Basil volatile oil vaginal suppository as well as preparation method and application thereof

Abstract

The invention discloses a basil volatile oil vaginal suppository as well as a preparation method and application thereof. The suppository is prepared by mixing a water-soluble matrix, a greasy matrix, basil volatile oil and an emulsifier. Wherein the water-soluble matrix is distilled water, polyethylene glycol 4000 and polyethylene glycol 6000, the greasy matrix is mixed fatty glyceride (stearin), and the ratio of the water-soluble matrix to the greasy matrix is 8: (8-10). The basil volatile oil vaginal suppository is moderate in hardness, not prone to deformation, good in plasticity and stability, moderate in dissolution time and good in solubility, can prevent medicine from being dissolved in a human body too fast or too slow, ensures that the medicine can be absorbed in the human body to achieve an ideal effect, can stably release the medicine in the vagina, can reduce stimulation to vaginal mucosa, and has a good application prospect. The traditional Chinese medicine composition has an accurate treatment effect and low side effects in treatment of vaginitis caused by candida albicans.

Description

Technical Field

[0001] The invention relates to the technical field of biomedicine, and more specifically to a basil volatile oil vaginal suppository and a preparation method and application thereof. Background Art

[0002] Vulvovaginal Candidiasis (VVC), also known as vulvovaginal candidiasis, is a vaginitis disease mainly caused by Candida infection. Candida albicans is the most common pathogen in Candida vaginitis. When the microenvironment in the vagina changes, Candida albicans will cause infection and inflammation. Candida vaginitis accounts for 20% to 25% of vaginitis infections. Infectious vaginitis is a common infectious disease in women of childbearing age, and Candida is the most common vaginal mucosal fungus. Its clinical symptoms are mainly increased secretions, which are like tofu dregs or curds, accompanied by vulvar itching, and frequent onset, and even induce cervicitis, infertility and miscarriage. A large number of epidemiological observation data have confirmed that in recent years, due to the extensive use of antibiotics, drug-resistant strains have emerged, especially vaginitis caused by Candida infection. The incidence rate has increased significantly every year. The vast majority of women of childbearing age have experienced Candida infection at least once in their lifetime, which will significantly interfere with the health of patients. Clinically, sexual transmission is an important way for women of childbearing age to suffer from Candida vaginitis. In addition, the low defense function of the vagina can also lead to the proliferation of Candida in the vagina. It is estimated that about 75% of women of childbearing age will be affected by Candida vaginitis, about half of whom will experience further attacks, and a small number of women (5% to 8%) will suffer from recurrent vulvovaginal candidiasis (RVVC).

[0003] In recent years, the incidence of candidal vaginitis has increased significantly due to the abuse of antibiotics and immunosuppressants. Several strategies have been adopted clinically to prevent and treat external vaginal candidiasis. However, most Candida species have been shown to be resistant to conventional antifungal drugs, posing a serious threat to patients' health. Compared with traditional antifungal drugs, traditional Chinese medicine and traditional Chinese medicine compound have the advantages of strong antifungal effect, stable efficacy, low toxicity and low resistance to drugs in the treatment of vaginitis. Among them, basil, a plant of the genus Ocimum basilicum of the family Labiatae, has a volatile oil that is a light yellow to yellow transparent liquid, mainly containing compounds such as alcohols, alkenes, ketones, heterocyclics, alkanes, aromatics and amines. Amber K et al. studied the mechanism of antifungal activity of holy basil essential oil and its active ingredients methyl chavicol (44.63%) and linalool (21.84%) against Candida albicans and confirmed that holy basil essential oil and its main ingredients methyl chavicol and linalool can interfere with the synthesis of ergosterol in fungi, thereby damaging the fungal cell membrane and destroying its integrity. Therefore, basil volatile oil exhibits certain antibacterial activity. At the same time, in the article "Preparation and Antibacterial Activity Study of Basil Volatile Oil Inclusion Compound", it was pointed out that after extracting basil volatile oil by steam distillation, the inclusion compound was prepared with hydroxypropyl-β-cyclodextrin, and its inhibition zone and minimum inhibitory concentration for Candida albicans were 1.12 cm and 3.79 mg / mL, respectively. Therefore, it is speculated that basil volatile oil has a certain therapeutic effect on vaginitis caused by Candida albicans.

