Application of lecithin in the preparation of drugs for the prevention and / or treatment of infertility

Abstract

This invention provides the application of lecithin in the preparation of drugs for the prevention and / or treatment of infertility, belonging to the field of biomedical preparation technology. Specifically, it relates to the application of lecithin in the preparation of drugs for the prevention and / or treatment of infertility, recurrent miscarriage, and / or uterine decidualization disorders. The lecithin can effectively reduce TNF-α levels in early pregnancy, improve uterine decidualization disorders, and increase endometrial receptivity, thereby increasing pregnancy rates and providing a new approach for the treatment of infertility and recurrent miscarriage.

Description

Technical Field

[0001] This application belongs to the field of biomedical preparation technology, specifically relating to the application of lecithin in the preparation of drugs for the prevention and / or treatment of infertility. Background Technology

[0002] Clinically, successful pregnancy in placental mammals (including humans) depends on maternal immune tolerance to a semi-allocarcinoma fetus. In the first few weeks of pregnancy, the maternal decidua is a crucial site for interaction between maternal leukocytes and fetal trophoblast cells. Insufficient recognition of fetal antigens can lead to implantation failure or pregnancy maintenance failure. The decidualization process is accompanied by unique recruitment and functional changes in immune cells. Abnormalities in the number or function of these immune cells can lead to an "attack" or "rejection" of the embryo, disrupting the decidualized microenvironment.

[0003] Female-related infertility includes endocrine disorders, abnormal immune regulation, impaired endometrial receptivity, and insufficient uterine blood flow. In cases of recurrent implantation failure (IIF), abnormal immune regulation directly causes or contributes to approximately 20%–40% of cases, and this percentage is even higher in the most difficult-to-treat patients. A characteristic of female immunological infertility is that it may involve a response to the partner's sperm (alloimmunity) or a response to the woman's own eggs or embryo (autoimmunity). Common methods to improve clinical pregnancy rates include assisted reproductive technology (ART), hormone therapy, traditional Chinese medicine, and TNF-α inhibitors. With increasing female age, the success rate of embryo implantation in ART significantly decreases; the efficacy of hormone therapy has not been clinically validated; while traditional Chinese medicine has been clinically proven to improve clinical pregnancy rates, its effects are limited, and its formulas contain hepatotoxic ingredients such as Polygonum multiflorum (He Shou Wu); early pregnancy exposure to TNF-α inhibitors may increase the risk of major birth defects. Summary of the Invention

[0004] This invention provides a new use for lecithin, namely, its application in the preparation of drugs for the prevention and / or treatment of infertility, which improves pregnancy rates by regulating endometrial receptivity, and is healthy, safe and free of toxic side effects.

[0005] This invention provides the use of lecithin in the preparation of medicaments for the prevention and / or treatment of infertility, recurrent miscarriage and / or uterine decidualization disorders.

[0006] Preferably, the lecithin comprises the following mass percentages: 10%~40% phosphatidylcholine, 5%~20% phosphatidylserine, 5%~30% phosphatidylethanolamine and 2%~20% phosphatidylinositol.

[0007] Preferably, the lecithin comprises the following metabolizable fatty acids in weight percentages: 4%~60% linoleic acid, 2%~25% α-linolenic acid, 2%~25% palmitic acid, 2%~25% oleic acid, 2%~10% stearic acid and 0.1%~2% myristic acid.

[0008] Preferably, the infertility or recurrent miscarriage includes those caused by obesity.

[0009] Preferably, the infertility includes decreased maternal reproductive function and / or reproductive dysfunction.

[0010] Preferably, the uterine decidualization disorder includes elevated levels of the inflammatory factor TNF-α and abnormal changes in the morphology and number of decidual tissue cells.

[0011] Preferably, the uterine decidualization disorder includes lipopolysaccharide-induced formation.

[0012] Preferably, the drug has at least one of the following pharmacological effects: reducing the risk of miscarriage, increasing the pregnancy rate, increasing the number and condition of embryos, and increasing placental weight.

