A traditional Chinese medicine composition for warming kidney, assisting pregnancy, promoting blood circulation and regulating menstruation, a preparation method, preparation and application thereof

Abstract

The application belongs to the technical field of traditional Chinese medicines, and provides a traditional Chinese medicine composition for warming kidney, assisting pregnancy, promoting blood circulation and regulating menstruation, a preparation method, a preparation and an application thereof. The traditional Chinese medicine composition comprises the following raw materials: salted cumin, vinegar-fried rhizoma corydalis, prepared rehmannia, angelica, red peony root, cassia twig, dried ginger, vinegar-fried myrrh, chuanxiong, vinegar-fried five spirit resins, mugwort leaf, taxillus, rhizoma dioscoreae, eucommia ulmoides, raspberry, salted semen astragali, purple quartz, deerhorn cream, salted baijiatian and licorice. The compounding of the above-mentioned medicinal ingredients conforms to the theory of traditional Chinese medicine syndrome differentiation. The kidney stores essence and is the main part of reproduction, so the seed for regulating menstruation focuses on kidney tonification. Women are based on blood, so the seed for regulating menstruation is precious in blood nourishment. Women are based on liver, and liver depression can cause infertility, and infertility can cause liver depression, so the seed for regulating menstruation is wonderful in liver smoothing. The curative effect is unique and the prognosis is ideal.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, and provides a traditional Chinese medicine composition that warms the kidneys and aids fertility, invigorates blood and regulates menstruation, as well as its preparation method, formulation and application. Background Technology

[0002] Common causes of infertility include ovulation disorders, fallopian tube blockage or adhesions, uterine developmental abnormalities, endometrial abnormalities, and chromosomal abnormalities, with ovulation disorders being the most prevalent. While some progress has been made in the treatment of infertility, the prognosis is often not optimistic due to the complexity of its causes. The *Suwen* (Plain Questions) chapter "On the Primordial Innocence of Antiquity" records, "At seven years old, a girl's kidney qi is abundant, her teeth change, and her hair grows longer. At fourteen, her *tiankui* (menstrual blood) arrives, the Ren and Chong meridians are vigorous, and menstruation occurs regularly, thus enabling her to conceive." Reproduction is fundamentally based on kidney qi, *tiankui*, and essence and blood. When kidney qi is abundant and *tiankui* matures, the functions of the Chong and Ren meridians are normal. Kidney deficiency is a significant cause of infertility, with many clinical causes producing different symptoms. Ultimately, these causes lead to abnormalities in kidney and Chong / Ren meridian function, preventing normal spermatogenesis and conception.

[0003] Chinese invention patent CN106110143B discloses a gynecological regeneration preparation, mainly composed of Angelica sinensis (processed with wine), Cyperus rotundus (processed with vinegar), Paeonia lactiflora, Rehmannia glutinosa (processed), donkey-hide gelatin, Poria cocos, Codonopsis pilosula, Astragalus membranaceus, Dioscorea opposita, Atractylodes macrocephala, Ligustrum lucidum (processed with wine), Tortoise shell (processed with vinegar), Cornus officinalis, Dipsacus asper, Eucommia ulmoides (processed with salt), Cistanche deserticola, Rubus idaeus, deer antler powder, Ligusticum chuanxiong, Salvia miltiorrhiza, Achyranthes bidentata, Leonurus japonicus, Corydalis yanhusuo, Panax notoginseng (processed with oil), Artemisia argyi (processed with vinegar), Foeniculum vulgare, Ligusticum striatum, Cuttlebone, Sanguisorba officinalis (processed with vinegar), Alpinia oxyphylla, Alisma plantago-aquatica, Nelumbo nucifera (processed with vinegar), Gentiana macrophylla, Lycium chinense root bark, Cynanchum paniculatum, Ailanthus altissima bark, amber, Scutellaria baicalensis (processed with wine), Ziziphus jujuba seed, Polygala tenuifolia (processed), Citrus reticulata peel, and Glycyrrhiza uralensis. It has the effects of nourishing blood and regulating menstruation, tonifying the liver and kidneys, warming the uterus and relieving pain. It can be used for irregular menstruation, prolonged leukorrhea, spotting, dysmenorrhea, and leukorrhea. This preparation can improve endometrial maturity, promote normal development of the endometrium and pinocytosis, thereby improving endometrial receptivity. It can also increase serum estrogen and progesterone levels in rats.

[0004] Currently, clinical treatment of such diseases with traditional Chinese medicine primarily focuses on warming the kidneys, neglecting the fact that fertility is a product of the union of Yin and Yang. The fertile window is a crucial transition period for women, where Yin meets Yang. While nourishing Yin, it is essential to pay attention to the generation of Yang energy to achieve Yin-Yang balance. For example, Tongrentang's Menstrual Regulating and Fertility Promoting Pills use deer antler as the principal ingredient; excessive consumption of tonifying substances can lead to blood loss and uncontrolled bleeding. Summary of the Invention

[0005] Addressing the problems of existing technologies, this invention, based on the principles of Traditional Chinese Medicine (TCM) diagnosis and treatment, emphasizes that the kidneys store essence and govern reproduction; therefore, regulating menstruation and promoting fertility focuses on tonifying the kidneys. Women's health is rooted in blood, so regulating menstruation and promoting fertility prioritizes nourishing the blood. Women's health is also heavily influenced by the liver; liver stagnation can lead to infertility, and infertility can be caused by liver stagnation, thus regulating menstruation and promoting fertility effectively addresses this by soothing the liver. Phlegm and blood stasis obstruct sperm and egg development; removing phlegm and clearing stasis is key to unblocking these pathways. This invention utilizes a compound of 20 Chinese herbs, including salt-processed fennel, vinegar-processed corydalis, prepared rehmannia root, angelica root, red peony root, cinnamon twig, dried ginger, vinegar-processed myrrh, chuanxiong rhizome, vinegar-processed five-spice powder, mugwort leaf, mulberry mistletoe, teasel root, eucommia bark, raspberry, salt-processed dodder seed, amethyst, deer antler powder, salt-processed morinda root, and licorice root. This combination demonstrates a significant and unique therapeutic effect on infertility, with an ideal prognosis.

