USE OF CTH INHIBITOR AND / OR XCT INHIBITOR FOR PREPARATION OF DRUGS FOR INHIBITING EMBRYO IMPLANTATION IN MAMMALS
Patent Information
- Application Number
- NL4000240
- Authority / Receiving Office
- NL · NL
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-05-23
- Filing Date
- 2025-10-14
- Publication Date
- 2026-07-02
- Estimated Expiration
- 2045-10-13
Smart Images
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Abstract
Description
TECHNICAL FIELD The present invention relates to the field of medical technology, and more particularly to a use of a CTH inhibitor and / or an xCT inhibitor in preparation of a drug for inhibiting embryo implantation in mammals. BACKGROUND Contraception is an essential measure for women of reproductive age to regulate fertility. It holds considerable significance in mastering the timing of childbirth, safeguarding both physical and mental health, improving quality of life, maintaining family stability, and at a broader level, regulating population growth, optimizing population structure, and promoting the sustainable development of society. Traditional contraceptives are generally classified into short-acting and long-acting contraceptives. Long-acting contraceptives, once administered, are difficult to regulate through human intervention. There prolonged pharmacological activity continuously affects the reproductive system of female mammals and may induce potentially irreversible adverse outcomes, including endocrine dysregulation impaired reproductive function.Due to these limitations, the clinical use of long-acting contraceptives has become increasingly restricted. In contrast, short-acting contraceptives offering flexible modulation, have emerged as a more widely adopted alternative. Currently, the short-acting contraceptives rely on hormponents, and frequent administration within a short timeframe may lead to undesirable side effects, such as early pregnancy-like reactions (e.g., nausea, fatigue) and menstrual cycle disorders. Therefore, current short-acting contraceptive stategegies still have room for improvement in terms of safety, convenience and comfort, and developing a new generation of innovative contraceptive methods with high efficacy and minimal adverse effects has become an important topic in the field of public health. Accordingly, the present invention is proposed. SUMMARY The objective of the present invention is to verify the use effect of cystathionine-y-lyase (CTH) inhibitors and solute carrier family 7 member 11 (xCT) inhibitors in inhibiting embryo implantation in mammals through experimental research, and, on this basis, to promote the research, development, and clinical translation of novel contraceptive drugs in mammals are explored. Thereby the invention provides new strategies and methodologies for contraceptive drug development. To achieve the above objective,the invention adopts the following technical solution: According to one aspect of the present invention, there is provided an use of a CTH inhibitor and / or an xCT inhibitor in the preparing of a medicament for inhibiting embryo implantation in mammals. The use of the CTH inhibitor and / or the xCT inhibitor in the preparing of the medicament for inhibiting embryo implantation in mammals is provided by the present invention, the inhibiting embryo implantation in mammals means that the CTH inhibitor and / or xCT inhibitor inhibits embryo implantation by impairing follicular ovulation, oocyte maturation and luteal function in mice. The application verifies the use effect of the cystathionine-y-lyase (CTH) inhibitor and the solute carrier family 7 member 11 (xCT) inhibitor in inhibiting embryo implantation in mammals through research, and through the research experiments, it is concluded that: First, administration of the xCT inhibitor and / or the CTH inhibitor may significantly inhibit the proliferation of luteinized granulosa cells in mice and reduces progesterone secretion; Second, by intraperitoneally injecting the xCT inhibitor and / or CTH inhibitor into a mouse model, it may markedly suppresses ovarian ovulation and the nuclear maturation rate of the ovulated oocytes; Finally, the present invention verifies the effect of the above xCT inhibitor and / or the above CTH inhibitor in preventing the formation of functional corpus luteum and embryo implantation. Therefore, the present application provides new