[0013] Preferably, the drug comprises at least one of the following dosage forms: tablets, capsules, powders, oral liquids, dry suspensions, pills, and granules.

[0014] Preferably, the lecithin content in the drug is 1% to 99% by mass.

[0015] This invention provides the application of lecithin in the preparation of drugs for the prevention and / or treatment of infertility, recurrent miscarriage, and / or uterine decidualization disorders. This invention conducted a pharmacodynamic evaluation of lecithin in a high-fat diet (HFD)-induced animal model. HE staining results showed that lecithin intervention improved the damage of uterine decidualization disorders in the model animals, specifically maintaining the morphology and arrangement of decidual tissue cells and preserving their activity. Pregnancy index detection results showed that, compared with the model group, the lecithin intervention group not only significantly reduced the average number of embryos resorbed and the risk of miscarriage, but also significantly increased the pregnancy rate, the number of intact unresorbed embryos, and the average total placental weight per animal. This indicates the role of lecithin intervention in improving reproductive function. Furthermore, the efficacy of lecithin in a lipopolysaccharide-induced decidualization disorder model animal was evaluated. HE staining showed that lecithin intervention improved LPS-induced decidualization disorder. Compared with the model group, lecithin intervention significantly improved embryonic development and alleviated uterine congestion in pregnant animals, indicating a reduction in miscarriage risk. It also restored embryonic color and volume to normal levels, effectively curbed the pathological manifestations of blastocyst atrophy and dissolution, significantly reduced embryo resorption rate, and decreased the levels of the inflammatory factor TNF-α in placental tissue and serum. These experimental results demonstrate that lecithin effectively improves maternal fertility, alleviates decidualization disorder, enhances endometrial receptivity, and ultimately increases pregnancy rate. Moreover, lecithin has no toxic side effects and exhibits good pharmaceutical safety. Attached Figure Description

[0016] Figure 1 The statistical results for the determination of lecithin components are as follows: DG: diacylglycerol; OAFHA: O-acyl-ω-hydroxy fatty acid; PA: phosphatidic acid; PC: phosphatidylcholine; PE: phosphatidylethanolamine; PG: phosphatidylglycerol; PI: phosphatidylinositol; PS: phosphatidylserine; TG: triglycerides; Other: other components. Figure 2 The image shows the base peak chromatogram of lecithin, where (top image) represents positive ion mode and (bottom image) represents negative ion mode. Figure 3 Changes in body weight (a) and energy intake (b) during the 12-week mouse modeling period; Figure 4 HE staining image of decidual tissue from c57BL / 6J mice (day 12.5 of gestation); Figure 5 The results of observation of uterine tissue in mice (day 12.5 of gestation); Figure 6 Results of weight changes in mice during pregnancy; Figure 7 HE staining image of decidual tissue from the control group mice; Figure 8 HE staining image of decidual tissue from a model mouse uterus; Figure 9 HE staining image of decidual tissue from mice in the lecithin intervention group; Figure 10 The results of uterine observation in the control group of pregnant mice; Figure 11 Results of uterine observation in pregnant mice in the LPS model group; Figure 12 The results of observation of the uterus in pregnant mice in the lecithin intervention group. Detailed Implementation

[0017] This invention provides the use of lecithin in the preparation of medicaments for the prevention and / or treatment of infertility, recurrent miscarriage and / or uterine decidualization disorders.

[0018] In this invention, the lecithin preferably comprises the following mass percentages: 10%~40% phosphatidylcholine, 5%~20% phosphatidylserine, 5%~30% phosphatidylethanolamine and 2%~20% phosphatidylinositol; it may also comprise 11%~30% phosphatidylcholine, 6%~15% phosphatidylserine, 5.1%~20% phosphatidylethanolamine and 3%~15% phosphatidylinositol; or it may comprise 11.29% phosphatidylcholine, 7.43% phosphatidylserine, 5.12% phosphatidylethanolamine and 3.27% phosphatidylinositol.