[0004] In the treatment of gynecological diseases, in addition to oral preparations and various lotions, Chinese medicine vaginal suppositories are also one of the gynecological preparations, and have significant therapeutic effects. Because Chinese medicine suppositories have the advantages of avoiding interactions with the stomach, intestines and other digestive tracts to inactivate drugs or stimulate drugs and the "first pass effect" of the liver, many new suppositories have been developed to achieve combined drug administration, rapid release and sustained release, so as to be applied in clinical practice to relieve patients' pain. Chinese medicine suppositories and vaginal suppositories not only have local and systemic therapeutic effects, but also have the advantages of simple operation, definite efficacy, and easy acceptance by patients. They are widely used in clinical practice and have achieved certain economic and social benefits. For example, patent CN107334727A discloses a eugenol / clove oil suppository for urethra or anus and a preparation method thereof. The main component of the suppository is eugenol / clove oil, which can effectively inhibit Staphylococcus aureus, Escherichia coli, and Shigella dysenteriae commonly found in the urinary system and digestive system. However, the long-term stability and validity period of the suppository prepared in the patent still need to be improved, and due to the different properties of different drugs, there are differences in the selection of suppository bases. At present, there is no report on the preparation of long-term stable, effective, soluble, and well-released vaginal suppositories using basil volatile oil as a single antibacterial component to treat vaginitis caused by Candida albicans. Summary of the invention

[0005] The purpose of the present invention is to overcome the above defects and shortcomings in the prior art and provide a basil volatile oil vaginal suppository.

[0006] The second object of the present invention is to provide a method for preparing a basil volatile oil vaginal suppository.

[0007] The third object of the present invention is to provide an application of a basil volatile oil vaginal suppository in preparing a product for treating vaginitis.

[0008] The above-mentioned object of the present invention is achieved through the following technical solutions: The invention provides a basil volatile vaginal oil suppository. The suppository is composed of a mixture of a water-soluble matrix, an oily matrix, basil volatile oil and an emulsifier; the water-soluble matrix is ​​distilled water, polyethylene glycol 4000 and polyethylene glycol 6000; the oily matrix is ​​mixed fatty acid glyceride (hard fat); and the mass ratio of the water-soluble matrix to the oily matrix in the suppository is 8:8-10.

[0009] Because the vaginal environment is relatively moist and the vaginal mucosa is relatively delicate, it is required to soften and slowly dissolve and release drugs at body temperature, and to play a role locally and continuously. In the selection of the matrix, it is necessary to avoid using highly irritating materials. In order to explore the vaginal suppository matrix suitable for coating basil oil, the present invention has found that the long-term stability and validity period of suppositories using only water-soluble matrix are poor, and suppositories using only oleaginous matrix will not only stimulate the vaginal mucosa but also release time too fast. Only by using a specific water-soluble matrix and an oleaginous matrix and mixing the two in a specific ratio to prepare a basil volatile oil vaginal suppository, can the suppository be formed and have moderate hardness, not easy to deform, good plasticity and stability, moderate dissolution time, good solubility, and prevent the drug from being absorbed too fast or too slowly in the human body, ensuring that the absorption of the drug in the body reaches the desired effect, and can stably release the drug in the vagina, and can reduce the stimulation to the vaginal mucosa. It has an accurate therapeutic effect in the treatment of vaginitis caused by Candida albicans, and can be directly applied to the affected part to quickly relieve symptoms; relative to oral medications, the concentration and absorption of suppositories in the body are low, and the side effects are low. The oily matrix is ​​a mixed fatty acid glyceride (stearin), which is a mixture of monoglycerides, diglycerides and triesters of C8-C18 saturated fatty acids. It has a relatively suitable melting point and can gradually soften at body temperature to release the drug.

[0010] Furthermore, the mixed fatty acid glyceride (hard fat) is type 36, and the melting point is 35-37° C. 35-37° C. is within the standard body temperature range of the human body, and this melting point is conducive to melting in the body and drug release when the suppository is used.

[0011] Furthermore, the mass ratio of the water-soluble matrix, the oily matrix, the basil volatile oil and the emulsifier is 8:8-10:1-2:1-2.

[0012] Furthermore, the mass ratio of the water-soluble matrix, the oily matrix, the basil volatile oil and the emulsifier is 8:9:1.6:1.8.