strategies and methodologies for the development of contraceptive drugs, and is of great significance for accurately regulating the microenvironment of embryo implantation and achieving safe and effective contraceptive intervention. Specifically, the present use relates to the following: 1. The use of the CTH inhibitor alone in preparing drugs for inhibiting embryo implantation in mammals; 2. The use of the xCT inhibitor alone in preparing drugs for inhibiting embryo implantation in mammals; 3. The use of the CTH inhibitor and the xCT inhibitor synergistic in preparing drugs for inhibiting embryo implantation in mammals. In an embodiment, the inhibiting embryo implantation in mammals means that the CTH inhibitor and / or the xCT inhibitor inhibits embryo implantation by impairing follicular ovulation, oocyte maturation, and corpus luteal function in mice. In an embodiment, the CTH inhibitor includes at least one of DL-propargylglycine, hydroxylamine, B-cyano-L-alanine and aminooxyacetic acid, preferably aminooxyacetic acid. In an embodiment, the xCT inhibitor includes at least one of sorafenib, HG106, SLC7A11- lN-2, erastin, and sulfasalazine, preferably sulfasalazine. In an embodiment, the mammals include humans, cynomolgus monkeys, sika deer, pigs, cattle, sheep, mice, and other animals, optionally mice. According to one aspect of the present invention, there is provided a contraceptive drug for use in mammals, where the contraceptive drug includes a CTH inhibitor and / or an xCT inhibitor. In an embodiment, the administration dosage of the CTH inhibitor used alone is 25-40 mg / kg. The administration dosage of the xCT inhibitor used alone is 25-100 mg / kg. In an embodiment, the administration dosage for the combined use of the CTH inhibitor and the xCT inhibitor is 25 mg / kg of the CTH inhibitor and 25 mg / kg of the xCT inhibitor. In an embodiment, the drug is formulated as an injectable preparation. Optionally, the unit dosage of the CTH inhibitor in the injection is 25-40 mg / ml, and the unit dosage of the xCT inhibitor in the injection is 25-100 mg / ml. Compared with the prior art, the beneficial effects of the present invention are as follows. The present invention verify the use effective of a cystathionine-y-lyase (CTH) inhibitor and a solute carrier family 7 member 11 (xCT) inhibitor in inhibiting embryo implantation in mammals through experimental research. The experimental results indicate that: on one hand, the xCT inhibitor and / or the CTH inhibitor markedly suppresses the proliferation of luteinized granulosa cells in mice and significantly reduces progesterone secretion; on the other hand, by in vivo injection administration of the xCT inhibitor and / or CTH inhibitor in a mouse model, not only significantly inhibit ovarian ovulation and the nuclear maturation rate of the ovulated oocytes, but also prevent the formation of functional corpus luteum and embryo implantation. lmportantly, on the premise without the requirement of exogenous hormonal supplementation, the present invention achieves effectively inhibits follicular ovulation, oocyte maturation, and corpus luteum function through structure inhibitors xCT / CTH protein. The embryo implantation is suppressed via multiple pathways, thereby achieving a contraceptive effect. Furthermore, the frequency and interval of administration may be optimized to minimize potential adverse effects associated with the inhibitors. Therefore, the present invention provides new strategies and methodologies for the development of contraceptive drugs, and is of substantial significance in precisely regulating microenvironment of embryo implantation, thereby safe and effective contraceptive intervention. BRIEF DESCRIPTION OF THE FIGURES In order to more clearly illustrate the specific embodiments of the present invention or the technical schemes of the prior art, the accompanying drawings referred to in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described herein represent only certain embodiments of the present invention, and and that other drawings may be derived therefrom by those skilled in the art without the exercise of inventive effort. Fig. 1 is a schematic diagram illustrating the effect of an xCT inhibitor and / or CTH inhibitor on inhibiting the proliferation of luteinized granulosa cells, as demonstrated in Embodiment 1 of the present invention; Fig. 2 is a schematic