A traditional Chinese medicine composition, preparation and application for improving ovarian function

Abstract

This invention relates to the field of traditional Chinese medicine (TCM) technology, specifically providing a TCM composition, preparation, and application for improving ovarian function. The TCM composition of this invention, by weight, comprises: 10-50 parts of Cuscuta chinensis, 5-35 parts of Cistanche deserticola, 10-50 parts of Lycium barbarum, 10-50 parts of Polygonatum sibiricum, 10-50 parts of Codonopsis pilosula, 5-25 parts of Atractylodes macrocephala, 5-25 parts of Nelumbo nucifera leaf, 5-25 parts of Dendrobium nobile, 5-30 parts of Lilium brownii, 5-30 parts of Rosa rugosa, 5-30 parts of Rosa chinensis var. chinensis, 5-25 parts of Paeonia lactiflora, 10-50 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea. Compared with existing technologies, the components of the TCM composition of this invention are scientifically formulated and synergistically act, exhibiting a better therapeutic effect on improving ovarian dysfunction. The preparation method is simple, with significant efficacy and no toxic side effects.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and more specifically, to a traditional Chinese medicine composition, preparation and application for improving ovarian function. Background Technology

[0002] Diminished ovarian reserve (DOR) is caused by a decrease in the number and / or quality of oocytes, leading to insufficient ovarian function and decreased fertility. It is accompanied by decreased anti-Müllerian hormone (AMH) levels, a reduced antral follicle count (AFC), and elevated basal FSH levels. DOR is divided into two categories: physiological DOR related to advanced age and pathological DOR inconsistent with age. Patients may experience one or more of the following: Reduced fertility: mainly manifested as infertility, difficulty conceiving, high risk of early miscarriage, recurrent miscarriage, poor responsiveness to Gn, and recurrent embryo implantation failure. In the early stages of DOR, natural ovulation still occurs, but the monthly pregnancy rate decreases from 20%–25% in normal women to 5%–10%, and spontaneous abortion and fetal chromosomal abnormalities are more likely to occur. Menstrual irregularities: DOR usually presents with regular menstruation, but can also manifest as various menstrual disorders, including infrequent or frequent menstruation, prolonged or shortened menstrual periods, amenorrhea, and fluctuating menstrual flow. Symptoms related to sex hormone deficiency or fluctuations vary in severity and are similar to menopausal symptoms, but are generally milder or less pronounced. Laboratory tests: AMH: AMH < 1.1 ng / ml; AFC: AFC < 5-7 in both ovaries; Basal FSH: Basal FSH ≥ 10 IU / L for two consecutive menstrual cycles. Currently, DOR treatment is lengthy and challenging, making it one of the hot topics and difficulties in clinical research in the field of reproductive health in recent years. Western medicine currently lacks a reliable treatment plan to effectively restore ovarian function and improve fertility rates for DOR. Clinically, hormone replacement therapy is the main approach, but relapse is common upon discontinuation, and long-term use increases the risk of cardiovascular disease and breast cancer. Decreased ovarian function delays a woman's conception time and affects the entire family's expected progress, placing significant pressure on patients. However, current technologies often have low cure rates for these diseases, thus there is an urgent need for a traditional Chinese medicine combination that can treat these conditions and increase the chances of conception. Summary of the Invention

[0003] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine composition, preparation and application for improving ovarian function. The components of the traditional Chinese medicine composition of the present invention are scientifically matched and work synergistically to improve ovarian dysfunction.

[0004] To achieve the above objectives, the present invention adopts the following technical solution:

[0005] A traditional Chinese medicine composition for improving ovarian function, comprising, by weight: 10-50 parts of Cuscuta chinensis, 5-35 parts of Cistanche deserticola, 10-50 parts of Lycium barbarum, 10-50 parts of Polygonatum sibiricum, 10-50 parts of Codonopsis pilosula, 5-25 parts of Atractylodes macrocephala, 5-25 parts of Nelumbo nucifera leaf, 5-25 parts of Dendrobium nobile, 5-30 parts of Lilium brownii, 5-30 parts of Rosa rugosa, 5-30 parts of Rosa chinensis var. chinensis, 5-25 parts of Paeonia lactiflora, 10-50 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea.

[0006] The following information, based on the Chinese Pharmacopoeia, the Dictionary of Traditional Chinese Medicine, and Chinese Herbal Medicine, introduces the properties, channels, functions, and indications of the main raw materials.