[0019] The lecithin preferably comprises the following metabolizable fatty acids in the following weight percentages: 4%~60% linoleic acid, 2%~25% α-linolenic acid, 2%~25% palmitic acid, 2%~25% oleic acid, 2%~10% stearic acid and 0.1%~2% myristic acid; it can also be 6%~30% linoleic acid, 2.5%~15% α-linolenic acid, 3%~15% palmitic acid, 3%~15% oleic acid, 3%~8% stearic acid and 0.2%~1% myristic acid; or it can be 7.8% linoleic acid, 3.4% α-linolenic acid, 3.3% palmitic acid, 3.4% oleic acid, 3.5% stearic acid and 0.4% myristic acid.

[0020] In this invention, the infertility or recurrent miscarriage preferably includes those caused by obesity. In an embodiment of this invention, the obesity is induced by a high-fat diet.

[0021] In this invention, the infertility preferably includes decreased maternal reproductive function and / or reproductive dysfunction. Decreased maternal reproductive function includes at least one of the following: maternal decidualization disorder, decreased endometrial receptivity, and maternal ovulation dysfunction. Maternal reproductive dysfunction includes maternal endometrial implantation disorder.

[0022] In this invention, the uterine decidualization disorder preferably includes elevated levels of the inflammatory factor TNF-α and abnormal changes in the morphology and number of decidual tissue cells. Elevated levels of the inflammatory factor TNF-α are a significant factor affecting pregnancy rates. Elevated TNF-α levels disrupt endometrial receptivity, inhibit the expression of endometrial epithelial cell adhesion molecules (such as LIF and integrin), leading to embryonic failure and implantation failure. Simultaneously, elevated TNF-α levels inhibit uterine decidualization, suppressing genes related to stromal cell decidualization, resulting in poor decidual development, insufficient angiogenesis, and insufficient nutrition and support for the embryo, leading to implantation failure and early miscarriage. Furthermore, as an inflammatory factor, TNF-α can induce a systemic inflammatory environment, activating NK cells and macrophages, producing more inflammatory factors. The maternal immune system rejects the embryo as a "foreign object," manifesting as recurrent implantation failure and recurrent miscarriage. High levels of TNF-α can also damage the embryo and oocytes, inducing embryonic cell apoptosis, leading to embryonic developmental arrest and increased fragmentation. In addition, TNF-α affects ovarian function and ovulation.

[0023] In this embodiment of the invention, the uterine decidualization disorder preferably includes lipopolysaccharide (LPS)-induced formation. Although LPS-induced animals did not exhibit significant weight gain, they still developed uterine decidualization disorder. Simultaneously, the model animals showed embryonic degenerative changes and exhibited a typical tendency to miscarry. Furthermore, the levels of TNF-α in the placental tissue and serum of the model animals were high, explaining the deterioration of embryonic development and increased embryo resorption rate, thus reducing the pregnancy rate.

[0024] In this invention, the drug preferably has at least one of the following pharmacological effects: reducing the risk of miscarriage, increasing the pregnancy rate, increasing the number and condition of embryos, and increasing placental weight.

[0025] In the embodiments of the present invention, whether in the obesity-induced infertility model or the uterine decidualization disorder model, administration of lecithin reversed the morphology and number of decidual cells, increased the number and quality of embryos, reduced the risk of miscarriage, and lowered the level of the inflammatory factor TNF-α.

[0026] In this invention, the drug preferably comprises at least one of the following dosage forms: tablets, capsules, powders, oral liquids, dry suspensions, pills, and granules. This invention does not impose any particular limitation on the type of drug; any preparation method for a drug dosage form well-known in the art can be used. The mass percentage of lecithin in the drug is preferably 1% to 99%, can be 5% to 90%, can be 10% to 80%, further can be 20% to 70%, and can be further 30% to 50%. The drug of this invention also includes pharmaceutically acceptable excipients. The selection of excipients is conventional and depends on the dosage form of the drug.

[0027] In this invention, the drug is suitable for use during preconception or early pregnancy. The preferred method of administration is oral. The dosage is based on the recommended dosage of lecithin. The recommended human dosage of lecithin is 0.02g-0.10g / kg body weight.

