Pharmaceutical composition for treating vaginal relaxation, preparation and preparation method

Abstract

The invention belongs to the technical field of medicines. The invention provides a pharmaceutical composition for treating vaginal relaxation, a preparation and a preparation method. The pharmaceutical composition provided by the invention is prepared from the following components in parts by weight: 30 to 40 parts of astragaloside, 30 to 35 parts of sargentgloryvine stem aqueous extract, 30 to 40 parts of valeriana jatamansi aqueous extract and 30 parts of chlorhexidine acetate. The medicine composition can effectively contract the vagina, has an obvious treatment effect on the vaginal relaxation syndrome, and can greatly improve the pelvic floor muscle strength of fast muscles. The components used in the invention contain traditional anti-inflammatory components, and can also play a corresponding anti-vaginitis role.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology, and in particular relates to a pharmaceutical combination, a preparation and a preparation method for treating vaginal relaxation. Background Art

[0002] Vaginal relaxation syndrome is a common gynecological disease. Common clinical manifestations include incomplete closure of the vaginal opening, open vestibule, exposed and bulging posterior vaginal wall, sexual dysfunction, etc. In severe cases, it may even be accompanied by pelvic organ prolapse.

[0003] At present, there are mainly surgical treatments, Western medicine non-surgical treatments and traditional Chinese medicine treatments for vaginal relaxation syndrome. Although surgical treatment is simple and effective, it has disadvantages such as difficult wound care and easy infection. Western medicine non-surgical treatments mainly include CO 2 Laser therapy, radiofrequency therapy and Er:YAG laser therapy, etc., these methods have the advantages of simple operation and good effect, but the disadvantage is that they require special equipment and have a certain threshold. TCM treatment is mainly based on traditional Chinese medicine theory. Traditional prescriptions include Buzhong Yiqi Decoction and Guipi Decoction. Modern innovative Chinese medicine includes Shenqi Wenyang Expansion Suppository. [1] Hejinshu anti-leakage cream [2] wait.

[0004] In addition to the above methods, people have also tried to use natural drug extracts to treat vaginal relaxation. For example, researchers used acorn extract on patients with vaginal relaxation. [3] After that, it can effectively achieve vaginal tightening.

[0005] Among the known treatment methods, traditional Chinese medicine has a relatively clear theoretical basis, and people can reasonably prescribe medicine according to different conditions of patients. However, apart from traditional Chinese medicine, people have not yet explored a clear theory on how to develop drugs for treating vaginal relaxation. Therefore, how to develop drugs for treating vaginal relaxation based on existing Western medicines and available natural plant extracts is an important challenge faced by this field.

[0006] References:

[0007] [1] Liu Mao, Yang Min, Li Shuzhen. Parallel, multicenter, open, randomized controlled clinical study of ginseng and astragalus warming yang expansion suppository in the treatment of vaginal relaxation [J / OL]. Electronic Journal of Practical Gynecological Endocrinology, 2022, 9(21): 62-65.

[0008] [2] Ren Liqin, Lin Junjin. Exploration of the mechanism of action and clinical efficacy of Jinshu Zhiluokang anti-leakage ointment in the treatment of vaginal relaxation and stress urinary incontinence [J]. Jilin Medicine, 2023, 44(1): 143-148.

[0009] [3]LORZADEH N, SEPAVAND F, SOLEIMANINEZHAD M, et al. The effect of extract of oak gall for vaginal tightening and rejuvenation in women with vaginalrelaxation[J]. Open Journal of Obstetrics and Gynecology, 2016, 6(13): 879-887. Summary of the invention

[0010] In view of the defects of the prior art, one of the purposes of the present invention is to provide a new drug combination for treating vaginal relaxation, which should overcome the inconvenience of surgical treatment and the disadvantage of poor effect of drug treatment in the prior art.

[0011] A drug combination for treating vaginal relaxation, comprising the following components by weight: 30-40 parts of astragaloside IV, 30-35 parts of Sargentophylla caulis water extract, 30-40 parts of spider perfume extract and 30 parts of chlorhexidine acetate.

[0012] Preferably, the preparation method of the spider perfume extract is: weigh spider perfume medicinal materials, crush them into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 30 minutes, combine the filtrate, concentrate to an extract state, and freeze-dry the extract into powder; the preparation method of the Sargassum spatholobi water extract is: weigh Sargassum spatholobi medicinal materials, crush them into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 45 minutes, combine the filtrate, concentrate to an extract state, and freeze-dry the extract into powder.

