Natural medicine pilatory and preparation method thereof

Abstract

The invention relates to the technical field of research and development of natural medicine hair restorers, and discloses a natural medicine hair restorer and a preparation method thereof.The natural medicine hair restorer comprises an active component and a gel preparation component, the active component is ginseng total saponin nano-micelle, and the gel preparation component is sodium alginate. A dopamine functionalized amphiphilic compound is self-assembled to form a nano-micelle, and total ginsenoside is encapsulated in the nano-micelle to prepare the total ginsenoside nano-micelle, and the drug loading capacity of the total ginsenoside serving as a hair growing drug in the total ginsenoside nano-micelle is 3-8%; the preparation method of the natural medicine pilatory comprises the following steps: uniformly mixing the carbomer resin 940 and the glycerol, adding a proper amount of purified water, after the carbomer resin 940 and the glycerol are fully swelled, adding the propylene glycol, the azone, the vitamin E and the ginseng total saponin nano-micelles, uniformly stirring, adjusting the pH value to 6-7 by using triethanolamine, and adding the purified water to obtain the natural medicine pilatory. The natural medicine hair restorer prepared by the invention has the beneficial technical effect of obviously promoting hair growth.

Description

Technical Field

[0001] The present invention relates to the technical field of research and development of natural medicine hair growth agents, and particularly relates to a natural medicine hair growth agent and a preparation method thereof. Background Art

[0002] Hair loss is a common hair disease in clinical practice, which can be divided into several types such as alopecia areata, seborrheic alopecia, chemotherapy-induced alopecia, senile alopecia, chronic telogen effluvium, post-illness alopecia, etc. Currently, the drugs for treating hair loss mainly include the following categories: (1) biological response modifiers: including retinoids, fibroblast growth factors, placental extract and embryonal extract, etc.; (2) immunomodulators: including tacrolimus, adrenal cortical hormones, cyclosporine, anthralin, etc.; (3) vasodilators: such as pilocarpine, carbopoloning cyclic adenosine monophosphate, lecithin, etc.; (4) local irritant hair growth drugs: such as aloenin, ginger juice, capsicum oleoresin garlic juice, cantharidin tincture, etc.; (5) anti-androgen drugs: such as finasteride, epristeride, spironolactone, estrogen, etc.; (6) potassium channel openers: such as minoxidil, diazoxide, etc.; (7) traditional Chinese medicine and others.

[0003] Currently, the chemical drugs applied in clinical treatment of hair loss have disadvantages of varying degrees of side effects and easy recurrence after drug withdrawal, and people have gradually turned their attention to the research of natural medicines.

[0004] Research has found that: ginseng extract has an obvious effect of 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 medicine hair growth agent, which uses total ginsenosides extracted from artificially cultivated ginseng powder as the active component of the hair growth drug, and uses a self-developed dopamine-functionalized amphiphilic compound as the drug carrier. The dopamine-functionalized amphiphilic compound encapsulates total ginsenosides and forms nano-micelles through self-assembly. This technical arrangement can promote the efficacy of total ginsenosides and improve the hair growth effect.

[0006] To achieve the above object, the present invention adopts the following technical scheme:

[0007] A natural medicine hair growth agent includes an active component and a gel preparation component. The active component is nano-micelles of total ginsenosides, which are formed by self-assembly of dopamine-functionalized amphiphilic compounds and encapsulate total ginsenosides inside the nano-micelles. The drug loading amount of the hair growth drug total ginsenosides in the nano-micelles of total ginsenosides is 3-8%.