[0006] The technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for warming the kidneys and aiding fertility, promoting blood circulation and regulating menstruation, comprising the following ingredients by weight: 0.8-1.2 parts salt-processed fennel, 0.8-1.2 parts vinegar-processed corydalis, 1.2-1.8 parts prepared rehmannia root, 0.8-1.2 parts angelica root, 0.8-1.2 parts red peony root, 0.8-1.2 parts cinnamon twig, 0.8-1.2 parts dried ginger, and 0.8-1.2 parts vinegar-processed myrrh. Chuanxiong 0.8-1.2 parts, vinegar-processed Wulingzhi 0.8-1.2 parts, Artemisia argyi 1.2-1.8 parts, Loranthus parasiticus 1.5-2.5 parts, Dipsacus asper 1.2-1.8 parts, Eucommia ulmoides 1.2-1.8 parts, Rubus idaeus 1.5-2.5 parts, salt-processed Cuscuta chinensis 2-4 parts, Amethyst 1.5-2.5 parts, Deer antler powder 1.5-2.5 parts, salt-processed Morinda officinalis 1.2-1.8 parts, and Glycyrrhiza uralensis 0.8-1.2 parts.

[0008] Preferably, the traditional Chinese medicine composition comprises, by weight, the following ingredients: 0.9-1.1 parts salt-processed fennel, 0.9-1.1 parts vinegar-processed corydalis, 1.4-1.6 parts prepared rehmannia root, 0.9-1.1 parts angelica root, 0.9-1.1 parts red peony root, 0.9-1.1 parts cinnamon twig, 0.9-1.1 parts dried ginger, 0.9-1.1 parts vinegar-processed myrrh, and 0.9-1 parts chuanxiong rhizome. 0.1 part, vinegar-processed five-spice powder 0.9-1.1 parts, mugwort 1.4-1.6 parts, mulberry mistletoe 1.8-2.2 parts, calamus root 1.4-1.6 parts, eucommia bark 1.4-1.6 parts, raspberry 1.8-2.2 parts, salt-processed dodder seed 2.5-3.5 parts, amethyst 1.8-2.2 parts, deer antler powder 1.8-2.2 parts, salt-processed morinda root 1.4-1.6 parts, and licorice 0.9-1.1 parts.

[0009] More preferably, the traditional Chinese medicine composition comprises, by weight, the following ingredients: 1 part salted fennel, 1 part vinegar-processed corydalis, 1.5 parts prepared rehmannia root, 1 part angelica root, 1 part red peony root, 1 part cinnamon twig, 1 part dried ginger, 1 part vinegar-processed myrrh, 1 part chuanxiong rhizome, 1 part vinegar-processed trogopterus dung, 1.5 parts mugwort leaf, 2 parts mulberry mistletoe, 1.5 parts dipsacus root, 1.5 parts eucommia bark, 2 parts raspberry, 3 parts salted dodder seed, 2 parts amethyst, 2 parts deer antler powder, 1.5 parts salted morinda root, and 1 part licorice root.

[0010] The efficacy of each ingredient in the traditional Chinese medicine composition of this invention is as follows: Salted fennel is a processed form of fennel, a traditional Chinese medicine. It is the dried, mature fruit of *Foeniculum vulgare* Mill., a plant in the Apiaceae family, which is cleaned and then processed with salt. It contains volatile oils, fatty oils, sterols, glycosides, alkaloids, and other active ingredients. It has the effects of warming the kidneys, dispelling cold, and relieving pain, and is often used to treat abdominal pain due to cold hernia, testicular torsion, menstrual cramps due to cold, and lower abdominal pain. In addition, salted fennel also has a certain effect on regulating qi and the stomach, and can help treat abdominal distension, vomiting, and poor appetite caused by spleen and stomach deficiency and qi stagnation.

[0011] Vinegar-processed Corydalis is a processed product of the traditional Chinese medicine Corydalis yanhusuo after being processed with vinegar. Corydalis yanhusuo is the dried tuber of the plant Corydalis yanhusuo WT Wang, belonging to the Papaveraceae family. It contains alkaloids, anthraquinones, sterols, triterpenoids, nucleosides, amino acids and their derivatives, alcohols and sugars, organic acids, inorganic acids, volatile oils, and trace elements. Traditional Chinese medicine believes that it is pungent and bitter in taste, warm in nature, and enters the liver and spleen meridians, possessing the effects of promoting blood circulation, regulating qi, and relieving pain. After being processed with vinegar, the qi-regulating and pain-relieving effects of Corydalis yanhusuo are enhanced. Clinically, it is often used to treat various pain syndromes caused by qi stagnation and blood stasis, such as chest and rib pain, abdominal pain, amenorrhea and dysmenorrhea, postpartum abdominal pain due to blood stasis, and swelling and pain from falls and injuries.

[0012] Prepared Rehmannia root is the dried tuberous root of Rehmannia glutinosa Libosch., a plant of the Scrophulariaceae family. It is processed and has the effects of nourishing blood and yin, replenishing essence and marrow. It is mainly used to treat blood deficiency syndrome and liver and kidney yin deficiency syndrome, thereby improving symptoms such as palpitations, irregular menstruation, soreness and weakness of the waist and knees, and hot flashes.

