Traditional Chinese medicine composition and traditional Chinese medicine gel for treating gynecological vaginitis and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition and traditional Chinese medicine gel for treating gynecological vaginitis and a preparation method thereof. The traditional Chinese medicine composition is prepared from sugarcane leaves, mango leaves, cinnamon leaves, citronella, gallnut, cortex phellodendri, rhizoma atractylodis, radix rubiae, fructus cnidii, pericarpium granati, radix sophorae flavescentis and alums. The traditional Chinese medicine gel comprises a traditional Chinese medicine composition and a gel matrix (Carbomer-940 and glycerol). The traditional Chinese medicine composition is subjected to water extraction and prepared into the gel, and the obtained traditional Chinese medicine gel has the effects of clearing away heat and drying dampness and killing parasites to relieve itching and is suitable for gynecological vagina inflammation, vulva infection and other symptoms. The traditional Chinese medicine composition can effectively prolong the duration of the medicine at the medication part, is beneficial to improving the medication compliance of a patient, can strengthen the treatment effect, and plays a key role in improving the compliance of the patient and enhancing the treatment effect of the medicine.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating gynecological vaginitis, a traditional Chinese medicine gel and a preparation method thereof. BACKGROUND

[0002] Gynecological vaginitis is the most common infectious disease of the female reproductive system, and belongs to the category of 'yin itching' and 'leukorrhea' in traditional Chinese medicine. The main symptoms are excessive leukorrhea, abnormal color, odor, vaginal mucosa hyperemia, burning sensation of the vulva, itching of the vulva and vagina, and restlessness, which greatly affects the life and work of patients.

[0003] At present, the guidelines for treating vaginitis recommend using antibiotics as the first-line treatment, such as metronidazole or clindamycin.

[0004] According to traditional Chinese medicine theory, the main cause of vaginitis is dampness, so clearing heat and removing dampness is an important strategy for treating vaginitis in traditional Chinese medicine. Traditional Chinese medicine has a long history of application in gynecological diseases. As early as the Eastern Han Dynasty, Zhang Zhongjing's 'Treatise on Febrile Diseases and Miscellaneous Diseases' recorded the treatment method of external use of traditional Chinese medicine for gynecological diseases, and 'Golden Chamber' introduced various external use of traditional Chinese medicine, including sitting medicine, washing, fumigation, moxibustion, massage, enema, and so on. The first record is'snake bedzi powder, warm yin sitting medicine' and 'wolf tooth soup for washing' for treating vaginal erosion and ulceration, which is praised by later generations as the beginning of external treatment of gynecology.

[0005] Traditional fumigation and sitz bath have the problems of complicated operation and inability of the medicine to act on the medication site for a long time. Gel is a thick liquid or semi-solid preparation with gel properties prepared from raw medicine and gelling aids. Compared with other vaginal administration forms, gel has the advantages of long residence time, high bioavailability, safety, and economy.

[0006] In summary, there is an urgent need for an external preparation for treating gynecological vaginitis with good adhesion, which can prolong the residence time of the drug, improve patient compliance and drug efficacy to meet the clinical needs. SUMMARY

[0007] The present application aims to provide a traditional Chinese medicine composition for treating gynecological vaginitis, a traditional Chinese medicine gel and a preparation method thereof. The traditional Chinese medicine gel has the effects of clearing heat and removing dampness, killing insects and relieving itching, and has certain in vitro anti-inflammatory activity and no irritation after multiple administrations in New Zealand rabbits.

[0008] In order to achieve the above-mentioned application purposes, the present application provides the following technical solutions:

[0009] The application provides a traditional Chinese medicine composition, which comprises the following components in parts by mass: sugarcane leaves 15-30 parts, mango leaves 10-20 parts, cassia leaves 5-10 parts, citronella 10-20 parts, gallnut 5-10 parts, yellow oakwood 5-15 parts, Chinese atractylodes 5-15 parts, madder 10-20 parts, cnidium 10-20 parts, pomegranate peel 5-15 parts, kuhns sophora 15-30 parts and alum 1-5 parts.

[0010] The application further provides a traditional Chinese medicine gel, which comprises the traditional Chinese medicine composition and a gel base.

[0011] Optionally, the gel base comprises carbomer-940 and glycerol, and the mass ratio of the carbomer-940 to the glycerol is 0.8-1.3:5-7.

[0012] Optionally, the mass ratio of the traditional Chinese medicine composition, the carbomer-940 and the glycerol is 15-20:0.8-1.3:5-7.

[0013] The application further provides a preparation method of the traditional Chinese medicine gel, comprising the following steps:

[0014] In parts by mass, the mixture of the sugarcane leaves, the mango leaves, the cassia leaves, the citronella, the gallnut, the yellow oakwood, the Chinese atractylodes, the madder, the cnidium, the pomegranate peel and the kuhns sophora is immersed in water to perform first extraction, so as to obtain a first raw residue and a first plant extract;

[0015] The first raw residue is immersed in water to perform second extraction, so as to obtain a second raw residue and a second plant extract;

[0016] The second raw residue is immersed in water to perform third extraction, and heated reflux extraction is performed for 1.5 hours; after the boiling is completed, the residue is removed through fine mesh filtration, so as to obtain a third plant extract;

[0017] The first plant extract, the second plant extract and the third plant extract are mixed to perform concentration; during the concentration, the alum powder is added, and the concentration is continued to obtain an extract A;

[0018] The carbomer-940 is mixed with water to perform swelling, so as to obtain a gel B;

[0019] The gel B, the extract A and the glycerol are mixed, and the pH is adjusted to 6 by using triethanolamine, so as to obtain the traditional Chinese medicine gel.

[0020] Optionally, the volume ratio of the mixture to water is 1:10; the temperature of the first extraction is 100 DEG C, and the time is 1.5 hours.