[0007] Cuscuta semen: Its properties are pungent, sweet, and neutral. It enters the kidney, liver, and spleen meridians. Its functions include tonifying the kidneys and replenishing essence, nourishing the liver and improving eyesight, stopping diarrhea, and calming the fetus. It is used for kidney deficiency causing lower back pain, impotence, seminal emission, frequent urination, and infertility due to cold uterus; liver and kidney deficiency causing blurred vision; spleen and kidney yang deficiency causing loose stools and diarrhea; and kidney deficiency causing threatened abortion.

[0008] Cistanche herba: Sweet, salty, and warm in nature. It enters the kidney and large intestine meridians. Functions: Tonifies the kidney and strengthens yang; primarily treats kidney yang deficiency, insufficient essence and blood, impotence, premature ejaculation, infertility due to cold uterus, lower back and knee weakness, and general weakness.

[0009] Goji berries (Lycii fructus): Sweet and neutral in nature. Enters the liver and kidney meridians. Functions: Nourishes the liver and kidneys, benefits essence and improves eyesight. Used for liver and kidney yin deficiency and premature aging.

[0010] Polygonatum rhizoma: Sweet and neutral in nature. It enters the spleen, lung, and kidney meridians. Its functions include tonifying qi and nourishing yin, strengthening the spleen, moistening the lungs, and benefiting the kidneys. It is used for yin deficiency and lung dryness, dry cough with little phlegm, lung and kidney yin deficiency, chronic cough due to overwork; spleen and stomach weakness; kidney essence deficiency, internal heat, and thirst.

[0011] Codonopsis radix: Sweet and neutral in nature. It enters the spleen and lung meridians. Its functions include tonifying spleen and lung qi, nourishing blood, and promoting the production of body fluids. It is primarily used to treat spleen and lung qi deficiency syndrome and qi and blood deficiency syndrome.

[0012] White peony root (Paeoniae radix alba): Bitter, sour, and slightly cold in nature. It enters the liver and spleen meridians. Functions: Nourishes blood and astringes yin, softens the liver and relieves pain, and calms liver yang. Used for liver blood deficiency and irregular menstruation; liver and spleen disharmony, chest, rib, and abdominal pain, and spasms and pain in the limbs; and liver yang hyperactivity, headache, and dizziness.

[0013] Lotus leaf (Nelumbinis folium): Bitter and neutral in nature. Functions: Clears summer heat and promotes diuresis. Mainly used to treat summer heat-related illnesses, spleen deficiency diarrhea, etc.

[0014] Dendrobium (Dendrobii caulis): Sweet and slightly cold in nature. It enters the stomach and kidney meridians; its functions include nourishing the stomach and promoting the production of body fluids, nourishing yin and clearing heat. It is primarily used to treat stomach and kidney yin deficiency syndrome.

[0015] Atractylodes macrocephalae rhizoma: Sweet, bitter, and warm in nature. It enters the spleen and stomach meridians. Functions: Tonifies qi and strengthens the spleen, dries dampness and promotes diuresis, stops sweating, and calms the fetus. Primarily treats spleen qi deficiency syndrome.

[0016] Rose (Rosaerugosaeflos): It is sweet, slightly bitter and warm in nature, and enters the liver and spleen meridians. It has the effects of soothing the liver and relieving depression, promoting blood circulation and relieving pain, without the drawbacks of being too dry and damaging to yin.

[0017] Rose (Rosae chinensis flos): It is sweet, slightly bitter, and neutral in nature, and enters the liver meridian. It has the effects of soothing the liver and relieving depression, promoting blood circulation and regulating menstruation, without harming the body's vital energy.

[0018] Lily (Lilium brownii): Sweet and cold in nature. Enters the heart and lung meridians. It is good at nourishing yin and moistening the lungs, clearing the heart and calming the mind. "Ben Cao Zheng Yi" says: "The lily flower closes at night and opens in the morning. It is very effective in treating liver fire rising and insomnia at night."

[0019] Salviae miltiorrhizae radix etrhizoma: Bitter and slightly cold in nature. It enters the heart, pericardium, and liver meridians. Functions: Activates blood circulation and regulates menstruation, removes blood stasis and relieves pain, calms the mind and relieves irritability. Indications: Irregular menstruation, amenorrhea, dysmenorrhea; feverish irritability, delirium, palpitations, and insomnia.

[0020] Celosia seed (Celosia semen): Bitter and slightly cold in nature. It enters the liver meridian. Functions: Clears heat and drains fire; used for dizziness due to liver fire.

[0021] Preferably, the traditional Chinese medicine composition for improving ovarian function comprises, by weight, 10-30 parts of Cuscuta chinensis, 5-15 parts of Cistanche deserticola, 10-30 parts of Lycium barbarum, 10-30 parts of Polygonatum sibiricum, 10-30 parts of Codonopsis pilosula, 5-15 parts of Atractylodes macrocephala, 5-15 parts of Nelumbo nucifera leaf, 5-15 parts of Dendrobium nobile, 5-10 parts of Lilium brownii, 5-10 parts of Rosa rugosa, 5-10 parts of Rosa chinensis var. chinensis, 5-15 parts of Paeonia lactiflora, 10-30 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea.