[0028] In this invention, a method for improving pregnancy rates is preferably provided, including administering lecithin.

[0029] The following examples illustrate the application of the lecithin provided by the present invention in the preparation of drugs for the prevention and / or treatment of infertility, but these examples should not be construed as limiting the scope of protection of the present invention.

[0030] Example 1 Compositional analysis of lecithin The composition of lecithin was determined using LCMS, employing a Waters ACQUITY UPLC I-Class plus / Thermo QE system. The specific steps are as follows: I. Pre-processing: 1. Take 100 μL of sample, add 100 μL of water and 300 μL of chloroform-methanol (V:V=2:1, including mixed internal standard), vortex for 30 s, sonicate for 10 min, and let stand overnight at -40℃; 2. Centrifuge for 10 min (12000 rpm, 4℃), take 150 μL of the lower chloroform layer and transfer it into an LC-MS vial to evaporate to dryness; 3. The lipid residue in the vial was reconstituted with 300 μL of isopropanol-methanol (V:V=1:1), vortexed for 30 s, and sonicated in ice water for 3 min; 4. Centrifuge for 10 min (12000 rpm, 4℃), and take 150 μL of the supernatant into an LC-MS vial with an inner liner for LC-MS analysis.

[0031] II. Chromatographic Detection Detection conditions: column temperature 55℃; mobile phase A: acetonitrile:water = 6:4 (v / v, containing 10mM ammonium acetate); mobile phase B: isopropanol:acetonitrile = 9:1 (v / v, containing 10mM ammonium acetate); flow rate 0.26 mL / min; injection volume 3 μL; ion source HESI; sample mass spectrometry signal acquisition using positive and negative ion scanning modes respectively. Data acquisition mode is DDA; scan method is Full MS / dd-MS2 (TOP 10).

[0032] See results Figure 1Among lecithin, the content of TG (triglyceride) is the highest, with a mass proportion of 29.12%; the content of DG (diacylglycerol) is 11.6%, ranking second; the mass proportion of PG (phosphatidylglycerol) is 11.29%, ranking third; the mass proportion of PS (phosphatidylserine) is 7.43%; the mass proportion of PE (phosphatidylethanolamine) is 5.12%; the mass proportion of PG (phosphatidylglycerol) is 4.16%; the mass proportion of PI (phosphatidylinositol) is 3.27%; the mass proportions of OAFHA (O-acyl-ω-hydroxy fatty acid) and PA (phosphatidic acid) are both 2.93%; the remainder is other components.

[0033] The base peak chromatogram of lecithin is shown in Figure 2 This lecithin contains TG, PC, PS, PE, and PI, etc. Among them, the metabolizable fatty acids include linoleic acid accounting for 7.8% of lecithin, α-linolenic acid accounting for 3.4% of lecithin, palmitic acid accounting for 3.3% of lecithin, oleic acid accounting for 3.4% of lecithin, stearic acid accounting for 3.5% of lecithin, and myristic acid accounting for 0.4% of lecithin.

[0034] Example 2 Animal experiments confirm the effect of lecithin on improving pregnancy rate 1. Drug source description: The lecithin used in the experiment is a dietary nutritional supplement product produced by Nature’s Care Manufacture Pty Limited in Australia. The recommended oral dosage for humans is 1.2 g - 3.6 g per day. Calculated based on an adult body weight of 60 kg, the equivalent dosage is 0.02 - 0.06 g / kg body weight. Converted according to the mouse coefficient of 9.1, it is approximately 0.182 - 0.546 g / kg body weight. The actual gavage amount of the phospholipid group in this animal experiment is 1.0 g / kg body weight each time.

