WO2014059880A1

WO2014059880A1 - Method for preparation of pomegranate-peel polyphenol gel used to treat gynecological inflammation

Info

Publication number: WO2014059880A1
Application number: PCT/CN2013/084674
Authority: WO
Inventors: 艾萨⋅阿吉艾克拜尔; 罗玉琴; 伊斯拉木⋅热比姑丽; 阿不都拉⋅热依木古丽; 来海中
Original assignee: 中国科学院新疆理化技术研究所; 新疆莎菲雅生物科技有限公司
Priority date: 2012-10-18
Filing date: 2013-09-30
Publication date: 2014-04-24
Also published as: CN102861116B; EA029649B1; EA201590591A1; CN102861116A

Abstract

A method for preparing a pomegranate-peel polyphenol gel used to treat gynecological inflammation comprises: preparing a pomegranate-peel polyphenol extract; dissolving the pomegranate-peel polyphenol extract by means of a humectant and/or a solubilizer; adding said dissolved extract to a dispersed gel matrix such that said extract is dispersed uniformly; adding a preservative, and then water as the last component; mixing uniformly, adjusting the pH value to 4.0-5.0 and obtaining said gel. Said gel is applicable to the prevention and treatment of gynecological inflammation caused by bacteria, such as vaginitis or cervicitis; the gel is easy to administer, well absorbed, and highly effective.

Description

Method for preparing pomegranate skin polyphenol gel for treating gynecological inflammation

Technical field

The invention relates to a method for preparing a pomegranate skin polyphenol gel for treating gynecological inflammation, in particular to a method for preparing vaginitis or cervicitis in gynecological inflammation caused by bacteria by using pomegranate peel polyphenol as raw material. Gelling agent.

Background technique

Vaginitis, cervicitis and other gynecological inflammation, seriously threaten women's health. Due to the particularity of female genital organs, gynecological inflammation has become a common and frequently-occurring disease in adult women. Its clinical manifestations are diverse, its causes are complex and often accompanied by a variety of serious complications, which have a great impact on women's life and work. Vaginitis is a general term for a variety of vaginal mucosal diseases caused by different causes. In the normal physiological state, the vagina has a natural defense function against the invasion of pathogens due to the characteristics of the anatomical tissue. When the natural defense function of the vagina is destroyed, the pathogen is easily invaded and causes vaginal inflammation. Clinically, vaginal inflammation is most common with bacterial vaginitis. Because of its easy to repeat, it is not easy to get better. According to the survey on female reproductive health in China, in the past year, 58.66% of adult women who had had vaginitis, 9.4% of them had repeated episodes more than 4 times; cervicitis is female genital The most common type of inflammation, accounting for more than half of married women. The main pathogens causing cervicitis are Staphylococcus, Streptococcus, Escherichia coli and anaerobic bacteria.

At present, the drugs for treating gynecological inflammation such as vaginitis and cervicitis are classified into internal medicine and external medicine. The internal medicines are mainly Chinese patent medicines, and the dosage forms include capsules, dropping pills, etc.; the external medicines are mainly chemical drugs, most of which contain metronidazole, clotrimazole and other drugs, and excessive use easily breaks the restriction relationship between vaginal flora. At the same time, the pathogenic bacteria are resistant, which leads to prolonged treatment period and prevents the disease from being effectively treated. Due to the anatomical and physiological characteristics of women, external treatment has special significance in gynecological clinics. In recent years, in the study of vaginitis and cervicitis, the Chinese medicine external treatment method has been used, and good results have been obtained. Vaginal topical medication has high clinical evaluation because of its high local drug concentration, low dosage, safe and effective. The vagina is rich in capillaries and lymphatic vessels, and the vagina has no clear nerve endings. The patient's pain is small when administered, and it is an effective drug release site for specific diseases such as cervicitis and vaginitis. By placing the drug in the vagina, it can be absorbed into the local or systemic blood circulation through the vaginal mucosa, avoiding the first pass of the liver and the physiological checkpoint effect of the gastrointestinal tract, and has better biocompatibility with the human body, which can enhance the adhesion. , has a sustained release and controlled release effect on the drug, making the lesion site effective

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Replacement page (Article 26) The increased concentration increases bioavailability and enhances the efficacy of the drug to achieve local or systemic treatment. Currently available drugs for vaginal route on the market include rinsing liquid, vaginal effervescent tablets, suppositories, membranes, etc.

