Traditional Chinese medicine composition for treating repeated planting failure as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of traditional Chinese medicine compositions, and particularly relates to a traditional Chinese medicine composition for treating repeated planting failure and a preparation method and application thereof. The traditional Chinese medicine composition disclosed by the invention has the effects of removing blood stasis, tonifying kidney and warming meridians by promoting blood circulation, removing blood stasis and tonifying kidney; furthermore, the uterus-warming and kidney-tonifying treatment traditional Chinese medicine composition is used for warming meridians and uterus, tonifying kidney and nourishing blood to improve the intimal receptivity; further, the post-transplantation implantation miscarriage prevention treatment traditional Chinese medicine composition is used for achieving the effects of strengthening heart, assisting embryo, nourishing blood, preventing miscarriage and supporting early pregnancy; the three groups of traditional Chinese medicine components are subjected to progressive three-stage treatment to realize systematic intervention from eliminating evil to strengthening the body resistance and then to miscarriage prevention, so that the embryo implantation rate and the clinical pregnancy rate of a patient with repeated implantation failure are improved.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine composition technology, specifically relating to a traditional Chinese medicine composition for treating recurrent planting failure, its preparation method, and its application. Background Technology

[0002] In recent years, the incidence of infertility has been increasing year by year. Assisted reproductive technology (ART) is an effective treatment for infertility and is widely used globally. ART refers to techniques that help infertile couples achieve pregnancy through medical means, mainly including two categories: artificial insemination (AI) and in vitro fertilization and embryo transfer (IVF-ET) and their derivative technologies. To date, despite many milestone advancements in ART technology, embryo implantation failure still occurs in 50% to 60% of IVF cycles. The incidence of recurrent implantation failure (RIF) is approximately 10% to 20%, and currently there are no clearly effective treatments in clinical practice. This places a heavy economic burden and psychological trauma on patients and their families, posing a significant challenge to clinicians and representing a key and difficult issue that urgently needs to be addressed in the field of assisted reproduction.

[0003] The causes of recurrent embryonic fibrosis (RIF) are complex, and Western medicine mainly classifies them into embryonic factors, endometrial factors, and other factors. Western medicine treatment primarily focuses on improving embryo quality in the laboratory, improving the uterine environment through intrauterine procedures, and improving immune and endocrine status with oral medications. However, due to high costs, the risk of complications from surgical procedures, and the poor efficacy of some medications, clinical efficacy remains unsatisfactory, and current treatment methods still cannot meet clinical needs. Some studies have found that integrated traditional Chinese and Western medicine treatment has a certain effect on promoting pregnancy. However, traditional Chinese medicine emphasizes individualized diagnosis and treatment based on the individual patient, making it difficult to widely apply in clinical practice.

[0004] Therefore, there is an urgent need to propose a systematic and scalable TCM general treatment method to solve the problems of unsatisfactory clinical efficacy and difficulty in promoting individualized treatment for RIF. Summary of the Invention

[0005] The purpose of this invention is to provide a traditional Chinese medicine composition for treating recurrent implantation failure, its preparation method, and its application. The traditional Chinese medicine composition can effectively improve the embryo implantation rate and clinical pregnancy rate in patients with recurrent implantation failure.

[0006] This invention provides a traditional Chinese medicine composition for treating recurrent embryo implantation failure, including a traditional Chinese medicine composition for post-implantation pregnancy support, comprising the following raw materials by weight: Cinnamon twig 14-16 parts, white peony root 14-16 parts, dodder seed 11-13 parts, raspberry 11-13 parts, teasel root 14-16 parts, fresh ginger 5-7 parts, jujube 29-31 parts, stir-fried eucommia bark 14-16 parts, angelica root 11-13 parts, astragalus root 19-21 parts, and prepared licorice root 5-7 parts.

[0007] Preferably, it also includes a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys, which, by weight, comprises the following raw materials: Cinnamon twig 14-16 parts, white peony root 14-16 parts, evodia fruit 4-6 parts, angelica root 11-13 parts, chuanxiong rhizome 7-9 parts, peach kernel 9-11 parts, trumpet creeper flower 19-21 parts, amethyst 29-31 parts, peony bark 9-11 parts, jujube 39-41 parts, raw ginseng 4-6 parts, asparagus root 19-21 parts, dodder seed 14-16 parts, raspberry 11-13 parts, achyranthes root 19-21 parts, stir-fried eucommia bark 19-21 parts, deer antler powder 5-7 parts, prepared licorice root 5-7 parts, stir-fried jujube seed 14-16 parts, coptis root 3-5 parts, donkey-hide gelatin beads 5-7 parts, prepared astragalus root 19-21 parts, epimedium 11-13 parts, lepidium seed 5-7 parts, and prepared aconite root 9-11 parts.

[0008] Preferably, the treatment also includes a traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys, which, by weight, comprises the following raw materials: 17-19 parts of cinnamon twig, 17-19 parts of white peony root, 4-6 parts of evodia fruit, 11-13 parts of angelica root, 7-9 parts of chuanxiong rhizome, 7-9 parts of ground beetle, 4-6 parts of leech, 9-11 parts of peach kernel, 9-11 parts of peony bark, and 7-9 parts of lepidium seed. The ingredients are: jujube (39-41 parts), raw ginseng (4-6 parts), dodder seed (14-16 parts), raspberry (11-13 parts), Sichuan achyranthes root (19-21 parts), stir-fried eucommia bark (19-21 parts), deer antler powder (5-7 parts), prepared licorice root (5-7 parts), stir-fried sour jujube seed (14-16 parts), coptis root (3-5 parts), donkey-hide gelatin beads (5-7 parts), safflower (7-9 parts), prepared astragalus root (19-21 parts), and prepared aconite root (9-11 parts).

