Medicinal preparation for improving ovarian function and preparation method thereof
By using a drug formulation containing berberine hydrochloride, asterone, and cane liver polysaccharide to synergistically regulate ovarian function, the problem of side effects from chemically synthesized drugs has been solved, achieving effective treatment for polycystic ovary syndrome.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-28
- Publication Date
- 2026-03-10
AI Technical Summary
Existing chemically synthesized drugs for the treatment of polycystic ovary syndrome (PCOS) have side effects, such as gastrointestinal irritation and difficulty in implantation of fertilized eggs. The traditional Chinese medicine ingredient asterone has not been reported in this field.
This pharmaceutical preparation, with berberine hydrochloride, asterone, and cane liver polysaccharide as the main components, is prepared by dry granulation process. It synergistically regulates ovarian function and improves ovulation disorders, insulin resistance, and menstrual cycle irregularities.
It significantly improves ovarian function in PCOS patients, reduces serum testosterone levels, restores menstrual cycles, reduces testosterone synthesis, and promotes LH and FSH balance, demonstrating safety and therapeutic potential.
Smart Images
Figure CN121622701A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biopharmaceutical manufacturing technology, specifically relating to a pharmaceutical preparation for improving ovarian function and its preparation method. Background Technology
[0002] Polycystic ovary syndrome (PCOS) is a common reproductive endocrine and metabolic disorder in women of reproductive age, characterized by ovulation disorders, hyperandrogenism, and polycystic ovarian morphology. It is often accompanied by insulin resistance and metabolic abnormalities. Patients frequently experience symptoms such as menstrual irregularities, hirsutism, acne, and infertility. The main cause is dysfunction of the hypothalamus-pituitary-ovarian axis, leading to elevated luteinizing hormone (LH) and relatively insufficient follicle-stimulating hormone (FSH), resulting in polycystic ovarian morphology. Insulin resistance and hyperinsulinemia promote ovarian androgen secretion, creating a vicious cycle.
[0003] Currently, the main drugs for treating PCOS are chemically synthesized drugs, such as insulin sensitizers, ovulation-inducing drugs, and anti-hyperandrogen drugs. While chemically synthesized drugs are effective in treating PCOS, they have side effects, such as gastrointestinal irritation and difficulty in implantation of fertilized eggs. Berberine hydrochloride is an alkaloid extracted from plants such as Coptis chinensis, Phellodendron amurense, and Gynostemma pentaphyllum, and has significant hypoglycemic, lipid-lowering, and insulin resistance-improving effects. Shionone is a triterpenoid compound extracted from the dried roots and rhizomes of Aster tataricus, a plant in the Asteraceae family. Traditional Chinese medicine believes that Aster tataricus has the effects of moistening the lungs, lowering qi, resolving phlegm, and relieving cough, and is often used to treat coughs. Recent pharmacological studies have found that shionone has potential anti-inflammatory and metabolic regulatory effects. Shionone has anti-inflammatory effects on various inflammatory diseases, but its application in the treatment of polycystic ovary syndrome has not been reported. Therefore, this invention provides a pharmaceutical preparation based on shionone to improve ovarian function. Summary of the Invention
[0004] The primary objective of this invention is to provide a pharmaceutical preparation for improving ovarian function.
[0005] A second objective of this invention is to provide a method for preparing a pharmaceutical preparation for improving ovarian function.
[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: This invention provides a pharmaceutical preparation for improving ovarian function, the pharmaceutical preparation comprising the following raw materials in parts by weight: 12-25 parts of berberine hydrochloride, 8-16 parts of asterone, 5-10 parts of *Cibotium barometz* polysaccharide, 10-20 parts of diluent, 5-9 parts of binder, and 1-6 parts of lubricant.
[0007] Preferably, the diluent is maltodextrin.
[0008] Preferably, the adhesive is microcrystalline cellulose.
[0009] Preferably, the lubricant is micronized silica gel.
[0010] Preferably, the preparation method of the *Cibotium barometz* polysaccharide includes the following steps: (1) First, the whole herb of the dog liver vegetable is crushed and dried to obtain a dry coarse powder; then, petroleum ether is added to the dry coarse powder for extraction to obtain dog liver vegetable residue; boiling water is added to the dog liver vegetable residue for extraction twice, and the extracts are combined; after removing the protein, the crude total polysaccharide of dog liver vegetable is obtained. (2) Add purified water to the crude total polysaccharide of *Gnaphalium affine* to dissolve it. Transfer the solution to a semi-permeable membrane dialysis bag with a molecular weight cutoff of 3500 Da. Dialyze it 3 times, combine the dialysis solutions, precipitate with alcohol, filter and vacuum dry to obtain *Gnaphalium affine* polysaccharide with a molecular weight of less than 3500 Da.