[0021] Optionally, the volume ratio of the first raw residue to water is 1:10; the temperature of the second extraction is 100 DEG C, and the time is 1.5 hours.

[0022] Optionally, the volume ratio of the secondary raw material residue and water is 1:10; the temperature of the third extraction is 100 DEG C, and the time is 1.5 h.

[0023] Optionally, the concentration of the extract A is 1 g crude drug / mL.

[0024] Optionally, the mass ratio of the carbomer-940 and water is 0.016-0.026:1; the temperature of the swelling is 4 DEG C, and the time is 12-24 h.

[0025] The application further provides application of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine gel in preparation of a medicine for treating gynecological vaginitis.

[0026] Compared with the prior art, the application has the following beneficial effects:

[0027] 1. The traditional Chinese medicine formula in the application is scientific and reasonable; cortex phellodendri and sophora flavescens are used for clearing lower dantian damp-heat and purging fire and detoxifying, and are main drugs for treating damp-heat sore, vaginal itching and leucorrhea; cnidium monnieri is used for killing insects and relieving itching, and is good at treating eczema, vaginal trichomonas and pruritus of vulva; sugarcane leaf and mango leaf are used for clearing heat and detoxifying, and are good at treating thirst and red urine caused by internal damp-heat; the whole formula is used for clearing heat and drying dampness, killing insects and relieving itching, and is suitable for treating gynecological vaginitis and pruritus of vulva.

[0028] 2. The raw materials used in the application are widely available; the sugarcane leaf is used as one of the raw materials, which changes crop waste into treasure, embodies the green environmental protection concept, and has important significance in resource utilization.

[0029] 3. The application optimizes the extraction process of the traditional Chinese medicine formula for the first time, screens the best extraction process parameters of the formula, and provides an experimental basis for development of external preparation of the formula.

[0030] 4. The application modifies the traditional use of the formula into a gel, so that the gel has good adhesion, can effectively increase the time of the drug in the medication site, has the characteristics of direct drug to the lesion, reduces the drug dosage and adverse reactions, not only helps to improve the patient's medication compliance, but also avoids the first-pass effect of oral drugs, strengthens the treatment effect, and plays a key role in improving the patient's compliance and enhancing the treatment effect of the drug.

[0031] 5. The gel for treating gynecological vaginitis provided by the application has a stable and reliable preparation process, is economical and practical, has good viscosity and spreading properties, and can provide a reference for improvement of traditional external preparation dosage forms. BRIEF DESCRIPTION OF DRAWINGS

[0032] Figure 1 It is a schematic diagram of the extraction process of the traditional Chinese medicine formula in the application;

[0033] Figure 2 Figure 8 is a graph showing the effect of different base gel forming conditions;

[0034] Figure 3 Figure 9 is a response surface plot (top) and contour plot (bottom) showing the effect of Carbopol-940, glycerin, and extract A amount on the overall score of the gel;

[0035] Figure 4 Figure 10 is a graph showing the effect of different treatment groups on RAW264.7 cell viability;

[0036] Figure 5 Figure 11 is a graph showing the effect of different drugs on RAW264.7 cell survival rate;

[0037] Figure 6 Figure 12 is a graph showing the effect of the gel on RAW264.7 cell NO, IL-1β, IL-6, and TNF-α secretion under LPS induction;

[0038] Figure 7 Figure 13 is a graph showing the skin condition of New Zealand rabbits during the observation period; Note: The skin condition of New Zealand rabbits could not be observed during the experiment because the rabbits' fur grew, so the rabbits were re-treated with depilation at 48 h. DETAILED DESCRIPTION

[0039] Various exemplary embodiments of the present application will now be described in detail with reference to the drawings. The detailed description is not intended to limit the present application, but rather to explain certain aspects, features, and embodiments of the present application.

[0040] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present application. Additionally, it is to be understood that where the application is herein described as comprising or having particular elements, this is intended to mean that the application encompasses a variety of embodiments including those in which the

[0041] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application. All documents mentioned herein are incorporated by reference to disclose and describe in detail the methods and / or materials which are related to the present application. In the case of conflict between the content of the specification and that of any document incorporated herein by reference, the content of the specification prevails.

[0042] Many modifications and variations to the illustrative embodiments described herein will be apparent to those skilled in the art from consideration of the specification and practice of the subject technology. Additional embodiments of the present technology will be apparent to those skilled in the art from consideration of the specification and practice of the subject technology. The specification and examples provided should be considered exemplary only.

[0043] As used herein, the terms "comprise", "comprising", "include", "including", "have", "having" and the like are open-ended and do not exclude additional elements or steps.

[0044] The raw materials used in the present application can be obtained commercially or prepared by prior art.

[0045] The present application provides a traditional Chinese medicine composition, comprising the following components in mass fraction: sugarcane leaves 15-30 parts, mango leaves 10-20 parts, cinnamon leaves 5-10 parts, citronella 10-20 parts, gallnut 5-10 parts, yellow bark 5-15 parts, atractylodes 5-15 parts, madder 10-20 parts, cnidium 10-20 parts, pomegranate peel 5-15 parts, bitter apricot kernel 15-30 parts, and alum 1-5 parts.

[0046] In the present application, the traditional Chinese medicine composition comprises 15-30 parts of sugarcane leaves, for example, 15 parts, 18 parts, 20 parts, 22 parts, 24 parts, 26 parts, 28 parts or 30 parts, etc.

[0047] In the present application, the traditional Chinese medicine composition comprises 10-20 parts of mango leaves, for example, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, etc.

[0048] In the present application, the traditional Chinese medicine composition comprises 5-10 parts of cinnamon leaves, for example, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, etc.

[0049] In the present application, the traditional Chinese medicine composition comprises 10-20 parts of citronella, for example, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, etc.