[0013] Furthermore, the mass ratio of distilled water, polyethylene glycol 4000 and polyethylene glycol 6000 in the water-soluble matrix is ​​1-2:2-3:3-5.

[0014] Furthermore, the mass ratio of distilled water, polyethylene glycol 4000 and polyethylene glycol 6000 in the water-soluble matrix is ​​1.6:2.4:4.

[0015] Furthermore, the mass ratio of the water-soluble matrix to the oily matrix in the suppository is 8: 9. The amount of the oily matrix and the water-soluble matrix has a great influence on the formability and hardness of the suppository. When the water-soluble matrix: the oily matrix = 8: 9, the suppository has good formability and moderate hardness.

[0016] Preferably, the suppository is made of the following raw materials in the following weight ratio: 1.6 parts of distilled water, 2.4 parts of polyethylene glycol 4000, 4 parts of polyethylene glycol 6000, 1.8 parts of emulsifier, 1.6 parts of basil volatile oil, and 9 parts of mixed fatty acid glyceride (hard fat). At this time, the suppository has the best plasticity, solubility, and stability, and has good release characteristics.

[0017] Furthermore, the emulsifier in the suppository is Tween-80.

[0018] The present invention provides a method for preparing the above-mentioned basil volatile oil vaginal suppository, comprising the following steps: S1. Mix distilled water, polyethylene glycol 4000 and polyethylene glycol 6000, heat and melt to obtain a water-soluble matrix; S2. The mixed fatty acid glyceride (stearin) is heated and melted to obtain an oily matrix; S3. Inject the oily matrix into the water-soluble matrix, add an emulsifier and basil volatile oil to mix, and demould to obtain the basil volatile oil vaginal suppository.

[0019] Furthermore, the heating temperature is 65-70° C. According to the properties of the main drug, a water bath melting temperature of 65-70° C. is selected to prevent the drug from being oxidized during the preparation process and causing a decrease in content.

[0020] Furthermore, the preparation method of basil volatile oil in step S3 is to mix basil with distilled water, heat and distill to extract.

[0021] Preferably, the dried basil plant is crushed, distilled water is added at a feed ratio of 1.0:30.0 (g:mL), mixed, and refluxed in a volatile oil extractor for 4 to 5 hours until the amount of oil in the measuring device no longer increases, heating is stopped, and volatile oil is obtained, dried, and a yellow oily liquid with an aromatic odor is obtained, namely, basil volatile oil. The average extraction rate of the prepared basil volatile oil is 0.607%.

[0022] Furthermore, the demoulding method in step S3 is to apply a lubricant of detergent: glycerol: 95% ethanol = 1: 0.5-1.5: 4-6 to the mold.

[0023] Furthermore, in order to facilitate demoulding in step S3, the lubricant applied to the mold is detergent: glycerol: 95% ethanol = 1:1:5.

[0024] The present invention aims at the volatile oil component of the herbal medicine plant basil, and extracts it by steam distillation according to its volatility. According to the volatile oil extraction rate and the oral drug dosage, the mass of the main drug contained in the corresponding proportion of the number of suppositories is obtained. In the preparation process, the mass of the oily matrix is ​​greater than the mass of the water-soluble matrix. At a certain temperature, the oily matrix is ​​slowly injected into the water-soluble matrix and stirred to mix well, so as to ensure that the suppository matrix has good formability, smooth surface, good stability, and basically uniform quality, and meets the quality standard requirements, and ensures the comfort and convenience of the patient when using it, and ensures that the suppository can be stably retained in the body and can release the drug evenly. Secondly, in order to ensure smooth demoulding, a lubricant needs to be applied to the mold, and the lubricant is detergent: glycerol: 95% ethanol = 1:1:5.

[0025] The invention also provides an application of a basil volatile oil vaginal suppository in preparing a product for treating vaginitis.

[0026] Furthermore, the vaginitis is candidal vaginitis.

[0027] Furthermore, the candidal vaginitis is candida albicans vaginitis.