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

[0009] Step 1: Citric acid acyl chloride was prepared by acyl chlorination reaction of the carboxyl functional group on 1 molar equivalent of citric acid with 3 molar equivalents of thionyl chloride under the catalysis of pyridine;

[0010] Step 2: Based on the nucleophilic substitution reaction mechanism, 1 molar equivalent of citric acid acyl chloride was esterified with 3 molar equivalents of octadecanol to obtain citric acid ester;

[0011] Step 3: Based on the nucleophilic addition - elimination reaction mechanism, 1 molar equivalent of hexaethylene glycol was esterified with 2 molar equivalents of succinic anhydride to obtain end - carboxylated polyethylene glycol;

[0012] Step 4: Polyethylene glycol dichloride was prepared by the reaction of converting the carboxyl group to an acyl chloride group of 1 molar equivalent of end - carboxylated polyethylene glycol with 2 molar equivalents of thionyl chloride;

[0013] Step 5: Dopamine - functionalized amphiphilic compound was prepared by first carrying out an esterification reaction based on the nucleophilic substitution reaction mechanism of 1 molar equivalent of polyethylene glycol dichloride with 1 molar equivalent of citric acid ester, and then carrying out an amidation reaction based on the nucleophilic substitution reaction mechanism with 1 molar equivalent of dopamine hydrochloride.

[0014] Preferably, the extraction method of total ginsenosides: Sieving the powder of artificially cultivated ginseng, weighing the raw material powder, adding a water - containing eutectic solvent, fully mixing in a centrifuge tube, ultrasonic extraction, adding absolute ethanol and centrifuging, then taking the supernatant, concentrating under reduced pressure, standing, and filtering through a microporous membrane to obtain total ginsenosides.

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

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

[0017] Preferably, the material - liquid ratio of the powder of artificially cultivated ginseng to the water - containing eutectic solvent is: 1 g of the powder of artificially cultivated ginseng needs to add 15 - 50 mL of the water - containing eutectic solvent.

[0018] Preferably, it includes the following raw materials in parts by weight:

[0019] 2 parts of carbomer resin 940;

[0020] 10 parts of glycerol;

[0021] 20 parts of 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 total ginsenoside nanomicelles;

[0025] Purified water, q.s. to 100 parts.

[0026] A preparation method of a natural medicine hair growth agent, which mixes carbomer resin 940 and glycerol, adds an appropriate amount of purified water, and after sufficient swelling, adds propylene glycol, azone, vitamin E and total ginsenoside nanomicelles, stirs evenly, adjusts the pH value to 6 - 7 with triethanolamine, adds purified water, and stirs evenly to obtain the natural medicine hair growth agent.

[0027] Preferably, the total ginsenoside nanomicelles are prepared by the thin - film dispersion method. The specific method is as follows: Dissolve the total ginsenoside extract and the dopamine - functionalized amphiphilic compound in absolute ethanol, evaporate under reduced pressure, and the obtained film is hydrated to obtain the total ginsenoside nanomicelles.

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

[0029] Pyridine catalyzes the acyl - chlorination reaction of the carboxyl functional group of citric acid with thionyl chloride to obtain citric acid acyl chloride, and citric acid acyl chloride then undergoes an esterification reaction with octadecanol to obtain citrate;

[0030] After hexaglycol undergoes terminal carboxylation and acyl - chlorination, it first undergoes an esterification reaction with citrate, and then an amidation reaction with dopamine hydrochloride to obtain a dopamine - functionalized amphiphilic compound;

[0031] Using total ginsenoside as the active component of the natural hair growth medicine and the dopamine - functionalized amphiphilic compound as the drug carrier, the total ginsenoside nanomicelles are prepared by encapsulating total ginsenoside with the dopamine - functionalized amphiphilic compound. The total ginsenoside nanomicelles and the preparation excipients in the natural medicine hair growth agent formula are prepared into a gel - like product. The test results of its hair growth effect show that: The natural medicine hair growth agent prepared by the present invention has achieved the beneficial technical effect of significantly promoting hair growth. Description of the Drawings

[0032] Figure 1 It is the chemical structural formula of the dopamine - functionalized amphiphilic compound. Detailed Description of the Invention

[0033] Example 1:

[0034] Synthesize citric acid acyl chloride: Weigh 5.7 g of citric acid, add 15 mL of tetrahydrofuran, stir at high speed to dissolve it fully, protect it with nitrogen, dropwise add 6.5 mL of thionyl chloride drop - by - drop under ice - bath conditions. After the addition is complete, stir for 0.5 h, then dropwise add 4 mL of pyridine, stir and react for 1 h, and then react at room temperature for 24 h. Filter, evaporate the solvent by rotary evaporation and then dry to obtain citric acid acyl chloride;