[0035] 2. Experimental animals and environmental conditions 32 SPF-grade C57BL / 6J female mice at 6 - 8 weeks old (about 20 g) and 15 male mice were provided by Shanghai Jiesijie Experimental Animal Co., Ltd. The production license number of the experimental animals is SCXK (Shanghai) 2023 - 0004. The ethical approval was reviewed and approved by the Animal Ethics Committee of Shanghai Institute of Biomedical Technology (2024 - 94). The experimental conditions were a barrier environment, with the environmental temperature during the experiment being 22°C - 25°C and the humidity being 50% - 60%. The low-fat feed and high-fat feed were provided by Nantong Tenuofei Feed Technology Co., Ltd.

[0036] Low-fat feed formulation (TP23302): 10% energy from fat, 71% from carbohydrates, and 19% from protein. Each kilogram of feed contains 194g casein and 194g L-cysteine, 673g dextrin and sucrose, 40g soybean oil and lard, 48g cellulose, and 45g minerals and vitamins.

[0037] High-fat feed formulation (TP23300): 60% energy from fat, 20.6% from carbohydrates, and 19.4% from protein. Add 267g casein, 157g dextrin, 89g sucrose, 33g soybean oil, 301g lard, 67g cellulose, 66g minerals, 13g vitamins, 4g L-cysteine, and 3g choline tartrate per kilogram of feed.

[0038] 3. Experimental Methods Mice were randomly divided into three groups based on their initial body weight: a control group (low-fat diet + purified water by gavage), a model group (high-fat diet + 0.2 ml purified water by gavage), and a phospholipid group (high-fat diet + 0.2 ml phospholipid by gavage). Feed was provided freely; the specific food intake was converted into energy intake. Figure 3 The letter 'b' indicates that the actual gavage dose for the phospholipid group in this animal experiment was 1.0 g / kg body weight per gavage.

[0039] Experimental steps: (1) Female mice were fed under the barrier system for about a week, with free access to food and water. After the adaptation period, the model group and phospholipid group were fed a high-fat diet, while the control group was fed a low-fat diet for 3 months.

[0040] (2) Starting from the 4th month, all mice were gavaged for 3 days with purified water or lecithin, and then put together in cages. Male mice were given an acclimatization diet for about a week in advance, with free access to food and water. Female mice were put together with male mice in a 2:1 ratio overnight, and the mice found to have vaginal plugs the next morning were defined as 0.5 days of gestation.

[0041] (3) Mice in each group continued to be administered purified water or lecithin by gavage for 11 days. The average weight of each mouse was 30g, and each mouse was given 0.2ml (150mg / ml) by gavage.

[0042] (4) Pregnant mice were euthanized by carbon dioxide asphyxiation on day 12.5 of gestation. On the day of euthanasia, the mice were deprived of their food and allowed free access to water for 6 hours. Uterine tissue was collected, preserved in formalin, and used to prepare paraffin-embedded tissue sections. The number and weight of embryos were recorded, and the morphology of the embryos was observed.

[0043] 4. Experimental Conclusions (1) Changes in mouse body weight and diet The model group and the lecithin intervention group (obese mice) had significantly higher average daily calorie intake than the control group (normal mice) due to being fed a high-fat diet, and their weight gain was significantly faster than the control group, exceeding it by more than 20%. Figure 3 (a) This demonstrates the successful establishment of an obese mouse model.

[0044] (2) HE staining results of mouse decidual tissue on day 12.5 of gestation Lecithin intervention rescued decidualization disorder in high-fat-fed female mice (model group). In the model group, decidual cells exhibited vacuolization and apoptosis, characterized by nuclear pyknosis (white arrows) accompanied by suspected macrophage infiltration (black arrows). In the control group and the lecithin intervention group, decidual cells were larger, with clear boundaries, dense arrangement, oval or nearly round nuclei, and uniformly stained cytoplasm. Specific detection methods were described below. Figure 4 .

[0045] (3) Pregnancy rate, number of embryos and uterine weight of mice in each group The results are shown in Table 1 and [see Table 1]. Figure 5 Compared with the control group, the high-fat-fed model group mice showed a lower pregnancy rate and placental weight, confirming successful model establishment. Compared with the model group, the lecithin intervention group not only significantly reduced the average number of embryos resorbed and the risk of miscarriage, but also significantly increased the pregnancy rate, the number of intact embryos that were not resorbed, and the average total placental weight per mouse, verifying the role of lecithin intervention in improving reproductive function.