[0009] Preferred options include traditional Chinese medicine compositions for treating blood stasis and tonifying the kidneys, traditional Chinese medicine compositions for treating uterine warming and tonifying the kidneys, and traditional Chinese medicine compositions for treating implantation and pregnancy support after transplantation. The herbal composition for removing blood stasis and tonifying the kidneys includes the following ingredients in parts by weight: 18 parts cinnamon twig, 18 parts white peony root, 5 parts evodia fruit, 12 parts angelica root, 8 parts chuanxiong rhizome, 8 parts ground beetle, 5 parts leech, 10 parts peach kernel, 10 parts peony bark, 8 parts lepidium seed, 40 parts jujube, 5 parts raw ginseng, 15 parts dodder seed, 12 parts raspberry, 20 parts Sichuan achyranthes root, 20 parts stir-fried eucommia bark, 6 parts deer antler powder, 6 parts prepared licorice root, 15 parts stir-fried jujube seed, 4 parts coptis root, 6 parts donkey-hide gelatin beads, 8 parts safflower, 20 parts prepared astragalus root, and 10 parts prepared aconite root. The traditional Chinese medicine composition for warming the uterus and tonifying the kidneys includes the following raw materials in parts by weight: 15 parts cinnamon twig, 15 parts white peony root, 5 parts evodia fruit, 12 parts angelica root, 8 parts chuanxiong rhizome, 10 parts peach kernel, 20 parts trumpet creeper flower, 30 parts amethyst, 10 parts peony bark, 40 parts jujube, 5 parts sun-dried ginseng, 20 parts asparagus root, 15 parts dodder seed, 12 parts raspberry, 20 parts Sichuan achyranthes root, 20 parts stir-fried eucommia bark, 6 parts deer antler powder, 6 parts prepared licorice root, 15 parts stir-fried jujube seed, 4 parts coptis root, 6 parts donkey-hide gelatin beads, 20 parts prepared astragalus root, 12 parts epimedium, 6 parts lepidium seed, and 10 parts prepared aconite root. The herbal composition for post-implantation pregnancy support includes the following ingredients in parts by weight: 15 parts cinnamon twig, 15 parts white peony root, 12 parts dodder seed, 12 parts raspberry, 15 parts dipsacus root, 6 parts fresh ginger, 30 parts jujube, 15 parts stir-fried eucommia bark, 12 parts angelica root, 20 parts astragalus root, and 6 parts prepared licorice root.

[0010] This invention also provides a method for preparing the traditional Chinese medicine composition for treating recurrent implantation failure as described in the above technical solution, comprising the following steps: After weighing each herb in the herbal composition for post-implantation pregnancy support according to the specified weight proportions, the herbs were mixed with water and soaked to obtain the first soaking herbal mixture. The first soaked herbal mixture is decocted for the first time, and the decoction is taken to obtain a herbal composition for post-implantation pregnancy support.

[0011] Preferably, the following steps are included: weighing each Chinese herb in the warming uterus and tonifying kidney Chinese herbal composition according to the weight proportions, then wrapping the lepidium seed in Chinese herbal decoction material and mixing it with other Chinese herbs except for donkey-hide gelatin beads and water to soak, thereby obtaining a second soaking Chinese herbal composition; After mixing the prepared aconite root in the second soaking herbal composition with water, decoct for 0.5 to 1 hour, then mix with the other soaking herbs for a second decoction. Take the decoction and mix it with donkey-hide gelatin beads to obtain a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys.

[0012] Preferably, the following steps are included: weighing each Chinese herb in the herbal composition for removing blood stasis and tonifying the kidney according to the weight proportions, then wrapping the lepidium seed in the herbal decoction material and soaking it with other Chinese herbs except for donkey-hide gelatin beads and water to obtain the third soaking herbal composition; After mixing the prepared aconite root in the third soaking herbal composition with water, decoct for 0.5 to 1 hour, then mix with the other soaking herbs for a third decoction. Take the decoction and mix it with donkey-hide gelatin beads to obtain a herbal composition for removing blood stasis and tonifying the kidney.

[0013] Preferably, the first decoction time is 0.5 to 1 hour, and the first decoction is performed 1 to 2 times. The second decoction time is 0.5 to 1 hour, and the second decoction is performed 1 to 2 times. The third decoction time is 0.5 to 1 hour, and the third decoction is performed 1 to 2 times.

[0014] The present invention also provides the application of the traditional Chinese medicine composition for treating recurrent embryo implantation failure as described in the above technical solution or the traditional Chinese medicine composition for treating recurrent embryo implantation failure prepared by the preparation method described in the above technical solution in the preparation of assisted reproductive drugs.

[0015] Preferably, the preparation of the assisted reproductive drug includes the preparation of a drug for treating recurrent embryo implantation failure.