[0050] In the present application, the traditional Chinese medicine composition comprises 5-10 parts of gallnut, for example, 5 parts, 6 parts, 7 parts, 8 parts, 9 parts or 10 parts, etc.

[0051] In the present application, the traditional Chinese medicine composition comprises 5-15 parts of yellow bark, for example, 5 parts, 8 parts, 10 parts, 12 parts, 14 parts or 15 parts, etc.

[0052] In the present application, the traditional Chinese medicine composition comprises 5-15 parts of atractylodes, for example, 5 parts, 8 parts, 10 parts, 12 parts, 14 parts or 15 parts, etc.

[0053] In the present application, the traditional Chinese medicine composition comprises 10-20 parts of Radix Sophorae Flavescentis, for example, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, etc.

[0054] In the present application, the traditional Chinese medicine composition comprises 10-20 parts of Radix Sophorae Flavescentis, for example, 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, 18 parts, 19 parts or 20 parts, etc.

[0055] In the present application, the traditional Chinese medicine composition comprises 5-15 parts of Fructus Punicae, for example, 5 parts, 8 parts, 10 parts, 12 parts, 14 parts or 15 parts, etc.

[0056] In the present application, the traditional Chinese medicine composition comprises 15-30 parts of Radix Sophorae Flavescentis, for example, 15 parts, 18 parts, 20 parts, 22 parts, 24 parts, 26 parts, 28 parts or 30 parts, etc.

[0057] In the present application, the traditional Chinese medicine composition comprises 1-5 parts of Alum, for example, 1 part, 2 parts, 3 parts, 4 parts or 5 parts, etc.

[0058] The present application also provides a traditional Chinese medicine gel, comprising the traditional Chinese medicine composition and a gel base.

[0059] In the present application, the gel base comprises Carbomer-940 and glycerol; the mass ratio of Carbomer-940 and glycerol is 0.8-1.3:5-7, for example, 0.8:5, 0.9:5, 1:5, 1.1:5, 1.2:5, 1.3:5, 1:6, 1:7 or 1:8, etc.

[0060] In the present application, the mass ratio of the traditional Chinese medicine composition, Carbomer-940 and glycerol is 15-20:0.8-1.3:5-7, for example, 15:0.8:5, 15:0.9:5, 15:1:5, 15:1.1:5, 15:1.2:5, 15:1.3:5, 15:1:6, 15:1:7, 15:1:8 or 20:1:5, etc.

[0061] The present application also provides a preparation method of the traditional Chinese medicine gel, comprising the following steps:

[0062] The mixture of sugarcane leaves, mango leaves, cinnamon leaves, citronella, gallnut, Chinese catalpa, atractylodes, Radix Sophorae Flavescentis, Radix Cnidii, Fructus Punicae and Radix Sophorae Flavescentis is immersed in water for the first extraction to obtain a first raw residue and a first plant extract;

[0063] The first raw residue is immersed in water for the second extraction to obtain a second raw residue and a second plant extract;

[0064] The secondary raw material residue is immersed in water, and third extraction is carried out, and heating reflux extraction is carried out for 1.5h; after boiling is completed, the residue is removed through fine mesh filtration to obtain a third plant extract;

[0065] The first plant extract, the second plant extract and the third plant extract are mixed, and concentration is carried out; when the solution is less, alum powder is added, and concentration is continuously carried out to obtain an extract A;

[0066] Carbomer-940 and water are mixed to obtain gel B through swelling;

[0067] The gel B, the extract A and glycerol are mixed, and the pH is adjusted to 6 by adding triethanolamine to obtain a traditional Chinese medicine gel.

[0068] The present application is to place sugarcane leaves, mango leaves, cinnamon leaves, citronella, gallnut, golden cypress, atractylodes, madder, cnidium, pomegranate peel and sophora in a round bottom flask to form a mixture, immerse the mixture in water, heat reflux extraction, and after boiling is completed, the residue is removed through fine mesh filtration to obtain a first plant extract.

[0069] In the present application, the volume ratio of the mixture to water is 1:10; the temperature of the first extraction is 100 DEG C, and the time is 1.5h.

[0070] The present application is to immerse the raw material residue after the first extraction in water to carry out second heating extraction, heat reflux extraction, and after boiling is completed, the residue is removed through fine mesh filtration to obtain a second plant extract.

[0071] In the present application, the volume ratio of the first raw material residue to water is 1:10; the temperature of the second extraction is 100 DEG C, and the time is 1.5h.

[0072] The present application is to immerse the raw material residue after the second extraction in water to carry out third heating extraction, heat reflux extraction for 1.5h, and after boiling is completed, the residue is removed through fine mesh filtration to obtain a third plant extract;

[0073] In the present application, the volume ratio of the second raw material residue to water is 1:10; the temperature of the third extraction is 100 DEG C, and the time is 1.5h.

[0074] The present application is to combine the first plant extract, the second plant extract and the third plant extract, and then heat concentration is carried out; when the solution is less, alum powder is added, and mixing is carried out, and concentration is continuously carried out to obtain an extract A.

[0075] In the present application, the concentration of the extract A is 1g crude drug / mL.

[0076] The present invention involves weighing a specific ratio of carbomer-940, adding pure water and stirring, and letting it stand overnight to allow it to fully swell, thereby obtaining gel B.

[0077] In this invention, the mass ratio of carbomer-940 to water is 0.016 to 0.026:1, for example, it can be 0.016:1, 0.018:1, 0.02:1, 0.022:1, 0.024:1 or 0.026:1, etc.; the swelling temperature is 4°C and the time is 12 to 24 hours.

[0078] This invention involves adding extract A and glycerin to extract B, adjusting the pH to approximately 6 with triethanolamine, and stirring thoroughly with a magnetic stirrer to obtain a gel.