[0013] Preferably, the drug combination consists of the following components in parts by weight: 30 parts of astragaloside IV, 30 parts of spider perfume extract, 30 parts of Sargentodoxa chinensis water extract and 30 parts of chlorhexidine acetate.

[0014] The present invention also provides a medicament for treating vaginal relaxation, wherein the medicament comprises the drug combination according to any one of claims 1 to 3.

[0015] The dosage form of the medicament is any preparation for vaginal administration.

[0016] Preferably, the dosage form of the medicament includes cream and hydrogel preparations.

[0017] Preferably, the gel matrix of the hydrogel preparation includes carbomer 676 and triethanolamine; the matrix of the cream includes stearic acid, octadecyl alcohol, liquid paraffin, white vaseline, Span-80, and Tween-80.

[0018] Another object of the present invention is to provide a method for preparing a medicament for treating vaginal relaxation, the method comprising mixing the drug combination with auxiliary materials required for the dosage form.

[0019] Preferably, the preparation method of the agent is: mix carbomer 676, triethanolamine and water in a weight ratio of 5:1:50, swell for 12 hours to obtain a first solution; add the drug combination to a 10v / v% ethanol aqueous solution so that the weight ratio of the drug combination to the ethanol aqueous solution is 3:5, and obtain a second solution after sufficient dispersion; mix the first solution and the second solution so that the weight ratio of the drug combination to carbomer 676 is 10:1, and fully stir at 40°C to obtain a hydrogel preparation.

[0020] Another object of the present invention is to provide the use of the above-mentioned drug combination in the preparation of a drug for treating vaginal relaxation.

[0021] In existing studies, astragaloside IV is mainly used as a drug for enhancing immunity, anti-virus, anti-stress and promoting cardiopulmonary function. As far as the inventor knows, it has not yet been used to treat vaginal relaxation. Chlorhexidine acetate is a traditional anti-inflammatory drug, commonly used to treat vaginitis, but it has not been reported to have a vaginal tightening effect.

[0022] Spider incense is a traditional Chinese medicine with the effects of promoting qi, dispelling cold, activating blood circulation and regulating menstruation. According to the theory of traditional Chinese medicine, spleen qi is responsible for ascending, which is used to maintain the relative stability of the position of internal organs. Spleen deficiency and qi collapse will cause diseases such as vaginal prolapse and organ prolapse. The medicinal properties of Sargassum spatholobi are bitter and flat, and it belongs to the large intestine and liver meridians. It has the effects of promoting menstruation and replenishing blood, antibacterial and anti-inflammatory, reducing swelling and dispersing nodules. It is mainly used to treat irregular menstruation, metrorrhagia and other symptoms. At present, there are many Chinese medicine prescriptions using spider incense and Sargassum spatholobi as raw materials, but there are not many effective prescriptions for vaginal relaxation, and they need to rely on the corresponding Chinese medicine compatibility principles, and it is not easy to develop a new Chinese medicine prescription.

[0023] Based on the modern drug research path, studying medicinal ingredients or drug combinations from the perspective of natural plant extracts is also a research method based on plant-derived drugs. This application has carried out corresponding research in this regard.

[0024] At the beginning of the study, the inventor considered using spider perfume and safflower as raw materials to explore whether there is a drug combination suitable for treating vaginal relaxation. As shown in the embodiments of the present invention, when spider perfume extract, safflower water extract, astragaloside IV and chlorhexidine acetate are used in combination, a significant effect of contracting the vagina can be exerted, but when the spider perfume extract is replaced by spider perfume alcohol extract or the safflower water extract is replaced by alcohol extract, the corresponding effect is greatly reduced. This shows that the components that can play a synergistic role with astragaloside IV and chlorhexidine acetate are the water-soluble components in spider perfume and safflower. At the same time, the drug combination of the present invention also contains chlorhexidine acetate. In order to prove whether the combination of chlorhexidine acetate with spider perfume extract, safflower water extract and astragaloside IV affects its anti-inflammatory effect, the present invention also conducted corresponding anti-inflammatory clinical trials. The test results show that the drug combination of the present invention also has a good anti-inflammatory effect on vaginitis.

[0025] Beneficial effects of the present invention:

[0026] The drug combination of the present invention can effectively contract the vagina, has an obvious therapeutic effect on vaginal relaxation syndrome, and can greatly improve the fast-twitch pelvic floor muscle strength. The ingredients used in the present invention contain traditional anti-inflammatory ingredients, and can also play a corresponding anti-vaginitis effect. DETAILED DESCRIPTION

[0027] The present invention is described in detail below through examples. It is necessary to point out that the following examples are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by technical personnel in this field based on the above invention content still fall within the scope of protection of the present invention.

