Traditional Chinese medicine composition for treating idiopathic asthenospermia and application thereof

Abstract

The invention relates to the technical field of medicines, and discloses a traditional Chinese medicine composition for treating idiopathic asthenospermia and application thereof. In the compatible traditional Chinese medicine prescription, the herba epimedii can tonify kidney and strengthen yang, the radix morindae officinalis can tonify kidney yang and tonify kidney essence, and the herba epimedii and the radix morindae officinalis are monarch drugs; the lily has the effects of clearing away lung heat and tranquilizing mind, has the effects of reinforcing the kidney and strengthening essence, and is used as a ministerial drug; and the flatstem milkvetch seed, the semen cuscutae, the cistanche and the astragalus membranaceus are combined to tonify qi and raise yang and are used as adjuvant drugs. The traditional Chinese medicine prescription is characterized in that specific ingredients of the ministerial drug lily are added. Lily returns to the lung channel, has the effects of nourishing yin and moistening the lung, and clearing away heart fire and soothing the nerves, and is often used for treating diseases such as yin deficiency and dry cough, dysphoria and palpitation, insomnia and dreaminess, wandering and the like, and the inventor finds that in the traditional Chinese medicine prescription, the lily is added as a ministerial drug, and the effects of tonifying the kidney and strengthening essence of the monarch drug can be enhanced.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a traditional Chinese medicine composition for treating idiopathic asthenozoospermia and an application thereof. Background Art

[0002] Idiopathic asthenozoospermia refers to a condition in which the percentage of sperm forward motility (PR) in semen is less than 32%, while other semen parameter reference values ​​are within the normal range, and its etiology and pathogenesis cannot be determined. Male infertility due to idiopathic asthenozoospermia is characterized by unknown etiology and long-term infertility. Modern medicine lacks effective treatment methods due to unclear research on the pathogenesis of idiopathic asthenozoospermia. Idiopathic asthenozoospermia has always been the focus and difficulty of our clinical research.

[0003] Western medicine generally believes that it is mainly caused by genetic diseases, congenital dysplasia, endocrine factors, vas deferens obstruction, varicose veins, genital tract infection, immune factors, metabolic and nutritional factors, drug factors, diet, environmental factors, bad living habits, etc. Western medicine does not have clear targeted methods and drug treatments. Currently, it mainly uses various hormone treatments, which have different limitations. For example: gonadotropin treatment is only effective for patients with hypogonadism and is expensive; androgen treatment has poor clinical efficacy and patients often find it difficult to accept the existence of side effects to varying degrees, including the possibility of persistent azoospermia, cholestasis, etc.

[0004] Traditional Chinese medicine generally believes that kidney deficiency is the main cause of asthenozoospermia, and tonifying the kidney and replenishing essence is the basis for treating asthenozoospermia and oligospermia. For example, the Chinese patent with application publication number CN111686170A discloses a Chinese medicine for treating asymptomatic idiopathic asthenozoospermia male infertility, which is obtained by combining Cuscuta, Astragalus, Fructus Lycii, Herba Epimedii, Herba Cistanches, Herba Morindae Officinalis, Ginseng, Bombyx mori, Cyathulae and Scald Leech, which has the effects of tonifying the kidney and replenishing essence, warming yang and invigorating qi, and promoting blood circulation and unblocking collaterals, and is used to improve and treat asymptomatic idiopathic asthenozoospermia of male infertility. However, the Chinese medicine provided by the patent is still not good enough in the treatment of idiopathic asthenozoospermia, and the art still needs the emergence of more effective drugs for the treatment of idiopathic asthenozoospermia. Summary of the invention

[0005] In order to solve the problem of improving and treating idiopathic asthenozoospermia, the present invention provides a Chinese medicine composition for treating idiopathic asthenozoospermia and its application. The present invention obtains a fermentation active drug for improving and treating idiopathic asthenozoospermia by mixing the Chinese medicine ingredients of epimedium, Morinda officinalis, lily, Astragalus complanatus, Cuscuta australis, Cistanche deserticola and Astragalus membranaceus with millet paste, and fermenting with Bifidobacterium bifida. The fermentation active drug obtained by the Chinese medicine combination of the present invention with a specific fermentation substrate millet paste and a fermentation strain has a good effect on treating idiopathic asthenozoospermia.

[0006] The specific technical scheme of the present invention is: In a first aspect, the present invention provides a Chinese medicine composition for treating idiopathic asthenozoospermia. The technical scheme of the Chinese medicine composition provided by the present invention comprises: the Chinese medicine composition comprises the following components: epimedium, Morinda officinalis, lily, Astragalus membranaceus, Cuscuta australis, Cistanche deserticola, and Astragalus membranaceus; the Chinese medicine composition is mixed and fermented with millet paste to prepare an active drug for treating idiopathic asthenozoospermia.