10 dosage forms. The rinsing liquid has a short action time and is not easy to penetrate deep into the vagina; the tablet is inconvenient to use, which may cause foreign body sensation in the vagina and easily damage the vagina; the suppository becomes liquid and easily flows out of the vagina, contaminating the clothes, so that the action time is short and the medicine is difficult All released; vaginal film agent is made of polymer film as a carrier to be inserted into the vagina. Although it is convenient to prepare, the contact surface between the drug and the mucosa is small. Gels are a class of macromolecular network systems containing two or more, consisting of solid-liquid two phases and having semi-solid properties. Dissolving or evenly dispersing the drug in the gel is a gelling agent, which has good adhesion and film-forming properties. Compared with other vaginal administration forms, it can prolong the residence time, is easy to apply, and can penetrate into the mucosal wrinkles. Pleated, no foreign body sensation, non-irritating, can improve patient compliance, and clean and easy to clean. It is one of the most active new drug formulations in the international pharmaceutical market in recent years, and it is also the most promising type of external use. drug.

Pomegranate peel is a variety contained in the Chinese Pharmacopoeia. It has the functions of sputum, hemostasis, and deworming. It is mainly used for diarrhea, chronic sputum, etc. In addition, pomegranate peel also has pharmacological activity that promotes healing of ulcer mucosa. The active ingredients of polyphenols contained in pomegranate peel, such as punical glucoside, ellagic acid, gallic acid, etc., have strong anti-inflammatory activities. However, the polyphenols are unstable, the temperature is high, and the heating time is long and easy to oxidize, resulting in low extraction rate and decreased activity. Therefore, the pomegranate peel is reduced by low temperature extraction and concentration technology to improve the stability and extraction rate of polyphenols. The macroporous resin adsorption technology is used to prepare the effective part of the pomegranate peel polyphenol with high purity. The invention and the Chinese patent

ZL200910113497. 7 "Preparation method and application of pomegranate skin polyphenol antibacterial anti-inflammatory external effervescent tablet", the literature "Preparation and quality control of pomegranate peel polyphenol gel", although pomegranate peel polyphenols are used as raw materials, but at different extraction temperatures and solvents Concentration, under the influence of different macroporous adsorption resin types, the content and content of polyphenols in the pomegranate peel extract and effective parts changed. The content of total polyphenols in the extract of pomegranate peel prepared by the invention is 60-80 wt%, and the content of ellagic acid in the total multi-point is 2-4 wt%, and the content of pomegranate is 15- 20 wt%. The literature "preparation and quality control of pomegranate peel polyphenol gel" does not indicate the preparation process of the extract and the proportion of the gel formulation, and the polyphenol active ingredient is controlled by gallic acid, which is inconsistent with the active ingredient of the present invention; In terms of the use of the present invention, the document reports that pomegranate polyphenol gel is used for the healing of acute and chronic skin wounds.

The invention applies the gel agent to the clinic, because the gel agent can produce better biocompatibility with the human body, can enhance the adhesion, has a sustained release and controlled release effect on the drug, and increases the effective concentration of the lesion site, thereby improving The bioavailability enhances the efficacy of the drug, improves patient compliance, and is clean and easy to clean. The anti-inflammatory pharmacodynamics of xylene induced by mouse anti-inflammatory effects on mouse ear swelling and carrageenan-induced toe swelling test showed that the pomegranate peel polyphenol gel of the present invention has better than pomegranate peel polyphenol effervescent tablets. Anti-inflammatory effect.