[0035] Synthesis of citrate ester: Weigh 5.9 g of citric acid acyl chloride, 19.5 g of octadecanol and 12 mL of triethylamine, add 50 mL of chloroform, stir and react for 1 h under ice bath conditions, then place it in a water bath at 40 °C and react for 12 h, filter, rotary evaporate to remove the solvent and then dry to obtain citrate ester;

[0036] Synthesis of terminal carboxylated polyethylene glycol: Mix 12.5 mL of hexaethylene glycol, 10 g of succinic anhydride and 10 mL of toluene, heat under reflux for 6 h, add chloroform, shake, let stand, filter, adjust the pH value of the filtrate to 2 - 3, extract with chloroform, rotary evaporate to remove chloroform, precipitate by freezing in diethyl ether, and dry 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, distill off the unreacted thionyl chloride and toluene under reduced pressure to obtain polyethylene glycol dichloride;

[0038] Preparation of dopamine-functionalized amphiphilic compound: Weigh 1.0 g of polyethylene glycol dichloride, 1.8 g of citrate ester and 0.5 mL of triethylamine, add 40 mL of N,N-dimethylformamide, react in a water bath at 80 °C for 10 h, cool to room temperature, protect with nitrogen, add 0.4 g of dopamine hydrochloride, stir and react at room temperature for 8 h, filter, precipitate by freezing in methyl tert-butyl ether, wash three times with methyl tert-butyl ether, and freeze-dry to obtain dopamine-functionalized amphiphilic compound;

[0039] The chemical structural formula of the dopamine-functionalized amphiphilic compound is shown in Figure 1 、The results of its hydrogen spectrum characterization 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), 6.70 - 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: Under the assistance of ultrasound, extract the total ginsenosides in ginseng powder through a hydrated eutectic solvent;

[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 total ginsenoside nanomicelles; wherein, the drug loading of total ginsenoside in the total ginsenoside nanomicelles is 5.6%;

[0058] Purified water, q.s. to 100 parts.

[0059] Example 5:

[0060] Preparation of natural medicine hair growth agent: Mix 2 parts by weight of carbomer resin 940 and 10 parts by weight of glycerol, add appropriate amount of purified water, and after sufficient swelling, add 20 parts by weight of propylene glycol, 1 part by weight of azone, 0.02 part by weight of vitamin E and 1.8 parts by weight of total ginsenoside nanomicelles, stir evenly, adjust the pH value to 6.5 with triethanolamine, add purified water to 100 parts by weight, stir evenly to obtain the natural medicine hair growth agent.

[0061] Example 6:

[0062] Hair growth effect test: Taking 40 severe hair loss patients of different types as subjects (random male-female ratio), 12 patients under 30 years old, 20 patients aged 30 - 50, and 8 patients aged 50 - 60. Apply the natural medicine hair growth agent to the scalp affected area every day, massage for 15 min, once in the morning and once in the evening, and continuously use it for half a year. At the same time, record in detail the adverse reactions that occur in all observed cases. The test results are shown in Table 1 below;

[0063] Table 1 Hair growth effect test results of natural medicine hair growth agent Hair growth efficacy Patients under 30 years old Patients aged 30 - 50 years old Patients aged 50 - 60 years old Cured 11 17 3 Markedly effective 1 2 4 Improved 0 1 1 Ineffective 0 0 0 Whether there are adverse reactions None None None

[0064] Note: The specific efficacy criteria are as follows: Cured - More than 90% of the hair loss area grows new hair, 1.0 cm higher than the scalp, and the distribution density, hair thickness, and color are the same as normal hair; Markedly effective - 50% - 90% of the hair loss area grows new hair, and there are more vellus hairs turning into terminal hairs during the treatment process; Improved - 10% - 50% of the hair loss area grows new hair (including vellus hairs), but the growth is slow;

[0065] Ineffective - No obvious new hair grows, or the new hair area is less than 10%, or hair loss continues.