[0028] Compared with the prior art, the present invention has the following beneficial effects: The invention provides a basil volatile oil vaginal suppository, which is composed of a water-soluble matrix, an oily matrix, basil volatile oil and an emulsifier. The basil volatile oil vaginal suppository prepared by using a specific water-soluble matrix and an oily matrix and mixing the two in a specific ratio can ensure that the suppository is formed and has moderate hardness, is not easy to deform, has good plasticity and stability, and has moderate dissolution time and good solubility. It can prevent the drug from being absorbed too quickly or too slowly in the human body, ensure that the absorption of the drug in the body reaches an ideal effect, can stably release the drug in the vagina, and can reduce the stimulation to the vaginal mucosa. It has an accurate therapeutic effect in the treatment of vaginitis caused by Candida albicans, can be directly applied to the affected area to quickly relieve symptoms; compared with oral drugs, the suppository has a lower concentration and absorption in the body, and has low side effects. Moreover, the vaginal suppository of the present invention avoids the use of multiple processes, professional equipment and high-quality raw materials, has a low production cost, and uses a single basil volatile oil component as an effective component, so that the efficacy evaluation and adverse reactions of the vaginal suppository during use are also easy to collect and count. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The invention discloses a preparation process of basil essential oil vaginal suppository. DETAILED DESCRIPTION

[0030] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0031] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0032] The mixed fatty acid glyceride (hard fat) is type 36, with a melting point of 35 to 37 degrees Celsius, and is purchased from Shandong Ruisheng Pharmaceutical Excipients Co., Ltd.

[0033] Example 1 Extraction of basil essential oil Take the dried basil plants, crush them with a YB-1000A high-speed multifunctional crusher (Yongkang Sufeng Industry and Trade Co., Ltd.), add distilled water at a feed ratio of 1.0:30.0 (g:mL), shake and mix, reflux extract in a volatile oil extractor for 4 to 5 hours, stop heating when the oil volume in the measuring device no longer increases, and obtain volatile oil. Dry with anhydrous sodium sulfate to obtain a yellow oily liquid with an aromatic odor, which is sealed in a suitable EP tube for storage.

[0034] After multiple extraction experiments, the average extraction rate of volatile oil was 0.607%.

[0035] Example 2 Inhibitory effect of basil volatile oil on Candida albicans The drug sensitivity test method was used to conduct antibacterial experiments on different concentrations of basil essential oil. Candida albicans liquid (10 6 ~10 7 CFU / mL) into the solid culture medium, and use a spreader to evenly spread the test strains of the bacterial suspension. Use acetone to dilute basil volatile oil into five concentration gradients of 100%, 50%, 25%, 12.5%, and 6.25%. Use sterilized tweezers to pick up the sterilized blank drug-sensitive tablets, soak them in five concentrations of basil volatile oil, soak them for 20 minutes, take them out, dry them slightly, and stick the drug-sensitive tablets on the plates that have been coated with Candida albicans. Each plate is pasted with three drug-sensitive tablets, which are positive control, blank control, and test volatile oil, forming an equilateral triangle. The positive control is 2% chlorhexidine solution (diluted according to the above concentration gradient), and the blank control is acetone. Incubate inverted in a water-insulated electric constant temperature incubator at 28°C for 48 hours, measure the diameter of the inhibition zone, and take the average value for analysis. The experiment was repeated 3 times.

[0036] The results are shown in Table 1. The volatile oils with concentrations of 100%, 50%, 25%, 12.5%, and 6.25% have an antibacterial effect on Candida albicans. When the volatile oil concentration is 100%, the average inhibition zone diameter is 17.00 mm, which is highly sensitive. When the volatile oil concentration is 50%, the average inhibition zone diameter is 14.20 mm; when the volatile oil concentration is 25%, the average inhibition zone diameter is 12.33 mm; when the volatile oil concentration is 12.5%, the average inhibition zone diameter is 10.67 mm, which is moderately sensitive. When the volatile oil concentration is 6.25%, the average inhibition zone diameter is 7.67 mm, which is low sensitivity. The blank control results have no inhibition zone, and the inhibition zones produced at different concentrations of the positive control are shown in Table 1.

[0037] Table 1 Antibacterial effect of different concentrations of basil essential oil on Candida albicans

[0038] Example 3 Optimization of the prescription of basil volatile oil vaginal suppository 1. Determination of volatile oil content in basil The dosage of the medicinal plant basil for oral administration and decoction is about 10-15g, and the dosage for suppositories is at least equivalent to the oral dosage. According to the extraction rate of basil volatile oil, the amount of basil volatile oil contained in each suppository is initially determined to be 0.08g, and the dosage is once a day, one tablet at a time. This product is mainly for adult use. In order to meet the requirements of suppository drug loading and molding, the suppository size (weight) is designed to be about 1.0 g / tablet.