diagram illustrating the effect of an xCT inhibitor and / or CTH inhibitor on suppressing progesterone secretion in luteinized granulosa cells, as demonstrated in Embodiment 1 of the present invention; Fig. 3 is a flowchart illustrating the prevention of follicular ovulation and corpus luteum formation by intraperitoneally injecting of xCT inhibitor and / or a CTH inhibitor in mice, as demonstrated in Embodiment 2 of the present invention; Fig. 4 is a a schematic diagram illustrating the effect of an xCT inhibitor and / or a CTH inhibitor on impairing follicular ovulation per mouse, 3 demonstrated in Embodiment 2 of the present invention; Fig. 5 is a schematic diagram illustrating the effect of xCT inhibitor and / or a CTH inhibitor the nuclear maturation of mouse oocytes, as demonstratedin Embodiment 2 of the present invention; Fig. 6 is a schematic diagram illustrating the effect of xCT inhibitor and / or a CTH inhibitor on impairing histone methylation and disrupting meiotic spindle assembly in in Mll oocytes as demonstrated in Embodiment 2 of the present invention; Fig. 7 is a schematic diagram illustrating the effect of an xCT inhibitor and / or a CTH inhibitor on impairing corpus luteum formation and progesterone secretion in mice, as demonstrated in Embodiment 2 of the present invention; Fig. 8 is a flowchart illustrating the blocking of embryo implantation in mice by in vivo injection of an xCT inhibitor and / or a CTH inhibitor, as demonstratedin Embodiment 2 of the present invention; Fig. 9 is a schematic diagram illustrating the effect of xCT inhibitor and / or CTH inhibitor on impairing embryo implantation in mice, as demonstrated in Embodiment 2 of the present invention. DESCRIPTION OF THE INVENTION The technical solutions of the present invention will be described clearly and completely below with reference to the embodiments. Obviously, the embodiments described herein are provided merely as examples, and do not represent the entirety of possible embodiments. Based on the disclosed embodiments, other embodiments that may be conceived by those of ordinary skill in the art without the exercise of inventive effort shall fall within the protection scope of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meanings as commonly understood by those of ordinary skill in the technical field. The terminology employed in the description of the present invention is intended solely for the purpose of describing specific embodiments, and is not to be construed as limiting the present invention. The experimental animals employed in the following embodiments of the present invention were SPF-grade ICR mice, obtained from Liaoning Changsheng Biotechnology Co., Ltd. The animals were maintained under controlled environmental conditions, with the ambient temperature set at 2226 °C, and were provided ad libitum access to food and water. All animal procedures were conducted in compliance with the relevant regulations of the Animal Welfare and Ethics Committee of the Special Animal Research Institute, Chinese Academy of Agricultural Sciences. Embodiment 1: Inhibition of xCT and CTH Suppresses proliferation and progesterone secretion of luteinized granulosa cells Fig. 1 schematic diagram illustrating the effect of the xCT inhibitor and / or CTH inhibitor on the proliferation of granulosa cells as described in the present embodiment. The data statistical analysis is performed by one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the bar chart indicate significant differences (P<0.05), and the same letters indicate no significant differences (P>0.05). Fig. 2 schematic diagram illustrating the effect of xCT inhibitor and / or CTH inhibitor on reducing progesterone secretion in granulosa cells as disclosed in the present embodiment. The data statistical analysis is performed by one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the bar chart indicate significant differences (P<0.05), and the same letters indicate no significant differences (P>0.05). In present embodiment, the effects of blocking the functions of the target proteins by administering specific inhibitors of xCT and CTH, either separately or in combination, on the proliferation of luteinized granulosa cells and progesterone synthesis are verified. The specific methodologies are described as follows: (1) Primary granulosa cell culture in vitro: Female ICR mice aged 21-23 