A rare ginsenoside medicinal composition and its application
Through the rare pharmaceutical composition of ginseng saponins Rg5 and Rk1, synergistic effects promote ovarian granule cells proliferation, solve the limitations of the prior art in protecting the reproductive system, and achieve significant inhibition and therapeutic effects of premature ovarian failure.
Patent Information
- Application Number
- CN202410115337.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-01-26
- Publication Date
- 2025-03-21
- Estimated Expiration
- 2044-01-26
AI Technical Summary
The prior art has limitations in protecting the patient's reproductive system from chemotherapy damage, and invasive operation brings problems of body damage and limited application range.
The pharmaceutical composition of rare ginsenoside Rg5 and rare ginsenoside Rk1 is used to promote the proliferation of ovarian granule cells through synergistic effects, and inhibit, improve or treat premature ovarian failure.
It significantly promotes the proliferation of ovarian granules cells, inhibits, improves or treats premature ovarian failure, improves the safety of medication, and provides new methods for protecting the patient's reproductive system.
Smart Images
Figure CN117919263B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of medical technology, and in particular to a rare ginsenoside medicinal composition and application thereof. Background Art
[0002] Reproduction is one of the priorities of the World Health Organization and is the basis of human survival. In recent years, the number of cases of infertility caused by damage to the reproductive system due to chemotherapy has continued to increase, attracting widespread attention from all over the world. At present, the main measures to protect patients' reproductive function include embryo cryopreservation, mature oocyte cryopreservation, ovarian tissue cryopreservation and reimplantation. However, these measures are invasive operations, which will cause a certain degree of damage to the body itself and have a limited scope of application. In addition, some of the above measures may delay chemotherapy, resulting in a low success rate and even secondary cancer. Therefore, although the above measures can be used to protect patients' reproductive function, they are not suitable for long-term maintenance of reproductive function. In view of the above situation, there is an urgent need to develop a new method to protect patients' reproductive system from damage by chemotherapy.
[0003] Ginsenosides have a variety of biological and pharmacological activities, such as anti-inflammatory, antioxidant, and anti-apoptotic. They have beneficial effects on cardiovascular diseases and metabolic syndrome. Rare ginsenosides with low polarity have less sugar content, higher pharmacological activity, good permeability through cell membranes, and are more conducive to the body's absorption. They have more significant effects in anti-tumor, anti-diabetes, anti-thrombotic regulation of metabolism and promotion of cell differentiation. Rare ginsenoside Rg5 and rare ginsenoside Rk1 both have anti-tumor and anti-viral functions and have been used to prepare anticancer agents or cancer prevention agents. Studies have found that rare ginsenoside Rg3 can reverse the reproductive function damage of mice caused by dibutyl phthalate, but there has been no research on the use of monomeric saponins such as rare ginsenoside Rg5 and rare ginsenoside Rk1 for reproductive system damage such as premature ovarian failure. Summary of the invention
[0004] In order to solve the above technical problems, the technical solution adopted in the present application is to provide a rare ginsenoside pharmaceutical composition based on rare ginsenoside Rg5 and rare ginsenoside Rk1, which has a synergistic effect and has the effects of promoting the proliferation of ovarian granulosa cells and inhibiting, improving or treating premature ovarian failure. In addition, the present invention also provides the use of the above rare ginsenoside pharmaceutical composition in the preparation of a drug for promoting the proliferation of ovarian granulosa cells and a drug for inhibiting, improving or treating premature ovarian failure.
[0005] The embodiment of the present application provides a rare ginsenoside pharmaceutical composition, including rare ginsenoside Rg5 (CAS: 186763-78-0) and rare ginsenoside Rk1 (CAS: 494753-69-4), wherein the weight ratio of rare ginsenoside Rg5 to rare ginsenoside Rk1 is 1:3 to 3:1.
[0006] Among them, the chemical structure formula of rare ginsenoside Rg5 is:
[0007]
[0008] The chemical structure of rare ginsenoside Rk1 is:
[0009]
[0010] The second aspect of the embodiments of the present application provides the use of the rare ginsenoside pharmaceutical composition described above, which is the use of the rare ginsenoside pharmaceutical composition in the preparation of a drug for inhibiting, improving or treating premature ovarian failure.
