Traditional Chinese medicine non-slip spray for treating primary premature ejaculation and preparation method of traditional Chinese medicine non-slip spray

Abstract

The invention discloses a traditional Chinese medicine anti-slip spray for treating primary premature ejaculation and a preparation method of the traditional Chinese medicine anti-slip spray. The spray takes asarum, gallnut, clove, epimedium, cynomorium songaricum and morinda officinalis as main raw materials, and is prepared by the processes of cleaning, drying, crushing, two times of ultrasonic heating extraction, concentrating, mixing and the like. According to the preparation method, ultrasonic extraction and enzymolysis technologies are adopted, the extraction rate of effective components is increased, and the prepared spray has the advantages of being remarkable in curative effect, high in safety, free of side effects and the like and can be used for treating primary premature ejaculation.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a slip-stopping spray for treating primary premature ejaculation and a preparation method thereof, which is prepared from asarum, gallnut, clove, epimedium, cynomorium and radix morindae officinalis as main raw materials through a specific process. BACKGROUND

[0002] Primary premature ejaculation is a common sexual dysfunction disease in men, which is defined as almost always ejaculating before or within 1 minute after inserting the vagina, and accompanied by significant distress or interpersonal interaction disorder due to premature ejaculation. According to statistics, about 20%-30% of adult men in the world are troubled by primary premature ejaculation, which seriously affects the quality of life and marital relationship of patients. At present, the methods for treating primary premature ejaculation in the clinic mainly include psychological treatment, behavior therapy and drug treatment. Psychological treatment and behavior therapy need to be adhered to for a long time, and the effect varies from person to person; drug treatment mainly uses 5-hydroxytryptamine reuptake inhibitors (such as dapoxetine), but this kind of drug has adverse reactions such as headache, nausea, drowsiness, and some patients are not sensitive to the drug. In addition, surgical treatment (such as dorsal penile nerve transection) has certain risks and may lead to permanent loss of sexual function. Traditional Chinese medicine has a long history and unique advantages in the treatment of male sexual dysfunction. The multi-component and multi-target characteristics of traditional Chinese medicine make it have less side effects while improving the symptoms of premature ejaculation. At present, there are some traditional Chinese medicine sprays for treating premature ejaculation on the market, but these sprays often have problems such as low extraction rate of effective components, unreasonable formula and poor stability, resulting in insignificant treatment effect. Therefore, it is of great clinical significance and market value to develop a high-efficiency, safe and stable traditional Chinese medicine slip-stopping spray. In the prior art, the preparation methods of traditional Chinese medicine extracts mainly include decoction method, immersion method and percolation method. These methods have the disadvantages of long extraction time, low efficiency and serious loss of effective components. Ultrasonic extraction technology is a new extraction technology that uses the cavitation effect, mechanical vibration and thermal effect of ultrasonic waves to promote the dissolution of effective components from medicinal materials. Compared with traditional extraction methods, ultrasonic extraction has the advantages of short extraction time, high efficiency and less loss of effective components. In addition, enzyme hydrolysis technology can destroy plant cell walls, making effective components more easily released, further improving the extraction rate. However, there is no report on the combination of ultrasonic extraction technology and enzyme hydrolysis technology for preparing traditional Chinese medicine sprays for treating primary premature ejaculation. Therefore, the present application provides a new preparation method, which improves the extraction rate of effective components through ultrasonic warming extraction and enzyme hydrolysis treatment, thereby improving the treatment effect of the spray. SUMMARY

[0003] OBJECTIVE The present application aims to provide a traditional Chinese medicine slip-stop spray for treating primary premature ejaculation and a preparation method thereof. The spray uses natural traditional Chinese medicines as raw materials, extracts effective components through a specific preparation process, and has the advantages of remarkable curative effect, high safety, and no side effects.

[0004] The specific technical solutions are as follows: (1) Raw material composition The slip-stop spray comprises the following raw materials: asarum, gallnut, clove, epimedium, cynomorium, and radix morindae officinalis. The weight proportions of the raw materials are as follows: asarum 10-30 parts, gallnut 15-35 parts, clove 10-25 parts, epimedium 20-40 parts, cynomorium 15-30 parts, and radix morindae officinalis 15-30 parts.

[0005] (2) Preparation process Raw material pretreatment Washing and drying: wash the asarum, gallnut, clove, epimedium, cynomorium, and radix morindae officinalis separately, remove impurities, and dry at 50-60℃ until the water content is less than 5%. The purpose of washing is to remove dust, sand, and other impurities on the surface of the medicinal materials to avoid affecting the subsequent extraction process and the quality of the spray. Drying to less than 5% water content can prevent the medicinal materials from mildewing and deteriorating during storage and subsequent processing, and also reduces the water content of the medicinal materials, which is beneficial to subsequent crushing.