[0013] Angelica sinensis (Oliv) Diels., a plant belonging to the genus Angelica in the family Apiaceae, is used as a root. It has the effects of nourishing blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements. It is mainly used to treat blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic pain, injuries from falls and blows, carbuncles and sores, and constipation due to intestinal dryness.

[0014] Red peony root is the dried root of *Paeonia lactiflora* Pall. or *Paeonia veitchii* Lynch, both belonging to the Ranunculaceae family. It contains paeoniflorin, paeoniflorin lactone, ethyl gallate, arbutin, paeoniflorin alcohol, oxypaeoniflorin, paeoniflorin benzoate, catechin, oxy-paeoniflorin, benzoylpaooniflorin, β-sitosterol-α-glucoside, albiflorin, and paeoniflorin-florigenone. It contains components such as 4-ethyl-paeoniflorin, galloylpaeoniflorin, galloylpaeoniflorin, paeoniflorin, β-pinen-10-enyl-β-vicianoside, la-cioflorin, paeoni-lactone A, carotene, and kaempferol. It has the effects of clearing heat and cooling blood, dispersing blood stasis and relieving pain. It is mainly used to treat heat entering the blood level, febrile rashes, hematemesis, epistaxis, red and swollen eyes, liver stagnation and hypochondriac pain, amenorrhea and dysmenorrhea, abdominal masses and pain, traumatic injuries, carbuncles and sores.

[0015] Cinnamon twigs are the dried young branches of Cinnamomum cassia Presl, a plant belonging to the Lauraceae family. They have the effects of inducing sweating and relieving muscle tension, warming and unblocking the meridians, assisting yang and promoting qi circulation, and calming and descending qi. They are mainly used to treat colds due to wind-cold, abdominal pain due to cold, amenorrhea due to cold stagnation, joint pain, phlegm retention, edema, palpitations, and sudden abdominal pain.

[0016] Dried ginger is the dried rhizome of Zingiber officinale Rosc., a plant belonging to the Zingiberaceae family. It has the effects of warming the middle jiao (spleen and stomach), dispelling cold, restoring yang and unblocking the meridians, and warming the lungs and resolving phlegm.

[0017] Myrrh in vinegar is made from the dried resin of the Burseraceae plant *Commiphora myrrha* Engl. or *Commiphora molmol* Engl., which is cleaned, stir-fried, and then sprayed with rice vinegar. The main chemical components of myrrh include resin, gum, volatile oil, salts (sulfates and benzoates), and acids (malic acid and acetic acid). It has the effects of promoting blood circulation, relieving pain, astringing, and promoting tissue regeneration. It is often used to treat various pain syndromes caused by qi stagnation and blood stasis, such as chest pain, stomach pain, dysmenorrhea, and postpartum abdominal pain.

[0018] Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort., a plant in the Apiaceae family. It contains various chemical components such as phthalides, organic acids, alkaloids, and polysaccharides. It has the effects of promoting blood circulation, regulating qi, dispelling wind, and relieving pain. It is mainly used to treat symptoms such as irregular menstruation, dysmenorrhea, headache, and rheumatic pain.

[0019] Vinegar-processed Five-Spice Feces is made from the dried feces of the flying squirrel *Trogopterus xanthipes* Milne-Edwards, which is cleaned, stir-fried, and then sprayed with rice vinegar. Its chemical components include nitrogenous compounds, triterpenoids, flavonoids, lignins, and trace elements. It possesses anti-inflammatory, blood-activating, analgesic, and hemostatic properties, and is commonly used to treat stomach pain, chest and rib pain, dysmenorrhea, menorrhagia, hematemesis, and postpartum lochia retention.

[0020] Artemisia argyi Levl. et Vant., a plant belonging to the genus Artemisia in the family Asteraceae, is a dried leaf. It has the effects of warming the meridians and stopping bleeding, dispelling cold and relieving pain, and eliminating dampness and relieving itching. It is mainly used to treat hematemesis, epistaxis, hemoptysis, hematochezia, metrorrhagia, bleeding during pregnancy, irregular menstruation, dysmenorrhea, threatened abortion, cold pain in the heart and abdomen, chronic diarrhea, cholera with muscle spasms, leukorrhea, eczema, scabies, hemorrhoids, and carbuncles.

[0021] Mulberry mistletoe is the dried leafy stem and branches of *Taxillus chinensis* (DC.) Danser, a plant belonging to the genus *Taxillus* in the family Loranthaceae. It has the effects of dispelling wind and dampness, tonifying the liver and kidneys, strengthening muscles and bones, and calming the fetus. It is mainly used to treat rheumatic pain, soreness and weakness of the lower back and knees, weakness of muscles and bones, metrorrhagia, threatened miscarriage, threatened abortion, dizziness, and vertigo.

[0022] Dipsacus root slices are a processed form of the traditional Chinese medicine Dipsacus root, specifically the dried root of the plant *Dipsacus asper Wall.* ex Henry (family Dipsacaceae). After cleaning and processing, it primarily functions to tonify the liver and kidneys, and strengthen tendons and bones. It is commonly used to treat liver and kidney deficiency, lower back and knee weakness, and rheumatic pain. Furthermore, Dipsacus root slices also have certain effects in healing fractures and stopping metrorrhagia, and can help treat injuries from falls, muscle and bone fractures, metrorrhagia, and threatened abortion.

[0023] Eucommia ulmoides Oliv., a plant belonging to the Eucommia genus of the Eucommiaceae family, is used for its bark. It is believed to tonify the liver and kidneys, strengthen muscles and bones, and calm the fetus. It is primarily used to treat liver and kidney deficiency, lower back and knee pain, weakness of muscles and bones, dizziness, threatened abortion, and fetal restlessness.