[0028] Example 1

[0029] 1. Raw materials:

[0030] Astragaloside IV: Hubei Jianchu Biopharmaceutical Co., Ltd.;

[0031] Spider fragrance, Perilla, Curcuma zedoaria, Sargentodoxae: purchased from local Chinese herbal medicine market;

[0032] Chlorhexidine acetate: purchased from local pharmacies.

[0033] 2. Drug Preparation

[0034] 2.1 Extraction equipment:

[0035] Spider perfume extract: weigh the spider perfume medicinal material and crush it into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 30 minutes, combine the filtrate, concentrate it into an extract, and freeze-dry the extract into powder.

[0036] Sargentodoxae water extract: Weigh Sargentodoxae medicinal materials and grind them into powder, add 10 times the weight of water and soak overnight, decoct twice, each time for 45 minutes, combine the filtrate, concentrate to an extract, and freeze-dry the extract into powder.

[0037] Spider incense alcohol extract: weigh spider incense medicinal materials and grind them into powder, add 10 times the weight of 60% ethanol aqueous solution to soak overnight, reflux extraction twice, each time for 90 minutes, combine the filtrate, concentrate under reduced pressure to an extract, and freeze-dry the extract into powder.

[0038] Alcohol extract of Sargentodoxa chinensis: Weigh Sargentodoxa chinensis medicinal materials and grind them into powder. Add 10 times the weight of 60% ethanol aqueous solution and soak overnight. Reflux extraction twice, each time for 75 minutes. Combine the filtrate, concentrate under reduced pressure to an extract, and freeze-dry the extract into powder.

[0039] Perilla water extract: weigh the Perilla medicinal material and crush it into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 30 minutes, combine the filtrate, concentrate it into an extract, and freeze-dry the extract into powder.

[0040] Curcuma water extract: Weigh the Curcuma medicinal material and grind it into powder. Add 10 times the weight of water and soak it overnight. Decoction it twice, 30 minutes each time. Combine the filtrate, concentrate it into an extract, and freeze-dry the extract into powder.

[0041] 2.2 Preparation of pharmaceutical composition:

[0042] Prepare the drug combinations for each group according to Table 1.

[0043] Table 1

[0044]

[0045]

[0046] Note: "√" in the table means that this ingredient is contained, and no "√" means that this ingredient is not contained. In each solution, the weight of each ingredient is the same.

[0047] 2.3 Preparation of drug hydrogel:

[0048] After preparing the drug combinations of each scheme according to Table 1, each drug combination is prepared into a hydrogel preparation. The specific method is: Carbomer 676, triethanolamine and water are mixed at a weight ratio of 5:1:50, and after swelling for 12 hours, a first solution is obtained; the drug combination of each scheme is added to a 10v / v% ethanol aqueous solution so that the weight ratio of the drug combination to the ethanol aqueous solution is 3:5, and after fully dispersed, a second solution is obtained; the first solution and the second solution are mixed so that the weight ratio of the drug combination to Carbomer 676 is 10:1, and the mixture is fully stirred at 40°C to obtain a hydrogel preparation.

[0049] 2.4 Preparation of drug-free hydrogel formulations:

[0050] Carbomer 676, triethanolamine and water were mixed in a weight ratio of 5:1:50 and swelled for 12 hours to obtain a hydrogel preparation.

[0051] 3. Animal Experiments

[0052] 3.1 Vaginal volume experiment

[0053] Postpartum, disease-free, normal-hair, and normal-eating female dogs (27, weighing 15-16 kg) were selected as test animals, 3 in each group. The test animals were intravenously injected (hind limbs) with the anesthetic sodium pentobarbital (3%, 1 mL / kg), and a plastic catheter with a leather balloon (connected with a pressure sensor) was inserted into the vagina of the test animal, and physiological saline was slowly injected to fill the balloon with liquid so that the catheter pressure was 30 mmHg / cm, and the balloon volume was recorded and calculated as the vaginal volume before medication (initial volume). After using the drug hydrogel prepared by the above schemes 1 to 8 for 10 days, the balloon volume was measured again according to the above method to investigate the change in vaginal volume before and after medication. The control group used a hydrogel without drug.