[0022] Preferably, the traditional Chinese medicine composition for improving ovarian function comprises, by weight, 20 parts of Cuscuta chinensis, 10 parts of Cistanche deserticola, 15 parts of Lycium barbarum, 15 parts of Polygonatum sibiricum, 15 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Nelumbo nucifera leaf, 10 parts of Dendrobium nobile, 5 parts of Lilium brownii, 5 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 15 parts of Paeonia lactiflora, 15 parts of Salvia miltiorrhiza, and 3 parts of Celosia argentea.

[0023] Preferably, the traditional Chinese medicine composition for improving ovarian function, by weight, comprises: 10 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 10 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 30 parts of Codonopsis pilosula, 15 parts of Atractylodes macrocephala, 15 parts of Nelumbo nucifera leaf, 15 parts of Dendrobium nobile, 10 parts of Lilium brownii, 5 parts of Rosa rugosa, 10 parts of Rosa chinensis var. chinensis, 15 parts of Paeonia lactiflora, 20 parts of Salvia miltiorrhiza, and 10 parts of Celosia argentea.

[0024] Preferably, the traditional Chinese medicine composition for improving ovarian function, by weight, comprises: 30 parts of Cuscuta chinensis, 15 parts of Cistanche deserticola, 30 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 15 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 5 parts of Dendrobium nobile, 5 parts of Lilium brownii, 5 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 5 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 3 parts of Celosia argentea.

[0025] Preferably, the traditional Chinese medicine composition for improving ovarian function, by weight, comprises: 10 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 10 parts of Lycium barbarum, 30 parts of Polygonatum sibiricum, 30 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 5 parts of Dendrobium nobile, 10 parts of Lilium brownii, 10 parts of Rosa rugosa, 10 parts of Rosa chinensis var. chinensis, 5 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 10 parts of Celosia argentea.

[0026] Preferably, the traditional Chinese medicine composition for improving ovarian function, by weight, comprises: 20 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 30 parts of Lycium barbarum, 15 parts of Polygonatum sibiricum, 10 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 15 parts of Dendrobium nobile, 5 parts of Lilium brownii, 10 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 10 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 5 parts of Celosia argentea.

[0027] Preferably, the traditional Chinese medicine composition for improving ovarian function, by weight, comprises: 20 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 20 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 20 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Nelumbo nucifera leaf, 10 parts of Dendrobium nobile, 8 parts of Lilium brownii, 8 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 14 parts of Paeonia lactiflora, 12 parts of Salvia miltiorrhiza, and 7 parts of Celosia argentea.

[0028] This invention also provides a method for preparing the aforementioned traditional Chinese medicine composition for improving ovarian function, comprising:

[0029] By weight, 10-50 parts of Cuscuta chinensis, 5-35 parts of Cistanche deserticola, 10-50 parts of Lycium barbarum, 10-50 parts of Polygonatum sibiricum, 10-50 parts of Codonopsis pilosula, 5-25 parts of Atractylodes macrocephala, 5-25 parts of Nelumbo nucifera leaf, 5-25 parts of Dendrobium nobile, 5-30 parts of Lilium brownii, 5-30 parts of Rosa rugosa, 5-30 parts of Rosa chinensis var. chinensis, 5-25 parts of Paeonia lactiflora, 10-50 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea are pulverized, mixed with water, and decocted for 1-2 hours. The decoction is collected and filtered. The residue is mixed with water and decocted for 1-2 hours. The decoctions are combined and dried to obtain a traditional Chinese medicine composition for improving ovarian function.

[0030] Preferably, the ratio of the raw material to water is 1:(3-5)g / ml; and the ratio of the filter residue to water is 1:(6-10)g / ml.

[0031] Preferably, the preparation method of the traditional Chinese medicine composition for improving ovarian function includes:

[0032] Wash all raw materials, remove impurities, dry them, chop them, and decoct them twice with water. For the first decoction, add 5 times the amount of water as the raw materials and decoct for 1.5 hours. Take the decoction and filter it. For the second decoction, add 6 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter them, and dry them to obtain the finished product.

[0033] The present invention also provides formulations comprising the aforementioned traditional Chinese medicine composition for improving ovarian function.

[0034] Preferably, the dosage form of the preparation is one of granules, oral liquid, pills, capsules or decoction.

[0035] The present invention also provides the application of the aforementioned traditional Chinese medicine composition for improving ovarian function in promoting ovarian cell proliferation.