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Replacement page (Article 26) Summary of the invention

The object of the present invention is to provide a method for preparing a pomegranate skin polyphenol gel for treating gynecological inflammation, which comprises using a pomegranate peel polyphenol extract as a raw material, and adding a pharmaceutically acceptable gel matrix material auxiliary material to the card wave. M, hypromellose or sodium carboxymethylcellulose, humectant is propylene glycol or a mixture of glycerin and propylene glycol, the solubilizer is Tween, the preservative is methylparaben or ethylparaben, and the pH adjuster is Made of triethanolamine; firstly prepare the pomegranate peel polyphenol extract, dissolve the pomegranate peel polyphenol extract with a moisturizer or/and a solubilizing agent, and add to the carbomer, hypromellose or carboxyl group dispersed with water. 。 The pomegranate skin polyphenol gel can be obtained by adding a preservative and a balance of water to 100 g, stirring evenly, adding triethanolamine to adjust the pH to 4. 0-5. The gel obtained by the method is used for the prevention and treatment of vaginitis or cervicitis caused by bacteria in gynecological inflammation, and has the characteristics of convenient administration, good absorption, and high curative effect.

The technical solution of the present invention is as follows:

The invention provides a method for preparing a pomegranate skin polyphenol gel for treating gynecological inflammation, wherein the method comprises a pomegranate peel polyphenol extract in an amount of 5-30 parts by weight, and the auxiliary material is a pharmaceutically acceptable gel matrix material as a card. Bom, hypromellose or sodium carboxymethylcellulose 0. 5-4 parts, humectant is propylene glycol or a mixture of glycerin and propylene glycol 5-20 parts, solubilizer is 0-2 parts of Tween, preservative is Methylparaben or ethylparaben ethyl ester 0. 1-0. 5 parts, the pH adjuster is made of triethanolamine; the gelatin is prepared by preparing the pomegranate peel polyphenol extract first, and then using the extract as a raw material, wherein The main active ingredients of the pomegranate peel polyphenol extract are total polyphenols, ellagic acid and punical glucoside. The specific operation is as follows:

Preparation of pomegranate peel polysaccharide extract - a, pomegranate peel pulverized into coarse powder, add 5-30 times pomegranate skin concentration of 35-49wt% ethanol warm immersion, temperature 71 - 85 ° C, extraction 1-4 times, The concentrating solution of the pomegranate peel is 0. 15-0.

b. Add the concentrated liquid obtained in step a to the treated HTO600 macroporous adsorption resin column, adsorb for 3-12 hours, first rinse with deionized water until the effluent is lighter, and then use 2-5 times column. The volume of 50-80wt% ethanol is eluted, the alcohol-containing eluate is collected, the ethanol is recovered, concentrated under reduced pressure and vacuum-dried into a dry extract, pulverized, and passed through a 80-120 mesh sieve to obtain a pomegranate peel polyphenol extract for use;

Preparation of gelling agent:

c. Dissolve the step p pomegranate peel polyphenol extract with a moisturizer or/and a solubilizing agent, and add it to a carbomer, hypromellose or sodium carboxymethylcellulose solution dispersed in water to disperse evenly. Add preservative and balance water

Replacement page (Article 26) The pomegranate peel polyphenol gel can be obtained by adding the triethanolamine to adjust the pH to 4. 0-5. 0. The content of the total polyphenol in the pomegranate peel polyphenol extract is 60-80% by weight.