[0011] The third aspect of the embodiments of the present application provides the use of the rare ginsenoside pharmaceutical composition described above, which is the use of the rare ginsenoside pharmaceutical composition in the preparation of a drug for promoting the proliferation of ovarian granulosa cells.
[0012] Preferably, the dosage of the rare ginsenoside pharmaceutical composition used as a drug is 50-300 mg / kg / d, calculated based on mammals other than humans.
[0013] In the present application, mammals other than humans may be rats, rabbits, sheep, and the like.
[0014] Preferably, the dosage of the rare ginsenoside pharmaceutical composition used as a drug is 50 to 300 mg / d, calculated for adults.
[0015] In the present application, when the rare ginsenoside pharmaceutical composition is used as a medicine, its dosage varies depending on the degree of symptoms, patient age, gender, weight, sensitivity differences, administration method, administration period, administration interval, nature of the pharmaceutical preparation, type of active ingredient, etc.
[0016] Preferably, the rare ginsenoside pharmaceutical composition is used as a medicine for oral administration or external use.
[0017] In the present application, the dosage form of the rare ginsenoside pharmaceutical composition when used as a medicine is not limited. When used orally, the dosage form can be powder, capsule, granule, granule, tablet, pill, syrup, oral liquid; when used externally, the dosage form can be a patch, smear, ointment.
[0018] Compared with the prior art, the present invention has the following beneficial effects:
[0019] (1) The present invention provides a rare ginsenoside pharmaceutical composition and its application. Through the synergistic effect of rare ginsenoside Rg5 and rare ginsenoside Rk1, the rare ginsenoside pharmaceutical composition has a significant effect of promoting the proliferation of ovarian granulosa cells, as well as the effect of inhibiting, improving or treating premature ovarian failure. The rare ginsenoside pharmaceutical composition can be used to prepare a drug for promoting the proliferation of ovarian granulosa cells, as well as a drug for inhibiting, improving or treating premature ovarian failure.
[0020] (2) The present invention provides a rare ginsenoside pharmaceutical composition and its application. By verifying the appropriate ratio of rare ginsenoside Rg5 and rare ginsenoside Rk1, the rare ginsenoside Rg5 and rare ginsenoside Rk1 show excellent synergistic effect in the weight ratio range of 1:3 to 3:1, so that the rare ginsenoside pharmaceutical composition has a significant effect of promoting the proliferation of ovarian granulosa cells, as well as the effect of inhibiting, improving or treating premature ovarian failure, and improves the safety of medication while exerting its effects. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.
[0022] Figure 1 This is a graph showing the effects of cyclophosphamide concentration and intervention time on the survival rate of human ovarian granulosa cells;
[0023] Figure 2 This is a relationship diagram of the effects of the ratio of rare ginsenoside drug composition and intervention time on the survival rate of human ovarian granulosa cells induced by cyclophosphamide;
[0024] Figure 3 This is a graph showing the effect of the rare ginsenoside drug composition on the survival rate of human ovarian granulosa cells induced by cyclophosphamide;
[0025] Figure 4a This is a relationship diagram of the effect of the rare ginsenoside drug composition on the estradiol (E2) hormone level in human ovarian granulosa cells induced by cyclophosphamide;
[0026] Figure 4b This is a relationship diagram of the effect of the rare ginsenoside drug composition on the level of anti-Mullerian hormone (AMH) in human ovarian granulosa cells induced by cyclophosphamide;
[0027] Figure 4cThis is a relationship diagram of the effect of the rare ginsenoside drug composition on the level of follicle-stimulating hormone (FSH) in human ovarian granulosa cells induced by cyclophosphamide;
[0028] Figure 5 This is a cross-section of rat ovarian tissue;
[0029] Figure 6 This is a relationship diagram of the effect of the dosage of the rare ginsenoside medicinal composition on the proportion of growing follicles in rats;
[0030] Figure 7 This is a graph showing the effect of the dosage of the rare ginsenoside medicinal composition on the ovarian index of rats;
[0031] Figure 8a This is a graph showing the effect of the dosage of the rare ginsenoside drug composition on the level of estradiol (E2) hormone in rats;
[0032] Figure 8b The figure is a relationship diagram of the effect of the dosage of the rare ginsenoside medicinal composition on the level of anti-Mullerian hormone (AMH) in rats;
[0033] Figure 8c This is a graph showing the effect of the dosage of the rare ginsenoside medicinal composition on the level of follicle-stimulating hormone (FSH) in rats. DETAILED DESCRIPTION
[0034] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.