[0016] Beneficial effects: This invention provides a traditional Chinese medicine composition for treating recurrent implantation failure. The composition utilizes three main treatments: a herbal composition for promoting blood circulation and tonifying the kidneys; a herbal composition for warming the uterus and tonifying the blood to improve endometrial receptivity; and a herbal composition for post-implantation implantation support to strengthen the heart, aid embryo development, nourish blood, and support early pregnancy. These three herbal formulas, through a progressive three-stage treatment, achieve a systematic intervention from "eliminating pathogens" to "strengthening the body's resistance" and finally to "supporting the pregnancy," thereby improving the embryo implantation rate and clinical pregnancy rate in patients with recurrent implantation failure. In practical application, the herbal compositions for promoting blood circulation and tonifying the kidneys and warming the uterus can be selectively taken based on the specific situation, avoiding the limitations of these two stages and demonstrating the flexible applicability of this herbal composition for treating recurrent implantation failure.

[0017] Furthermore, this invention, through standardized prescription design, covers the common TCM syndromes of uterine deficiency and cold, and uterine stagnation in recurrent implantation failure. It also corresponds to Western medicine diagnoses of recurrent implantation failure accompanied by multiple uterine fibroids, endometriosis, chocolate cysts, teratomas, cardiolipin syndrome, and patients requiring aspirin, heparin, etc., as indicated by Western medicine. This solves the problem of inconsistent treatment plans and difficulty in large-scale clinical promotion caused by the individualized syndrome differentiation and treatment of traditional Chinese medicine.

[0018] Meanwhile, the traditional Chinese medicine composition for treating recurrent embryo implantation failure described in this invention can achieve a seamless integration of traditional Chinese and Western medicine approaches to prevent pregnancy loss. In the post-implantation stage, the traditional Chinese medicine composition for preventing pregnancy loss reduces the pregnancy loss rate and makes up for the shortcomings of insufficient support in Western medicine after implantation. Detailed Implementation

[0019] This invention provides a traditional Chinese medicine composition for treating recurrent embryo implantation failure, including a traditional Chinese medicine composition for post-implantation and pregnancy support, comprising the following ingredients by weight: 14-16 parts of cinnamon twig, 14-16 parts of white peony root, 11-13 parts of dodder seed, 11-13 parts of raspberry, 14-16 parts of dipsacus root, 5-7 parts of ginger, 29-31 parts of jujube, 14-16 parts of stir-fried eucommia bark, 11-13 parts of angelica root, 19-21 parts of astragalus root, and 5-7 parts of prepared licorice root.

[0020] In one embodiment, the traditional Chinese medicine composition for post-implantation pregnancy support treatment is based on the principles of strengthening the heart and assisting embryo formation, and nourishing blood and supporting pregnancy. In one embodiment, the traditional Chinese medicine composition for post-implantation pregnancy support treatment comprises the following raw materials in parts by weight: 15 parts cinnamon twig, 15 parts white peony root, 12 parts dodder seed, 12 parts raspberry, 15 parts dipsacus root, 6 parts fresh ginger, 30 parts jujube, 15 parts stir-fried eucommia bark, 12 parts angelica root, 20 parts astragalus root, and 6 parts prepared licorice root.

[0021] As one implementation method, the traditional Chinese medicine composition for treating recurrent embryo implantation failure also includes a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys. By weight, this composition comprises the following ingredients: 14-16 parts cinnamon twig, 14-16 parts white peony root, 4-6 parts evodia fruit, 11-13 parts angelica root, 7-9 parts chuanxiong rhizome, 9-11 parts peach kernel, 19-21 parts trumpet creeper flower, 29-31 parts amethyst, and 9-11 parts peony bark. The ingredients are: 39-41 parts jujube, 4-6 parts raw ginseng, 19-21 parts asparagus root, 14-16 parts dodder seed, 11-13 parts raspberry, 19-21 parts Sichuan achyranthes root, 19-21 parts stir-fried eucommia bark, 5-7 parts deer antler powder, 5-7 parts prepared licorice root, 14-16 parts stir-fried jujube seed, 3-5 parts coptis root, 5-7 parts donkey-hide gelatin beads, 19-21 parts prepared astragalus root, 11-13 parts epimedium, 5-7 parts lepidium seed, and 9-11 parts prepared aconite root. As one embodiment, the aforementioned warming uterus and kidney-tonifying herbal composition is based on the principles of warming the meridians and uterus, and tonifying the kidney and nourishing blood. As one implementation method, while retaining the basic formula of the traditional Chinese medicine composition for warming the uterus and tonifying the kidneys, those skilled in the art can make appropriate additions or subtractions to the basic formula according to the patient's secondary symptoms. The types and dosages of the added or subtracted drugs can be routinely adjusted based on the common knowledge of those skilled in the art. For example, adding asparagus, amethyst, and trumpet creeper can treat female infertility; or adding epimedium can enhance the kidney-tonifying and fertility-aiding effects. As one embodiment, the traditional Chinese medicine composition for warming the uterus and tonifying the kidneys described in this invention comprises the following raw materials in parts by weight: 15 parts of cinnamon twig, 15 parts of white peony root, 5 parts of evodia fruit, 12 parts of angelica root, 8 parts of chuanxiong rhizome, 10 parts of peach kernel, 20 parts of trumpet creeper flower, 30 parts of amethyst, 10 parts of peony bark, 40 parts of jujube, 5 parts of raw ginseng, 20 parts of asparagus root, 15 parts of dodder seed, 12 parts of raspberry, 20 parts of achyranthes root, 20 parts of stir-fried eucommia bark, 6 parts of deer antler powder, 6 parts of prepared licorice root, 15 parts of stir-fried jujube seed, 4 parts of coptis root, 6 parts of donkey-hide gelatin beads, 20 parts of prepared astragalus root, 12 parts of epimedium, 6 parts of lepidium seed, and 10 parts of prepared aconite root.