[0024] Raspberry is the immature fruit of *Rubus chingii* Hu, a plant belonging to the genus *Rubus* in the Rosaceae family. It has the effects of tonifying the kidneys, strengthening essence, reducing urination, nourishing the liver, and improving eyesight. It is mainly used for spermatorrhea, enuresis, frequent urination, impotence, premature ejaculation, and blurred vision.

[0025] Salt-processed dodder seed is the dried, mature seed of *Cuscuta australis* R.Br. or *Cuscutachinensis* Lam., belonging to the Convolvulaceae family. It is processed through cleaning and salting. Salt-processed dodder seed primarily tonifies the liver and kidneys, strengthens essence and reduces urination, and calms the fetus. It is commonly used to treat impotence, seminal emission, enuresis, leukorrhea, kidney deficiency leading to threatened abortion, and fetal restlessness.

[0026] Amethyst is a fluorite group of halide minerals, mainly containing calcium fluoride (CaF2). It has the effects of warming the kidneys and uterus, calming the mind and soothing the nerves, and warming the lungs and relieving asthma. It is mainly used to treat kidney yang deficiency, infertility due to cold uterus, palpitations, insomnia, and cough and asthma due to deficiency and cold.

[0027] Deer antler powder is the antler fragment removed from the antlers of the sika deer (Cervus nippon Temminck) or red deer (Cervus elaphus Linnaeus). It has the effects of warming the kidneys and invigorating yang, astringing and stopping bleeding. It is mainly used to treat spleen and kidney yang deficiency, excessive leukorrhea, enuresis and frequent urination, metrorrhagia, and non-healing sores.

[0028] Salt-processed Morinda officinalis is the dried root of Morinda officinalis How, a plant in the Rubiaceae family, which is processed with salt. This product is mainly produced in Guangdong and Guangxi provinces. It primarily has the effect of tonifying the kidneys and strengthening yang, and is often used to treat impotence, premature ejaculation, lower back and knee weakness, infertility due to cold uterus, and irregular menstruation caused by kidney yang deficiency.

[0029] Licorice is derived from the dried roots and rhizomes of Glycyrrhiza uralensis, Glycyrrhiza inflata, or Glycyrrhiza glabra, all belonging to the legume family. It has the effects of tonifying the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, and relieving spasms and pain. It is often used to treat spleen and stomach weakness, insufficient heart qi, heat toxicity syndrome, cough and asthma, abdominal or limb spasms and pain. It can also harmonize various medicines, alleviate drug toxicity, and balance the properties of medicinal materials, and is widely used in prescriptions.

[0030] In this invention, the herbal composition uses salt-processed fennel as the principal ingredient, which regulates qi, dispels cold, warms the meridians, and relieves pain. Vinegar-processed corydalis invigorates blood, promotes qi circulation, and relieves pain; prepared rehmannia root nourishes blood and yin; angelica root nourishes blood, regulates menstruation, invigorates blood, and relieves pain; red peony root disperses blood stasis and relieves pain; cinnamon twig warms and unblocks the meridians, assists yang, and transforms qi; dried ginger slices warm the middle jiao and dispel cold; vinegar-processed myrrh invigorates blood and relieves pain; chuanxiong rhizome invigorates blood and promotes qi circulation; and vinegar-processed five-spice powder invigorates blood and removes blood stasis. These serve as assistant ingredients, contributing to invigorating blood, removing blood stasis, and relieving pain. Artemisia argyi dispels cold and warms the meridians; mulberry mistletoe and teasel root tonify the liver and kidneys and strengthen tendons and bones; eucommia bark and raspberry tonify the kidneys and nourish yin; salt-processed dodder seed tonifies the kidneys and benefits essence; amethyst warms the kidneys and assists yang; deer antler powder tonifies kidney yang; raw licorice root warms the middle jiao; and prepared morinda root warms the kidneys and strengthens yang. These herbs serve as adjuvant ingredients, contributing to the balance of yin and yang and aiding in fertility. The principal, assistant, adjuvant, and adjuvant ingredients in this formula work together to warm the kidneys, aid fertility, invigorate blood, and regulate menstruation.

[0031] Secondly, the present invention also provides a method for preparing any of the above-mentioned traditional Chinese medicine compositions, comprising the following steps: (1) Take salted fennel, vinegar-processed corydalis, prepared rehmannia root, angelica, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, eucommia bark, raspberry, deer antler powder and salted morinda root, grind them into fine powder and sieve them, and mix them thoroughly to obtain mixed medicinal powder; (2) Take dried ginger, vinegar-processed five-spice powder, mugwort leaves, salt-processed dodder seeds, amethyst, and licorice, add water and decoct, then concentrate the filtrate into a clear paste; (3) Mix the clear paste and the mixed powder thoroughly and dry to obtain the final product.

[0032] As some specific embodiments of the present invention, in step (2), the decoction is performed 1-3 times, and the amount of water added each time is 10-15 times the total mass of dried ginger, vinegar-processed five-spice powder, mugwort leaves, salted dodder seeds, amethyst and licorice; each decoction is performed for 0.5-1.5 hours.

[0033] As some specific embodiments of the present invention, in step (2), the relative density of the ointment at 60°C is 1.30-1.35.

[0034] Thirdly, the present invention also provides a traditional Chinese medicine preparation, which is prepared by combining a traditional Chinese medicine composition or a traditional Chinese medicine composition prepared by any of the above-described methods with pharmaceutically acceptable excipients.

[0035] Preferably, the pharmaceutically acceptable excipients include one or more of microcrystalline cellulose, povidone, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch; preferably sodium carboxymethyl cellulose.