Claims

1. A natural medicine hair growth agent, characterized in that, It includes an active component and a gel preparation component. The active component is total ginsenoside nanomicelles, which are prepared by self-assembling dopamine-functionalized amphiphilic compounds to form nanomicelles and encapsulating total ginsenosides inside the nanomicelles. The drug loading of the hair growth drug total ginsenosides in the total ginsenoside nanomicelles is 3-8%.

2. The natural medicine hair growth agent according to claim 1, characterized in that, The chemical formula structural formula of the dopamine-functionalized amphiphilic compound is: 。 3. The natural medicine hair growth agent according to claim 1, characterized in that The preparation method of the dopamine-functionalized amphiphilic compound is as follows: Step 1: Citric acid acyl chloride is prepared by acyl chlorination reaction of the carboxyl functional group on 1 molar equivalent of citric acid with 3 molar equivalents of thionyl chloride under the catalysis of pyridine. Step 2: Based on the nucleophilic substitution reaction mechanism, 1 molar equivalent of citric acid acyl chloride reacts with 3 molar equivalents of octadecanol to prepare citric acid ester. Step 3: Based on the nucleophilic addition-elimination reaction mechanism, 1 molar equivalent of hexaethylene glycol reacts with 2 molar equivalents of succinic anhydride to prepare end-carboxylated polyethylene glycol. Step 4: Polyethylene glycol dichloride is prepared by reacting 1 molar equivalent of end-carboxylated polyethylene glycol with 2 molar equivalents of thionyl chloride to convert the carboxyl group into an acyl chloride group. Step 5: Dopamine-functionalized amphiphilic compound is prepared by first reacting 1 molar equivalent of polyethylene glycol dichloride with 1 molar equivalent of citric acid ester through an esterification reaction based on the nucleophilic substitution reaction mechanism and then reacting with 1 molar equivalent of dopamine hydrochloride through an amidation reaction based on the nucleophilic substitution reaction mechanism.

4. The natural medicine hair growth agent according to claim 1, characterized in that, The extraction method of total ginsenosides: Sieve the powder of artificially cultivated ginseng, weigh the raw material powder, add a hydrated eutectic solvent, place it in a centrifuge tube and mix well, extract by ultrasonic wave, add anhydrous ethanol and centrifuge, take the supernatant, concentrate under reduced pressure, let it stand, filter with a microporous membrane to obtain total ginsenosides.

5. The natural medicine hair growth agent according to claim 4, characterized in that, The 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-propanediol in a volume ratio of 1:

1.

6. The natural medicine hair growth agent according to claim 4, characterized in that The water content of the hydrated eutectic solvent is 35-50%.

7. The natural medicine hair growth agent according to claim 4, characterized in that, The material-liquid ratio of the powder of artificially cultivated ginseng to the hydrated eutectic solvent is: 1 g of the powder of artificially cultivated ginseng needs to add 20 mL of the hydrated eutectic solvent.

8. A natural medicine hair growth agent according to any one of claims 1-7, characterized in that, It includes the following raw materials in parts by weight: 2 parts of carbomer resin 940; 10 parts of glycerol; 20 parts of propylene glycol; 0.5-1.5 parts of azone; 0.01-0.05 parts of vitamin E; 1.5-2 parts of total ginsenoside nanomicelles; Purified water, added to 100 parts.

9. The preparation method of a natural medicine hair growth agent according to claim 8, characterized in that, Mix carbomer resin 940 and glycerol, add an appropriate amount of purified water, wait until it swells sufficiently, then add propylene glycol, azone, vitamin E and total ginsenoside nanomicelles, stir evenly, adjust the pH value to 6-7 with triethanolamine, add purified water, and stir evenly to prepare a natural drug hair growth agent.

10. The preparation method of a natural medicine hair growth agent according to claim 9, characterized in that, The total ginsenoside nanomicelles are prepared by the thin film dispersion method. The specific method is: Co-dissolve the total ginsenoside extract and the dopamine-functionalized amphiphilic compound in absolute ethanol, evaporate under reduced pressure, and the obtained film is hydrated to prepare total ginsenoside nanomicelles.

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