[0022] As one embodiment, the traditional Chinese medicine composition for treating recurrent implantation failure according to the present invention further includes a traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys. By weight, the traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys includes the following ingredients: 17-19 parts of cinnamon twig, 17-19 parts of white peony root, 4-6 parts of evodia fruit, 11-13 parts of angelica root, 7-9 parts of chuanxiong rhizome, 7-9 parts of ground beetle, 4-6 parts of leech, 9-11 parts of peach kernel, and peony bark. The herbal composition for removing blood stasis and tonifying the kidneys consists of 9-11 parts of Lepidium apetalum, 7-9 parts of Ziziphus jujuba, 39-41 parts of Ziziphus jujuba, 4-6 parts of raw ginseng, 14-16 parts of Cuscuta chinensis, 11-13 parts of Rubus idaeus, 19-21 parts of Achyranthes bidentata, 19-21 parts of stir-fried Eucommia ulmoides, 5-7 parts of deer antler powder, 5-7 parts of prepared licorice root, 14-16 parts of stir-fried Ziziphus jujuba var. spinosa, 3-5 parts of Coptis chinensis, 5-7 parts of donkey-hide gelatin beads, 7-9 parts of Carthamus tinctorius, 19-21 parts of prepared Astragalus membranaceus, and 9-11 parts of prepared Aconitum carmichaelii. As one embodiment, the herbal composition for removing blood stasis and tonifying the kidneys is based on the principles of promoting blood circulation, removing blood stasis, tonifying the kidneys, and warming the meridians. As one implementation method, while retaining the basic formula of the traditional Chinese medicine composition for removing blood stasis and tonifying the kidney, those skilled in the art can make appropriate additions and subtractions to the basic formula according to the patient's secondary symptoms. The types and dosages of the added or subtracted drugs can be routinely adjusted based on the common knowledge of those skilled in the art. For example, after deleting Trichosanthes root, ginger, Scutellaria baicalensis, egg yolk, Rehmannia glutinosa, wolfberry, deer antler glue, tortoise shell glue, and Cornus officinalis, the following additions can be made with different effects: 1. Adding peach kernel, safflower, and leech to strongly promote blood circulation and remove blood stasis; 2. Adding stir-fried jujube seed to calm the mind and aid sleep; 3. Adding Astragalus membranaceus to strongly promote blood circulation and remove blood stasis without harming the body's vital energy; 4. Adding Rubus idaeus, which, when combined with Cuscuta chinensis, tonifies the kidney and strengthens essence. As one implementation method, the traditional Chinese medicine composition for removing blood stasis and tonifying the kidney includes the following raw materials in parts by weight: 18 parts of cinnamon twig, 18 parts of white peony root, 5 parts of evodia fruit, 12 parts of angelica root, 8 parts of chuanxiong rhizome, 8 parts of ground beetle, 5 parts of leech, 10 parts of peach kernel, 10 parts of peony bark, 8 parts of lepidium seed, 40 parts of jujube, 5 parts of raw ginseng, 15 parts of dodder seed, 12 parts of raspberry, 20 parts of Sichuan achyranthes root, 20 parts of stir-fried eucommia bark, 6 parts of deer antler powder, 6 parts of prepared licorice root, 15 parts of stir-fried jujube seed, 4 parts of coptis root, 6 parts of donkey-hide gelatin beads, 8 parts of safflower, 20 parts of prepared astragalus root, and 10 parts of prepared aconite root.

[0023] In this invention, as one embodiment, the traditional Chinese medicine composition for treating recurrent embryo implantation failure simultaneously includes a traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys, a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys, and a traditional Chinese medicine composition for post-implantation and pregnancy support. In this invention, the traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys primarily focuses on powerfully promoting blood circulation and removing blood stasis, clearing stagnation in the uterus, warming the meridians and dispelling cold, improving the uterine environment, while also warming yang and tonifying qi, eliminating pathogens without harming the body's vital energy; the traditional Chinese medicine composition for warming the uterus and tonifying the kidneys warms the meridians and uterus, tonifies the kidneys, nourishes blood and replenishes essence, improves endometrial receptivity, and creates optimal conditions for embryo implantation; the traditional Chinese medicine composition for post-implantation and pregnancy support aids embryo implantation, promotes fetal heartbeat and embryonic development, and reduces the risk of early pregnancy loss.

[0024] This invention also provides a method for preparing the traditional Chinese medicine composition for treating recurrent implantation failure as described in the above technical solution, comprising the following steps: The herbs in the post-implantation pregnancy-stabilizing herbal composition are weighed according to their respective weight proportions and then mixed with water for soaking to obtain a first soaking herbal mixture. The first soaking herbal mixture is then decocted for the first time, and the resulting liquid is collected to obtain the post-implantation pregnancy-stabilizing herbal composition. As one embodiment, the amount of water used for soaking should preferably be 3-5 cm above the herbs. As another embodiment, the amount of water used for the first decoction should preferably be 3-5 cm above the herbs; the first decoction time is 0.5-1 hour, and the first decoction is performed 1-2 times.