days are administered intraperitoneally injection of pregnant mare serum gonadotropin (PMSG, 5 lU / mouse) to induce follicular development. After 48 hours, the mice are euthanized by cervical dislocation. Bilateral ovaries are aseptically excised, and excess adipose tissue and mesentery are carefully removed using ophthalmic scissors under a stereomicroscope. The ovaries are subsequently washed three times with phosphate-buffered saline PBS supplemented with penicillin and streptomycin, and then transferred into DMEM / F12 basic medium. Follicular puncture is performed using a 1 mL syringe to release granulosa cells into the medium. the resulting cell suspension is filtered through a 40 um cell resulting to remove oocytes, cumulus-oocyte complexes (COCs), and tissue fragments. The filtered is collected into a 15 mL centrifuge tube and centrifuged at 300 x 9 for 5 minutes, after which the supernatant is discarded. Red blood cell lysis is performed by adding a threefold volume of erythrocyte lysis buffer and incubating at room temperature for 1 minute. The suspension is Centrifugation is centrifuged again at 300 x 9 for 5 minutes, and the supernatant is removed. The removed cell pellet is resuspended in PBS and subjected to centrifugation at 300 x 9 for 5 minutes, with this washing step repeated three times. Cell viability is assessed by trypan blue exclusion. When the viability exceeds 90%, the isolated murine granulosa cells are seeded into culture dishes or multiwell plates at a density of 3 >< 105 cells / mL in complete medium (DMEM / F12 supplemented with 10% fetal bovine serum and 50 U / mL penicillinstreptomycin). The cultures are maintained in a humidified incubator at 37°C under 5% COZ atmosphere. (2) When the confluency of the primary granulosa cells cultured in vitro reaches approximately 60%-70%, the culture medium is replaced with an incomplete medium (DMEM / F12 + 50 U / mL penicillin and streptomycin), and xCT inhibitors sulfasalazine (SSZ; 400 uM), erastin (20 uM), and CTH inhibitor aminooxyacetic acid (AOAA; 3 mM) are added. Experimental groups are established, including single-agent treatment groups and combination treatment groups from SSZ+AOAA and Erastin+AOAA. After 24 hours of treatment then the medium is replaced with incomplete medium supplemented with 20 nM PMA and 10 ulVl forskolin, and the cells are further incubated for 8 hours to induce luteinization of granulosa cells. Thereafter, the proliferation of luteinized granulosa cells and the progesterone content are detected, respectively. The experimental groups are defined as follows: SSZ single-agent treatment group: 400 ulVl SSZ is added alone to the incomplete medium; AOAA single-agent treatment group: 3 mM AOAA is added alone to the incomplete medium; Erastin single-agent treatment group: 20 uM Erastin is added alone to the incomplete medium; SSZ+AOAA combination group: 400 uM SSZ and 3 mM AOAA are added in combination to the incomplete medium; Erastin+AOAA combination group: 20 ulVl Erastin and 3 mM AOAA are added in combination to the incomplete medium. The corresponding test results are presented in Figs. 1 and 2. As illustrated in Fig. 1, the single-drug treatment with SSZ, Erastin, or AOAA all significantly reduces the proliferation of luteinized granulosa cells. Moreover, the inhibitory effects observed in the SSZ+AOAA and Erastin+AOAA combined treatment groups were significantly greater than that those in the SSZ or Erastin single-drug treatment groups, whereas no significant difference from the inhibitory effect of the AOAA single-drug treatment. As illustrated in Fig. 2, the single-drug treatment with SSZ, Erastin, or AOAA significantly reduces the progesterone secretion in luteinized granulosa cells; the inhibitory effect observed in of the SSZ+AOAA and Erastin+AOAA combined treatment groups is significantly greater than that those in the Erastin single-drug treatment group, but showed no significant difference when compared with the inhibitory effects of the SSZ and AOAA single-drug treatment. These results suggesting that xCT and CTH regulate the proliferation and progesterone secretion of luteinized granulosa cells through a common signaling pathway. Embodiment 2: in vivo inhibition of xCT and CTH to impair oocyte maturation, corpus luteum formation, and embryo implantation Fig. 3 is a flow chart illustrating the inhibition of follicular ovulation