[0011] Preferably, in step (1), the ratio of dried coarse powder to petroleum ether is 1g:10-12mL.
[0012] Preferably, in step (1), the ratio of the amount of dog liver vegetable residue to boiling water is 1g:10-12mL.
[0013] Preferably, in step (1), the extraction time for adding petroleum ether is 1-2 hours; the extraction time for each time boiling water is added is 1-2 hours.
[0014] Preferably, in step (2), dialysis is performed for 3-4 hours each time; the temperature of alcohol precipitation is 4°C and the time is 12 hours.
[0015] This invention provides a method for preparing a pharmaceutical preparation for improving ovarian function. The preparation method includes the following steps: weighing each raw material according to the ratio, mixing them evenly, and then granulating them by dry method to obtain the final product.
[0016] Compared with the prior art, the main advantages of the present invention are as follows: This invention provides a pharmaceutical preparation for improving ovarian function and its preparation method. The pharmaceutical composition consists of berberine hydrochloride, asterone, and *Cibotium barometzii* polysaccharide. Berberine hydrochloride can reduce dyslipidemia and improve ovulation disorders; asterone can inhibit inflammation and alleviate insulin resistance; *Cibotium barometzii* polysaccharide improves polycystic ovarian changes, reduces testosterone synthesis, and lowers serum testosterone (T) levels by regulating endocrine function and adjusting hormone levels. The combination of these three ingredients synergistically regulates menstrual cycle disorders caused by polycystic ovary syndrome and improves insulin resistance. Significant improvements are observed in luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH / FSH ratio, demonstrating potential for treating polycystic ovary syndrome and a broad market prospect. Attached Figure Description
[0017] Figure 1 Morphological diagram of fibroblasts in Experimental Example 1 of this invention. Detailed Implementation
[0018] The technical solution of the present invention will be further described below with reference to specific embodiments. However, those skilled in the art should understand that the following embodiments are only for illustrating the present invention and should not be regarded as limiting the present invention. Specific conditions not specified in the embodiments are performed according to conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used are all conventional products obtained through commercial channels.
[0019] Example 1 This embodiment provides a pharmaceutical preparation for improving ovarian function, the pharmaceutical preparation comprising the following raw materials in parts by weight: 20 parts berberine hydrochloride, 12 parts asterone, 8 parts cantorella polysaccharide, 15 parts diluent (maltodextrin), 7 parts binder (microcrystalline cellulose), and 4 parts lubricant (micronized silica gel).
[0020] The preparation method of Canis lucidum polysaccharide in this embodiment includes the following steps: (1) First, the whole herb of the dog liver vegetable is crushed and dried to obtain a dry coarse powder; then, petroleum ether is added to the dry coarse powder and extracted for 1.5 h to obtain dog liver vegetable residue. The ratio of dry coarse powder to petroleum ether is 1 g: 12 mL; after the petroleum ether in the dog liver vegetable residue is evaporated, boiling water is added and extracted twice, 1.5 h each time. The extracts are combined. The ratio of dog liver vegetable residue to boiling water is 1 g: 10 mL; protein is removed according to the Sevage method to obtain crude total polysaccharide of dog liver vegetable. (2) Add purified water to the crude total polysaccharide of *Gnaphalium affine* to dissolve it. The ratio of crude total polysaccharide of *Gnaphalium affine* to purified water is 5g:12mL. Transfer the solution to a semi-permeable membrane dialysis bag with a molecular weight cutoff of 3500Da. Dialyze 3 times, 4h each time. Combine the dialysis solutions and precipitate them with alcohol at 4℃ for 12h. Then filter and vacuum dry to obtain *Gnaphalium affine* polysaccharide with a molecular weight lower than 3500Da.
[0021] This embodiment provides a method for preparing a pharmaceutical preparation for improving ovarian function. The preparation method includes the following steps: weighing each raw material according to the ratio, mixing them evenly, and then granulating them by dry method to obtain the final product.
[0022] Example 2 This embodiment provides a pharmaceutical preparation for improving ovarian function, the pharmaceutical preparation comprising the following raw materials in parts by weight: 25 parts berberine hydrochloride, 16 parts asterone, 10 parts cantorella polysaccharide, 20 parts diluent (maltodextrin), 9 parts binder (microcrystalline cellulose), and 6 parts lubricant (micronized silica gel).