[0054] Table 2

[0055]

[0056] As shown in Table 1, astragaloside IV, spider perfume extract, Sargassum spatholobi water extract and chlorhexidine acetate have a more obvious effect in promoting vaginal contraction. As shown in the results of Scheme 1, Scheme 5, Scheme 6 and Scheme 7, astragaloside IV, spider perfume extract, Sargassum spatholobi water extract and chlorhexidine acetate have a synergistic effect. When any of the components is missing, the effect of vaginal contraction is not significant. In addition, as shown in Scheme 4, the Curcuma zedoaria extract has an antagonistic effect on astragaloside IV, spider perfume extract, Sargassum spatholobi water extract and chlorhexidine acetate. When the Curcuma zedoaria extract is added, the effect of vaginal contraction will be seriously affected.

[0057] The reason why the present invention considers the extract of Curcuma zedoaria when designing the experimental scheme is that it is one of the important components of Jinshu Zhiluokang anti-leakage ointment, and the ointment composed of it and phytoestrogen-soy isoflavones can effectively treat vaginal relaxation (Ren Liqin, Lin Junjin. Exploration of the mechanism of action and clinical efficacy of Jinshu Zhiluokang anti-leakage ointment in the treatment of vaginal relaxation and stress urinary incontinence [J]. Jilin Medicine, 2023, 44 (1): 143-148). The reason why Perilla frutescens, Spider Fragrance, Sargentodoxae and Chlorhexidine acetate are considered is that they have all been used to prepare anti-inflammatory drugs.

[0058] Example 2

[0059] Based on the animal experiment results obtained in Scheme 1 of Example 1, the ratio of each component was adjusted to prepare different drug combinations according to Table 3.

[0060] Table 3

[0061]

[0062] The test was carried out according to the animal experiment method of Example 1, and the results are shown in Table 4.

[0063] Table 4

[0064]

[0065] As shown in Tables 3 and 4, when the contents of astragaloside IV, spider perfume extract, Sargentodoxae water extract and chlorhexidine acetate are the same or similar, a better vaginal contraction effect can be obtained; however, as shown in the experimental results of Scheme 12, when the content of astragaloside IV is high and the contents of spider perfume extract, Sargentodoxae water extract and chlorhexidine acetate are low, the vaginal contraction effect is greatly reduced. This shows that when astragaloside IV, spider perfume extract, Sargentodoxae water extract and chlorhexidine acetate play a synergistic role, they are still limited by the ratio of the three.

[0066] Example 3

[0067] The hydrogel preparations obtained from Scheme 1 in Example 1 and Schemes 9-11 in Example 2 were selected for clinical trials.

[0068] Women aged 40 to 50 years old, who were sexually active and had vaginal relaxation syndrome were selected as volunteers, a total of 100, divided into 5 groups, 20 in each group. Among them, 4 groups used the hydrogel preparations obtained by Scheme 1 in Example 1 and Schemes 9-11 in Example 2, respectively, and inserted the hydrogel preparations into the vagina every night before going to bed for 2 consecutive weeks; the control group used a hydrogel preparation without drug ingredients, and inserted the hydrogel preparations into the vagina every night before going to bed for 2 consecutive weeks. The pelvic floor muscle strength electromyography was used to evaluate the fast muscle pelvic floor muscle strength before and after medication. The diagnostic criteria for vaginal relaxation included in this experiment: the transverse diameter of the vagina is 2 to 3 fingers. The results are shown in Table 5.

[0069] Table 5

[0070]

[0071] As shown in Table 5, in clinical trials, the present invention can significantly improve the fast-twitch pelvic floor muscle strength of patients with vaginal relaxation.

[0072] Example 4

[0073] The hydrogel preparation obtained in Scheme 1 of Example 1 was selected for clinical trial. Volunteers with bacterial vaginitis were selected as subjects, a total of 10, the oldest was 32 years old and the youngest was 27 years old. Clinical symptoms were used as the judgment standard. The disappearance of all clinical symptoms was considered cured, the clinical symptoms were significantly alleviated as effective, and the clinical symptoms were ineffective without change. The hydrogel preparation was inserted into the vagina before going to bed every night for 2 consecutive weeks. Results: 4 cases were cured and 6 cases were effective.