[0025] As one embodiment, the preparation method further includes the following steps: weighing each herb in the warming uterus and tonifying kidney traditional Chinese medicine composition according to its weight proportions; then wrapping the Lepidium apetalum in a traditional Chinese medicine decoction bag and soaking it with other herbs and water to obtain a second soaked herbal composition; mixing the prepared Aconitum carmichaelii in the second soaked herbal composition with water and decocting it for 0.5-1 hour, then mixing it with the other soaked herbs except for the donkey-hide gelatin beads for a second decoction; mixing the decoction with the donkey-hide gelatin beads to obtain the warming uterus and tonifying kidney traditional Chinese medicine composition. As one embodiment, the amount of water used during the soaking should be 3-5 cm above the herbs. As one embodiment, the amount of water used during the second decoction should be 3-5 cm above the herbs; the first decoction time is 0.5-1 hour, and the second decoction is performed 1-2 times.

[0026] As one embodiment, the preparation method further includes the following steps: weighing each herb in the herbal composition for removing blood stasis and tonifying the kidney according to its weight proportions; then wrapping the Lepidium apetalum in a herbal decoction bag and soaking it with other herbs and water to obtain a third soaking herbal composition; mixing the prepared Aconitum carmichaelii in the third soaking herbal composition with water and decocting for 0.5-1 hour, then mixing it with the other soaked herbs (preferably submerged by 3-5 cm) for a third decoction; and mixing the decoction with donkey-hide gelatin beads to obtain the herbal composition for removing blood stasis and tonifying the kidney. As one embodiment, the amount of water used during the soaking should preferably be 3-5 cm above the herbs. As one embodiment, the amount of water used during the third decoction should preferably be 3-5 cm above the herbs; the third decoction time is 0.5-1 hour, and the third decoction is performed 1-2 times.

[0027] This invention also provides the application of the traditional Chinese medicine composition for treating recurrent embryo implantation failure described in the above-described technical solutions, or the traditional Chinese medicine composition for treating recurrent embryo implantation failure prepared by the preparation method described in the above-described technical solutions, in the preparation of assisted reproductive drugs. As one embodiment, the preparation of assisted reproductive drugs includes the preparation of a drug for treating recurrent embryo implantation failure.

[0028] In this invention, the therapeutic indicator for taking the traditional Chinese medicine composition for treating recurrent embryo implantation failure is successful pregnancy after embryo transfer with smooth fetal heartbeat and embryonic development, i.e., clinical pregnancy. If the patient conceives spontaneously during the medication period, the treatment is switched to the traditional Chinese medicine composition for implantation and pregnancy maintenance after embryo transfer, with smooth fetal heartbeat and embryonic development as the main outcome indicator. If the patient has never had an implantation before, but implantation occurs after taking the medication, even if it is a biochemical pregnancy, it can be considered an improvement.

[0029] The traditional Chinese medicine composition for treating recurrent implantation failure described in this invention can form a progressive three-step general treatment for recurrent implantation failure in practical applications. It is mainly for patients clinically diagnosed with recurrent implantation failure, accompanied by multiple uterine fibroids, endometriosis, chocolate cysts, teratomas, anticardiolipin syndrome, and those requiring aspirin or heparin according to Western medicine indications. Patients with severely diminished ovarian reserve or polycystic ovary syndrome are excluded. The three groups of traditional Chinese medicine compositions form a progressive three-step treatment for recurrent implantation failure. The three progressive interventions can improve the uterine environment, enhance endometrial receptivity, regulate uterine qi and blood, tonify the kidneys and replenish essence to stabilize pregnancy, thereby improving embryo implantation rate and clinical pregnancy rate.

[0030] To further illustrate the present invention, the following embodiments describe the technical solutions provided by the present invention in detail, but they should not be construed as limiting the scope of protection of the present invention.

[0031] Example 1 A traditional Chinese medicine composition for treating recurrent implantation failure comprises a formula for removing blood stasis and tonifying the kidneys, a formula for warming the uterus and tonifying the kidneys, and a formula for preventing miscarriage after embryo transfer. The specific formulation and preparation method are as follows: The formula for removing blood stasis and tonifying the kidneys consists of: 18g cinnamon twig, 18g white peony root, 5g evodia fruit, 12g angelica root, 8g chuanxiong rhizome, 8g ground beetle, 5g leech, 10g peach kernel, 10g peony bark, 8g lepidium seed (wrapped and decocted), 40g jujube, 5g raw ginseng, 15g dodder seed, 12g raspberry, 20g Sichuan achyranthes root, 20g stir-fried eucommia bark, 6g deer antler powder, 6g prepared licorice root, 15g stir-fried jujube seed, 4g coptis root, 6g donkey-hide gelatin beads, 8g safflower, 20g prepared astragalus root, and 10g prepared aconite root (decocted first). The specific steps for simmering in water are as follows: Before decocting, soak all Chinese herbs except for donkey-hide gelatin beads for 30 minutes; Place 10g of prepared aconite root in a decoction container, add sufficient water, and decoct separately for 30 minutes to reduce toxicity and preserve efficacy. Wrap 8g of lepidium seed in clean gauze and tie it tightly. Use the decocted aconite root and its liquid as the base liquid, and add all other medicinal materials except for the donkey-hide gelatin beads (including the wrapped lepidium seed). Add water until the medicinal materials are completely submerged and about 3cm above the surface. Bring to a boil over high heat, then reduce to low heat and simmer for 30 minutes. Stir occasionally during the decoction process. After the first decoction, filter out the liquid. Add water again to the dregs (slightly less than the first decoction), bring to a boil over high heat, then reduce to low heat and continue simmering for 30 minutes. Filter out the liquid and combine it with the first decoction. Reheat the combined liquid to a boil, then turn off the heat. Add 6g of donkey-hide gelatin beads and stir until completely dissolved.