[0023] The preparation method of Canis lucidum polysaccharide in this embodiment includes the following steps: (1) First, the whole herb of the dog liver vegetable is crushed and dried to obtain a dry coarse powder; then, petroleum ether is added to the dry coarse powder and extracted for 2 hours to obtain dog liver vegetable residue. The ratio of dry coarse powder to petroleum ether is 1g:12mL. After the petroleum ether in the dog liver vegetable residue is evaporated, boiling water is added and extracted twice, 2 hours each time. The extracts are combined. The ratio of dog liver vegetable residue to boiling water is 1g:12mL. Protein is removed according to the Sevage method to obtain crude total polysaccharide of dog liver vegetable. (2) Add purified water to the crude total polysaccharide of *Gnaphalium affine* to dissolve it. The ratio of crude total polysaccharide of *Gnaphalium affine* to purified water is 5g:12mL. Transfer the solution to a semi-permeable membrane dialysis bag with a molecular weight cutoff of 3500Da. Dialyze 3 times, 4h each time. Combine the dialysis solutions and precipitate them with alcohol at 4℃ for 12h. Then filter and vacuum dry to obtain *Gnaphalium affine* polysaccharide with a molecular weight lower than 3500Da.
[0024] This embodiment provides a method for preparing a pharmaceutical preparation for improving ovarian function. The preparation method includes the following steps: weighing each raw material according to the ratio, mixing them evenly, and then granulating them by dry method to obtain the final product.
[0025] Example 3 This embodiment provides a pharmaceutical preparation for improving ovarian function, the pharmaceutical preparation comprising the following raw materials in parts by weight: 12 parts berberine hydrochloride, 8 parts asterone, 5 parts cantorella polysaccharide, 10 parts diluent (maltodextrin), 5 parts binder (microcrystalline cellulose), and 1 part lubricant (micronized silica gel).
[0026] The preparation method of Canis lucidum polysaccharide in this embodiment includes the following steps: (1) First, the whole herb of the dog liver vegetable is crushed and dried to obtain a dry coarse powder; then, petroleum ether is added to the dry coarse powder and extracted for 1 hour to obtain dog liver vegetable residue. The ratio of dry coarse powder to petroleum ether is 1g:10mL. After the petroleum ether in the dog liver vegetable residue is evaporated, boiling water is added and extracted twice, 1 hour each time. The extracts are combined. The ratio of dog liver vegetable residue to boiling water is 1g:10mL. Protein is removed according to the Sevage method to obtain crude total polysaccharide of dog liver vegetable. (2) Add purified water to the crude total polysaccharide of *Gnaphalium affine* to dissolve it. The ratio of crude total polysaccharide of *Gnaphalium affine* to purified water is 5g:12mL. Transfer the solution to a semi-permeable membrane dialysis bag with a molecular weight cutoff of 3500Da. Dialyze 3 times, 3h each time. Combine the dialysis solutions and precipitate them with alcohol at 4℃ for 12h. Then filter and vacuum dry to obtain *Gnaphalium affine* polysaccharide with a molecular weight lower than 3500Da.
[0027] This embodiment provides a method for preparing a pharmaceutical preparation for improving ovarian function. The preparation method includes the following steps: weighing each raw material according to the ratio, mixing them evenly, and then granulating them by dry method to obtain the final product.
[0028] Comparative Example 1 The difference between this comparative example and the embodiment is that the *Cibotium barometz* polysaccharide is replaced with a large molecular weight *Cibotium barometz* polysaccharide with a molecular weight greater than 3500 Da; otherwise, it is the same as in embodiment 1.
[0029] Comparative Example 2 The difference between this comparative example and the embodiment is that asterone in the pharmaceutical preparation raw materials is omitted, while the rest is the same as in Example 1.
[0030] Experimental Example 1 (1) Mouse fibroblasts were cultured in a 37°C, 5% CO2 cell culture incubator in DMEM / F12 medium containing 10% FBS, 100 U / mL penicillin, and 100 μg / mL streptomycin. When the mouse fibroblasts reached 70% confluence, they were digested with 0.25% trypsin, centrifuged at 1600 rpm for 5 min, resuspended, counted, and the cell density was adjusted to 1×10⁻⁶. 4 The cells / mL were seeded into a 96-well plate at a rate of 100 μL / well.