[0039] 2. Preparation of suppositories The preparation flow chart of suppositories is as follows Figure 1 As shown: Take the prescribed amount of PEG4000 (polyethylene glycol 4000) and PEG6000 (polyethylene glycol 6000) and place them in an evaporating dish. Take the prescribed amount of distilled water and add the distilled water into the evaporating dish containing polyethylene glycol. Heat it in a water bath at 65-70°C. Stop heating when 2 / 3 of the matrix is ​​melted and stir to make it completely dissolved to obtain a water-soluble matrix.

[0040] Take the prescribed amount of mixed fatty acid glyceride (stearin) in an evaporating dish, heat it in a water bath at 65-70°C, stop heating when 2 / 3 of the base is melted, and stir to make it completely dissolved to obtain an oily base.

[0041] Slowly pour the oily base into the water-soluble base, stir evenly, add the prescribed content of Tween-80 and basil essential oil and stir evenly. When the mixture becomes viscous, cool it down slightly and pour it into a suppository mold coated with a lubricant (the prescription is: detergent: glycerin: 95% ethanol = 1:1:5). After cooling and solidifying, trim off the overflowing part of the mold and demold it to obtain a vaginal suppository containing basil essential oil.

[0042] 3. Determination of the proportion of water-soluble matrix and oily matrix in suppositories The matrix selected for the suppository prescription and the dosage ratio of the drug need to be designed reasonably and need to have appropriate plasticity, solubility, stability and other properties to ensure that the preparation process of the vaginal suppository proceeds smoothly and can provide appropriate release characteristics. Among them, the ratio of water-soluble matrix to oily matrix is ​​a key influencing factor. Therefore, different ratios of water-soluble matrix to oily matrix are set to explore the molding effect on the appearance of vaginal suppositories.

[0043] The results are shown in Tables 2 and 3. When the ratio of the water-soluble matrix to the oily matrix is ​​8:9, and the water-soluble matrix contains PEG6000 and PEG4000, and the oily matrix is ​​mixed fatty acid glyceride (hard fat), the suppository can be formed and has moderate hardness. Therefore, in order to achieve the purpose of the present invention, the present invention adopts the following prescription design: 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil volatile oil, and 4.50g of mixed fatty acid glyceride (hard fat) to prepare 10 basil volatile oil vaginal suppositories that inhibit Candida albicans.

[0044] Table 2 Screening of suppository prescriptions combining water-soluble base and oily base

[0045] Table 3 Effects of different oily bases on water-soluble bases and oily base combined suppositories

[0046] 4. Comparison of different matrix suppository prescriptions In order to screen out suppositories with the best plasticity, solubility and stability, the present invention performs prescription optimization: Prescription 1: Only water-soluble matrix was used, namely, 1.70 g of distilled water, 2.55 g of PEG4000 (polyethylene glycol 4000), 4.25 g of PEG6000 (polyethylene glycol 6000), 0.90 g of Tween-80, and 0.80 g of basil essential oil. The water-soluble matrix was PEG6000: PEG4000: distilled water = 5:3:2, and 10 basil essential oil vaginal suppositories were prepared by hot melt method.

[0047] Prescription 2: Only an oily matrix, i.e., 0.80 g of basil essential oil, 0.90 g of Tween-80, and 8.50 g of mixed fatty acid glycerides (stearate), was used to prepare 10 basil essential oil vaginal suppositories by the hot melt method.

[0048] Prescription 3: A combination of water-soluble matrix and oily matrix was used. The optimal ratio was adjusted and screened by adjusting the ratio of the water-soluble matrix and the oily matrix. Finally, 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil essential oil, and 4.50g of 34-type mixed fatty acid glyceride (stearin) were determined. Water-soluble matrix: oily matrix = 8:9, 10 basil essential oil vaginal suppositories were prepared by hot melt method.