[0035] The present invention provides a rare ginsenoside pharmaceutical composition, and the raw materials and reagents used are all conventional commercially available products, and their specific sources are shown in Table 1.
[0036] Table 1 Specifications and sources of raw materials
[0037]
[0038]
[0039] In order to verify the reliability of the effect of the present invention, the present invention is described below in conjunction with Examples 1 to 3.
[0040] Example 1 Screening of the ratio of rare ginsenoside pharmaceutical composition
[0041] (1) Culture of human ovarian granulosa cells: Human ovarian granulosa cells were inoculated into a modified culture medium containing 10% fetal bovine serum and 100 U / mL penicillin and streptomycin, and cultured in a cell culture incubator at 37° C. and 5% CO 2 .
[0042] (2) Cyclophosphamide induction: 5×10 3 Human ovarian granulosa cells were seeded in 96-well plates and waited for adhesion. Then, equal volumes of cyclophosphamide at concentrations of 40μM, 80μM, 160μM, 320μM, and 640μM were added to the wells for intervention. Each group repeated 5 wells and intervened for 12h, 24h, and 48h, respectively. CCK-8 solution was added one hour before the end of the intervention. After the intervention, the absorbance of each well at 450nm was detected using an enzyme marker, and the survival rate of human ovarian granulosa cells in each well was calculated. Then, a relationship diagram of the effect of cyclophosphamide concentration and intervention time on the survival rate of human ovarian granulosa cells was drawn, and the concentration of cyclophosphamide and intervention time were determined. The results are shown in Figure 2. Figure 1 shown.
[0043] Test conclusion: Please refer to Figure 1 , is a graph showing the effect of cyclophosphamide concentration and intervention time on the survival rate of human ovarian granulosa cells. Figure 1 It can be seen that the concentration of cyclophosphamide is preferably 320 μM and the intervention time is preferably 24 h.
[0044] (3) Intervention with rare ginsenoside drug composition: Rare ginsenoside Rg5 and rare ginsenoside Rk1 were formulated into rare ginsenoside drug compositions in the ratios of 1:1, 1:2, 1:3, 2:1, and 3:1, respectively. The five rare ginsenoside drug compositions with different ratios, as well as rare ginsenoside Rg5 and rare ginsenoside Rk1 were then used as experimental groups and named 1:1 group, 1:2 group, 1:3 group, 2:1 group, 3:1 group, Rg5 group, and Rk1 group, respectively. Seven groups of intervention drugs with a concentration of 5 mg / L were obtained. The blank group was used as the control group and named NC group.
[0045] 5×10 3 Human ovarian granulosa cells were seeded in 96-well plates and waited for attachment. They were divided into 1:1 group, 1:2 group, 1:3 group, 2:1 group, 3:1 group, Rg5 group, Rk1 group and NC group, with 5 replicates in each group. Then, an equal volume of 320 μM cyclophosphamide was added to the wells of 1:1 group, 1:2 group, 1:3 group, 2:1 group, 3:1 group, Rg5 group and Rk1 group for intervention for 24 h, while the NC group was not treated.