The active ingredient of the total polyphenol in the pomegranate peel polyphenol extract is 2-4% by weight of ellagic acid and 15-20% by weight of punny glucoside. The pomegranate peel polyphenol gel obtained by the method of the invention has fine and uniform texture and stable quality, and no obvious changes are observed under the influence of light, heat and low temperature. In the preparation of the prevention and treatment of gynecological inflammation caused by bacteria, vaginitis or cervicitis, the combination of a new drug dosage form and a purified traditional Chinese medicine enhances the efficacy and the comfort and adaptability of the medicine. detailed description

Example 1

Preparation of Pomegranate Peel Polyphenol Extract - Pomegranate peel was pulverized into coarse powder, 5 times pomegranate skin was added to a concentration of 35 wt% ethanol, and the temperature was 71 ° C, extracted once, for 3 hours, filtered, and the filtrate was decompressed. The concentrated liquid containing 0.15 g of pomegranate peel per ml;

Add the concentrate to the processed HPD600 macroporous adsorption resin column, adsorb for 6h, first elute with deionized water until the effluent is lighter, then elute with 2 times column volume of 50wt% ethanol. The alcohol-containing eluate is collected, the ethanol is recovered, concentrated under reduced pressure, and vacuum-dried into an extract, pulverized, and passed through a 80 mesh sieve to obtain a pomegranate peel polyphenol extract, wherein the total polyphenol content of the extract is 62 wt%, 鞣4重量%; The content of the pomegranate is 15. 4wt%;

Preparation of gelling agent - Take 5 parts of humectant propylene glycol and 10 parts of pomegranate peel extract, firstly dissolve, add to 2 parts of carbomer dispersed with water, disperse evenly, add preservative hydroxybenzyl ester 0. 1 part, the remaining amount of water to 100g, drip into the triethanolamine to adjust the pH of 4. 0, stir and hook, you can get the pomegranate skin polyphenol gel. Example 2:

Preparation of pomegranate peel polyphenol extract:

Pomegranate peel was pulverized into coarse powder, 8 times pomegranate skin was added to a concentration of 49 wt% ethanol, immersed at a temperature of 75 V, extracted twice, each time for 2 hours, filtered, and the filtrate was combined to recover ethanol under reduced pressure, and concentrated to contain pomegranate per mL. 0. 18g of concentrated liquid;

4

Replacement page (Article 26) The concentrate was added to the treated HPD600 macroporous adsorption resin column, adsorbed for 8 h, first eluted with deionized water until the effluent was nearly colorless, and then eluted with 3 column volumes of 60 wt% ethanol. The alcohol-containing eluate is collected, the ethanol is recovered, concentrated under reduced pressure, and vacuum-dried into an extract, pulverized, and passed through a 100 mesh sieve to obtain a pomegranate peel extract, wherein the total polyphenol content in the pomegranate peel polyphenol extract is 2wt% _; yttrium glucoside content of 16. 2wt% _;

Preparation of gelling agent:

5份。 The humectant propylene glycol 5 parts and 15 parts of the pomegranate peel extract was uniformly dissolved and dissolved, and added to the water-dispersed hypromellose solution in 3 parts, evenly dispersed, and then added 0.1. The balance of water to 100g, drip triethanolamine to adjust _P H 4. 5, stir evenly, you can get pomegranate peel polyphenol gel. Example 3:

5小时,过滤过滤,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, The concentrated liquid containing 0.22g of pomegranate peel per ml of ethanol;

Add the concentrate to the processed HPD600 macroporous adsorption resin column, adsorb for 12h, first elute with distilled water until the effluent is nearly colorless, and then elute with 4 times column volume of 60wt% ethanol. The alcohol eluent is recovered, the ethanol is recovered, concentrated under reduced pressure and vacuum-dried into an extract, pulverized, and passed through a 120 mesh sieve to obtain a pomegranate peel polyphenol extract, wherein the total polyphenol content in the pomegranate peel polyphenol extract is 75 wt%. 6重量% _; The content of the saponin is 16. 6wt% _;

Preparation of gelling agent:

Take 10 parts of humectant glycerin and 5 parts of propylene glycol, 20 parts of pomegranate peel extract, grind and dissolve first, add to 3 parts of sodium carboxymethyl cellulose solution dispersed with water, disperse evenly, add preservative methylparaben 0. 1 part, the balance of water to 100g, drip into the triethanolamine to adjust the pH 4. 8, stir evenly, you can get the pomegranate skin polyphenol gel. Example 4:

Preparation of Pomegranate Peel Polyphenol Extract - Pomegranate peel is pulverized into coarse powder, 20 times pomegranate skin is added to a concentration of 45 wt% ethanol, temperature is 74 ° C, extracted twice, each time for 3 hours, filtered, and the filtrate is combined. The concentrated liquid containing 0.18 g of pomegranate peel per ml of ethanol;

Replacement page (Article 26) The concentrate was added to the treated HPD600 macroporous adsorption resin column, adsorbed for 10 h, first eluted with deionized water until the effluent was nearly colorless, and then eluted with 5 column volumes of 80 wt% ethanol. The alcohol-containing eluate is collected, the ethanol is recovered, concentrated under reduced pressure, and vacuum-dried into an extract, pulverized, and passed through a 100 mesh sieve to obtain a pomegranate peel polyphenol extract, wherein the total polyphenol content in the pomegranate peel polyphenol extract is 53 wt. % 安安_{; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;}

Preparation of gelling agent - take 5 parts of humectant glycerin and 10 parts of propylene glycol, 1 part of solubilizing agent Tween, 30 parts of pomegranate peel extract, firstly dissolved, added to 2 parts of carbomer solution dispersed with water, dispersed Uniformly, adding 0.3 mg of the preservative, it is added to the triethanolamine to adjust the pH to 5.0, and the mixture is evenly stirred to obtain a pomegranate peel polyphenol gel. Example 5

Preparation of pomegranate peel polyphenol extract:

Pomegranate peel was pulverized into coarse powder, 10 times pomegranate skin was added to a concentration of 40 wt% ethanol, and the temperature was 80 ° C. The mixture was extracted 3 times for 2 hours each time, filtered, and the filtrate was combined to recover ethanol under reduced pressure.毫升的浓缩液 containing 0.16g of pomegranate peel;

Add the concentrate to the processed HPD600 macroporous resin column, adsorb for 6h, first elute with distilled water until the effluent is nearly colorless, and then elute with 4 times column volume of 70wt% ethanol, collect The alcohol-containing eluent is recovered, the ethanol is recovered, concentrated under reduced pressure and vacuum-dried into an extract, pulverized, and passed through a 120 mesh sieve to obtain a pomegranate peel polyphenol extract, wherein the total polyphenol content in the pomegranate peel polyphenol extract is 71 wt%. 6wt% _;石榴酸酸_{; ; ; ; ; ; ; ;} 17 _; 17 17 17 17 17 17 17 17

Preparation of gelling agent:

Take 15 parts of humectant propylene glycol, 2 parts of solubilizing agent Tween, 25 parts of pomegranate peel extract, grind and dissolve first, add to 4 parts of sodium carboxymethyl cellulose solution dispersed with water, disperse evenly, add preservative hydroxybyl 5 parts, the remaining amount of water to 100g, drip into the triethanolamine to adjust the pH to 4. 3, stir the hook, you can get the pomegranate skin polyphenol gel. Example 6:

Preparation of pomegranate peel polyphenol extract:

Pomegranate peel is pulverized into coarse powder, 20 times pomegranate skin is added to a concentration of 45 wt% ethanol, and the temperature is 85 ° C.

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Replacement page (Article 26) 5克的浓缩液; concentrating liquid containing 0.15g of pomegranate peel per ml of ethanol;

Add the concentrate to the processed HPD600 macroporous resin column, adsorb for 12h, first elute with distilled water until the effluent is nearly colorless, and then elute with 3 times column volume of 60wt% ethanol. The alcohol eluent is recovered, the ethanol is recovered, concentrated under reduced pressure and vacuum-dried into an extract, pulverized, and passed through a 80 mesh sieve to obtain a pomegranate peel polyphenol extract, wherein the total polyphenol content in the pomegranate peel polyphenol extract is 66 wt%. 8wt% _;石榴酸酸_{; ; ; ; ; ; ; ; ; ; ; ; ;}

Preparation of gelling agent:

2份,余量。 The humectant propylene glycol 5 parts, the pomegranate skin extract 15 parts of the first time, the first time, the amount of the carbomer solution was dispersed in water, the dispersion was uniform, and then added to the preservative. The water is added to 100 g, and triethanolamine is added dropwise to a pH of 4.5. The mixture is uniformly stirred to obtain a pomegranate peel polyphenol gel.