[0046] Table 1. Statistics on pregnancy outcomes in mice of different treatment groups

[0047] Note: Lecithin intervention group vs. model group Fisher's exact test p <0.05; &Control group vs. model group Fisher's exact test p <0.05.

[0048] Example 3 Animal experiments have demonstrated that lecithin improves uterine decidualization disorders and enhances endometrial receptivity. 1. Sample: The lecithin used in the experiment was a dietary supplement product manufactured by Nature's Care Manufacture Pty Limited in Australia. The actual gavage dose for the phospholipid group in this animal experiment was 2.0g / kg body weight per gavage.

[0049] 2. Experimental animals and environmental conditions: 24 SPF-grade ICR female mice, 6 - 8 weeks old (20 g - 30 g), and 12 male mice were provided by Shanghai Jiesijie Experimental Animal Co., Ltd. The production license number of experimental animals is SCXK (Shanghai) 2023 - 0004. The ethical approval was reviewed and approved by the Animal Ethics Committee of Shanghai Institute of Biomedical Technology (2024 - 94). The experimental conditions were barrier environment, and the environmental temperature during the experiment was 22℃ - 25℃, and the humidity was 50% - 60%.

[0050] 3. Experimental methods The experiments were randomly divided into 3 groups according to the initial body weight of the mice. There were 8 mice in the control group (gavage with pure water), 8 mice in the model group (gavage with LPS + pure water), and 8 mice in the lecithin intervention group (gavage with LPS + lecithin).

[0051] 4. Detection indexes and methods: The levels of inflammatory factor TNF-α in blood and uterine tissues were analyzed using a TNF-α ELISA quantitative detection kit (Shanghai Enzyme-linked Biotechnology Co., Ltd.), and the detection range was 7.8 - 500 pg / mL.

[0052] After the mice were sacrificed, blood was collected from the heart using a serum separation tube, coagulated at room temperature for 30 minutes, and then centrifuged at 1000×g for 15 minutes. The serum was immediately taken out and stored at a temperature of ≤ - 20℃. Avoid repeated freeze-thaw cycles.

[0053] The uterine placental tissue was rinsed with pre-cooled PBS (0.01 M, pH = 7.4) to remove residual blood (lysed red blood cells in the homogenate would affect the detection results). After weighing, the tissue was minced. The minced tissue and the corresponding volume of PBS (at a weight-to-volume ratio of 1:9, for example, 1 g of tissue sample corresponded to 9 mL of PBS) were added to a glass homogenizer and thoroughly ground on ice or using a homogenizer. To further lyse tissue cells, the homogenate could be ultrasonically disrupted or subjected to repeated freeze-thaw. Finally, the homogenate was centrifuged at 5000×g for 5 - 10 minutes, and the supernatant was taken for detection.

[0054] 5. Experimental procedures: (1) Female mice were fed under the barrier system for about one week, with free access to food and water. After the adaptation period ended, mating was carried out at around 5 pm in the evening, with a male-to-female ratio of 2:1. The next morning at 8:00, the female mice were examined for vaginal plugs. Female mice with detected vaginal plugs were considered to have had mating behavior and were recorded as pregnant at 0.5 d.

[0055] (2) Gavage started 3 days before cohabitation and continued for 7 days after cohabitation. Each mouse was gavaged with 0.2 ml (lecithin 500 mg / ml) each time. All mice were intraperitoneally injected with 4 μg (0.1 mL) of LPS on the 8.5th day of pregnancy.

[0056] (3) Pregnant mice were euthanized by carbon dioxide asphyxiation on day 9.5 of gestation. TNF-α levels in fasting whole blood collected from the heart were detected by ELISA. Uterine and placental tissues were collected; a portion was preserved in formalin for paraffin-embedded tissue sections, and the other portion was frozen and preserved for TNF-α detection. Embryo morphology was observed.