[0031] The original culture medium in the 96-well plates was aspirated, and 100 μL of DMEM / F12 medium containing the drug formulation (containing 10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin, and 50 μg / mL *Gnaphalium affine* polysaccharide prepared in Example 1) was added. The plates were then cultured for 24 h, constituting Experiment 1. The original culture medium in the 96-well plates was aspirated, and 100 μL of DMEM / F12 medium containing the drug formulation (containing 10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin, and 50 μg / mL asterone) was added. The plates were then cultured for 24 h, constituting Experiment 2. A blank control group was also set up; the original culture medium in the 96-well plates was aspirated, and DMEM / F12 medium (containing 10% FBS, 100 U / mL penicillin, and 100 μg / mL streptomycin) was added. The plates were then cultured for 24 h. A positive control group was set up. The original culture medium in the 96-well plate was aspirated, and DMEM / F12 medium (containing 10% FBS, 100 U / mL penicillin, 100 μg / mL streptomycin, and 5% phenol) was added. The plates were then cultured for another 24 hours. The fibroblast status was observed, and the results are as follows: Figure 1 As shown in the figure. Among them, (a) is the blank control group, (b) is the positive control group, (c) is the experimental group 1, and (d) is the experimental group 2.
[0032] Depend on Figure 1 It is evident that the cell morphology of Experiment 1, Experiment 2 and the blank control group is similar, which is the normal morphology of mouse fibroblasts. This indicates that the cane liver polysaccharide and asterone in the raw materials of the drug preparation of this invention did not cause damage to the morphology of mouse fibroblasts and are safe.
[0033] (2) Twenty-one-day-old SPF-grade female Wistar rats were randomly divided into a control group and an Example 1 group, with six rats in each group. After one week of acclimatization, the Example 1 group was administered 100 mg / kg of the drug preparation obtained in Example 1 by gavage daily; the control group was administered 10 mL / kg of physiological saline by gavage daily. After one week, the rats exhibited normal behavior and activity, slight weight gain, no adverse reactions, no obvious symptoms of poisoning, and no deaths. The drug preparation of this invention is safe.
[0034] Experimental Example 2 Twenty-one-day-old SPF-grade female Wistar rats were selected and acclimatized for two days. Starting at 23 days of age, the rats were subcutaneously injected daily into the neck and back with DHEA 6 mg / 100 g + 0.2 mL of injectable sesame oil for 20 consecutive days. Vaginal exfoliative cytology was performed for 10 days. Rats whose vaginal epithelial cells maintained a persistent keratinized state were designated as DHEA-induced polycystic ovary syndrome (PCOS) animal models and entered into subsequent experiments; those with atypical results were discarded. The model rats were fasted at 8 PM that evening, and blood was collected from the orbital vein at 8 AM the following morning for fasting blood glucose and insulin levels. The insulin resistance index was calculated using the formula: Rat Insulin Resistance Index = Fasting Blood Glucose × Fasting Insulin / 22.5. Rats with an insulin resistance index greater than 2.7 were considered successful PCOS animal models and entered into subsequent experiments.
[0035] Wister rats that successfully developed the model were randomly divided into 6 groups (model group, Example 1 group, Example 2 group, Example 3 group, Comparative Example 1 group, and Comparative Example 2 group), with 12 rats in each group. An additional 12 Wister rats that did not develop the model served as a blank control group. Example 1-3 and Comparative Example 1-2 groups were administered the corresponding drug preparation by gavage at 100 mg / kg daily for 28 consecutive days. The blank control group and model group were administered physiological saline at 10 mL / kg daily for 28 consecutive days. The rats' activity level, diet, urination and defecation, fur, and body weight were observed weekly.
[0036] (1) Ten days after the last administration, vaginal cytology was performed on rats. The changes in the rat estrous cycle were observed according to the histological characteristics of vaginal smears at each stage of the estrous cycle. The estrous cycle recovery rate in groups 1-3 of Examples was over 80%, and the estrous cycle recovery rate in groups 1-2 of Comparative Examples was over 70%. These differences were statistically significant compared to the model group without drug intervention. This indicates that the drug formulation of the present invention has a significant effect on improving the estrous cycle in rats with polycystic ovary syndrome.
[0037] (2) After the last administration, blood was collected from the orbital vein of rats in the proestrus stage based on vaginal exfoliative cytology examination, and the serum insulin levels of the rats were measured at fasting, 60 min after a meal, and 120 min after a meal. The results are shown in Table 1.
[0038] Table 1. Effects on serum insulin levels (n=12) Note: Compared with the blank control group: ## P<0.01, # P < 0.05; Compared with the model group: **P < 0.01, *P < 0.05 As shown in Table 1, the serum insulin levels in the model group at each time point were significantly higher than those in the blank control group; the serum insulin levels in the Example 1-3 groups and the Comparative Example 1-2 groups at each time point were significantly lower than those in the model group, and the serum insulin levels in the Example 1-3 groups at each time point were lower than those in the Comparative Example 1-2 groups.