[0032] The formula for warming the uterus and tonifying the kidneys consists of: 15g cinnamon twig, 15g white peony root, 5g evodia fruit, 12g angelica root, 8g chuanxiong rhizome, 10g peach kernel, 20g trumpet creeper flower, 30g amethyst, 10g peony bark, 40g jujube, 5g raw ginseng, 20g asparagus root, 15g dodder seed, 12g raspberry, 20g achyranthes root, 20g stir-fried eucommia bark, 6g deer antler powder, 6g prepared licorice root, 15g stir-fried jujube seed, 4g coptis root, 6g donkey-hide gelatin beads, 20g prepared astragalus root, 12g epimedium, 6g lepidium seed (wrapped and decocted), and 10g prepared aconite root (decocted first). The specific steps for simmering in water are as follows: Before decocting, soak all Chinese herbs except for donkey-hide gelatin beads for 30 minutes; First, decoct 10g of prepared aconite root separately for 30 minutes. Crush 30g of amethyst and wrap 6g of lepidium seed in a decoct. Use the decocted aconite root liquid and crushed amethyst as the base liquid, then add all the other medicinal materials (including the wrapped lepidium seed) except for the donkey-hide gelatin beads. Add sufficient water, bring to a boil over high heat, then simmer over low heat for 30 minutes. After filtering the first decoction, add water to the dregs, bring to a boil again over high heat, then simmer over low heat for 30 minutes. Filter the decoction and combine it with the first decoction. Heat the combined decoction to a boil, then turn off the heat and add 6g of donkey-hide gelatin beads, stirring until completely dissolved.

[0033] The formula for post-implantation pregnancy support consists of: 15g cinnamon twig, 15g white peony root, 12g dodder seed, 12g raspberry, 15g dipsacus root, 6g fresh ginger, 30g jujube, 15g stir-fried eucommia bark, 12g angelica root, 20g astragalus root, and 6g prepared licorice root. The specific steps for simmering in water are as follows: Wash all medicinal herbs thoroughly and set aside. Soak the herbs for 30 minutes before decocting. Slice the ginger. Place all herbs in a decoction container and add enough water to submerge the herbs by about 2-3 cm. Bring to a boil over high heat, then simmer over low heat for 30 minutes. Strain the first decoction. Add an appropriate amount of water to the dregs, bring to a boil over high heat, then simmer over low heat for another 30 minutes. Strain the decoction and combine it with the first decoction.

[0034] Example 2 The method for treating recurrent implantation failure using the herbal composition from Example 1 is divided into three stages, as detailed below: The first stage is the treatment to remove blood stasis and tonify the kidneys: 3 months before the embryo transfer plan, if the patient has a clear Western medical diagnosis and corresponding imaging examination, and presents with symptoms such as chills all over the body, chills in the lower body, dry mouth and thirst in the upper body, easy to get inflamed, coldness in the lower back / abdomen before and after menstruation, dark menstrual blood with clots, dark lips, dark tongue, and ecchymosis, the patient can take the formula to remove blood stasis and tonify the kidneys. Dosage: Decocted in water and taken twice a day, half an hour after breakfast and lunch. Each dose is 200mL, and 5mL of rice wine is added to the medicine. The treatment period is 2 months.

[0035] The second stage is uterine warming and kidney tonifying treatment, which is taken one month before embryo transfer. The purpose of taking the uterine warming and kidney tonifying treatment formula is to help improve the receptivity of the patient's endometrium and help with implantation. Dosage: Decocted in water and taken twice a day, half an hour after breakfast and lunch, with each dose being 200 mL; treatment duration is 1 month.

[0036] The third stage is post-implantation pregnancy support treatment, which involves taking the post-implantation pregnancy support treatment formula after the patient's embryo transfer. Dosage: Decocted in water and taken twice daily, half an hour after breakfast and lunch, warm. Each dose is 200 mL. The treatment lasts for 6 to 8 weeks, or until the fetal heart rate and embryo are normal and then medication is discontinued.

[0037] Example 3 Thirty-seven patients with recurrent embryo implantation failure were treated according to the treatment method described in Example 2. All 37 patients were treated at Peking Union Medical College Hospital and provided informed consent for this statistical analysis. Medication was administered sequentially according to the treatment method described in Example 2, starting from the initial medication period. If a patient did not proceed to the planned embryo transfer cycle or the transfer was delayed during the first phase of medication, the first phase of medication was extended. The second phase of medication was generally scheduled for approximately one month before the embryo transfer. If a patient suddenly changed their transfer plan during the first phase of medication, the first phase of medication was discontinued, and the third phase of medication was initiated. The case report forms (CRFs) of the 37 patients during clinical treatment are detailed in Table 1.

[0038] Table 1 Case report of 37 patients

[0039] Note: In Table 1, "dropout" refers to patients who temporarily stop treatment because they do not have an urgent need to have children.

[0040] Table 1 shows that, starting from February 2025 and up to the date of this invention submission, a total of 37 patients were included: 1 under 30 years old, 11 between 30 and 35 years old, 17 between 36 and 39 years old, and 8 40 years and older. Of these, 17 underwent embryo transfer (excluding spontaneous pregnancies), 2 experienced miscarriages, and 9 achieved successful pregnancies. Among these, Ms. Yang (patient 3 in Table 1) had her third successful transfer, and Ms. Ma (patient 20 in Table 1) had her second successful transfer. Four patients conceived spontaneously.