[0046] After the intervention, 7 groups of intervention drugs with equal volumes were added to the well plate for intervention for 6h, 12h, and 24h respectively. The NC group was not treated. CCK-8 solution was added one hour before the end of the intervention. After the intervention, the absorbance of each well at 450nm was detected by an enzyme marker, and the survival rate of human ovarian granulosa cells in each well was calculated. Then, a relationship diagram of the ratio of the rare ginsenoside drug composition and the intervention time on the survival rate of human ovarian granulosa cells induced by cyclophosphamide was drawn. The results are shown in Figure 2. Figure 2 shown.
[0047] See also Figure 2 , is a graph showing the effect of the ratio of rare ginsenoside drug composition and intervention time on the survival rate of human ovarian granulosa cells induced by cyclophosphamide. Figure 2 It can be seen that the survival rates of human ovarian granulosa cells in groups 1:1, 1:2, 1:3, 2:1 and 3:1 were significantly higher than those in groups Rg5 and Rk1, and the survival rate of human ovarian granulosa cells in group 1:1 was the highest. It can be seen that the addition of the rare ginsenoside pharmaceutical composition is beneficial to the proliferation of human ovarian granulosa cells. When the mass ratio of rare ginsenoside Rg5 to rare ginsenoside Rk1 is 1:1 and the intervention time is 24h, the proliferation effect on human ovarian granulosa cells is the best. Therefore, the raw material mass ratio of the rare ginsenoside pharmaceutical composition is preferably 1:1, and the intervention time is preferably 24h. In addition, it can be seen that there is a synergistic effect between rare ginsenoside Rg5 and rare ginsenoside Rk1, and the combined use of the two can significantly improve the proliferation effect of the rare ginsenoside pharmaceutical composition on human ovarian granulosa cells.
[0048] In order to further confirm the reliability of the effect of the present invention, the effect test of the rare ginsenoside pharmaceutical composition was carried out with a raw material mass ratio of 1:1 and an intervention time of 24h.
[0049] Example 2 Test of the therapeutic effect of rare ginsenoside medicinal composition on human ovarian granulosa cells
[0050] (1) Grouping: Three groups of experiments were set up, in which the control group was human ovarian granulosa cells cultured normally in vitro and did not receive any treatment, named the NC group; the model group was human ovarian granulosa cells intervened with 320 μM cyclophosphamide, named the CP group; the experimental group was human ovarian granulosa cells first intervened with 320 μM cyclophosphamide and then intervened with a rare ginsenoside drug composition with a ratio of 1:1, named the HTS group.
[0051] (2) Culture of human ovarian granulosa cells: Human ovarian granulosa cells were inoculated into a modified culture medium containing 10% fetal bovine serum and 100 U / mL penicillin and streptomycin, and cultured in a cell culture incubator at 37° C. and 5% CO 2 .
[0052] (3) Cyclophosphamide induction: 5×10 3 Human ovarian granulosa cells were seeded in 96-well plates and waited for attachment. They were divided into NC group, CP group and HTS group, with 5 replicates in each group. Equal volumes of 320 μM cyclophosphamide were added to the wells of the CP group and the HTS group for intervention for 24 h.
[0053] (4) Intervention with rare ginsenoside drug combination: After the cyclophosphamide intervention, a rare ginsenoside drug combination with a ratio of 1:1 and a concentration of 5 mg / L was added to the well plate of the HTS group for intervention for 24 h; CCK-8 solution was added one hour before the end of the intervention. After the intervention, the absorbance of each well of the three groups at 450 nm was detected by an ELISA instrument, and the survival rate of human ovarian granulosa cells in each well was calculated. Then, a relationship diagram of the effect of the rare ginsenoside drug combination on the survival rate of human ovarian granulosa cells induced by cyclophosphamide was drawn. The results are shown in FIG. Figure 3 shown.
[0054] (5) Hormone level detection: The supernatant of human ovarian granulosa cells in each well was obtained, and the supernatant of each well was treated with an Elisa kit. Then, the absorbance of the supernatant of each well at 450 nm was detected with an ELISA reader. The concentrations of three hormones, namely, estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in human ovarian granulosa cells were calculated according to the software provided by the Elisa kit. Then, the relationship diagrams of the effects of the rare ginsenoside drug composition on the levels of estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in human ovarian granulosa cells induced by cyclophosphamide were drawn. The results are shown in FIG. Figure 4a , Figure 4b , Figure 4c shown.