[0079] The present invention also provides the use of the above-mentioned traditional Chinese medicine composition or the above-mentioned traditional Chinese medicine gel in the preparation of a medicament for treating gynecological vaginitis.

[0080] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0081] Example 1: Extraction of Traditional Chinese Medicine Formula

[0082] (1) Weigh out 15 parts sugarcane leaves, 10 parts mango leaves, 5 parts cinnamon leaves, 10 parts lemongrass, 5 parts gallnut, 5 parts phellodendron bark, 5 parts atractylodes, 10 parts madder root, 10 parts cnidium fruit, 5 parts pomegranate peel, 15 parts sophora flavescens, and 1 part alum, and set aside.

[0083] (2) Place sugarcane leaves, mango leaves, cinnamon leaves, lemongrass, gallnut, phellodendron bark, atractylodes, madder, cnidium, pomegranate peel and sophora flavescens in a round-bottom flask, add water 10 times the total weight of the herbs to submerge the herbs, heat and reflux at 100℃ for 1.5h, after decoction, filter through a fine mesh to remove the residue of the raw materials and obtain a primary plant extract;

[0084] (3) After the first extraction, add 10 times the amount of water to the raw material residue to soak the medicinal material and carry out a second heating extraction. Heat and reflux at 100℃ for 1.5h. After boiling, filter through a fine mesh to remove the raw material residue and obtain a secondary plant extract.

[0085] (4) After the second extraction, add 10 times the amount of water to the raw material residue to soak the medicinal material and carry out a third heating extraction. Heat and reflux at 100°C for 1.5 hours. After boiling, filter through a fine mesh to remove the residue and obtain the three-stage plant extract.

[0086] (5) Combine the primary plant extract, the secondary plant extract and the tertiary plant extract, and heat and concentrate. When the solution is less, add alum powder, mix well, and continue to concentrate to 1 g of crude drug / mL to obtain the extract A.

[0087] Preparation of the gel of Example 2

[0088] 1. Experimental method

[0089] 1.1 Matrix selection

[0090] Weigh the carboxymethylcellulose sodium, hydroxypropylmethylcellulose and pure water in the proportions shown in Table 1, stir, and place at 4°C overnight to allow full swelling. Add the proportion of extract A and glycerol, and adjust the pH to about 6 with triethanolamine. Stir well with a magnetic stirrer to obtain the gel. Observe the gel formation of different matrices.

[0091] Table 1: Design of screening test of different gel matrices

[0092]

[0093] 1.2 Gel preparation

[0094] Weigh the prescribed amount of carboxymethylcellulose sodium, stir with pure water, and place at 4°C overnight to allow full swelling. Add the prescribed amount of extract A and glycerol, and adjust the pH to about 6 with triethanolamine. Stir well with a magnetic stirrer to obtain the gel.

[0095] 1.3 Evaluation index and scoring standard

[0096] The in vitro release rate, stability (as the sum of centrifugal stability, cold stability and heat stability, all of which are used to investigate the stability of the gel), spreadability, viscosity and appearance are used as the investigation indexes, and the scoring standards are shown in Table 2.

[0097] 1.3.1 Determination of in vitro release rate

[0098] 1.3.1.1 Drawing of standard curve

[0099] Take about 10 mg of rutin reference substance, accurately weigh, add 60% ethanol to prepare a 0.102 mg / mL reference substance solution. Accurately pipette 1, 2, 3, 4, 5 mL of the reference substance solution into 10 mL volumetric flasks, respectively, add 0.4 mL of 5% NaNO2 solution, mix well, add 0.4 mL of 10% Al(NO3)3 solution, mix well, finally add 4 mL of 1 mol / L NaOH solution, shake well, and then add 60% ethanol to constant volume. Take another 1 mL of 60% ethanol as a blank, and operate as above. Measure the absorbance at 509 nm. Take the rutin concentration (mg / mL) as the abscissa and the absorbance value (A) as the ordinate to draw a standard curve, and obtain the regression equation Y = 12.429X + 0.014 (R 2 = 0.9997) with good linear relationship in the range of 0.0102 mg / mL to 0.051 mg / mL of the reference substance.

[0100] 1.3.1.2 In vitro release rate determination method

[0101] Take about 2 g of the gel and place it in a dialysis bag with a molecular weight cut-off of 8000-14000. Use 200 mL of 20% ethanol physiological saline as the release medium. Place the dialysis bag in the release medium, and take samples at 1, 2, 4, 6, 8, 10, 12, and 24 h, with 5 mL of sample taken each time. At the same time, add an equal volume of release medium at the same temperature. Operate according to the method in item 1.3.1.1, with the release medium as a blank control. Measure the absorbance at 509 nm, and calculate the cumulative release rate of total flavonoids at different time points.

[0102]

[0103] In the formula, Q is the cumulative release rate at the nth time point (%), V0 is the volume of the release medium (200 mL), V is the volume of each sample (5 mL), Cn and Ci are the measured concentrations at the nth and ith sampling times, and ω is the total flavonoid content in the sample.

[0104] 1.3.2 Stability determination

[0105] 1.3.2.1 Centrifugal stability

[0106] Take 5 g of the gel and centrifuge at 3000 r / min for 15 min, and observe the layering of the gel.

[0107] 1.3.2.2 Cold resistance stability

[0108] Take 5 g of the gel in a 5 mL centrifuge tube, and place it at -20°C for 24 h. Observe the layering of the gel.

[0109] 1.3.2.3 Heat resistance stability

[0110] Take 5 g of gel in a 5 mL centrifuge tube, place at 50°C for 24 h, observe the gel layering.

[0111] Table 2 score standard

[0112]

[0113] 1.4 AHP-CRITIC mixed weighting method to determine the weight of each index

[0114] 1.4.1 AHP method to determine the weight coefficient

[0115] The importance of 5 indicators is determined by pairwise comparison: in-vitro release > stability > spreadability = viscosity > appearance, on this basis, the priority matrix is established, see Table 3. The priority matrix is processed to calculate the weight coefficient of each index.