[0036] Preferably, the concentration of the traditional Chinese medicine composition for improving ovarian function is 50–150 μg / mL.

[0037] Preferably, the concentration of the traditional Chinese medicine composition for improving ovarian function is 50-100 μg / mL, more preferably 100 μg / mL.

[0038] Preferably, the ovarian cells include granulosa cells.

[0039] The present invention also provides the aforementioned traditional Chinese medicine composition for improving ovarian function, or the application of the aforementioned preparation in the preparation of products for the prevention and / or treatment of ovarian insufficiency.

[0040] The herbal composition of this invention comprises: Cuscuta chinensis and Cistanche deserticola to tonify the kidneys and replenish essence; Lycium barbarum and Polygonatum sibiricum to nourish the liver and kidneys, serving as the principal herbs; Codonopsis pilosula, Atractylodes macrocephala, and Nelumbo nucifera to strengthen the spleen and promote diuresis; and Dendrobium nobile to benefit the stomach and generate fluids, collectively serving as the assistant herbs to tonify acquired essence and nourish innate essence; Paeonia lactiflora to nourish and soothe the liver, nourish blood and astringe yin; Rosa rugosa to regulate qi, relieve depression, and promote blood circulation and remove blood stasis; and Rosa chinensis to soothe the liver, regulate qi, invigorate blood, and regulate menstruation, all entering the liver meridian and mutually promoting each other, serving as the adjuvant herbs; Celosia argentea to clear liver fire; Salvia miltiorrhiza to remove blood stasis, promote new blood production, invigorate blood, and regulate menstruation; and Lilium brownii to calm the mind and soothe the nerves, serving as the guiding herbs. The entire formula is neither cooling nor drying, collectively tonifying the kidneys and replenishing essence, soothing the liver and relieving depression, strengthening the spleen and invigorating blood, regulating menstruation, and promoting fertility. The components of the herbal composition of this invention are scientifically formulated and work synergistically to improve ovarian dysfunction, exhibiting good therapeutic effects. The preparation method is simple, with significant efficacy and no toxic side effects. Detailed Implementation

[0041] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0042] To further illustrate the present invention, the following embodiments are provided for detailed description. The raw materials used in the following embodiments and comparative examples of the present invention are all commercially available products.

[0043] Example 1

[0044] The traditional Chinese medicine composition for improving ovarian dysfunction in this embodiment is composed of the following raw materials:

[0045] 20g of Cuscuta chinensis, 10g of Cistanche deserticola, 15g of Lycium barbarum, 15g of Polygonatum sibiricum, 15g of Codonopsis pilosula, 10g of Atractylodes macrocephala, 10g of Nelumbo nucifera leaf, 10g of Dendrobium nobile, 5g of Lilium brownii, 5g of Rosa rugosa, 5g of Rosa chinensis var. chinensis, 15g of Paeonia lactiflora, 15g of Salvia miltiorrhiza, and 3g of Celosia argentea.

[0046] The preparation method of the traditional Chinese medicine composition for improving ovarian dysfunction in this embodiment is as follows:

[0047] Wash all the above raw materials, remove impurities, dry them, chop them, and decoct them twice with water. For the first decoction, add 5 times the amount of water as the raw materials and decoct for 1.5 hours. Take the decoction and filter it. For the second decoction, add 6 times the amount of water and decoct for 1.5 hours. Combine the decoctions, filter them, and dry them to obtain the finished product.

[0048] The raw material composition of the traditional Chinese medicine composition for improving ovarian dysfunction in Examples 2-6 is shown in Table 1.

[0049] Table 1. Traditional Chinese medicine compositions for improving ovarian dysfunction in Examples 1-6 (unit: g)

[0050] Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 dodder 20 10 30 10 20 20 Cistanche deserticola 10 5 15 5 5 5 Goji berries 15 10 30 10 30 20 Polygonatum 15 10 10 30 15 10 Codonopsis pilosula 15 30 15 30 10 20 Atractylodes macrocephala 10 15 5 5 5 10 lotus leaf 10 15 5 5 5 10 Dendrobium 10 15 5 5 15 10 lily 5 10 5 10 5 8 roses 5 5 5 10 10 8 Rose 5 10 5 10 5 5 White peony root 15 15 5 5 10 14 Salvia miltiorrhiza 15 20 10 10 10 12 Celosia argentea 3 10 3 10 5 7

[0051] The preparation methods of the traditional Chinese medicine compositions for improving ovarian dysfunction in Examples 2-6 are the same as those in Example 1.

[0052] Comparative Example 1

[0053] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Salvia miltiorrhiza. The amount of Celosia argentea missing is allocated to the corresponding components according to the proportion of other substances.