[0049] Prescription 4: A combination of water-soluble matrix and oily matrix was used. The optimal ratio was adjusted and screened by adjusting the ratio of the water-soluble matrix and the oily matrix. Finally, 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil volatile oil, and 4.50g of 36-type mixed fatty acid glyceride (stearin) were determined. Water-soluble matrix: oily matrix = 8:9, 10 basil volatile oil vaginal suppositories were prepared by hot melt method.

[0050] Prescription 5: A combination of water-soluble matrix and oily matrix was used. The optimal ratio was adjusted and screened by adjusting the ratio of the water-soluble matrix and the oily matrix. Finally, 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil volatile oil, and 4.50g of 38-type mixed fatty acid glyceride (stearin) were determined. Water-soluble matrix: oily matrix = 8:9, 10 basil volatile oil vaginal suppositories were prepared by hot melt method.

[0051] Prescription 6: A combination of water-soluble matrix and oily matrix was used. The optimal ratio was adjusted and screened by adjusting the ratio of the water-soluble matrix and the oily matrix. Finally, 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil volatile oil, and 4.50g of 40-type mixed fatty acid glyceride (stearin) were determined. Water-soluble matrix: oily matrix = 8:9, 10 basil volatile oil vaginal suppositories were prepared by hot melt method.

[0052] Prescription 7: A combination of water-soluble matrix and oily matrix was used. The optimal ratio was adjusted and screened by adjusting the ratio of the water-soluble matrix and the oily matrix. Finally, 0.80g of distilled water, 1.20g of PEG4000 (polyethylene glycol 4000), 2.00g of PEG6000 (polyethylene glycol 6000), 0.90g of Tween-80, 0.80g of basil essential oil, and 4.50g of monostearate were determined. Water-soluble matrix: oily matrix = 8:9, 10 basil essential oil vaginal suppositories were prepared by hot melt method.

[0053] Referring to the quality standards in the Suppository column of Part 4 General Chapter 0107 of the 2020 edition of the "Chinese Pharmacopoeia", the appearance properties and melting time of the three prescription suppositories were screened to obtain the prescription with the best plasticity, solubility and stability.

[0054] The results are shown in Table 4. The water-soluble matrix and the oily matrix combined matrix of prescription 3 have a complete and smooth appearance, moderate hardness and good plasticity. The melting time of the pure water-soluble matrix of prescription 1 is more than 40 minutes, and the melting time of the pure oily matrix of prescription 2 is 23 minutes and 13 seconds. Compared with the water-soluble matrix and the oily matrix combined matrix, the pure water-soluble matrix has a long dissolution time and a short dissolution time of the pure oily matrix. The water-soluble matrix and the oily matrix combined matrix are selected, with moderate dissolution time and good solubility, which prevents the drug from being absorbed too quickly or too slowly in the human body, and ensures that the absorption of the drug in the body achieves the ideal effect. At the same time, the pure water-soluble matrix suppository shows a slight dissolution phenomenon after being placed at room temperature for 1 hour. Compared with the pure oily matrix, the water-soluble matrix and the oily matrix combined matrix, the pure water-soluble matrix suppository has poor stability. In summary, the water-soluble matrix and the oily matrix combined matrix suppository prescription is the best. At the same time, different types of mixed fatty acid glycerides (hard fat) and monostearate glyceryl (prescription 4-prescription 7) were compared, and it was found that the stability and solubility of mixed fatty acid glycerides (hard fat) were better than those of monostearate glyceryl. Since different types of mixed fatty acid glycerides (hard fat) have different dissolution temperatures, type 36 mixed fatty acid glycerides (hard fat) were comprehensively selected as the oily base in the suppository of the present invention.

[0055] Table 4 Screening of different matrix suppository prescriptions

[0056] Example 4 Quality Inspection of Optimal Prescription of Basil Volatile Oil Vaginal Suppository According to the preparation method and preferred prescription in Example 3, 10 complete basil volatile oil vaginal suppositories were prepared, weighed, and their properties were observed. The quality was evaluated with reference to the quality standards under the Suppository column of Part 4 General Chapter 0107 of the 2020 edition of the Chinese Pharmacopoeia.

[0057] 1. Appearance inspection All three batches of suppositories were white conical suppositories with a complete and smooth appearance. The suppositories were well formed, with moderate hardness, not easy to deform, and good plasticity. After being placed at room temperature for 1 hour, no dissolution was observed on the surface, indicating good stability.