[0006] Crushing: use a supermicro crusher to crush the dried medicinal materials into 100-150 mesh powder to increase the specific surface area and promote subsequent extraction. Crushing to 100-150 mesh can greatly increase the specific surface area of the medicinal material powder, thereby increasing the contact area between the effective components and the extraction solvent, accelerating the extraction speed, and improving the extraction efficiency.

[0007] First ultrasonic wave warming extraction (preparation of extraction liquid A) Enzymatic treatment and pH adjustment: put the traditional Chinese medicine powder into an ultrasonic wave generating tank, add 2 times the mass of purified water, stir uniformly, add 0.8% of the mass of pure water of citric acid monohydrate, adjust the pH to 9.5-10, then add 5% of the mass of the raw material of a mixture of cellulase and glucanase, and keep at 50-60℃ for 30 min to decompose the plant cell wall. The purpose of adding purified water is to serve as an extraction solvent to dissolve part of the water-soluble components. Adjusting the pH to 9.5-10 by adding citric acid monohydrate is to create an alkaline environment suitable for enzyme action. Cellulase and glucanase can decompose cellulose and glucan in the plant cell wall, making the effective components in the cells more easily released.

[0008] Ultrasonic extraction: start a 300W ultrasonic generator, treat at 50-60℃ for 1-1.5h, use cavitation effect to promote the dissolution of effective ingredients; then add 2 times the mass of 95-98% ethanol, continue ultrasonic treatment for 1-1.5h, extract fat-soluble ingredients. The cavitation effect of ultrasonic can produce micro-bubbles in the liquid, and the high pressure and high temperature generated when the bubbles burst can destroy the cell structure of medicinal materials, making the effective ingredients more easily dissolved. First extract water-soluble ingredients with water, then extract fat-soluble ingredients with high-concentration ethanol, which can achieve comprehensive extraction of different properties of effective ingredients in medicinal materials.

[0009] Filtration: filter with a 1μm microfiltration membrane to obtain extract A and first filter residue. The 1μm microfiltration membrane can effectively remove impurities and solid particles in the extract, improving the purity and clarity of the extract.

[0010] Second ultrasonic warming extraction (preparation of extract B): add 4 times the mass of 50-60% ethanol to the first filter residue, and perform ultrasonic warming extraction at 50-60℃ for 1-1.5h to extract residual water-soluble ingredients (such as Chinese gall tannin and Acanthopanax senticosus amino acid), and filter to obtain extract B. The first filter residue still contains some residual effective ingredients, and the second extraction can improve the extraction rate of effective ingredients. Using 50-60% ethanol as the extraction solvent can extract some ingredients that have low solubility in water but high solubility in certain concentration of ethanol, such as Chinese gall tannin and Acanthopanax senticosus amino acid, etc.

[0011] Concentration and mixing Combination and concentration: combine extract A and B into extract C, and place it in a vacuum tank for reflux concentration to obtain concentrated extract A. Vacuum concentration can be carried out at a lower temperature to avoid decomposition of effective ingredients at high temperature, while improving the concentration efficiency.

[0012] Product preparation: mix 99% yohimbine hydrochloride with 10 times the mass of 99% ethanol to obtain solution B, and then mix it with concentrated extract A to prepare the finished product spray. Yohimbine hydrochloride is a central stimulant that can increase the excitability of the sexual nervous system, and cooperates with traditional Chinese medicine extract to enhance the therapeutic effect of the spray. Adding ethanol as a solvent can make each component fully dissolved to form a uniform spray solution. Beneficial effects

[0013] Raw materials are naturally safe: the invention uses natural traditional Chinese medicines such as asarum, Chinese gall, clove, epimedium, cynomorium, and Acanthopanax as raw materials, does not contain harmful chemical substances, has high safety, and has no side effects.

[0014] High extraction efficiency: By ultrasonic heating extraction and enzymatic treatment, the plant cell wall is destroyed, the dissolution of effective components is promoted, and the extraction rate of effective components is improved. Compared with the traditional extraction method, the extraction efficiency of the present application is increased by 30%-50%.

[0015] Comprehensive ingredients: The two extraction processes are adopted to extract water-soluble ingredients and fat-soluble ingredients, respectively, to realize the comprehensive extraction of effective ingredients in medicinal materials and improve the efficacy of the spray.

[0016] Good stability: The preparation process of the present application is scientific and reasonable, and the prepared spray has good stability and is not prone to precipitation, discoloration and other phenomena during storage.

[0017] Convenient to use: The spray dosage form is convenient to use, can be directly sprayed, has rapid action and significant effect. DETAILED DESCRIPTION

[0018] Example 1: Raw material pretreatment Washing and drying: Take 20g of Asarum, 25g of gallnut, 15g of clove, 30g of Epimedium, 20g of Cynomorium, and 20g of Morindae, respectively, wash them clean with clean water, remove impurities, and put them into an oven to dry at 55℃ until the water content is <5%.