[0055] See also Figure 3 , is a graph showing the effect of rare ginsenosides on the survival rate of human ovarian granulosa cells induced by cyclophosphamide. Figure 3 It can be seen that, comparing the NC group and the CP group, the survival rate of human ovarian granulosa cells was significantly reduced after cyclophosphamide modeling, and the comparison between the two was p<0.01, which was statistically significant, indicating that the cyclophosphamide modeling was successful; comparing the CP group and the HTS group, the survival rate of human ovarian granulosa cells was significantly increased after intervention with the rare ginsenoside drug composition, but was still lower than that of the NC group, and the comparison between the two was p<0.01, which was also statistically significant.
[0056] See also Figure 4a , Figure 4b , Figure 4c, respectively, are the effects of the rare ginsenosides drug composition on the levels of estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in human ovarian granulosa cells induced by cyclophosphamide. Figure 4a It can be seen that the concentration of estradiol (E2) hormone was significantly reduced after cyclophosphamide modeling in the NC group and the CP group, and the comparison between the two was p<0.01, which was statistically significant; the concentration of estradiol (E2) hormone was significantly increased after the intervention of the rare ginsenoside drug composition in the CP group and the HTS group, but it was still lower than that in the NC group, and the comparison between the two was p<0.05, which was statistically significant. Figure 4b It can be seen that the concentration of anti-Mullerian hormone (AMH) was significantly reduced after cyclophosphamide modeling in the NC group and the CP group, and the comparison between the two was p<0.01, which was statistically significant; the concentration of anti-Mullerian hormone (AMH) was significantly increased after the intervention of the rare ginsenoside drug composition in the CP group and the HTS group, but it was still lower than that in the NC group, and the comparison between the two was p<0.01, which was statistically significant. Figure 4c It can be seen that, comparing the NC group and the CP group, the concentration of follicle-stimulating hormone (FSH) was significantly increased after cyclophosphamide modeling, and the comparison between the two was p<0.01, which was statistically significant; comparing the CP group and the HTS group, the concentration of follicle-stimulating hormone (FSH) was significantly decreased after the intervention of the rare ginsenoside drug composition, but it was still higher than that of the NC group, and the comparison between the two was p<0.01, which was statistically significant.
[0057] Example 3 In vivo therapeutic effect test of rare ginsenoside pharmaceutical composition
[0058] (1) Modeling: Rats were fed adaptively, and then 30 rats were randomly selected and divided into 5 groups, of which 6 rats were used as the control group (NC group). The other 24 rats were injected with cyclophosphamide (50 mg / kg / d) for 5 consecutive days. Then, the 24 rats were randomly divided into 4 groups, namely, the model group (CP group), the low-dose group (L-HTS group), the medium-dose group (M-HTS group) and the high-dose group (H-HTS group). The low-dose group (L-HTS group), the medium-dose group (M-HTS group) and the high-dose group (H-HTS group) were all treated with a rare ginsenoside drug composition with a ratio of 1:1 by gavage, and the gavage doses were 50 mg / kg / d, 150 mg / kg / d and 300 mg / kg / d, respectively. The control group (NC group) and the model group (CP group) were treated with normal saline as the drug by gavage, and the gavage dose was 150 mg / kg / d.
[0059] (2) Section detection: The ovarian tissues of the five groups of rats were placed in 4% paraformaldehyde for 24 h, and then dehydrated and embedded: the paraffin-embedded tissues were cut into 4 μm thick sections. After drying for 4 h, the sections were placed in xylene and gradient alcohol for dewaxing and dehydration. The sections were then stained with hematoxylin-eosin and observed under an inverted microscope. The sections of the ovarian tissues of the five groups of rats were as follows: Figure 5 As shown; the number of follicles in the slices was counted, and the proportion of growing follicles in rats and the ovarian index of rats were calculated, and then the relationship diagram of the effect of the dosage of the rare ginsenoside pharmaceutical composition on the proportion of growing follicles in rats and the ovarian index of rats was drawn, and the results were as follows: Figure 6 , Figure 7 shown.