[0054] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0055] Comparative Example 2

[0056] The difference between the traditional Chinese medicine composition in this comparative example and that in Example 1 is that this comparative example only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Salvia miltiorrhiza missing is allocated to the corresponding components according to the proportion of other substances.

[0057] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0058] Comparative Example 3

[0059] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Salvia miltiorrhiza, and Celosia argentea. The amount of Paeonia lactiflora missing is allocated to the corresponding components according to the proportion of other substances.

[0060] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0061] Comparative Example 4

[0062] The difference between the traditional Chinese medicine composition in this comparative example and that in Example 1 is that this comparative example only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Salvia miltiorrhiza, Paeonia lactiflora, and Celosia argentea. The amount of Rosa rugosa missing is allocated to the corresponding components according to the proportion of other substances.

[0063] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0064] Comparative Example 5

[0065] The difference between the traditional Chinese medicine composition in this comparative example and that in Example 1 is that this comparative example only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Salvia miltiorrhiza, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Dendrobium nobile missing is allocated to the corresponding components according to the proportion of other substances.

[0066] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0067] Comparative Example 6

[0068] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Salvia miltiorrhiza, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of lotus leaf missing is allocated to the corresponding components according to the proportion of other substances.

[0069] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0070] Comparative Example 7

[0071] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Codonopsis pilosula, Salvia miltiorrhiza, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Atractylodes macrocephala missing is allocated to the corresponding components according to the proportion of other substances.

[0072] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0073] Comparative Example 8

[0074] The difference between the traditional Chinese medicine composition in this comparative example and that in Example 1 is that this comparative example only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Polygonatum sibiricum, Salvia miltiorrhiza, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Codonopsis pilosula missing is allocated to the corresponding components according to the proportion of other substances.

[0075] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0076] Comparative Example 9

[0077] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Lycium barbarum, Salvia miltiorrhiza, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Polygonatum sibiricum missing is allocated to the corresponding components according to the proportion of other substances.

[0078] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0079] Comparative Example 10

[0080] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Cistanche deserticola, Salvia miltiorrhiza, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Lycium barbarum missing is allocated to the corresponding components according to the proportion of other substances.

[0081] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0082] Comparative Example 11

[0083] The difference between the traditional Chinese medicine composition in this comparative example and that in Example 1 is that this comparative example only includes Cuscuta chinensis, Lycium barbarum, Salvia miltiorrhiza, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Cistanche deserticola missing is allocated to the corresponding components according to the proportion of other substances.

[0084] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0085] Comparative Example 12

[0086] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Lycium barbarum, Cistanche deserticola, Salvia miltiorrhiza, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa rugosa, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of Cuscuta chinensis missing is allocated to the corresponding components according to the proportion of other substances.

[0087] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0088] Comparative Example 13

[0089] The traditional Chinese medicine composition in this comparative example differs from that in Example 1 in that it only includes Cuscuta chinensis, Lycium barbarum, Cistanche deserticola, Salvia miltiorrhiza, Polygonatum sibiricum, Codonopsis pilosula, Atractylodes macrocephala, Nelumbo nucifera leaf, Dendrobium nobile, Lilium brownii, Rosa chinensis, Paeonia lactiflora, and Celosia argentea. The amount of missing Rosa chinensis is allocated to the corresponding components according to the proportion of other substances.

[0090] The preparation method of the traditional Chinese medicine composition in this comparative example is the same as that in Example 1.

[0091] Comparative Example 14

[0092] The difference between the traditional Chinese medicine composition of this comparative example and that of Example 1 lies in the preparation method of the traditional Chinese medicine composition of this comparative example, which includes the following steps:

[0093] Wash all raw materials, remove impurities, air dry, chop, and decoct twice with ethanol. For the first decoction, add 5 times the amount of ethanol as the raw materials and decoct for 1.5 hours. Collect the decoction and filter. For the second decoction, add 6 times the amount of ethanol as the raw materials and decoct for 1.5 hours. Combine the decoctions, filter, and dry to obtain the finished product.

[0094] Experimental Example 1

[0095] This experimental case investigated the effect of the traditional Chinese medicine compositions obtained in the examples and comparative examples on the proliferation of ovarian granulosa cells, specifically including the following steps:

[0096] (1) Take 8-10 week old SPF mice and inject human chorionic gonadotropin into the peritoneal cavity of the mice; 48 hours later, sacrifice the mice and take the ovaries, clean them, remove the fat and capsule, and set them aside for later use.