[0116] Table 3 priority matrix table

[0117]

[0118] 1.4.2 CRITIC method to determine the weight coefficient

[0119] The experimental results are standardized to eliminate the dimension, the formula is (index value-minimum index value) / (maximum index value-minimum index value) x 100%, after eliminating the dimension, import SPSSAU (https: / / spssau.com / ) to calculate the index correlation matrix, then calculate the contrast intensity (σj), conflict (Rj), comprehensive weight (Hj), weight (Wj), and finally get the weight coefficient of each index.

[0120] 1.4.3 AHP-CRITIC mixed weighting method to determine the weight coefficient

[0121] AHP method and CRITIC method are combined to calculate the comprehensive weight (W 综合-ij ), the formula (W 综合-ij ) = W AHP-ij x W CRITIC-ij / ∑W AHP-ij x W CRITIC-ij , get the comprehensive weight coefficient of each index.

[0122] To evaluate the rationality of AHP-CRITIC mixed weighting, the correlation analysis of the comprehensive scores obtained by the three weighting methods is carried out by factor analysis of SPSS software, to judge whether the comprehensive scores obtained by the three weighting methods are consistent. Then the correlation analysis of the weight coefficients obtained by AHP method and CRITIC method is carried out, to judge whether the information reflected by the two methods has superposition.

[0123] 1.5 single factor experiment

[0124] Through the preliminary experiment, it is known that the amount of carbomer-940 (A), the amount of glycerol (B) and the amount of extract A (C) have greater influence on the formation of gel, so the three factors are selected for the preliminary screening of the dosage range, and the single factor design table is shown in Table 4.

[0125] Table 4 Single factor test design table

[0126]

[0127] 1.5.1 Investigation of the amount of carbomer-940

[0128] According to the operation under item “1.2”, the amount of extract A added is 15.0 g, the amount of glycerol is 5.0 g, the amount of pure water is 50.0 g, and the amount of carbomer-940 is 0.3 g, 0.8 g, 1.3 g and 1.8 g respectively. The gel is scored according to the scoring standard.

[0129] 1.5.2 Investigation of the amount of glycerol

[0130] According to the operation under item “1.2”, the amount of carbomer-940 is fixed at 1.0 g, the amount of pure water is 50.0 g, the amount of extract A added is 15.0 g, and the amount of glycerol is 3.0 g, 5.0 g, 7.0 g and 9.0 g respectively. The gel is scored according to the scoring standard.

[0131] 1.5.3 Investigation of the amount of extract A

[0132] According to the operation under item “1.2”, the amount of carbomer-940 is fixed at 1.0 g, the amount of pure water is 50.0 g, the amount of glycerol added is 5.0 g, and the amount of extract A added is 10.0 g, 15.0 g, 20.0 g and 25.0 g respectively. The gel is scored according to the scoring standard.

[0133] 1.6 Box-Behnken response surface method for optimizing the preparation process

[0134] The optimal dosage range of each gel matrix is screened by single factor experiment, Box-Behken design is carried out by Design-Expert 13 software, and the factor and level table is shown in Table 5. The in vitro release degree, stability, spreading property, viscosity and appearance of the gel are used as evaluation indexes, the weight coefficients of the above indexes are calculated by AHP-CRITIC mixed weighting method, and the comprehensive score is calculated.

[0135] Table 5 Response surface factor and level table

[0136]

[0137] 1.7 Process verification

[0138] To verify the accuracy of the response surface experiment results, combined with the actual environment, the laboratory scale verification process was verified according to the optimal process parameters, and 5 batches of gels were prepared. The scoring criteria in item 1.3 were used for scoring, and the comprehensive score was calculated according to the comprehensive score formula.

[0139] 2 Experimental results

[0140] 2.1 Matrix selection

[0141] The experimental results show that the gel prepared by Carbopol-940 has moderate appearance, uniformity, viscosity and good spreadability. Although sodium carboxymethyl cellulose is basically shaped, the viscosity is relatively thick, and the hydroxypropyl methyl cellulose shaping condition is not good, and the extract A cannot be uniformly dispersed, and there are stratification and more bubbles; therefore, Carbopol-940 is selected as the matrix of the gel for further study. The results are as follows Figure 2 .

[0142] 2.2 Determination of weight of each index by AHP-CRITIC mixed weighting method

[0143] 2.2.1 Determination of weight coefficient by AHP method

[0144] According to the priority matrix results, the weight coefficients of in vitro release, stability, spreadability, viscosity and appearance are 0.2356, 0.2088, 0.1870, 0.1993 and 0.1693 respectively, the maximum eigenvalue (λ) is 5.0707, the consistency index (CI) is 0.0177, the random consistency index (RI) is 1.12 according to the table, and the consistency ratio (CR) is 0.0158<0.1, which indicates that the priority matrix passes the consistency test, and the weight coefficients of each evaluation index are effective.

[0145] 2.2.2 Determination of weight coefficient by CRITIC method

[0146] The experimental results were standardized to eliminate the dimension, and the formula was (index value-minimum index value) / (maximum index value-minimum index value) x 100%, and after eliminating the dimension, the online software SPSSAU (https: / / spssau.com / ) was introduced for correlation analysis, and finally the weight coefficients of in vitro release, stability, spreadability, viscosity and appearance were 0.2914, 0.1492, 0.1853, 0.1728 and 0.2032 respectively.

[0147] 2.2.3 Determination of weight coefficient by AHP-CRITIC mixed weighting method

[0148] The comprehensive weight formula was used to calculate the weight coefficients of in vitro release, stability, spreadability, viscosity and appearance, which were 0.3377, 0.1533, 0.1705, 0.1694 and 0.1692 respectively.