and corpus luteum formation in mice by in vivo administration of xCT and / or CTH inhibitor, as provided in this Embodiment; Fig. 4 is a schematic diagram illustrating the effect of xCT and / or CTH inhibitor on follicular ovulation in mice, as provided in this Embodiment; The data statistical analysis is performed by one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the scatter plot indicate significant differences (P<0.05), and the same letters indicate no significant differences (P>0.05). Fig. 5 is a schematic diagram illustrating the effect of xCT and / or CTH inhibitor on the nuclear maturation of mouse oocytes, as provided in this embodiment; The data statistical analysis is performed by one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different uppercase letters marked above the scatter plot indicate extremely significant differences (P<0.01), and the same letters indicate no significant differences (P>0.05). Fig. 6 is a schematic diagram illustrating the effect of xCT and / or CTH inhibitor on histone methylation and meiotic spindle structure in mature mouse mice oocytes, as provided in this embodiment; Where Fig. 6A is a representative image of H3K4me3 immunofluorescence staining following in vivo administration of xCT and / or CTH inhibitors, where red represents H3K4me3; green represents cx-tubulin; and blue represents DNA. Scale bar: 10 pm; Fig. 6B is a statistical analysis diagram of differences in H3K4me3 fluorescence intensity; Fig. 6C is a representative image of H3K9me3 immunofluorescence staining in mature oocytes following in vivo administration of inhibitors, where red represents H3K9me3; green represents d-tubulin; and blue represents DNA. Scale bar: 10 pm; Fig. 6D is a statistical analysis diagram of differences in H3K9me3 fluorescence intensity;Fig. 6E is a statistical analysis diagram of abnormal meiotic spindle assembly in mature oocytes induced by in vivo injection of inhibitors; statistical analysis for Fig. 6B, Fig. 6D, and Fig. 6E is performed using one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the scatter plots and bar charts indicate significant differences (P<0.05), whereas identical letters indicate no significant differences (P>0.05). Fig. 7 is a schematic diagram illustrating the effect of xCT and / or CTH inhibitor on corpus luteum formation and progesterone secretion in mice,as provided in this embodiment; Where Fig. 7A is a representative image of abnormal ovulation sites (also referred to as early corpus rubrum) in the ovaries caused by in vivo injection of inhibitors, red arrows represent abnormal ovulation sites in ovarian tissue, scale bar: 10 mm; Fig. 7B is a quantitative analysis diagram of abnormal ovulation points induced by different treatments; Fig. 7C is a quantitative analysis diagram of changes in serum progesterone levels following in vivo injection of inhibitors; data statistical analysis in Fig. 7B and Fig. 7C is performed by one-way analysis of variance (One- way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the bar charts indicate significant differences (P<0.05), and the same letters indicate no significant differences (P>0.05). Fig. 8 is a flow chart illustrating the blocking of embryo implantation in mice induced by in vivo administration of xCT / CTH inhibitor provided in this embodiment; Fig. 9 is a schematic diagram illustrating the effect of xCT inhibitor and / or CTH inhibitor on impairing embryo implantation in mice provided in this embodiment; Where in Fig. 9A presents a representative image showing the effect of in vivo administration of inhibitors on embryo implantation,with red arrows indicating implantation sites in uterine tissue, scale bar: 10 mm; in Fig. 9, B presents a quantitative analysis diagram illustrating embryo implantation failure caused under different treatments conditions; data statistical analysis is performed by one-way analysis of variance (One-way ANOVA) and Tukey's test for multiple comparisons. Different lowercase letters marked above the scatter plot indicate significant differences (P<0.05), and the same letters indicate no significant differences (P>0.05). (1) In this Embodiment, mice are used as model organisms to evaluate the effects of xCT and CTH inhibitors on impairing follicular ovulation, oocyte maturation, corpus luteum formation, and embryo implantation. It should be emphasized that mice, as widely recognized