[0036] As some specific embodiments of the present invention, the preparation method of the traditional Chinese medicine preparation is as follows: take the traditional Chinese medicine composition, pulverize it into fine powder, add excipients and mix thoroughly, then dry and granulate or add water to make pills, and the preparation is obtained.

[0037] Fourthly, the present invention also provides the application of any of the above-described traditional Chinese medicine compositions, traditional Chinese medicine compositions prepared by any of the above-described preparation methods, or traditional Chinese medicine preparations described above in the preparation of drugs for treating kidney tonification and fertility enhancement, and promoting blood circulation and regulating menstruation.

[0038] Compared with the prior art, the present invention has the following beneficial effects: The herbal composition of this invention adopts the TCM theory of syndrome differentiation and treatment. Salt-processed fennel is the principal herb, regulating qi, dispelling cold, warming the meridians, and relieving pain. Vinegar-processed corydalis invigorates blood, promotes qi circulation, and relieves pain; prepared rehmannia root nourishes blood and yin; angelica root nourishes blood, regulates menstruation, invigorates blood, and relieves pain; red peony root disperses blood stasis and relieves pain; cinnamon twig warms and unblocks the meridians, assists yang, and transforms qi; dried ginger slices warm the middle jiao and dispel cold; vinegar-processed myrrh invigorates blood and relieves pain; chuanxiong rhizome invigorates blood and promotes qi circulation; vinegar-processed five-spice powder invigorates blood and removes blood stasis. These are all assistant herbs, playing the roles of invigorating blood, removing blood stasis, and relieving pain. Artemisia argyi dispels cold and warms the meridians; mulberry mistletoe and teasel root tonify the liver and kidneys and strengthen tendons and bones; eucommia bark and raspberry tonify the kidneys and nourish yin; salt-processed dodder seed tonifies the kidneys and benefits essence; amethyst warms the kidneys and assists yang; deer antler powder tonifies kidney yang; raw licorice root warms the middle jiao; and prepared morinda root warms the kidneys and strengthens yang. These herbs are all adjuvant herbs, playing the role of yin and yang harmonizing and assisting in female fertility. The formula, consisting of principal, assistant, adjuvant, and guiding herbs, works together to warm the kidneys, aid fertility, invigorate blood circulation, and regulate menstruation. Detailed Implementation

[0039] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0040] Example 1 A traditional Chinese medicine composition, comprising the following ingredients: 10g of salted fennel, 10g of vinegar-processed corydalis, 15g of prepared rehmannia root, 10g of angelica root, 10g of red peony root, 10g of cinnamon twig, 10g of dried ginger, 10g of vinegar-processed myrrh, 10g of chuanxiong rhizome, 10g of vinegar-processed trogopterus dung, 15g of mugwort leaf, 20g of mulberry mistletoe, 15g of dipsacus root, 15g of eucommia bark, 20g of raspberry, 30g of salted dodder seed, 20g of amethyst, 20g of deer antler powder, 15g of salted morinda root, and 10g of licorice root.

[0041] The specific preparation method is as follows: Take salt-processed fennel, vinegar-processed corydalis, prepared rehmannia root, angelica root, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, eucommia bark, raspberry, deer antler powder, and salt-processed morinda root. Grind them into fine powder and sieve them. Mix them thoroughly to obtain a mixed medicinal powder. Take dried ginger, vinegar-processed trogopterus dung, mugwort leaf, salt-processed dodder seed, amethyst, and licorice root and decoct them in water (see Table 1 for specific decoction process parameters). Filter the decoction and concentrate the filtrate to a clear extract with a relative density of 1.30-1.35 (60℃). Mix the clear extract with the above mixed medicinal powder and dry it to obtain the final product.

[0042] The hyperoside content of the extracts obtained from different extraction processes was determined according to the method for determining hyperoside content in Cuscuta chinensis, Part I, Chinese Pharmacopoeia 2020. The results are shown in Table 1.

[0043] The chromatographic conditions were as follows: column: ACQUITY UPLC BEH C18 column (50×2.1mm, 1.7μm); mobile phase: acetonitrile-0.1% phosphoric acid solution (13:87); flow rate: 0.3mL / min; column temperature: room temperature; detection wavelength: 360nm; injection volume: 1.0μL.

[0044] Preparation of reference standards: Take the extract, centrifuge (3500 rpm / 15 min), take 5 mL of the supernatant from each group, evaporate to dryness in a water bath, transfer with methanol and make up to 5 mL, filter through a microporous membrane (0.22 μm) to obtain the reference standard.

[0045] Sample content determination: According to General Chapter 0512 of the 2020 edition of the Chinese Pharmacopoeia, 1.0 μL of the reference solution and each test solution were accurately pipetted into the liquid chromatograph and determined. The results are shown in Table 1.

[0046] Table 1

[0047] Note: The amount of water added is based on the total mass of dried ginger, vinegar-processed ginseng, mugwort, salted dodder seed, amethyst, and licorice.

[0048] It can be seen that when the amount of water added is 8-12 times, the extraction time is 1-2 hours, and the number of extractions is 1-3 times, the hyperoside content is above 10mg and the dry extract is above 1.5g. The extraction effect is better when the amount of water added is 10-12 times. Among them, the process of adding 12 times the amount of water, extracting 3 times, and extracting for 1 hour each time is the best.

[0049] Example 2 A traditional Chinese medicine composition, comprising the following ingredients: 8g of salted fennel, 12g of vinegar-processed corydalis, 18g of prepared rehmannia root, 12g of angelica root, 12g of red peony root, 12g of cinnamon twig, 12g of dried ginger, 12g of vinegar-processed myrrh, 12g of chuanxiong rhizome, 12g of vinegar-processed trogopterus dung, 18g of mugwort leaf, 25g of mulberry mistletoe, 18g of dipsacus root, 18g of eucommia bark, 25g of raspberry, 40g of salted dodder seed, 25g of amethyst, 25g of deer antler powder, 18g of salted morinda root, and 12g of licorice root.