[0097] (2) In the mixed basal culture medium, use a No. 25 needle to puncture the follicles in the ovary, take granulosa cells, add enzymes for digestion, centrifuge and discard the supernatant; in the mixed complete culture medium, resuspend the cell pellet, inoculate it in a culture dish and culture, change the medium every 24 hours, and after the granulosa cells adhere to the wall and grow for 24 hours, blow the cells off the wall of the cell culture flask to make a single cell suspension.

[0098] (3) Centrifuge the single-cell suspension in a centrifuge tube at 1000 rpm for 5 minutes. Remove the supernatant, add culture medium, and gently pipette to disperse the cells evenly. Count the cells using a cell counting chamber, adjusting the cell count to 10 × 10⁶ cells / mL. 4 / ml.

[0099] (4) Seed the evenly dispersed cells into 96-well plates, adding 100 μl of granular cells to each well, with 5 wells per column, for a total of 2.5 ml. Incubate at 37°C in a CO2 incubator for 24 hours.

[0100] (4) Set up experimental groups and perform drug treatment. Add different groups of traditional Chinese medicine compositions to the well plates respectively. Incubate at 37℃ in a CO2 incubator for 24 hours.

[0101] Experimental group 1: 50 μg / mL of the traditional Chinese medicine composition obtained in Example 1;

[0102] Experimental group 2: 100 μg / mL of the traditional Chinese medicine composition obtained in Example 1;

[0103] Experimental group 3: 200 μg / mL of the traditional Chinese medicine composition obtained in Example 1;

[0104] Experimental comparison groups 1-14: 100 μg / mL of the traditional Chinese medicine composition obtained from comparative examples 1-14, respectively.

[0105] (5) MTT assay for cell proliferation. In step (4), after culturing for 24 h, the plate was removed, and 20 μl of MTT solution was added to each well. After incubation for another 4 h, the plate was terminated, and the supernatant was discarded. 150 μl of DMSO was added to each well, and the plate was shaken for 10 minutes to allow the blue-purple MTT crystals to gradually dissolve. The OD value of each well at 490 nm was measured using a microplate reader. The OD value of wells with only culture medium was used as the control group. The experimental results are shown in Table 1.

[0106] Table 1

[0107]

[0108]

[0109] As shown in Table 1, compared with the comparative example, the traditional Chinese medicine composition of Example 1 of the present invention has a better effect on promoting the proliferation of granulocytes, and the traditional Chinese medicine composition of Example 1 with a concentration of 100 μg / mL has the best effect.

[0110] Experimental Example 2

[0111] This experimental case investigated the effects of the traditional Chinese medicine compositions obtained in the examples and comparative examples on improving ovarian function, specifically including the following steps:

[0112] I. Clinical Data

[0113] 1. Basic information: The traditional Chinese medicine composition of the present invention was applied to 360 clinical observation cases, aged 18-45 years.

[0114] 2. Clinical manifestations:

[0115] (1) Reduced fertility: mainly manifested as infertility, difficulty in conception, easy early miscarriage, recurrent miscarriage, poor response to Gn, and repeated embryo implantation failure. In the early stage of DOR, natural ovulation still exists, but the monthly pregnancy probability of patients decreases from 20% to 25% of normal women to 5% to 10%, and spontaneous abortion and fetal chromosomal abnormalities are more likely to occur.

[0116] (2) Menstrual disorders: DOR usually has regular menstruation, but it can also manifest as various menstrual disorders, including infrequent or frequent menstruation, prolonged or shortened menstrual period, amenorrhea, and varying menstrual flow.

[0117] (3) Symptoms related to sex hormone deficiency or fluctuation: The degree of manifestation varies, similar to menopausal symptoms, but generally milder or less obvious.

[0118] II. Treatment Methods and Course of Treatment

[0119] Experimental Group 1: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 1), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and three courses of treatment.

[0120] Experimental Group 2: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 2), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and 3 courses of treatment.

[0121] Experimental Group 3: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 3), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and 3 courses of treatment.

[0122] Experimental Group 4: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 4), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and three courses of treatment.

[0123] Experimental Group 5: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 5), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and three courses of treatment.

[0124] Experimental Group 6: A traditional Chinese medicine composition of the present invention for improving ovarian dysfunction (Example 6), one dose per day, decocted in water and taken in two divided doses while warm, 15 days as one course of treatment, and 3 courses of treatment.

[0125] III. Treatment Results

[0126] Criteria for judging therapeutic efficacy:

[0127] Cure: Clinical symptoms disappear or pregnancy occurs, laboratory tests return to normal, and other symptoms disappear.

[0128] Effective: Clinical symptoms are reduced or the intervals between attacks are prolonged, and laboratory tests show improvement.

[0129] Ineffective: No changes were observed in clinical symptoms or laboratory tests.

[0130] The total number of effective cases = (cured + effective), and the overall effective rate = (cured + effective) / total number of cases %.