experimental animals in human disease research and drug development, exhibit significant structural and function similarities in their reproductive systems to those of humans, while also possessing the advantage of a short reproductive cycle. In the present study, mice were therefore selected to assess both the efficacy and safety of the candidate contraceptive agents. The resulting data provide essential experimental evidence supporting the translational potential of these inhibitors for human contraceptive applications, thereby offering valuable reference significance for the future development and clinical transformation of novel contraceptive technologies. In this embodiment, sexually mature female mice aged 8-10 weeks are selected, each mouse receives an intraperitoneally injected of cloprostenol (PG) at a dose of 0.1 mg / mouse to induce luteolysis. To dissolve the corpus luteum. After 16 hours, pregnant mare serum gonadotropin (PMSG) is administered at a close of 5 lU / mouse to stimulate to follicular development. After 48 hours, human chorionic gonadotropin (hCG) is administered at a dose of 5 lU / mouse to trigger follicular ovulation. Simultaneously, at the time of PMSG administration, a CTH inhibitor and / or xCT inhibitor is administered, and the specific experimental treatment groups are defined as follows: CTH inhibitor group: 25 mg / kg AOAA is administered alone; xCT inhibitor group: 25 mg / kg SSZ is administered alone; combined administration group: 25 mg / kg SSZ and 25 mg / kg AOAA are administered simultaneously. For all of the above groups, The route of administration is intraperitoneal injection, and the administration is repeated every 48 hours. (2) 12 hours following hCG injection, oocytes are collected for the ovulation rate and oocyte nuclear maturation status; 2 days following hCG injection, mouse serums and ovaries tissues are harvested to assess the effects of the inhibitors on progesterone secretion and corpus luteum formation, and the specific experimental process is schematically illustrated in Fig. 3. Meanwhile, as demonstrated in the results of Fig. 4, the number of ovulations in the AOAA group and SSZ group is significantly reduced compared with the control group, whereas the combined treatment of AOAA and SSZ exhibits a pronounced inhibitory effect. Further statistics analysis on the oocyte nuclear maturation rate indicates that, compared with the control group, the nuclear maturation rate in the AOAA group and SSZ group is significantly reduced, whereas the combined AOAA and SSZ inhibition group demonstrates the lowest maturation rate, and the detailed results are detailed in Fig. 5. (3) In this embodiment, immunofluorescence analysis was conducted on the Mil-stage mature oocytes in the control group, AOAA treatment group, and SSZ treatment group. Compared with the control group, the modification level of histone H3 lysine 4 trimethylation (H3K4me3) in the AOAA or SSZ treatment group is significantly reduced, and the corresponding results are presented in Fig. 6A and Fig. 68. Meanwhile, AOAA or SSZ treatment may also reduce the modification level of histone H3 lysine 9 trimethylation (H3K9me3), and The corresponding are presented in Fig. 6C and Fig. 6D. In Combination with cx-tubulin immunofluorescence staining, it was observed that,compared with the control group, the incidence of abnormal meiotic spindles in oocytes of the AOAA or SSZ treatment group was significantly increased, as shown in Fig. 6E. The results show that even if the oocytes undergo nuclear maturation after AOAA or SSZ treatment, they are accompanied by abnormal epigenetic modification and abnormal meiotic spindle organization. It is worth noting that the AOAA and SSZ combined inhibition group inhibits follicular ovulation and oocyte nuclear maturation, so the effect of the AOAA and SSZ combined inhibition group on histone modification and meiotic spindle assembly might not be detected. Ovaries and serum of each treatment group were collected 2 days after hCG injection. Compared with the control group, intraperitoneal administration of AOAA or SSZ , either alone or in combination significantly increase the incidence of abnormal ovulatory structures, including follicles exhibiting hyperemia without rupture and follicles arrested at the corpus hemorrhagicum stage. the detailed results are presented in Fig. 7A and Fig. 7B. lntraperitoneal