[0149] The correlation analysis of the comprehensive scores obtained by the three weighting methods was performed by SPSS21 software. The correlation coefficients of AHP and CRITIC, AHP and AHP-CRITIC, and CRITIC and AHP-CRITIC were 0.993, 0.982, and 0.995, respectively. The correlation of the comprehensive scores obtained by the three weighting methods was significant (P < 0.01), indicating that the comprehensive scores obtained by the three weighting methods were consistent. The correlation analysis of the weight coefficients of the in vitro release, stability, spreadability, viscosity, and appearance obtained by the three weighting methods showed that the correlation coefficient of the weight coefficients of the indexes obtained by AHP and CRITIC was 0.54, and the correlation was not significant, indicating that the information reflected by AHP and CRITIC did not have superposition. In summary, the weight coefficients of the in vitro release, stability, spreadability, viscosity, and appearance obtained by the AHP-CRITIC hybrid weighting calculation had high reliability.

[0150] The final gel comprehensive score formula was: comprehensive score (Z) = (in vitro release / in vitro release maximum) x 100 x 0.3377 + (stability score / stability highest score) x 100 x 0.1533 + (spreadability score / spreadability highest score) x 100 x 0.1705 + (viscosity score / viscosity highest score) x 100 x 0.1694 + (appearance score / appearance highest score) x 100 x 0.1692.

[0151] 2.3 Single factor experiment

[0152] 2.3.1 Carbopol-940 dosage investigation

[0153] The experimental results showed that the greater the amount of carbopol-940, the greater the viscosity of the gel. When the amount of carbopol-940 was 0.3 g, the gel could not be formed even if the pH of the gel was adjusted to 7.8. Therefore, the amount of carbopol-940 should not be less than 0.3 g. When the amount of carbopol-940 was 0.8 g, the surface of the gel was smooth and the viscosity was slightly small. When the amount of carbopol-940 was 1.3 g, the surface of the gel was smooth and delicate and the viscosity was slightly large. When the amount of carbopol-940 was 1.8 g, the surface of the gel was rough and the texture was viscous. Therefore, the amount of carbopol-940 was selected to be between 0.8 g and 1.3 g. The score results are shown in Table 6.

[0154] Table 6 Score table for carbopol-940 dosage investigation

[0155]

[0156] 2.3.2 Glycerol dosage investigation

[0157] The experimental results show that when the amount of glycerol is 3 g, the gel appearance is uniform, the spreading property is good, the stability is good, and the viscosity is slightly small. When the amount of glycerol is 5 g, the gel appearance is uniform and smooth. When the amount of glycerol is 7 g, the gel appearance is uniform and the viscosity is slightly large. When the amount of glycerol is 9 g, the gel gloss is slightly poor, the fineness is not enough, and the viscosity is slightly thick. Therefore, the amount of glycerol is selected to be between 5 g and 7 g. The scoring results are shown in Table 7.

[0158] Table 7 Evaluation table of glycerol amount

[0159]

[0160] 2.3.3 Extract A amount investigation

[0161] The experimental results show that when the amount of extract A is 10 g, the gel appearance is rough and the texture is relatively thick. When the amount of extract A is 15 g, the gel appearance is uniform and the surface is slightly rough. When the amount of extract A is 20 g, the gel surface is smooth and fine, the gloss is good, and the viscosity is moderate. When the amount of extract A is 25 g, the gel spreading property is good and the viscosity is slightly low. Therefore, the amount of extract A is selected to be between 15 g and 20 g. The scoring results are shown in Table 8.

[0162] Table 8 Evaluation table of extract A amount

[0163]

[0164]

[0165] 2.4 Box-Behnken response surface method optimization of preparation process

[0166] The binomial fitting analysis by Design-Expert 13 software obtains the equation Y = 91.70-1.04A+2.79B+1.50C+0.2750AB-1.57AC-0.1300BC-4.51A 2 -2.84B 2 -5.34C 2

[0167] (R 2 = 0.9737, P < 0.05), which indicates that the binomial fitting effect is good. The optimal parameters predicted by Design-Expert 13 software are: the amount of carbomer-940 is 1.018 g, the amount of glycerol is 6.483 g, and the amount of extract A is 17.882 g. Based on the operability and convenience in actual application, the optimal prescription is adjusted to: the amount of carbomer-940 is 1.0 g, the amount of glycerol is 6.5 g, and the amount of extract A is 17.9 g. The Box-Behnken response surface design table and results of the gel are shown in Table 9, and the response surface graph of each factor on the comprehensive score of the gel prescription is shown in Figure 1.Figure 3 .

[0168] From Table 10, the model P is 0.0001 (P < 0.05 is significant at the level), the lack of fit P = 0.7481 > 0.05, indicating that the equation is not significant, the fitting degree is good, and the model can be used to predict and analyze the gel prescription. R2= 0.9737, indicating that the model has high correlation with the measured value, and can accurately predict the actual situation. R2Adj = 0.9399, indicating that the model can explain 93.99% of the change of the response value.

[0169] Table 9 Box-Behnken response surface design table and results of gel

[0170]

[0171]

[0172] 2.5 Process verification

[0173] The results are shown in Tables 2-10, and the appearance, viscosity and stability of the 5 batches of gels are good. The verification process index score and comprehensive score results are shown in Table 11, and the average value of the comprehensive score is 94.76.

[0174] Table 11 Process verification results

[0175]

[0176] Example 3 In vitro anti-inflammatory activity study of gel

[0177] 1 Experimental method

[0178] 1.1 Preparation of drugs

[0179] 1.2 Preparation of gel mother liquor

[0180] Take about 3 g of gel, accurately weigh, and place in a 50 mL centrifuge tube. Add 10% FBS-containing DMEM medium to 30 mL, vortex, ultrasonic, and filter sterilize through a 0.22 μm microporous filter for standby.