[0131] 1. The number of cases with therapeutic effects in each experimental group for improving ovarian dysfunction is shown in Table 2 below.

[0132] Table 2

[0133] Number of cases Recovery (example) Valid (example) Invalid (example) Total effective (examples) Experimental group 1 60 20 37 3 57 Experimental group 2 60 19 36 5 55 Experimental group 3 60 18 37 5 55 Experimental group 4 60 15 38 7 53 Experimental group 5 60 16 38 6 54 Experimental group 6 60 18 37 5 55

[0134] 2. The percentage of cases showing improved treatment outcomes for ovarian hypofunction is shown in Table 3 below.

[0135] Table 3

[0136]

[0137]

[0138] No adverse reactions were observed in the observed cases, indicating that the traditional Chinese medicine composition for improving ovarian dysfunction of the present invention is safe and reliable. The results of the above clinical trials and Tables 2 and 3 show that the traditional Chinese medicine composition of the present invention has good efficacy in improving ovarian dysfunction, with a high overall effective rate. Specifically, experimental group 1 showed better treatment effects than the other experimental groups, indicating that the components in Example 1 have optimal synergistic effects and a better effect on improving ovarian function.

[0139] Experimental Example 3

[0140] This experimental example investigated the long-term effects of the traditional Chinese medicine composition obtained in Example 1, specifically including:

[0141] Ms. Wang, 28 years old, had been trying to conceive for over a year without success. Four months prior, she began experiencing shortened menstrual cycles, lighter menstrual flow, and symptoms such as irritability and insomnia. Her AMH level was 0.46 ng / ml. After three courses of treatment with the medication of this invention, her menstrual cycles became more regular, her menstrual flow increased, and her symptoms of irritability and insomnia significantly improved. During the fourth course of treatment, ultrasound monitoring of ovulation guided intercourse to induce pregnancy.

[0142] Ms. Chai, female, 42 years old, had been infertile for over 8 years despite not using contraception. She underwent 8 IVF cycles at other hospitals and our hospital without obtaining transferable embryos. Her AMH level was 0.35 ng / ml. She experienced hot flashes, sweating, irritability, restlessness, and insomnia. After three cycles of treatment with the medication described in this invention, she underwent another round of ovulation induction at our hospital, resulting in the retrieval of 4 eggs and 2 embryos. Currently, due to adenomyosis, embryo transfer has not yet been performed.

[0143] Ms. An, 40 years old, had been trying to conceive for one year without success. Six months prior, she experienced a shortened menstrual cycle, slightly reduced menstrual flow, and premenstrual breast tenderness and discomfort. Her AMH level was 0.25 ng / ml. After three courses of treatment with the medication described in this invention, she underwent assisted reproductive technology at our hospital and became pregnant.

[0144] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A traditional Chinese medicine composition for improving ovarian function, characterized in that, The product is composed of the following raw materials by weight: 10-50 parts of Cuscuta chinensis, 5-35 parts of Cistanche deserticola, 10-50 parts of Lycium barbarum, 10-50 parts of Polygonatum sibiricum, 10-50 parts of Codonopsis pilosula, 5-25 parts of Atractylodes macrocephala, 5-25 parts of Nelumbo nucifera leaf, 5-25 parts of Dendrobium nobile, 5-30 parts of Lilium brownii, 5-30 parts of Rosa rugosa, 5-30 parts of Rosa chinensis var. chinensis, 5-25 parts of Paeonia lactiflora, 10-50 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea.

2. The traditional Chinese medicine composition for improving ovarian function according to claim 1, characterized in that, The product is composed of the following raw materials by weight: 10-30 parts of Cuscuta chinensis, 5-15 parts of Cistanche deserticola, 10-30 parts of Lycium barbarum, 10-30 parts of Polygonatum sibiricum, 10-30 parts of Codonopsis pilosula, 5-15 parts of Atractylodes macrocephala, 5-15 parts of Nelumbo nucifera leaf, 5-15 parts of Dendrobium nobile, 5-10 parts of Lilium brownii, 5-10 parts of Rosa rugosa, 5-10 parts of Rosa chinensis var. chinensis, 5-15 parts of Paeonia lactiflora, 10-30 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea.