[0050] The specific preparation method is as follows: The preparation method is the same as in Example 1 (using the optimal process of Example 1).

[0051] Example 3 A traditional Chinese medicine composition, comprising the following ingredients: 12g of salted fennel, 8g of vinegar-processed corydalis, 12g of prepared rehmannia root, 8g of angelica root, 8g of red peony root, 8g of cinnamon twig, 8g of dried ginger, 8g of vinegar-processed myrrh, 8g of chuanxiong rhizome, 8g of vinegar-processed trogopterus dung, 12g of mugwort leaf, 15g of mulberry mistletoe, 12g of teasel root, 12g of eucommia bark, 15g of raspberry, 20g of salted dodder seed, 15g of amethyst, 15g of deer antler powder, 12g of salted morinda root, and 8g of licorice root.

[0052] The preparation method is the same as in Example 1 (using the optimal process of Example 1).

[0053] Comparative Example 1 A traditional Chinese medicine composition, comprising the following ingredients: 15g salt-processed fennel seeds, 5g vinegar-processed corydalis rhizome, 15g prepared rehmannia root, 15g angelica root, 10g red peony root, 10g cinnamon twig, 15g dried ginger, 10g vinegar-processed myrrh, 10g chuanxiong rhizome, 10g vinegar-processed trogopterus dung, 15g mugwort leaf, 20g mulberry mistletoe, 15g dipsacus root, 15g eucommia bark, 20g raspberry, 30g salt-processed dodder seed, 20g amethyst, 20g deer antler powder, 15g salt-processed morinda root, and 10g licorice root.

[0054] The preparation method is the same as in Example 1 (using the optimal process of Example 1).

[0055] Comparative Example 2 A traditional Chinese medicine composition, comprising the following ingredients: 10g salted fennel, 20g vinegar-processed corydalis, 15g prepared rehmannia root, 10g angelica root, 10g red peony root, 10g cinnamon twig, 10g dried ginger, 10g vinegar-processed myrrh, 10g vinegar-processed trogopterus dung, 15g mugwort leaf, 35g mulberry mistletoe, 15g eucommia bark, 20g raspberry, 30g salted dodder seed, 20g amethyst, 20g deer antler powder, 15g salted morinda root, and 10g licorice root.

[0056] The specific preparation method is as follows: Take salt-processed fennel, vinegar-processed corydalis, prepared rehmannia root, angelica root, red peony root, cinnamon twig, vinegar-processed myrrh, mulberry mistletoe, eucommia bark, raspberry, deer antler powder, and salt-processed morinda root. Grind them into fine powder and sieve them. Mix them thoroughly to obtain a mixed medicinal powder. Take dried ginger, vinegar-processed trogopterus dung, mugwort leaf, salt-processed dodder seed, amethyst, and licorice root and decoct them in water (using the best process in Example 1). Filter the decoction and concentrate the filtrate to a clear extract with a relative density of 1.30-1.35 (60℃). Mix the clear extract with the above mixed medicinal powder and dry it to obtain the final product.

[0057] Comparative Example 3 A traditional Chinese medicine composition, comprising the following ingredients: 10g salted fennel, 10g vinegar-processed corydalis, 15g prepared rehmannia root, 10g angelica root, 10g red peony root, 10g cinnamon twig, 10g dried ginger, 10g vinegar-processed myrrh, 10g chuanxiong rhizome, 10g vinegar-processed trogopterus dung, 15g mugwort leaf, 20g mulberry mistletoe, 15g dipsacus root, 20g eucommia bark, 30g raspberry, 30g salted dodder seed, 15g amethyst, 15g deer antler powder, 10g salted morinda root, and 10g licorice root.

[0058] The preparation method is the same as in Example 1 (using the optimal process of Example 1).

[0059] Comparative Example 4 A traditional Chinese medicine composition, comprising the following ingredients: 10g salted fennel, 10g vinegar-processed corydalis, 15g prepared rehmannia root, 10g angelica root, 10g red peony root, 10g cinnamon twig, 10g dried ginger, 10g vinegar-processed myrrh, 10g chuanxiong rhizome, 10g vinegar-processed trogopterus dung, 15g mugwort leaf, 20g mulberry mistletoe, 15g teasel root, 30g salted dodder seed, 20g amethyst, 20g deer antler powder, 15g salted morinda root, and 10g licorice root.

[0060] The specific preparation method is as follows: Take salt-processed fennel, vinegar-processed corydalis, prepared rehmannia root, angelica root, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, deer antler powder, and salt-processed morinda root. Grind them into fine powder and sieve them. Mix them thoroughly to obtain a mixed medicinal powder. Take dried ginger, vinegar-processed trogopterus dung, mugwort leaf, salt-processed dodder seed, amethyst, and licorice root and decoct them in water (using the best process in Example 1). Filter the decoction and concentrate the filtrate to a clear extract with a relative density of 1.30-1.35 (60℃). Mix the clear extract with the above mixed medicinal powder and dry it to obtain the final product.

[0061] Comparative Example 5 A traditional Chinese medicine composition, comprising the following ingredients: 10g salted fennel, 10g vinegar-processed corydalis, 15g prepared rehmannia root, 10g angelica root, 10g red peony root, 10g cinnamon twig, 10g dried ginger, 10g vinegar-processed myrrh, 10g chuanxiong rhizome, 10g vinegar-processed trogopterus dung, 15g mugwort leaf, 20g mulberry mistletoe, 15g dipsacus root, 15g eucommia bark, 20g raspberry, 30g salted dodder seed, and 10g licorice root.