[0058] 2. Weight difference check Take 10 test samples and accurately weigh the total weight on a BT125D 1 / 100,000 analytical balance (Shanghai Tianmei Balance Instrument Co., Ltd.). After obtaining the average particle weight, accurately weigh each particle. Compare the weight of each particle with the average particle weight. According to the provisions of the 2020 edition of the Chinese Pharmacopoeia, no more than 1 particle shall exceed the weight difference limit, and the limit shall not be exceeded by 1 times.

[0059] The results are shown in Tables 5 to 7. According to the requirements of the 2020 edition of the "Chinese Pharmacopoeia", the average particle weight is above 1.0g and below 3.0g, and the weight difference limit is ±7.5%. After inspection of the three batches of suppositories, there were 0 suppositories that exceeded the weight difference limit, and 0 suppositories that exceeded the limit by 1 times, proving that the weight difference inspection of the three batches of suppositories met the regulations.

[0060] Table 5 Batch 1 weight difference limit check

[0061] Table 6 Batch 2 weight difference limit check

[0062] Table 7 Batch 3 weight difference limit check

[0063] 3. Melting time limit inspection Take 3 test samples, place them at room temperature for 1 hour, and then place them on the lower circular plates of the 3 metal frames of the RBY-4A automatic melting time limit tester (Tianjin Tianda Tianfa Technology Co., Ltd.), insert them into their respective sleeves, and fix them with hooks. Vertically immerse the above devices in a container containing no less than 4L of 37.0℃±0.5℃ water, and the upper end should be 90 mm below the water surface. A rotator is installed in the container to flip the device in the solution once every 10 minutes and record its dissolution time.

[0064] The results are shown in Table 8. According to the melting time data of three batches of suppositories, the suppositories can be completely dissolved within 24 minutes to 32 minutes, and the solubility is good.

[0065] Table 8 Results of the melting time limit inspection of each batch of suppositories

Claims

1. A basil volatile oil vaginal suppository, characterized in that: The suppository is composed of a mixture of a water-soluble matrix, an oily matrix, basil volatile oil and an emulsifier; the water-soluble matrix is ​​distilled water, polyethylene glycol 4000 and polyethylene glycol 6000; the oily matrix is ​​mixed fatty acid glyceride (hard fat); the mass ratio of the water-soluble matrix to the oily matrix in the suppository is 8:8-10.

2. The basil volatile oil vaginal suppository according to claim 1, characterized in that: The mass ratio of the water-soluble matrix, the oily matrix, the basil volatile oil and the emulsifier is 8:8-10:1-2:1-2.

3. The basil volatile oil vaginal suppository according to claim 1, characterized in that: The mass ratio of the distilled water, polyethylene glycol 4000 and polyethylene glycol 6000 is 1-2:2-3:3-5.

4. The basil volatile oil vaginal suppository according to claim 1, characterized in that: The suppository is prepared from the following raw materials in weight ratio: 1.6 parts of distilled water, 2.4 parts of polyethylene glycol 4000, 4 parts of polyethylene glycol 6000, 1.8 parts of emulsifier, 1.6 parts of basil volatile oil, and 9 parts of mixed fatty acid glyceride (hard fat).

5. The basil volatile oil vaginal suppository according to any one of claims 1 to 4, characterized in that: The emulsifier is Tween-80.

6. The method for preparing the basil volatile oil vaginal suppository according to any one of claims 1 to 4, characterized in that: The following steps are involved: S1. Mix distilled water, polyethylene glycol 4000 and polyethylene glycol 6000, heat and melt to obtain a water-soluble matrix; S2. The mixed fatty acid glyceride (stearin) is heated and melted to obtain an oily matrix; S3. Inject the oily matrix into the water-soluble matrix, add an emulsifier and basil volatile oil to mix, and demould to obtain the basil volatile oil vaginal suppository.

7. The preparation method according to claim 6, characterized in that: The heating temperature is 65-70°C.

8. The preparation method according to claim 6, characterized in that: The preparation method of the basil volatile oil in step S3 is to mix basil with distilled water, heat and distill to extract.

9. Use of the basil volatile oil vaginal suppository according to any one of claims 1 to 4 in the preparation of a product for treating vaginitis.

10. The use according to claim 9, characterized in that: The vaginitis is candidal vaginitis.

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