3. The traditional Chinese medicine composition for improving ovarian function according to claim 1, characterized in that, The product is composed of the following raw materials by weight: 20 parts Cuscuta chinensis, 10 parts Cistanche deserticola, 15 parts Lycium barbarum, 15 parts Polygonatum sibiricum, 15 parts Codonopsis pilosula, 10 parts Atractylodes macrocephala, 10 parts Nelumbo nucifera, 10 parts Dendrobium nobile, 5 parts Lilium brownii, 5 parts Rosa rugosa, 5 parts Rosa chinensis, 15 parts Paeonia lactiflora, 15 parts Salvia miltiorrhiza, and 3 parts Celosia argentea. Alternatively, by weight, the traditional Chinese medicine composition for improving ovarian function consists of the following raw materials: 10 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 10 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 30 parts of Codonopsis pilosula, 15 parts of Atractylodes macrocephala, 15 parts of Nelumbo nucifera leaf, 15 parts of Dendrobium nobile, 10 parts of Lilium brownii, 5 parts of Rosa rugosa, 10 parts of Rosa chinensis var. chinensis, 15 parts of Paeonia lactiflora, 20 parts of Salvia miltiorrhiza, and 10 parts of Celosia argentea. Alternatively, by weight, the traditional Chinese medicine composition for improving ovarian function consists of the following raw materials: 30 parts of Cuscuta chinensis, 15 parts of Cistanche deserticola, 30 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 15 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 5 parts of Dendrobium nobile, 5 parts of Lilium brownii, 5 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 5 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 3 parts of Celosia argentea. Alternatively, by weight, the traditional Chinese medicine composition for improving ovarian function consists of the following raw materials: 10 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 10 parts of Lycium barbarum, 30 parts of Polygonatum sibiricum, 30 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 5 parts of Dendrobium nobile, 10 parts of Lilium brownii, 10 parts of Rosa rugosa, 10 parts of Rosa chinensis var. chinensis, 5 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 10 parts of Celosia argentea. Alternatively, by weight, the traditional Chinese medicine composition for improving ovarian function consists of the following raw materials: 20 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 30 parts of Lycium barbarum, 15 parts of Polygonatum sibiricum, 10 parts of Codonopsis pilosula, 5 parts of Atractylodes macrocephala, 5 parts of Nelumbo nucifera leaf, 15 parts of Dendrobium nobile, 5 parts of Lilium brownii, 10 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 10 parts of Paeonia lactiflora, 10 parts of Salvia miltiorrhiza, and 5 parts of Celosia argentea. Alternatively, by weight, the traditional Chinese medicine composition for improving ovarian function consists of the following raw materials: 20 parts of Cuscuta chinensis, 5 parts of Cistanche deserticola, 20 parts of Lycium barbarum, 10 parts of Polygonatum sibiricum, 20 parts of Codonopsis pilosula, 10 parts of Atractylodes macrocephala, 10 parts of Nelumbo nucifera leaf, 10 parts of Dendrobium nobile, 8 parts of Lilium brownii, 8 parts of Rosa rugosa, 5 parts of Rosa chinensis var. chinensis, 14 parts of Paeonia lactiflora, 12 parts of Salvia miltiorrhiza, and 7 parts of Celosia argentea.

4. The method for preparing the traditional Chinese medicine composition for improving ovarian function according to claim 1, characterized in that, include: By weight, 10-50 parts of Cuscuta chinensis, 5-35 parts of Cistanche deserticola, 10-50 parts of Lycium barbarum, 10-50 parts of Polygonatum sibiricum, 10-50 parts of Codonopsis pilosula, 5-25 parts of Atractylodes macrocephala, 5-25 parts of Nelumbo nucifera leaf, 5-25 parts of Dendrobium nobile, 5-30 parts of Lilium brownii, 5-30 parts of Rosa rugosa, 5-30 parts of Rosa chinensis var. chinensis, 5-25 parts of Paeonia lactiflora, 10-50 parts of Salvia miltiorrhiza, and 3-10 parts of Celosia argentea are pulverized, mixed with water, and decocted for 1-2 hours. The decoction is collected and filtered. The residue is mixed with water and decocted for 1-2 hours. The decoctions are combined and dried to obtain a traditional Chinese medicine composition for improving ovarian function.

5. A formulation, characterized in that, The traditional Chinese medicine composition for improving ovarian function as described in any one of claims 1-3.

6. The formulation according to claim 5, characterized in that, The dosage form of the preparation is one of granules, oral liquid, pills, capsules or decoction.

7. The use of the traditional Chinese medicine composition for improving ovarian function according to any one of claims 1-3 in the preparation of a drug for promoting ovarian cell proliferation.

8. The application according to claim 7, characterized in that, The dosage of the traditional Chinese medicine composition for improving ovarian function is 50-150 μg / mL.

9. The application according to claim 7, characterized in that, The ovarian cells include granulosa cells.

10. The traditional Chinese medicine composition for improving ovarian function according to any one of claims 1-3, or the use of the preparation of the formulation according to claim 5 or 6 in the preparation of a drug for the prevention and / or treatment of ovarian insufficiency.

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