Example 7

Pomegranate skin polyphenol gel for the preparation of a pharmacodynamic experiment for the prevention and treatment of gynecological inflammation caused by bacteria, vaginitis or cervicitis:

(1) Toxicological test research

Vaginal mucosal irritation test

New Zealand female white rabbits, 6 rats, weighing 1. 8-2. 0kg, the test object is the solution of the highest application liquid 5 times concentration, the control group is treated with normal saline, and the experimental animals are slowly injected with 2ml test solution to dye the vagina. Toxic, the control group of animals were treated with normal saline. After 24 hours of exposure, the animals were sacrificed by air-plugging. The entire vagina was removed by laparotomy. The longitudinal incision was performed. The eyes were visually observed for hyperemia and edema. Then the vagina was placed in 10 % formalin solution was fixed for more than 24h, and the two ends of the vagina and the central part were selected for filming, HE staining, histopathological examination, according to the "Disinfection Technical Specifications" (2002 edition) vaginal mucosal stimulation response scoring standard table And the intensity scale, the vaginal mucosal irritation score and intensity were evaluated. The test results are shown in Table 1:

Table 1 Scoring of vaginal mucosal irritation response of rabbits in rabbits (sickness test results)

Replacement page (Article 26) 3 1.9 0 0 0 3 3 Average score 9 9

4 1.9 0 0 0 3 3 Toxic group 5 2.0 0 0 0 3 3

6 1.9 0 0 0 3 3 Average score 9 9 It can be seen from the test results in Table 1 that the difference between the average score of vaginal mucosal stimuli in the test group and the average score of the control group is 0, according to the Disinfection Technical Specification (2002 edition) The vaginal mucosal stimuli intensity scale is non-irritating.

(2) In vivo pharmacodynamic test study:

Xylene-induced ear swelling test in mice:

50 Kunming mice, weighing 18-22 g, were randomly divided into 5 groups, 10 in each group, which were control group, pomegranate skin polyphenol gel low, medium and high dose groups (0.14 g/kg). 0.28 g/kg, 0.56 g/kg), pomegranate peel polyphenol effervescent tablets (0.30 g/kg); each drug group was given the corresponding drug by intragastric administration, and the control group was given an equal volume of 0.5% CMC-Na, once a day. 7 days in a row, after the last administration for 1 hour, each mouse was evenly coated with lml/lOg on the outside of the right ear, and the left ear was used as a control. After lh, the mice were sacrificed by cervical dislocation. The same part of the left and right ears was treated with a 9 mm diameter sclera. The ear was punched down, and the weight of the ear was weighed by an electronic balance. The difference between the weight of the two ears was the degree of swelling. The mean and standard deviation of the ear swelling of each group were calculated, and the inhibition rate of swelling was calculated. The results are shown in Table 2. .

Inhibition rate = (average ear swelling in the control group - mean ear swelling in the administration group) / average ear swelling in the control group χ 100%. Table 2 Effect of xylene on mouse ear swelling test (x±S)

Remarks: *p<0.05, "p<0.01 compared with the control group

The data in Table 2 shows that: the pomegranate peel polyphenol gel 髙 dose group (0.56 g / kg) has obvious inhibition of mouse ears

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Replacement page (Article 26) The effect of swelling, pomegranate skin polyphenol effervescent tablets also have the same effect.