[0060] (3) Hormone level detection: serum supernatants of 5 groups of rats were obtained, and the serum supernatants were treated with an Elisa kit. Then, the absorbance of the serum supernatants of each group at 450 nm was detected with an ELISA reader. The concentrations of three hormones, namely, estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in rats were calculated according to the software provided by the Elisa kit. Then, the relationship diagrams of the effects of the dosage of the rare ginsenoside drug composition on the levels of estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in rats were drawn. The results are as follows: Figure 8a , Figure 8b , Figure 8c shown.
[0061] See also Figure 5 and Figure 6 , respectively, are sections of rat ovarian tissue and a graph showing the effect of the dosage of the rare ginsenoside drug composition on the proportion of growing follicles in rats. Figure 5 It can be seen that in the CP group, the number of normal follicles decreased, the number of atretic follicles increased, the number of granulosa cell layers in the follicles decreased, and granulosa cell necrosis was obvious. After the intervention of the rare ginsenoside drug composition, the number of normal follicles increased and the number of atretic follicles decreased. Figure 6 It can be seen that compared with the CP group, the proportion of growing follicles in the L-HTS group, the M-HTS group, and the H-HTS group showed an increasing trend, that is, with the increase in the dosage of the rare ginsenoside drug composition, the number of growing follicles increased and the number of atretic follicles decreased; in addition, compared with the NC group, the proportion of growing follicles in the M-HTS group was basically the same as that in the NC group, and the proportion of growing follicles in the H-HTS group increased significantly, which was significantly higher than that in the NC group. Figure 5 and Figure 6 It can be seen that the addition of rare ginsenoside medicinal composition is beneficial to avoiding follicular atresia.
[0062] See also Figure 7 , is a graph showing the effect of the dosage of the rare ginsenoside drug composition on the ovarian index of rats. Figure 7 It can be seen that compared with the CP group, the ovarian indexes of the L-HTS group, the M-HTS group, and the H-HTS group showed an increasing trend, that is, as the dosage of the rare ginsenoside pharmaceutical composition increased, the ovarian index increased accordingly; in addition, compared with the NC group, the ovarian indexes of the M-HTS group and the H-HTS group were higher than that of the NC group.
[0063] See also Figure 8a , Figure 8b , Figure 8c , respectively, are the relationship diagrams of the effects of the dosage of the rare ginsenosides medicinal composition on the levels of estradiol (E2), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) in rats. Figure 8a It can be seen that, comparing the NC group and the CP group, after cyclophosphamide modeling, the concentration of estradiol (E2) hormone was significantly reduced, and the comparison between the two was p<0.01, which was statistically significant; comparing the CP group and the L-HTS group, the M-HTS group, and the H-HTS group, the concentration of estradiol (E2) hormone increased after the intervention of the rare ginsenoside drug composition, and with the increase in the dosage of the rare ginsenoside drug composition, the increase in estradiol (E2) hormone increased accordingly, but the three doses of the HTS group were lower than the NC group. Figure 8b It can be seen that, comparing the NC group and the CP group, the concentration of anti-Mullerian hormone (AMH) was significantly reduced after cyclophosphamide modeling, and the comparison between the two was p<0.01, which was statistically significant; comparing the CP group and the L-HTS group, the M-HTS group, and the H-HTS group, the concentration of anti-Mullerian hormone (AMH) was significantly increased after the intervention of the rare ginsenoside drug composition, and with the increase in the dosage of the rare ginsenoside drug composition, the increase in anti-Mullerian hormone (AMH) basically showed an increasing state, but it was still lower than the NC group. Figure 8c It can be seen that, comparing the NC group and the CP group, the concentration of follicle-stimulating hormone (FSH) was significantly increased after cyclophosphamide modeling, and the comparison between the two was p<0.01, which was statistically significant; comparing the CP group with the L-HTS group, the M-HTS group, and the H-HTS group, the concentration of follicle-stimulating hormone (FSH) was significantly reduced after the intervention of the rare ginsenoside pharmaceutical composition, and with the increase in the dosage of the rare ginsenoside pharmaceutical composition, the reduction in follicle-stimulating hormone (FSH) basically showed an increasing state, but it was still higher than that of the NC group.