[0041] The therapeutic effects of the traditional Chinese medicine composition of the present invention were analyzed based on the case reports of 37 patients in Table 1 as follows: First, compared with Western medicine-assisted reproductive treatment alone, this invention significantly improves the clinical pregnancy rate.

[0042] According to existing literature [He Y, Shi S, Su X, Chen G, Zhao X. Incidence of pregnancy outcomes among patients with recurrent implantation failure: a systematic review and meta-analysis. BMC Pregnancy Childbirth. 2025 Nov 10;25(1):1184. doi: 10.1186 / s12884-025-08372-8. PMID: 41214571; PMCID:PMC12604203.], patients with recurrent implantation failure generally have low clinical pregnancy rates after receiving conventional Western medicine assisted reproductive treatment. Studies show that their clinical pregnancy rate is about 20% to 35%, and it further decreases with increasing age, uterine lesions (such as fibroids, endometriosis, polyps, etc.) or immune abnormalities (such as antiphospholipid syndrome).

[0043] Of the 37 RIF patients included in this invention, as of the statistical time point: 17 patients took medication and underwent transplantation (excluding those who conceived spontaneously), with a total of 21 transplantation cycles. Among them, 9 patients achieved successful pregnancies, with a total of 9 gestation cycles, resulting in a clinical pregnancy rate of approximately 42.86% (9 / 21). If the 4 patients who conceived spontaneously are included, the total number of successful pregnancies is 13, which shows a significantly better pregnancy outcome than that of Western medicine treatment alone in the evaluable population.

[0044] Second, the patients are older and their conditions are more complex, making treatment more difficult, but good results have still been achieved.

[0045] The diagnosis of recurrent reproductive fibroids (RIF) typically targets women under 40 years of age. However, this invention included 8 patients aged 40 and above (21.6%), with the oldest being 45 years old. Most patients had multiple uterine fibroids, endometriosis, chocolate cysts, antiphospholipid syndrome, a history of tuberculosis, and polyp removal, among other complex reproductive system conditions. Advanced age and complex comorbidities are independent risk factors affecting embryo implantation and pregnancy maintenance, typically leading to a further decline in the success rate of Western medicine treatments. In this invention, even in this more challenging patient group, multiple successful pregnancies were achieved (including patients aged 44 and 45), demonstrating the significant advantages of the herbal composition in improving the uterine environment and pregnancy outcomes in older, complex cases.

[0046] Third, some patients achieved natural pregnancy, reflecting an overall improvement in the reproductive environment.

[0047] Of the 37 patients, 4 achieved natural pregnancy during medication (2 of which were continuous pregnancies). The occurrence of natural pregnancy suggests that this invention is not limited to endometrial preparation and pregnancy support in assisted embryo transfer cycles, but can also restore the patient's own reproductive endocrine balance, fallopian tube function, egg quality, and uterine environment through overall conditioning, thereby increasing the possibility of natural conception. The traditional Chinese medicine composition of this invention, while "invigorating blood and tonifying the kidneys, warming the uterus and nourishing blood", also takes into account "harmonizing qi and blood, and balancing yin and yang", which may have a positive impact on ovarian function, ovulation mechanism and embryonic development potential in some patients.

[0048] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for treating recurrent embryo implantation failure, characterized in that, The herbal composition for post-implantation pregnancy support includes the following ingredients by weight: Cinnamon twig 14-16 parts, white peony root 14-16 parts, dodder seed 11-13 parts, raspberry 11-13 parts, teasel root 14-16 parts, fresh ginger 5-7 parts, jujube 29-31 parts, stir-fried eucommia bark 14-16 parts, angelica root 11-13 parts, astragalus root 19-21 parts, and prepared licorice root 5-7 parts.

2. The traditional Chinese medicine composition for treating recurrent implantation failure according to claim 1, characterized in that, It also includes a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys, which, by weight, comprises the following raw materials: Cinnamon twig 14-16 parts, white peony root 14-16 parts, evodia fruit 4-6 parts, angelica root 11-13 parts, chuanxiong rhizome 7-9 parts, peach kernel 9-11 parts, trumpet creeper flower 19-21 parts, amethyst 29-31 parts, peony bark 9-11 parts, jujube 39-41 parts, raw ginseng 4-6 parts, asparagus root 19-21 parts, dodder seed 14-16 parts, raspberry 11-13 parts, achyranthes root 19-21 parts, stir-fried eucommia bark 19-21 parts, deer antler powder 5-7 parts, prepared licorice root 5-7 parts, stir-fried jujube seed 14-16 parts, coptis root 3-5 parts, donkey-hide gelatin beads 5-7 parts, prepared astragalus root 19-21 parts, epimedium 11-13 parts, lepidium seed 5-7 parts, and prepared aconite root 9-11 parts.

3. The traditional Chinese medicine composition for treating recurrent embryo implantation failure according to claim 1 or 2, characterized in that, It also includes a traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys. By weight, the traditional Chinese medicine composition for removing blood stasis and tonifying the kidneys includes the following raw materials: 17-19 parts of cinnamon twig, 17-19 parts of white peony root, 4-6 parts of evodia fruit, 11-13 parts of angelica root, 7-9 parts of chuanxiong rhizome, 7-9 parts of ground beetle, 4-6 parts of leech, 9-11 parts of peach kernel, 9-11 parts of peony bark, 7-9 parts of lepidium seed, 39-41 parts of jujube, 4-6 parts of raw ginseng, 14-16 parts of dodder seed, 11-13 parts of raspberry, 19-21 parts of Sichuan achyranthes root, 19-21 parts of stir-fried eucommia bark, 5-7 parts of deer antler powder, 5-7 parts of prepared licorice root, 14-16 parts of stir-fried jujube seed, 3-5 parts of coptis root, 5-7 parts of donkey-hide gelatin beads, 7-9 parts of safflower, 19-21 parts of prepared astragalus root, and 9-11 parts of prepared aconite root.