Effect of carrageenan on swelling of foot and foot in mice - 50 Kunming mice, weighing 18-22g, were randomly divided into 5 groups, 10 in each group, respectively, vehicle control group, pomegranate skin polyphenol gel low , medium and high three dose groups 0. 14 g / kg, 0. 28 g / kg, 0. 56 g / kg), pomegranate peel polyphenol effervescent tablets (0. 30 g / kg); The stomach was given the corresponding drug, and the vehicle control group was given an equal volume of 0.5% CMC-Na once a day for 7 consecutive days. 5小时, After the end of the inflammation, 0. 5h, respectively, after the end of the inflammation, respectively, the mice were treated with an electronic digital micrometer to determine the thickness of the left hind paw. Lh, 2h, 6h used electronic digital micrometer to measure the thickness of left hind paw, so that the difference between the thickness of the foot and the foot before and after the inflammation as the degree of swelling, calculate the mean and standard deviation of the swelling of the foot and ankle in each group, and calculate the inhibition of the swelling of the ankle. Rate, the results are shown in Table 4 of Table 3;

Inhibition rate = (average foot swelling in the control group - average ankle swelling in the drug-administered group) / average foot swelling in the control group χΐοο% _; Table 3 Effect of carrageenan-induced swelling of the athlete's foot (x ± S, N =10)

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Replacement page (Article 26) Remarks: Compared with the control group, *P<0.05, -·ρ<0.01

The data in Table 4 of Table 3 indicate that: the high dose group of pomegranate peel polyphenol gel (0.56 g/kg) has obvious inhibitory effect on ear swelling of mice at 0.5 h after inflammation, and the pomegranate peel polyphenol effervescent tablets have the same effect.

10

Replacement page (Article 26)

Claims

Rights request

1. A method for preparing a pomegranate peel polyphenol gel for treating gynecological inflammation, characterized in that the gel is composed of 5 to 30 parts by weight of pomegranate peel polyphenol extract, and the auxiliary materials are pharmaceutically acceptable gels. The glue matrix material is carbomer, hypromellose or carboxymethylcellulose sodium 0.5 to 4 parts, the humectant is 5 to 20 parts of propylene glycol or a mixture of glycerol and propylene glycol, the solubilizing agent Tween is 0 to 2 parts, The preservative is 0.1 to 0.5 parts of methylparaben or ethylparaben, and the pH regulator is made of triethanolamine; the main active ingredients of the pomegranate peel polyphenol extract are total polyphenols and ellagic acid. and punicalagin, the specific operation is carried out according to the following steps:

Preparation of pomegranate peel polyphenol extract - a. Crush the pomegranate peel into coarse powder, add 5 to 30 times the amount of pomegranate peel to a concentration of 35 to 49 wt% ethanol and warm soak at a temperature of 71 to 85°C, extraction 1 to 4 15-0.2g pomegranate peel concentrate per mL;

b. Add the concentrated solution obtained in step a to the processed HPD600 macroporous adsorption resin column, adsorb for 3 to 12 hours, first rinse with deionized water until the color of the effluent is lighter, and then use 2-5 times the column Elute with 50~80wt% ethanol by volume, collect the alcohol-containing eluate, recover the ethanol, concentrate under reduced pressure and dry under vacuum to form a dry extract, crush it and pass through a 80-120 mesh sieve to obtain the pomegranate peel polyphenol extract for later use;

Preparation of gel:

c. Dissolve the pomegranate peel polyphenol extract in step b with a humectant or/and solubilizer first, add it to the water-dispersed carbomer, hypromellose or carboxymethylcellulose sodium solution, disperse evenly, and then Add the preservative and remaining water to 100g, stir evenly, add triethanolamine to adjust the pH to 4.0-5.0, and obtain a pomegranate peel polyphenol gel.

2. The method according to claim 1, characterized in that the total polyphenol content in the pomegranate peel polyphenol extract is 60~80wt%.

3. The method according to claim 2, characterized in that the content of ellagic acid, the active ingredient of total polyphenols in the pomegranate peel polyphenol extract, is 2 to ½ t%, and the content of punicalagin is 15 to 20 wt%. .

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Replacement Page (Rule 26)