m, 2H), 1.33-1.43(m, 94H), 0.87-0.89(t, 9H).

[0041] Example 2:

[0042] Extraction of total ginsenosides: Extraction of total ginsenosides from ginseng powder using a water-containing deep eutectic solvent with the aid of ultrasound;

[0043] Among them, the deep eutectic solvent mainly uses choline chloride as a hydrogen bond donor, and can be prepared by mixing choline chloride with any one of 1,4-butanediol, urea, glycerol, ethylene glycol, citric acid, and 1-2-propylene glycol in a volume ratio of 1: (0.5-4);

[0044] Since the viscosity of deep eutectic solvents is usually high, which will hinder the extraction efficiency, water needs to be added to reduce its viscosity. Considering the differences in the ratios of deep eutectic solvents, it is best to control the water content of the deep eutectic solvents in the range of 35-50%;

[0045] In order to ensure that the ginseng powder is in full contact with the deep eutectic solvent without hindering the mass transfer, the optimal ratio is to control the material-liquid ratio to 1g of ginseng powder and add (15-50)mL of aqueous deep eutectic solvent.

[0046] The deep eutectic solvent of this embodiment is prepared by using choline chloride and 1,4-butanediol in a volume ratio of 1:1. The water content of the deep eutectic solvent is 40%, and the material-liquid ratio is 1g of ginseng powder and 20mL of the water-containing deep eutectic solvent.

[0047] The extraction experiment of total ginsenosides was as follows: artificially cultivated ginseng powder (Xi'an Tianyi Biotechnology Co., Ltd.) was sieved through a 50-mesh sieve, 10 g of raw material powder was weighed, 80 mL of distilled water, 60 mL of choline chloride and 60 mL of 1,4-butanediol were added, and the mixture was placed in a centrifuge tube and fully mixed. Ultrasonic extraction was performed for 20 min (ultrasonic power 258 W), 225 mL of anhydrous ethanol was added and centrifuged for 10 min, the supernatant was taken, concentrated under reduced pressure to 20 mL, allowed to stand for 2 h, and filtered with a 0.45 μm microporous membrane to obtain total ginsenoside extract.

[0048] Example 3:

[0049] Ginseng total saponin nano-micelles were prepared by thin film dispersion method: 5 mL of ginseng total saponin extract and 2.5 g of dopamine functionalized amphiphilic compound were dissolved in 25 mL of anhydrous ethanol, evaporated under reduced pressure, and the obtained film was hydrated to obtain ginseng total saponin nano-micelles.

[0050] Example 4:

[0051] A natural medicine hair growth agent comprises the following raw materials in parts by weight:

[0052] 2 parts of Carbomer resin 940;

[0053] 10 parts glycerin;

[0054] 20 parts propylene glycol;

[0055] 1 part Azone;

[0056] 0.02 parts of vitamin E;

[0057] 1.8 parts of ginsenoside nano-micelles; wherein, the drug loading amount of ginsenosides in the ginsenoside nano-micelles is 5.6%;

[0058] Purified water, add to 100 parts.

[0059] Embodiment 5:

[0060] Preparation of a natural medicinal hair growth agent: 2 parts by weight of carbomer resin 940 and 10 parts by weight of glycerol are mixed, an appropriate amount of purified water is added, and after sufficient swelling, 20 parts by weight of propylene glycol, 1 part by weight of azone, 0.02 parts by weight of vitamin E, and 1.8 parts by weight of ginseng total saponin nano-micelles are added, and the mixture is stirred evenly. The pH value is adjusted to 6.5 with triethanolamine, and purified water is added to 100 parts by weight, and the mixture is stirred evenly to prepare the natural medicinal hair growth agent.

[0061] Example 6:

[0062] Hair growth effect test: 40 patients with severe hair loss of different types (male and female ratio randomized) were selected as subjects, including 12 patients under 30 years old, 20 patients aged 30-50 years old, and 8 patients aged 50-60 years old. They used a natural medicine hair growth agent to apply to the affected scalp and massage for 15 minutes daily, once in the morning and evening, for six months. Detailed records of adverse reactions were kept for all observed cases. The test results are shown in Table 1 below.

[0063] Table 1 Test results of hair growth effects of natural medicinal hair growth agents

[0064] Hair growth effect Patients under 30 years old Patients aged 30-50 years Patients aged 50-60 years cure 11 17 3 Significant effect 1 2 4 Improvement 0 1 1 invalid 0 0 0 Any adverse reactions none none none

[0065] Note: The specific efficacy criteria are:

[0066] Cured - New hair grows in more than 90% of the hair loss area, 1.0 cm above the scalp, with the same distribution density, hair thickness and color as normal hair;

[0067] Significantly effective—50%-90% of the hair loss area grows new hair, and many vellus hairs turn into terminal hair during the treatment process;

[0068] Improvement - 10-50% of the hair loss area grows new hair (including villi), but the growth is slow;

[0069] Ineffective—no obvious new hair growth or the new hair area is less than 10% or hair loss continues.