[0019] Pulverization: Put the dried medicinal materials into an ultrafine pulverizer and pulverize them to 120 mesh powder.

[0020] First ultrasonic heating extraction (preparation of extract A) Enzymatic treatment and pH adjustment: Put the traditional Chinese medicine powder into an ultrasonic generator tank, add 2 times the mass (i.e. 200g) of purified water, stir uniformly, then add 0.8% (i.e. 1.6g) of citric acid monohydrate, adjust the pH to 9.8, and then add 5% (i.e. 5g) of cellulase and glucanase mixture of the raw material mass, and keep it at 55℃ for 30min.

[0021] Ultrasonic extraction: Start a 300W ultrasonic generator, treat at 55℃ for 1.2h, then add 2 times the mass (i.e. 200g) of 95% ethanol, and continue ultrasonic treatment for 1.2h.

[0022] Filtering: Filter with a 1μm micro filter membrane to obtain extract A and first filter residue.

[0023] Second ultrasonic heating extraction (preparation of extract B): Add 4 times the mass (i.e. 400g) of 55% ethanol to the first filter residue, and perform ultrasonic heating extraction at 55℃ for 1.2h, and filter to obtain extract B.

[0024] Concentration and mixing Combination and concentration: combine extract A and B into extract C, put into vacuum tank, and perform reflux concentration at 60°C until the volume of the concentrated solution is 1 / 10 of the original volume, to obtain concentrated extract A.

[0025] Finished product preparation: weigh 1g of 99% yohimbine hydrochloride, add 10 times the mass (i.e. 10g) of 99% ethanol, mix uniformly to obtain solution B, then mix solution B with concentrated extract A, stir uniformly, and prepare 100ml of finished product spray.

[0026] Example 2: raw material pretreatment Cleaning and drying: weigh 10g of asarum, 15g of gallnut, 10g of clove, 20g of epimedium, 15g of cynomorium, and 15g of radix morindae officinalis, clean them with clean water respectively, remove impurities, and put them into an oven to dry at 50°C until the moisture content is <5%.

[0027] Pulverization: put the dried medicinal materials into a supermicro pulverizer and pulverize to 100 mesh powder.

[0028] First ultrasonic warming extraction (preparation of extract A) Enzymatic treatment and pH adjustment: put the traditional Chinese medicine powder into an ultrasonic generator tank, add 2 times the mass (i.e. 100g) of purified water, stir uniformly, then add 0.8% (i.e. 0.8g) of citric acid monohydrate, adjust the pH to 9.5, and then add 5% (i.e. 2.5g) of a mixture of cellulase and glucanase based on the mass of the raw material, and incubate at 50°C for 30min.

[0029] Ultrasonic extraction: start a 300W ultrasonic generator, treat at 50°C for 1h, then add 2 times the mass (i.e. 100g) of 98% ethanol, and continue ultrasonic treatment for 1h.

[0030] Filtration: filter with a 1μm microfiltration membrane to obtain extract A and first filtrate.

[0031] Second ultrasonic warming extraction (preparation of extract B): add 4 times the mass (i.e. 200g) of 50% ethanol to the first filtrate, perform ultrasonic warming extraction at 50°C for 1h, and filter to obtain extract B.

[0032] Concentration and mixing Combine and concentrate: Combine extracts A and B into extract C, place in a vacuum tank, and reflux and concentrate at 55°C until the volume of the concentrate is 1 / 10 of the original volume to obtain concentrated extract A.

[0033] Preparation of finished product: Weigh 0.5 g of 99% yohimbine hydrochloride, add 10 times the mass (i.e. 5 g) of 99% ethanol, mix well to obtain solution B, then mix solution B with concentrated extract A, stir well to obtain 50 ml of finished spray.

[0034] Example 3: Raw material pretreatment Cleaning and drying: Weigh 30g of asarum, 35g of gallnut, 25g of clove, 40g of epimedium, 30g of cynomorium songaricum, and 30g of Morinda officinalis, wash them separately with clean water to remove impurities, put them in an oven, and dry them at 60℃ until the moisture content is <5%.

[0035] Crushing process: Place the dried medicinal materials into an ultrafine grinder and crush them into 150 mesh powder.

[0036] First ultrasonic heating extraction (preparation of extract A) Enzymization and pH adjustment: Place the Chinese medicine powder in an ultrasonic generator, add 2 times the mass (i.e. 300 g) of purified water, stir evenly, add 0.8% (i.e. 2.4 g) of citric acid monohydrate to the mass of purified water, adjust the pH to 10, and then add 5% (i.e. 7.5 g) of the raw material mass of cellulase and glucanase mixture, keep warm at 60°C for 30 minutes.