[0181] 1.3 Preparation of metronidazole vaginal gel mother liquor

[0182] Take about 1 g and about 0.1 g of metronidazole vaginal gel, respectively, accurately weigh, and place in a 50 mL centrifuge tube. Add 10% FBS-containing DMEM medium to 10 mL, vortex, ultrasonic, and filter sterilize through a 0.22 μm microporous filter for standby.

[0183] 1.4 Effect of gel and metronidazole vaginal gel on the survival rate of RAW264.7 cells

[0184] The metronidazole vaginal gel dose is expressed as 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (C6H9N3O3), and the gel dose is expressed as the dry paste amount.

[0185] The RAW264.7 cells in the logarithmic growth phase were uniformly inoculated in a 96-well plate at 1×10 5 Different concentrations of gel (6360, 3180, 1590, 795, 636, 318, 159, 79.5, 39.75 μg / mL) and different concentrations of metronidazole vaginal gel (750, 375, 187.5, 93.75, 75, 37.5, 18.75, 9.38, 4.69 μg / mL) were set up, and a control group without drugs was set up. The cells in each group were cultured for 24 h after treatment, and then treated by MTS method. The absorbance value was measured at 490 nm by a microplate reader, and the cell survival rate was calculated.

[0186]

[0187] 1.5 Effect of gel and metronidazole vaginal gel on the activity of inflammatory macrophages

[0188] The cells in the logarithmic growth phase were uniformly inoculated in a 96-well plate at 1×10 5 The cells in the logarithmic growth phase were uniformly inoculated in a 96-well plate at 1×10

[0189] 1.6 Effect of gel on the content of NO, TNF-α, IL-1β and IL-6

[0190] The cells in the logarithmic growth phase were uniformly inoculated in a 96-well plate at 2×10 6The 12-well plate was uniformly inoculated with 1 mL / mL, 1 mL per well, and 3 replicate wells were set for each group according to the experimental grouping. The blank group (Control), the model group (Model) was added with 100 μL of LPS with a final mass concentration of 1 μg / mL, the positive group (Positive, metronidazole vaginal gel, 93.75 μg / mL); the gel high-dose group (GGSY-Gel High, 795 μg / mL), the gel medium-dose group (GGSY-Gel Medium, 397.5 μg / mL), and the gel low-dose group (GGSY-Gel Low, 198.75 μg / mL) were mixed with 1 μg / mL LPS per well, 1 mL per well. After the cells in each group were treated, they were placed in a 37°C, 5% CO2 incubator for 24 hours. The cell culture supernatant was collected, the standard was diluted according to the NO, TNF-α, IL-6, and IL-1β kit instructions, the corresponding standard curve was drawn, and the content was calculated.

[0191] 2 Experimental results

[0192] 2.1 Effect of gel and metronidazole vaginal gel on the survival rate of RAW264.7 cells

[0193] The results are shown in Figure 4 A, compared with the blank control group, 3180 and 6360 μg / mL gel showed inhibition of RAW264.7 cells, and 1590 μg / mL showed no inhibition, but compared with 795 μg / mL, at a concentration of 1590 μg / mL, a large number of cells died, so 795, 397.5, and 198.75 μg / mL were selected as the high, medium, and low dose groups for subsequent experiments. As shown in Figure 4 B, compared with the blank control group, metronidazole vaginal gel with a concentration greater than 37.5 μg / mL showed inhibition of RAW264.7 cells, and a large number of cells died when the concentration was greater than 375 μg / mL. Although 93.75 μg / mL had an inhibitory effect on RAW264.7 cells, the cell viability was not lower than that of the normal group, so 93.75 μg / mL was selected as the administration concentration of metronidazole vaginal gel.

[0194] 2.2 Effect of gel and metronidazole vaginal gel on the activity of inflammatory macrophages

[0195] The results are shown in Figure 5 As shown in the results of giving the administration dose of gel and metronidazole vaginal gel to inflammatory macrophages under item 2.1, the selected administration concentration of metronidazole vaginal gel, the high, medium, and low doses of gel did not show significant cytotoxicity to inflammatory macrophages, and the above administration concentrations were confirmed to be safe for inflammatory macrophages.

[0196] 2.3 Effect of the gel on the contents of NO, TNF-α, IL-1β and IL-6

[0197] As shown in Fig. Figure 6 Compared with the blank control group, the contents of NO, IL-1β, TNF-α and IL-6 in the supernatant of the RAW264.7 cells of the model group were significantly increased (P<0.01); as shown in Fig. Figure 6 A, compared with the model group, the contents of NO in the supernatant of the cells treated with the gel at various doses and the metronidazole vaginal gel were reduced (P<0.01) in a dose-dependent manner. As shown in Fig. Figure 6 B, compared with the model group, the contents of IL-1β in the supernatant of the RAW264.7 cells treated with the gel at medium and high doses were reduced (P<0.01). As shown in Figs. Figure 6 C and D, compared with the model group, the contents of TNF-α and IL-6 secreted by the RAW264.7 cells were significantly reduced (P<0.01) in the groups treated with the metronidazole vaginal gel and the gel (except the group treated with the gel at a low dose).

[0198] Example 4 Study on the skin irritation of the gel after multiple administrations

[0199] 1. Experimental method

[0200] 1.1 Grouping of animals and skin treatment

[0201] Ten healthy New Zealand rabbits, half male and half female, were divided into intact skin and damaged skin groups, 5 rabbits in each group. The tested substance was directly applied to the prepared skin area using the self-comparison method of the same body left and right sides, and a dressing was used for fixation. 24 h before administration, the New Zealand rabbits were depilated on both sides of the back, and the depilation area on each side was about 6 cm x 8 cm. The damaged skin was treated as follows: the non-hair area was disinfected with 75% ethanol, and after the ethanol evaporated, the skin was rubbed back and forth with sandpaper until the skin slightly bled.