Claims

1. A natural medicine hair growth agent, characterized in that: The invention comprises an active component and a gel preparation component. The active component is ginsenoside nano-micelles, which are formed by self-assembly of a dopamine-functionalized amphiphilic compound into nano-micelles and encapsulate ginsenosides inside the nano-micelles. The drug loading capacity of ginsenosides, a hair growth drug, in the ginsenoside nano-micelles is 3-8%. The chemical formula of the dopamine functionalized amphiphilic compound is: 。 2. A natural medicine hair growth agent according to claim 1, characterized in that: The preparation method of dopamine functionalized amphiphilic compound is as follows: Step 1: 1 molar equivalent of the carboxyl functional group on citric acid reacts with 3 molar equivalents of thionyl chloride in the presence of pyridine to prepare citric acid chloride; Step 2: Based on the nucleophilic substitution reaction mechanism, 1 molar equivalent of citric acid chloride and 3 molar equivalents of octadecanol undergo esterification reaction to prepare citrate; Step 3: Based on the nucleophilic addition-elimination reaction mechanism, 1 molar equivalent of hexaethylene glycol and 2 molar equivalents of succinic anhydride undergo esterification reaction to prepare terminal carboxyl polyethylene glycol; Step 4: 1 molar equivalent of terminal carboxyl-containing polyethylene glycol and 2 molar equivalents of thionyl chloride are reacted to convert the carboxyl group into an acyl chloride group to prepare polyethylene glycol dichloride; Step 5: 1 molar equivalent of polyethylene glycol dichloride is first reacted with 1 molar equivalent of citrate to undergo an esterification reaction based on a nucleophilic substitution reaction mechanism, and then reacted with 1 molar equivalent of dopamine hydrochloride to undergo an amidation reaction based on a nucleophilic substitution reaction mechanism to prepare a dopamine functionalized amphiphilic compound.

3. A natural medicine hair growth agent according to claim 1, characterized in that: The extraction method of total ginsenosides is as follows: artificially cultivated ginseng powder is sieved, the raw material powder is weighed, a water-containing low eutectic solvent is added, and the mixture is placed in a centrifuge tube and fully mixed. Ultrasonic extraction is performed, anhydrous ethanol is added and the mixture is centrifuged, and the supernatant is collected. The mixture is concentrated under reduced pressure, allowed to stand, and filtered through a microporous membrane to obtain total ginsenosides.

4. A natural medicine hair growth agent according to claim 3, characterized in that: The deep eutectic solvent uses choline chloride as a hydrogen bond donor, and is prepared by mixing choline chloride with any one of 1,4-butanediol, urea, glycerol, ethylene glycol, citric acid, and 1-2-propylene glycol in a volume ratio of 1:

1.

5. A natural medicine hair growth agent according to claim 3, characterized in that: The water content of the aqueous deep eutectic solvent is 35-50%.

6. A natural medicine hair growth agent according to claim 3, characterized in that: The material-liquid ratio of artificially cultivated ginseng powder and aqueous deep eutectic solvent is: 20 mL of aqueous deep eutectic solvent is required to add 1 g of artificially cultivated ginseng powder.

7. A natural medicine hair growth agent according to any one of claims 1 to 6, characterized in that: The composition comprises the following raw materials in parts by weight: 2 parts of Carbomer resin 940; 10 parts glycerin; 20 parts propylene glycol; 0.5-1.5 parts of azone; 0.01-0.05 parts of vitamin E; 1.5-2 parts of ginsenoside nano-micelles; Purified water, add to 100 parts.

8. The method for preparing a natural medicine hair growth enhancer according to claim 7, characterized in that: Carbomer resin 940 and glycerin are mixed, and an appropriate amount of purified water is added. After sufficient swelling, propylene glycol, azone, vitamin E and ginseng total saponin nano-micelles are added and stirred evenly. The pH value is adjusted to 6-7 with triethanolamine, and purified water is added and stirred evenly to prepare a natural medicine hair growth agent.

9. The method for preparing a natural medicine hair growth enhancer according to claim 8, characterized in that: Ginseng total saponin nano-micelles are prepared by a thin film dispersion method, which specifically comprises the following steps: dissolving ginseng total saponin extract and dopamine functionalized amphiphilic compound in anhydrous ethanol, evaporating under reduced pressure, and hydrating the obtained thin film to obtain ginseng total saponin nano-micelles.

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