4. The traditional Chinese medicine composition for treating recurrent embryo implantation failure according to claim 3, characterized in that, This includes traditional Chinese medicine compositions for treating blood stasis and tonifying the kidneys, traditional Chinese medicine compositions for treating uterine warming and tonifying the kidneys, and traditional Chinese medicine compositions for treating implantation and pregnancy support after transplantation. The herbal composition for removing blood stasis and tonifying the kidneys includes the following ingredients in parts by weight: 18 parts cinnamon twig, 18 parts white peony root, 5 parts evodia fruit, 12 parts angelica root, 8 parts chuanxiong rhizome, 8 parts ground beetle, 5 parts leech, 10 parts peach kernel, 10 parts peony bark, 8 parts lepidium seed, 40 parts jujube, 5 parts raw ginseng, 15 parts dodder seed, 12 parts raspberry, 20 parts Sichuan achyranthes root, 20 parts stir-fried eucommia bark, 6 parts deer antler powder, 6 parts prepared licorice root, 15 parts stir-fried jujube seed, 4 parts coptis root, 6 parts donkey-hide gelatin beads, 8 parts safflower, 20 parts prepared astragalus root, and 10 parts prepared aconite root. The traditional Chinese medicine composition for warming the uterus and tonifying the kidneys includes the following raw materials in parts by weight: 15 parts cinnamon twig, 15 parts white peony root, 5 parts evodia fruit, 12 parts angelica root, 8 parts chuanxiong rhizome, 10 parts peach kernel, 20 parts trumpet creeper flower, 30 parts amethyst, 10 parts peony bark, 40 parts jujube, 5 parts sun-dried ginseng, 20 parts asparagus root, 15 parts dodder seed, 12 parts raspberry, 20 parts Sichuan achyranthes root, 20 parts stir-fried eucommia bark, 6 parts deer antler powder, 6 parts prepared licorice root, 15 parts stir-fried jujube seed, 4 parts coptis root, 6 parts donkey-hide gelatin beads, 20 parts prepared astragalus root, 12 parts epimedium, 6 parts lepidium seed, and 10 parts prepared aconite root. The herbal composition for post-implantation pregnancy support includes the following ingredients in parts by weight: 15 parts cinnamon twig, 15 parts white peony root, 12 parts dodder seed, 12 parts raspberry, 15 parts dipsacus root, 6 parts fresh ginger, 30 parts jujube, 15 parts stir-fried eucommia bark, 12 parts angelica root, 20 parts astragalus root, and 6 parts prepared licorice root.

5. A method for preparing the traditional Chinese medicine composition for treating recurrent implantation failure as described in any one of claims 1 to 4, characterized in that, Includes the following steps: After weighing each herb in the herbal composition for post-implantation pregnancy support according to the specified weight proportions, the herbs were mixed with water and soaked to obtain the first soaking herbal mixture. The first soaked herbal mixture is decocted for the first time, and the decoction is taken to obtain a herbal composition for post-implantation pregnancy support.

6. The preparation method according to claim 5, characterized in that, Includes the following steps: Weigh each herb in the herbal composition for warming the uterus and tonifying the kidneys according to the weight proportions. Then, wrap the lepidium seed in the herbal decoction material and mix it with the other herbs except for donkey-hide gelatin beads and water to soak, thus obtaining the second soaking herbal composition. After mixing the prepared aconite root in the second soaking herbal composition with water, decoct for 0.5 to 1 hour, then mix with the other soaking herbs for a second decoction. Take the decoction and mix it with donkey-hide gelatin beads to obtain a traditional Chinese medicine composition for warming the uterus and tonifying the kidneys.

7. The preparation method according to claim 5 or 6, characterized in that, The process includes the following steps: weighing each herb in the herbal composition for removing blood stasis and tonifying the kidneys according to the weight proportions; then wrapping the Lepidium seed in a herbal decoction bag and mixing it with other herbs except for donkey-hide gelatin beads and water to soak, thus obtaining the third soaking herbal composition; After mixing the prepared aconite root in the third soaking herbal composition with water, decoct for 0.5 to 1 hour, then mix with the other soaking herbs for a third decoction. Take the decoction and mix it with donkey-hide gelatin beads to obtain a herbal composition for removing blood stasis and tonifying the kidney.

8. The preparation method according to claim 7, characterized in that, The first decoction time is 0.5 to 1 hour, and the first decoction is performed 1 to 2 times. The second decoction time is 0.5 to 1 hour, and the second decoction is performed 1 to 2 times. The third decoction time is 0.5 to 1 hour, and the third decoction is performed 1 to 2 times.

9. The use of the traditional Chinese medicine composition for treating recurrent embryo implantation failure as described in any one of claims 1 to 4, or the traditional Chinese medicine composition for treating recurrent embryo implantation failure prepared by the preparation method described in any one of claims 5 to 8, in the preparation of assisted reproductive drugs.

10. The application according to claim 9, characterized in that, The preparation of assisted reproductive drugs includes the preparation of drugs for treating recurrent embryo implantation failure.

Images