[0074] Example 5

[0075] The drug combination of Scheme 1 in Example 1 is selected to prepare the cream, and the specific preparation method is as follows:

[0076] 8 g of stearic acid, 12 g of octadecyl alcohol, 10 g of liquid paraffin, 10 g of white vaseline, and 1.5 g of Span-80 were melted and mixed in a water bath at 80° C. as the oil phase, and 6.0 g of Tween-80, 5 mL of propylene glycol, 0.2 g of sodium benzoate, and 90 mL of double distilled water were evenly dissolved at 80° C. as the water phase; the oil phase was slowly added to the water phase, stirred and emulsified to obtain a matrix, and placed at room temperature for use; 1.5 g of the pharmaceutical composition of Scheme 1 was slowly added to water until it was just completely dissolved, and then the aforementioned matrix was added, and the cream was obtained after stirring.

[0077] (1) The cream obtained in this example was subjected to an anti-inflammatory clinical trial. Volunteers with bacterial vaginitis were selected as subjects, a total of 8 people, the oldest was 36 years old and the youngest was 33 years old. The clinical symptoms were used as the judgment standard. The disappearance of all clinical symptoms was considered cured, the clinical symptoms were significantly alleviated as effective, and the clinical symptoms were ineffective without change. The cream was applied to the vagina every night before going to bed for 2 consecutive weeks. Results: 3 cases were cured and 5 cases were effective.

[0078] (2) The cream obtained in this example was subjected to a clinical trial on fast-twitch pelvic floor muscle strength. Women aged 40 to 50 years old, sexually active, and with vaginal relaxation syndrome were selected as volunteers, a total of 40, divided into 2 groups, 20 in each group. The control group was an emulsified matrix without the drug combination of Scheme 1. Every night before going to bed, the cream of this example or the emulsified matrix of the control group was inserted into the vagina for 2 consecutive weeks. Pelvic floor muscle strength electromyography was used to evaluate the fast-twitch pelvic floor muscle strength before and after medication. The diagnostic criteria for vaginal relaxation included in this experiment: the transverse diameter of the vagina is 2 to 3 fingers. The results are shown in Table 6.

[0079] Table 6

[0080]

Claims

1. A drug combination for treating vaginal relaxation, characterized in that: According to weight, the drug combination consists of the following components Composition: 30-40 parts of astragaloside IV, 30-35 parts of Sargentodoxa chinensis water extract, 30-40 parts of spider perfume extract and 30 parts of chlorhexidine acetate.

2. The drug combination according to claim 1, characterized in that The preparation method of the spider perfume extract is as follows: weigh spider perfume medicinal materials, crush them into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 30 minutes, combine the filtrate, concentrate to an extract state, and freeze-dry the extract into powder; the preparation method of the Sanguinea chinensis water extract is as follows: weigh Sanguinea chinensis medicinal materials, crush them into powder, add 10 times the weight of water to soak overnight, decoct twice, each time for 45 minutes, combine the filtrate, concentrate to an extract state, and freeze-dry the extract into powder.

3. The drug combination according to claim 1 or 2, characterized in that: According to weight, the drug combination consists of the following components Composition: 30 parts of astragaloside IV, 30 parts of spider perfume extract, 30 parts of Sargentodoxa chinensis water extract and 30 parts of chlorhexidine acetate.

4. A medicament for treating vaginal relaxation, characterized in that: The medicament comprises the drug combination according to any one of claims 1 to 3.

5. The medicament according to claim 4, characterized in that The dosage form of the medicament is any preparation for vaginal administration.

6. The drug according to claim 5, characterized in that The dosage form of the medicament includes cream and hydrogel preparation.

7. The agent according to claim 6, characterized in that The gel matrix of the hydrogel preparation includes carbomer 676 and triethanolamine; the matrix of the cream includes stearic acid, octadecyl alcohol, liquid paraffin, white vaseline, Span-80 and Tween-80.

8. A method for preparing a medicament for treating vaginal relaxation, characterized in that: The preparation method comprises mixing the drug combination according to any one of claims 1 to 3 with the auxiliary materials required for the dosage form according to claim 5 or 6.

9. The preparation method according to claim 8, characterized in that: The preparation method of the agent is as follows: Carbomer 676, triethanolamine and water are mixed at a weight ratio of 5:1:50, and the mixture is swollen for 12 hours to obtain a first solution; the drug combination is added to a 10 v / v% ethanol aqueous solution so that the weight ratio of the drug combination to the ethanol aqueous solution is 3:5, and the second solution is obtained after sufficient dispersion; the first solution and the second solution are mixed so that the weight ratio of the drug combination to Carbomer 676 is 10:1, and the mixture is fully stirred at 40° C. to obtain a hydrogel preparation.

10. Use of the drug combination according to claims 1 to 3 in the preparation of a drug for treating vaginal relaxation.

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