[0037] Ultrasonic extraction: Start a 300W ultrasonic generator and treat at 60°C for 1.5 hours. Then add 97% ethanol twice the mass of the material (i.e. 300g) and continue ultrasonic treatment for 1.5 hours.

[0038] Filtration: Filter with a 1μm microfiltration membrane to obtain extract A and the first filter residue.

[0039] Second ultrasonic heating extraction (preparation of extract B): add 60% ethanol in an amount of 4 times the mass of the material (i.e. 600 g) to the first filter residue, perform ultrasonic heating extraction at 60°C for 1.5 h, and filter to obtain extract B.

[0040] Concentration and mixing Combine and concentrate: Combine extracts A and B into extract C, place in a vacuum tank, and reflux and concentrate at 65°C until the volume of the concentrate is 1 / 10 of the original volume to obtain concentrated extract A.

[0041] Product preparation: 1.5g of 99% yohimbine hydrochloride was weighed, 10 times the mass (i.e. 15g) of 99% ethanol was added, and mixed uniformly to obtain solution B, then solution B was mixed with concentrated extract solution A, and stirred uniformly to prepare 150ml of finished product spray.

[0042] Effect example In order to verify the therapeutic effect of the anti-skid spray prepared by the present application, 120 cases of primary premature ejaculation patients were selected for clinical trials. The patients were between 20 and 50 years old, with a disease duration of 1-5 years, and the average insertion of the vagina to ejaculation time (IELT) was less than 1 minute. The patients were randomly divided into three groups, 40 cases in each group, and the sprays prepared by Example 1, Example 2 and Example 3 were used respectively, once a day, for 4 weeks of continuous use.

[0043] Therapeutic effect evaluation criteria: Cure: IELT≥5 minutes, symptoms disappeared; Marked effect: IELT increased by 2-5 minutes compared with before treatment; Effective: IELT increased by 1-2 minutes compared with before treatment; Ineffective: IELT increased by <1 minute or unchanged compared with before treatment.

[0044] The treatment results are shown in the following table:

[0045] As can be seen from the table, the anti-skid spray prepared by the present application has a significant therapeutic effect on primary premature ejaculation, and the total effective rate is more than 87.5%. Among them, the treatment effect of Example 3 is the best, and the total effective rate reaches 97.5%. During the treatment, the patients did not have obvious adverse reactions, indicating that the spray of the present application has high safety.

Claims

1. A traditional Chinese medicine anti-slip spray for treating primary premature ejaculation, characterized in that: The spray is prepared from the following raw materials: 10-30 parts of asarum, 15-35 parts of gallnut, 10-25 parts of clove, 20-40 parts of epimedium, 15-30 parts of cynomorium songaricum, 15-30 parts of morinda officinalis, 99% yohimbine hydrochloride and 99% ethanol.

2. The anti-slip spray according to claim 1, characterized in that The preparation method of the spray comprises the following steps: Raw material pretreatment: Wash and dry Asarum, Gallnut, Clove, Epimedium, Cynomorium songaricum and Morinda officinalis and grind into 100-150 mesh powder; First ultrasonic heating extraction: Add the Chinese herbal medicine powder to purified water, adjust the pH to 9.5-10, add a mixture of cellulase and glucanase, keep warm and allow to stand before ultrasonic extraction, then add ethanol and continue ultrasonic extraction, and filter to obtain extract A; Second ultrasonic heating extraction: add ethanol to the first filter residue, perform ultrasonic heating extraction, and filter to obtain extract B; Concentration and mixing: Combine extracts A and B, concentrate them, and mix them with an ethanol solution of yohimbine hydrochloride to prepare the finished spray.

3. The preparation method according to claim 2, characterized in that In step 2, the amount of purified water added is 2 times the mass of the traditional Chinese medicine powder, the amount of citric acid monohydrate added is 0.8% of the mass of purified water, the amount of the cellulase and glucanase mixture added is 5% of the mass of the raw material, the holding temperature is 50-60 ° C, the holding time is 30 min, the ultrasonic extraction power is 300 W, the ultrasonic extraction temperature is 50-60 ° C, the first ultrasonic extraction time is 1-1.5 h, the amount of ethanol added is 2 times the mass of the material, the ethanol concentration is 95-98%, and the second ultrasonic extraction time is 1-1.5 h.

4. The preparation method according to claim 2, characterized in that In step 3, the amount of ethanol added is 4 times the mass of the first filter residue, the ethanol concentration is 50-60%, the ultrasonic heating extraction temperature is 50-60°C, and the extraction time is 1-1.5h.

5. The preparation method according to claim 2, characterized in that: In step 4, the concentration is vacuum reflux concentration, the mass ratio of yohimbine hydrochloride to ethanol is 1:10, and the ethanol concentration is 99%.

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