[0062] The specific preparation method is as follows: Take salt-processed fennel, vinegar-processed corydalis, prepared rehmannia root, angelica root, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, eucommia bark, and raspberry, grind them into fine powder and sieve them, and mix them thoroughly to obtain a mixed medicinal powder; take dried ginger, vinegar-processed trogopterus dung, mugwort leaf, salt-processed dodder seed, and licorice root, add water and decoct (using the best process in Example 1), filter the decoction, and concentrate the filtrate to a clear paste with a relative density of 1.30-1.35 (60℃); mix the clear paste with the above mixed medicinal powder, dry it, and you will get the final product.

[0063] Comparative Example 6 A traditional Chinese medicine composition, comprising the following ingredients: 10g salt-processed fennel, 10g motherwort, 15-5g prepared rehmannia root, 10g angelica root, 5g donkey-hide gelatin, 10g red peony root, 10g cinnamon twig, 10g dried ginger, 10g vinegar-processed myrrh, 5g chuanxiong rhizome, 5g white peony root, 10g vinegar-processed five-spice powder, 15g mugwort leaf, 20g mulberry mistletoe, 15g dipsacus root, 15g eucommia bark, 20g raspberry, 30g salt-processed dodder seed, 20g amethyst, 20g deer antler powder, 15g salt-processed morinda root, and 10g poria cocos.

[0064] The specific preparation method is as follows: Take salt-processed fennel, motherwort, prepared rehmannia root, angelica root, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, eucommia bark, raspberry, deer antler powder, and salt-processed morinda root. Grind them into fine powder and sieve them. Mix them thoroughly to obtain a mixed medicinal powder. Take dried ginger, vinegar-processed trogopterus dung, mugwort leaf, salt-processed dodder seed, amethyst, and poria cocos. Add water and decoct (using the best process in Example 1). Filter the decoction and concentrate the filtrate to a clear extract with a relative density of 1.30-1.35 (60℃). Mix the clear extract with the above mixed medicinal powder and dry it to obtain the final product.

[0065] Test Example 1: In vivo pharmacodynamic test Healthy, mature female KM mice (5-6 weeks old, weighing 25-30g) with normal reproductive function were selected. Before the experiment, they had free access to drinking water. After a 7-day acclimatization period, they were randomly divided into 11 groups: a normal control group, a model group, Examples 1-3 groups, and Comparative Examples 1-6 groups, with 10 mice in each group. Except for the normal control group, the other groups were intraperitoneally injected with busulfan solution (concentration 30mg / kg, solvent: water, containing 3.75mL / kg DMSO). The control group was intraperitoneally injected with 3.75mL / kg DMSO. After 30 days of routine feeding, Examples 1-3 groups and Comparative Examples 1-6 groups were administered the corresponding traditional Chinese medicine composition by gavage at 350mg / kg / day, while the normal control group and model group were administered an equal volume of distilled water by gavage. The administration lasted for 4 weeks. Twenty-four hours after the last administration, blood was collected from the abdominal aorta, centrifuged at 3000 rpm for 15 min, and serum was separated. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) in the serum were measured using an ELISA kit. The results are shown in Table 2. Then, the rats were sacrificed, dissected, and the ovaries were removed, weighed, and the ovarian coefficient and oocyte malformation rate were calculated (ovarian coefficient = ovarian weight / body weight × 1000; oocyte malformation rate = (total number of ovulations - normal MII phase cells) / total number of ovulations). The results are shown in Table 3.

[0066] Table 2. Serum sex hormone levels in mice of each group (n=10, X±s)

[0067] Note: Compared with the normal control group, && P<0.01; compared with the model group, # P <0.05, ## P <0.01; compared with Example 1 group, ^ P <0.05, ^^ P <0.01.

[0068] Table 3. Ovulation index and oocyte malformation rate of mice in each group (n=10, X±s)

[0069] Note: Compared with the normal control group, && P < 0.01; compared with the model group, # P < 0.05 ## P < 0.01; compared with Example 1 group, ^ P <0.05, ^^ P <0.01.

[0070] As can be seen from the data in Tables 2 and 3, compared with the normal control group, the serum FSH and LH levels of mice in the model group were significantly reduced and the E2 level was significantly increased; at the same time, the ovulation coefficient was significantly reduced and the oocyte malformation rate was significantly increased, indicating that the infertility model was successfully established.

[0071] Compared with the model group, the mice in Examples 1-3 of this invention showed significantly lower FSH and LH levels, significantly higher E2 levels, significantly higher ovulation coefficients, and significantly lower oocyte malformation rates, indicating that the composition of this invention can restore infertility caused by busulfan and can restore it to normal levels.

[0072] Compared with the model group, although the serum estrogen level, ovarian coefficient and oocyte malformation rate of mice in Comparative Examples 1-6 were also improved to varying degrees, they were significantly worse than those in Examples 1-3, and the differences were statistically significant. This shows that the traditional Chinese medicine composition of the present invention has a more significant therapeutic effect on improving infertility in specific components and proportions.

[0073] Example 4: A pill with warming and fertility-aiding effects, the specific steps are as follows: Take the traditional Chinese medicine composition of Example 1, pulverize it into fine powder (pass through a 120-mesh sieve), and mix it thoroughly with excipients (concentrated pill 1: sodium carboxymethyl cellulose; concentrated pill 2: microcrystalline cellulose; concentrated pill 3: hydroxypropyl methylcellulose; concentrated pill 4: sodium carboxymethyl starch) at a mass ratio of 7:3. Then add water to make pills to obtain the corresponding concentrated pills.