[0057] 6. Experimental Conclusions (1) Changes in mouse body weight and diet See results Figure 6 There were no significant differences in the average daily food intake and body weight changes among the three groups of mice. p> 0.05).

[0058] (2) HE staining image of mouse uterine decidual tissue (see image below) Figure 7 , Figure 8 and Figure 9 In the control group, decidual cells were morphologically normal and tightly packed. In the model group, decidual cells were fewer in number, varied in shape and size, and showed cytoplasmic edema and even vacuolization; pyknosis of the nuclei and deeply stained apoptotic bodies were also observed. In contrast, decidual cells in the lecithin intervention group were morphologically regular, with clear boundaries and dense arrangement; the nuclei were oval or nearly round, and the cytoplasm was uniformly stained. This indicates that lecithin intervention improved LPS-induced uterine decidualization disorders.

[0059] (3) Results of uterine appearance in the two groups of pregnant mice are shown in the figure. Figure 10 , Figure 11 and Figure 12 In the LPS model group, significant congestion was observed in the uterus of pregnant mice, and the embryonic tissue was dark brown and significantly smaller than that of normal surviving embryos. The blastocyst structure showed degenerative changes such as atrophy and dissolution, exhibiting a typical tendency towards miscarriage. However, after lecithin intervention, the embryonic development of the pregnant mice was significantly improved, uterine congestion was alleviated, embryonic color and volume returned to normal levels, and the pathological manifestations of blastocyst atrophy and dissolution were effectively contained.

[0060] The effect of lecithin on the embryo absorption rate in mice is shown in Table 2. The data show that the intervention of lecithin significantly reduced the embryo absorption rate in pregnant mice, specifically to 12.6%.

[0061] Table 2 Embryo resorption rate (%) in the two groups of pregnant mice

[0062] Note: Compared to the LPS model group. P < 0.001 (students't-test) (4) The ELISA results of mouse placental tissue and serum are shown in Table 3. The results showed that the level of the inflammatory factor TNF-α decreased significantly after lecithin intervention (students't-test).

[0063] Table 3. Effects of lecithin intervention on TNF-α levels in tissues and serum.

[0064] Lecithin group vs. LPS model group.

[0065] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. The use of lecithin in the preparation of drugs for the prevention and / or treatment of infertility, recurrent miscarriage and / or uterine decidualization disorders.

2. The application according to claim 1, characterized in that, The lecithin comprises the following percentages by weight: 10%~40% phosphatidylcholine / 5%~20% phosphatidylserine / 5%~30% phosphatidylethanolamine HE and 2%~20% phosphatidylinositol.

3. The application according to claim 1 or 2, characterized in that, The lecithin comprises the following metabolizable fatty acids in weight percentages: 4%~60% linoleic acid, 2%~25% α-linolenic acid, 2%~25% palmitic acid, 2%~25% oleic acid, 2%~10% stearic acid and 0.1%~2% myristic acid.

4. The application according to claim 1, characterized in that, The infertility or recurrent miscarriage mentioned includes those caused by obesity.

5. The application according to claim 1 or 4, characterized in that, The infertility mentioned includes decreased maternal reproductive function and / or reproductive dysfunction.

6. The application according to claim 1, characterized in that, The aforementioned uterine decidualization disorder includes elevated levels of the inflammatory factor TNF-α and abnormal changes in the morphology and number of decidual tissue cells.

7. The application according to claim 1 or 6, characterized in that, The uterine decidualization disorder includes lipopolysaccharide-induced formation.

8. The application according to claim 1, characterized in that, The drug has at least one of the following effects: reducing the risk of miscarriage, increasing the pregnancy rate, increasing the number and condition of embryos, and increasing placental weight.

9. The application according to claim 1, characterized in that, The drug includes at least one of the following dosage forms: tablets, capsules, powders, oral liquids, dry suspensions, pills, and granules.

10. The application according to any one of claims 1, 2, 4, 6, 8, and 9, characterized in that, The mass percentage of lecithin in the drug is 1% to 99%.

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