administration of AOAA and SSZ, administration alone or in combination, significantly reduced the serum progesterone levels, as shown in Fig. 7C. This suggests that luteal function is impaired, and xCT and CTH affect female reproduction by regulating both ovulation and luteal function. (4) To investigate the effect of xCT and CTH inhibitors on embryo implantation, in mice, sexually mature female mice aged 8-10 weeks are selected, and 0.1 mg / mouse of PG is intraperitoneally injected to induce corpus luteum regression. After 16 hours, 5 lU / mouse of PMSG is injected, and 48 hours later, 5 lU / mouse of hCG is injected to induce synchronized estrus. After hCG administration, the female mice are paired with males, and the next morning, if a vaginal plug is found, it is recorded as gestation day 0.5 (GD 0.5). Meanwhile, the CTH inhibitor and / or xCT inhibitor is administered when PMSG is injected, and the specific administration groups are as follows: CTH inhibitor group: 25 mg / kg of AOAA was administered alone; xCT inhibitor group: 25 mg / kg of SSZ was administered alone; combined administration group: 25 mg / kg of SSZ and 25 mg / kg of AOAA were administered simultaneously. The administration route of the above administration groups is intraperitoneal injection, and the administration is repeated every 48 hours for a total of 4 administrations. On gestation day 5.5 (GD 5.5), 0.5 mg / mouse of Chicago sky blue dye was injected via the tail vein to visualize uterine implantation sites, then the mice are sacrificed to collect the uterus and count the number of implantation sites, and the specific process is illustrated in Fig. 8. The results demonstrate that compared with the control group, the AOAA group and SSZ group significantly reduce the number of embryo implantation sites by 65.0% and 49.7% respectively, while the combined administration of AOAA and SSZ completely inhibited embryo implantation, and the detailed results are presented in Fig. 9. Finally, it should be noted that the above embodiments are provided solely to illustrate the technical solutions of the present invention and are not intended to limit the scope thereof. Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that various modifications may be made to the technical solutions disclosed therein, or that some or all of the technical features may be substituted with alternative elements. Such modifications or substitutions do not depart from the essential scope of the technical solutions of the embodiments of the present invention.
Claims
1. Use of a CTH inhibitor and / or an xCT inhibitor in the preparation of a pharmaceutical composition for inhibiting embryo implantation in mammals.
2. Application pursuant to Conclusion 1, involving the inhibition of embryo implantation in mammals relates to inhibition by the CTH inhibitor and / or xCT inhibitor of the follicular ovulation, oocyte maturation, and luteal function in mice to inhibit embryo implantation reaches.
3. Application of claim 1, where the CTH inhibitor is at least one of DL-propargylglycine, comprises hydroxylamine, β-cyano-L-alanine and amino-oxyacetic acid, preferably amino- oxyacetic acid 4. The use in accordance with claim 1, whereby the xCT inhibitor is at least one of sorafenib, HG106, SLC7A11-IN-2, comprises erastine and sulfasalazine, preferably sulfasalazine.
5. A pharmaceutical composition for contraception for use in mammals, where the composition includes the CTH inhibitor and / or the xCT inhibitor.
6. The pharmaceutical composition for contraception in mammals according to conclusion 5, where the administration dose of the CTH inhibitor is only 25-40 mg / kg; and the the administration dose of the xCT inhibitor alone is 25-100 mg / kg.
7. The pharmaceutical composition for contraception in mammals according to conclusion 5, where the administration dose for combined use of the CTH inhibitor and the xCT inhibitor is: 25 mg / kg of the CTH inhibitor and 25 mg / kg of the xCT inhibitor.
8. The pharmaceutical composition for contraception in mammals according to conclusion 5, where the composition is formulated as an injectable preparation.
9. The contraceptive pharmaceutical composition in mammals according to claim 8, where the unit dose of the CTH inhibitor in the injectable preparation is 25-40 mg / ml; and the unit dose of the xCT inhibitor in the injectable preparation is 25-100 mg / ml.