[0074] Test Example 2: Stability Assessment The concentrated pills were placed at 40℃±2℃ and 75%±5% relative humidity for 6 months, and tested according to the key stability test items. Samples were taken at the end of months 0, 3, and 6 of the test period to observe the properties of the preparation. The dissolution time and moisture content of the three batches of samples were checked according to the relevant requirements of the General Chapter 0108 Pills in Part IV of the 2020 edition of the Chinese Pharmacopoeia to observe the stability of the samples. The results are shown in Table 4.

[0075] Table 4 Stability Test Results

[0076] As can be seen from Table 5, the concentrated pills prepared by the present invention can be stably stored for 6 months under accelerated conditions. Among them, the concentrated pills prepared with sodium carboxymethyl cellulose or hydroxypropyl cellulose as excipients can be stably stored for more than 9 months under the aforementioned conditions, and the stability is further improved. The traditional Chinese medicine composition of the present invention has better stability under the preferred excipients of sodium carboxymethyl cellulose or hydroxypropyl cellulose, and even more preferably sodium carboxymethyl cellulose.

[0077] Test Example 3: Clinical Trial From December 2018 to December 2020, this formula was used to treat 1,000 cases of habitual abortion and threatened abortion in clinical observation. The patients were treated with concentrated pill 1 prepared in Example 4, one pill twice a day, for a course of 3 months.

[0078] The treatment results are statistically analyzed as follows: Cured: 841 cases (84.1%); Effective: 141 cases (14.1%); Ineffective: 18 cases (1.8%); Overall effective rate: 98.2%.

[0079] No adverse reactions have occurred in clinical applications over many years, and no liver or kidney damage has been observed with long-term use (more than 3 months).

[0080] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A traditional Chinese medicine composition for warming the kidneys and aiding fertility, promoting blood circulation and regulating menstruation, characterized in that, The product is made from the following ingredients by weight: 0.8-1.2 parts salted fennel seeds, 0.8-1.2 parts vinegar-processed corydalis rhizome, 1.2-1.8 parts prepared rehmannia root, 0.8-1.2 parts angelica root, 0.8-1.2 parts red peony root, 0.8-1.2 parts cinnamon twig, 0.8-1.2 parts dried ginger, 0.8-1.2 parts vinegar-processed myrrh, 0.8-1.2 parts chuanxiong rhizome, and vinegar-processed five-spice powder. The ingredients are: 0.8-1.2 parts of sesame oil, 1.2-1.8 parts of mugwort, 1.5-2.5 parts of mulberry mistletoe, 1.2-1.8 parts of teasel root, 1.2-1.8 parts of eucommia bark, 1.5-2.5 parts of raspberry, 2-4 parts of salted dodder seed, 1.5-2.5 parts of amethyst, 1.5-2.5 parts of deer antler powder, 1.2-1.8 parts of salted morinda root, and 0.8-1.2 parts of licorice root.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The following ingredients are used in the following proportions by weight: 1 part salted fennel, 1 part vinegar-processed corydalis, 1.5 parts prepared rehmannia root, 1 part angelica root, 1 part red peony root, 1 part cinnamon twig, 1 part dried ginger, 1 part vinegar-processed myrrh, 1 part chuanxiong rhizome, 1 part vinegar-processed trogopterus dung, 1.5 parts mugwort leaf, 2 parts mulberry mistletoe, 1.5 parts dioscorea bulbifera, 1.5 parts eucommia bark, 2 parts raspberry, 3 parts salted dodder seed, 2 parts amethyst, 2 parts deer antler powder, 1.5 parts salted morinda root, and 1 part licorice root.

3. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, Includes the following steps: (1) Take salted fennel, vinegar-processed corydalis, prepared rehmannia root, angelica, red peony root, cinnamon twig, vinegar-processed myrrh, chuanxiong rhizome, mulberry mistletoe, teasel root, eucommia bark, raspberry, deer antler powder and salted morinda root, grind them into fine powder and sieve them, and mix them thoroughly to obtain mixed medicinal powder; (2) Take dried ginger, vinegar-processed five-spice powder, mugwort leaves, salt-processed dodder seeds, amethyst, and licorice, add water and decoct, then concentrate the filtrate into a clear paste; (3) Mix the clear paste and the mixed powder thoroughly and dry to obtain the final product.

4. The preparation method according to claim 3, characterized in that, In step (2), the decoction is performed 1-3 times, and the amount of water added each time is 10-15 times the total mass of dried ginger, vinegar-processed five-spice powder, mugwort leaves, salted dodder seeds, amethyst and licorice; each decoction is performed for 0.5-1.5 hours.

5. The preparation method according to claim 3, characterized in that, In step (2), the relative density of the ointment at 60°C is 1.30-1.

35.

6. A traditional Chinese medicine preparation, characterized in that, It is prepared from a traditional Chinese medicine composition and pharmaceutically acceptable excipients, wherein the traditional Chinese medicine composition is the traditional Chinese medicine composition according to claim 1 or 2 or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 3-5.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that, The pharmaceutically acceptable excipients include one or more of the following: microcrystalline cellulose, povidone, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch.

8. The traditional Chinese medicine preparation according to claim 7, characterized in that, The pharmaceutically acceptable excipient is sodium carboxymethyl cellulose.

9. The traditional Chinese medicine preparation according to any one of claims 6-8, characterized in that, The preparation method of the traditional Chinese medicine preparation is as follows: take the traditional Chinese medicine composition, pulverize it into fine powder, add excipients and mix thoroughly, then dry and granulate or add water to make pills to obtain the preparation.

10. The use of the traditional Chinese medicine composition according to claim 1 or 2, the traditional Chinese medicine composition prepared by any of the preparation methods according to claims 3-5, or the traditional Chinese medicine preparation according to any of claims 6-9 in the preparation of drugs for warming the kidneys and assisting fertility, and for promoting blood circulation and regulating menstruation.

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