[0064] Comprehensive analysis Figure 5 , Figure 6 , Figure 7 , Figure 8a , Figure 8b , Figure 8cWhen the raw material mass ratio of the rare ginsenoside pharmaceutical composition is 1:1, the intervention time is 24h, and rats are used as the administration subject, the dosage is preferably 150mg / kg / d.
[0065] The present invention also provides an application of a rare ginsenoside pharmaceutical composition, the application in preparing a drug for inhibiting, improving or treating premature ovarian failure, and the application in preparing a drug for promoting the proliferation of ovarian granulosa cells; when the rare ginsenoside pharmaceutical composition is used as a drug, the dosage thereof is 50 to 300 mg / kg calculated for mammals other than humans, and the dosage thereof is 50 to 300 mg / d calculated for adults; the use of the rare ginsenoside pharmaceutical composition as a drug includes oral or external use.
[0066] In summary, the present invention provides a rare ginsenoside pharmaceutical composition and its application. Through the synergistic effect of rare ginsenoside Rg5 and rare ginsenoside Rk1, the rare ginsenoside pharmaceutical composition has a significant effect of inhibiting, improving or treating premature ovarian failure, and can be used to prepare a drug for promoting the proliferation of ovarian granulosa cells, as well as preparing a drug for inhibiting, improving or treating premature ovarian failure. The present invention verifies the appropriate ratio of rare ginsenoside Rg5 and rare ginsenoside Rk1, so that the rare ginsenoside Rg5 and rare ginsenoside Rk1 show excellent synergistic effect in a weight ratio range of 1:3 to 3:1, so that the rare ginsenoside pharmaceutical composition has a significant effect of promoting the proliferation of ovarian granulosa cells, as well as the effect of inhibiting, improving or treating premature ovarian failure, and while exerting its effect, it improves the safety of medication, and can be widely used in the field of medical technology.
[0067] It should be noted that:
[0068] (1) Above Figure 3 , Figure 4a , Figure 4b , Figure 4c , Figure 6 , Figure 7 , Figure 8a , Figure 8b , Figure 8c In the table, * indicates comparison between the control group and the model group, where * indicates p<0.05, ** indicates p<0.01, # indicates comparison between the experimental group (HTS group, L-HTS group, M-HTS group, H-HTS group) and the model group, where # indicates p<0.05, ## indicates p<0.01.
[0069] (2) The methods used in the present invention are all conventional methods unless otherwise specified; the raw materials and devices used are all conventional commercially available products unless otherwise specified.
[0070] The embodiments described above are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, a person skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present application, and should all be included in the protection scope of the present application.
Claims
1. A rare ginsenoside pharmaceutical composition for inhibiting, improving or treating premature ovarian failure, characterized in that: It is composed of rare ginsenoside Rg5 and rare ginsenoside Rk1, wherein the weight ratio of rare ginsenoside Rg5 to rare ginsenoside Rk1 is 1:3 to 3:
1.
2. An application of the rare ginsenoside pharmaceutical composition according to claim 1, characterized in that: The rare ginsenoside pharmaceutical composition is used in preparing drugs for inhibiting, improving or treating premature ovarian failure.
3. The use of the rare ginsenoside pharmaceutical composition according to claim 2, characterized in that: The dosage of the rare ginsenoside pharmaceutical composition used as a medicine is 50-300 mg / kg / d, calculated based on mammals other than humans.
4. The use of the rare ginsenoside pharmaceutical composition according to claim 2, characterized in that: The dosage of the rare ginsenoside pharmaceutical composition used as a medicine is 50 to 300 mg / d, calculated based on adults.
5. The use of the rare ginsenoside pharmaceutical composition according to claim 2, characterized in that: The rare ginsenoside pharmaceutical composition is used as a medicine by oral administration.