[0039] (3) After the last administration, blood was collected from the abdominal aorta of rats in the proestrus stage based on vaginal exfoliative cytology. Serum testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and LH / FSH levels were measured by enzyme-linked immunosorbent assay (ELISA). The results are shown in Table 2.
[0040] Table 2 Effects on serum sex hormone levels (n=12) Note: Compared with the blank control group: ## P<0.01, # P < 0.05; Compared with the model group: **P < 0.01, *P < 0.05 Table 2 shows that the serum T and LH levels and LH / FSH ratio of rats in the model group were significantly higher than those in the blank control group, while the serum FSH level of rats in the model group was significantly lower than that in the blank control group. The serum T and LH levels and LH / FSH ratio of rats in Examples 1-3 and Comparative Example 1 were significantly lower than those in the model group, while the serum T and LH levels and LH / FSH ratio of rats in Comparative Example 2 showed a decreasing trend. The serum FSH levels of rats in Examples 1-3 and Comparative Example 1 were significantly higher than those in the model group, while the serum FSH level of rats in Comparative Example 2 showed an increasing trend. The serum T and LH levels and LH / FSH ratio of rats in Examples 1-3 were lower than those in Comparative Example 1-2. The serum FSH levels of rats in Examples 1-3 were higher than those in Comparative Example 1-2.
[0041] In summary, the pharmaceutical composition of this invention comprises berberine hydrochloride, asterone, and *Cibotium barometzii* polysaccharide. Berberine hydrochloride can reduce dyslipidemia and improve ovulation disorders; asterone can inhibit inflammation and alleviate insulin resistance; *Cibotium barometzii* polysaccharide improves polycystic ovarian changes, reduces testosterone synthesis, and lowers serum testosterone (T) levels by regulating endocrine function and adjusting hormone levels. The combination of these three components synergistically regulates menstrual cycle disorders caused by polycystic ovary syndrome and reverses insulin resistance, significantly improving indicators such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and the LH / FSH ratio.
[0042] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. The basic principles and main features of the present invention have been described above with specific implementation schemes. Based on the present invention, some modifications or substitutions can be made, but these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of protection claimed by the present invention.
Claims
1. A pharmaceutical preparation for improving ovarian function, characterized by, The pharmaceutical preparation comprises the following raw materials in parts by weight: berberine hydrochloride 12-25 parts, shionone 8-16 parts, dogbane polysaccharide 5-10 parts, diluent 10-20 parts, binder 5-9 parts, lubricant 1-6 parts.
2. The pharmaceutical preparation for improving ovarian function according to claim 1, wherein The diluent is malt dextrin.
3. The pharmaceutical preparation for improving ovarian function according to claim 1, wherein The binder is microcrystalline cellulose.
4. The pharmaceutical preparation for improving ovarian function according to claim 1, wherein The lubricant is micro-powder silica gel.
5. The pharmaceutical preparation for improving ovarian function according to claim 1, wherein The preparation method of the dogbane polysaccharide comprises the following steps: (1) first, the dogbane whole plant is crushed and dried to obtain dry coarse powder; then petroleum ether is added to the dry coarse powder for extraction to obtain dogbane residues; the dogbane residues are added with boiling water for extraction twice, and the extraction liquid is combined; after removing the protein, the dogbane crude total polysaccharide is obtained; (2) the dogbane crude total polysaccharide is added with purified water for dissolution, and the dissolved solution is transferred to a semi-permeable membrane dialysis bag with a molecular weight cut-off of 3500 Da for dialysis for 3 times; the dialysate is combined, alcohol precipitated, filtered, and vacuum dried to obtain dogbane polysaccharide with a molecular weight lower than 3500 Da.
6. The pharmaceutical preparation for improving ovarian function according to claim 5, wherein In the step (1), the dry coarse powder and petroleum ether are used in a ratio of 1g:10-12mL.
7. The pharmaceutical preparation for improving ovarian function according to claim 5, wherein In the step (1), the dogbane residues and boiling water are used in a ratio of 1g:10-12mL.
8. The pharmaceutical preparation for improving ovarian function according to claim 5, wherein In the step (1), the petroleum ether is added for extraction for 1-2h; when the boiling water is added, the extraction time is 1-2h each time.
9. The pharmaceutical preparation for improving ovarian function according to claim 5, wherein In the step (2), the dialysis time is 3-4h each time; the alcohol precipitation temperature is 4℃, and the time is 12h.
10. The method of claim 1-9, wherein the pharmaceutical preparation for improving ovarian function is prepared by, The preparation method comprises the following steps: the raw materials are weighed according to the proportion, mixed uniformly, and then dry granulated to obtain the product.