[0202] 1.2 Administration method

[0203] The left depilation area of the New Zealand rabbit was coated with 0.5 g of the gel as the administration group, and the administration area was about 4 cm x 4 cm. The right depilation area was coated with 0.5 g of the blank gel as the control group, and the application area was equal to that of the administration group. The administration was performed twice a day with an interval of not less than 4 h, and the administration was continuously performed for 7 days. One hour after the removal of the drug each time, before each administration, and 1, 24, 48 and 72 h after the removal of the drug after the last application, the administration site was observed for erythema and edema, and the scores were calculated according to Table 12. The average value of the skin reaction scores at each time point in each group was calculated, and the irritation intensity was evaluated according to Table 13. At the same time, the normality of the diet, excretion and other living behaviors of the New Zealand rabbits in each group, the normality of the body weight gain, and the death condition were observed during the experiment.

[0204] 1.3 Evaluation criteria

[0205] See Tables 12 and 13.

[0206] Table 12 Skin irritation reaction score standard table

[0207]

[0208] Table 13 Skin irritation intensity evaluation standard table

[0209]

[0210] 2 Experimental results

[0211] During the experiment, the New Zealand rabbits in the intact skin group and the damaged skin group were normal in activity, and there were no abnormal conditions in water drinking and food intake; compared with before administration, the body weight changes of the New Zealand rabbits in the intact skin group and the damaged skin group had no significant difference (P>0.05) after 7 days of continuous administration and during the observation period after the last removal of the drug, and the results were as follows in Table 14.

[0212] One hour after the last administration and removal of the drug, the intact skin group of the gel group had 1 New Zealand rabbit with moderate erythema, no edema, and the average irritation reaction was 0.4; the damaged skin group had 2 New Zealand rabbits with mild erythema, no edema, and the average irritation reaction was 0.4; according to the “Skin irritation intensity evaluation standard table”, the above conditions were non-irritating; the blank gel group had no erythema and edema phenomenon in the New Zealand rabbits with intact skin and damaged skin 1, 24, 48 and 72 hours after the last administration and removal of the drug, and the average irritation reaction was 0, which was non-irritating, and the results were shown in Table 15. Figure 7 .

[0213] Table 14 Effect of gel multiple administration skin irritation test on New Zealand rabbit body weight (X±SD, n=5)

[0214]

[0215] Table 15 Gel multiple administration skin irritation test observation period irritation reaction results (n=5)

[0216]

[0217]

[0218] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the art, several improvements and refinements can be made without departing from the principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition, characterized in that, The composition comprises the following components in mass fraction: sugarcane leaves 15-30 parts, mango leaves 10-20 parts, cinnamon leaves 5-10 parts, citronella 10-20 parts, gallnut 5-10 parts, yellow bark 5-15 parts, Chinese atractylodes 5-15 parts, madder 10-20 parts, cnidium 10-20 parts, pomegranate peel 5-15 parts, sophora 15-30 parts, and alum 1-5 parts.

2. A traditional Chinese medicine gel, characterized in that, The application relates to a traditional Chinese medicine composition and a gel base.

3. The traditional Chinese medicine gel of claim 2, characterized in that, The gel base comprises carbomer-940 and glycerol, and the mass ratio of the carbomer-940 and the glycerol is 0.8-1.3:5-7.

4. The traditional Chinese medicine gel of claim 2, characterized in that, The mass ratio of the traditional Chinese medicine composition, the carbomer-940 and the glycerol is 15-20. 0.8～1.3：5～7。 5. The preparation method of the traditional Chinese medicine gel according to any one of claims 2-4, characterized in that, The application relates to a traditional Chinese medicine composition and a gel base. The mixture of the sugarcane leaves, the mango leaves, the cinnamon leaves, the citronella, the gallnut, the yellow bark, the Chinese atractylodes, the madder, the cnidium, the pomegranate peel and the sophora is immersed in water to carry out first extraction, and first raw material residue and first plant extract are obtained. The first raw material residue is immersed in water to carry out second extraction, and second raw material residue and second plant extract are obtained. The second raw material residue is immersed in water to carry out third extraction, and the third extraction is carried out by heating and refluxing for 1.5 h; after boiling, the residue is removed through fine mesh filtration, and third plant extract is obtained. The first plant extract, the second plant extract and the third plant extract are mixed and concentrated, alum powder is added during the concentration, and extract A is obtained by continuing the concentration. The carbomer-940 and water are mixed to carry out swelling, and gel B is obtained. The gel B, the extract A and glycerol are mixed, and the pH is adjusted to 6 by using triethanolamine, and a traditional Chinese medicine gel is obtained.

6. The preparation method according to claim 5, characterized in that, The volume ratio of the mixture and water is 1:10; the temperature of the first extraction is 100 DEG C, and the time is 1.5 h.

7. The preparation method according to claim 5, characterized in that, The volume ratio of the first raw material residue and water is 1:10; the temperature of the second extraction is 100 DEG C, and the time is 1.5 h.

8. The preparation method according to claim 5, characterized in that, The volume ratio of the second raw material residue and water is 1:10; the temperature of the third extraction is 100 DEG C, and the time is 1.5 h.

9. The preparation method according to claim 5, characterized in that, The concentration of the extract A is 1 g crude drug / mL; The mass ratio of the carbomer-940 and water is 0.016-0.026:1; the temperature of the swelling is 4 DEG C, and the time is 12-24 h.

10. The application of the traditional Chinese medicine composition in claim 1 or the traditional Chinese medicine gel in any one of claims 2-4 in the preparation of a medicine for treating gynecological vaginitis.

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