[0007] The present invention obtains a fermentation active drug for improving and treating idiopathic asthenozoospermia by mixing a Chinese medicinal component of epimedium, Morinda officinalis, lily, Astragalus membranaceus, Cuscuta australis, Cistanche deserticola and Astragalus membranaceus with millet paste, and then fermenting the mixture with the millet paste. The fermentation active drug obtained by fermenting the Chinese medicinal components with a specific fermentation substrate millet paste has a good effect on treating idiopathic asthenozoospermia.

[0008] In the Chinese medicine prescription of the present invention, Epimedium nourishes the kidney and strengthens yang, Morinda officinalis nourishes kidney yang and benefits kidney essence, and the two are the main medicines; Lilium, by clearing lung heat and calming the mind, can strengthen the effect of nourishing the kidney and benefiting essence, and is the ministerial medicine; Astragalus, Cuscuta, Cistanche and Astragalus are used together to nourish qi and raise yang, and are the adjuvant medicines. In this Chinese medicine prescription, it is special that the specific proportion of the ministerial medicine lily is added. Lily belongs to the lung meridian, has the effects of nourishing yin and moistening the lungs, clearing the heart and calming the mind, and is often used to treat symptoms such as yin deficiency and dry cough, restlessness and palpitations, insomnia and dreaminess, and mental confusion. The inventor found that in this Chinese medicine prescription, adding lily as a ministerial medicine can strengthen the effect of the main medicine of nourishing the kidney and benefiting essence.

[0009] Preferably, in the mixed fermentation, fermentation is carried out by adding Bifidobacterium bifidum.

[0010] More preferably, in the mixed fermentation, fermentation is carried out by adding Bifidobacterium bifidum and Lactobacillus plantarum LP45.

[0011] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 8-12 parts of Epimedium, 10-20 parts of Morinda officinalis, 7-14 parts of Lilium, 10-20 parts of Astragalus membranaceus, 10-17 parts of Cuscuta australis, 5-15 parts of Cistanche deserticola, and 15-20 parts of Astragalus membranaceus.

[0012] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 6-10 parts of turtle shell, 2-5 parts of Phyllanthus urinaria, 5-10 parts of red peony root, and 10-15 parts of Salvia miltiorrhiza.

[0013] Biejia belongs to the liver and kidney meridians, and has the effects of nourishing yin and suppressing yang, softening and dispersing nodules; Phyllanthus urinaria can remove pathogenic heat in the body and has the effect of eliminating accumulation; Red peony root helps to relieve the symptoms of liver qi stagnation, and can be used to relieve emotional instability and mental tension; Salvia miltiorrhiza can clear the heart and relieve troubles, and improve restlessness and insomnia. By adding a specific ratio of Biejia, Phyllanthus urinaria, Red peony root, and Salvia miltiorrhiza, the effect of the Chinese medicine prescription of the present invention on the treatment of idiopathic asthenospermia can be further improved, and the effect of strengthening the effect can be played.

[0014] Preferably, in the mixed fermentation, the mixing mass ratio of the Chinese medicine composition to the millet paste is 1:0.8-1.6.

[0015] In a second aspect, the present invention provides use of the above-mentioned Chinese medicine composition in the treatment of idiopathic asthenozoospermia.

[0016] In a third aspect, the present invention provides a pharmaceutical preparation comprising the above-mentioned traditional Chinese medicine composition, which is any one of granules, mixtures, pills, syrups, powders, pastes, capsules and tablets.

[0017] The above-mentioned Chinese medicine composition is mixed with a pharmaceutically acceptable carrier, such as a diluent, a disintegrant, a binder, a lubricant, a stabilizer, etc., to prepare any one of granules, mixtures, pills, syrups, powders, pastes, capsules and tablets, which can be used for the treatment of idiopathic asthenozoospermia.

[0018] In a fourth aspect, the present invention provides a method for preparing a granule for treating idiopathic asthenozoospermia, comprising the following steps: Step S1: preparing millet paste: mixing millet with pure water, heating and soaking the millet for a period of time to soften the millet, crushing and homogenizing the millet, and then high-temperature steaming to gelatinize the rice paste to obtain millet paste; Step S2: preparing a Chinese herbal decoction: placing epimedium, Morinda officinalis, lily, Astragalus complanatus, Cuscuta australis, Cistanche deserticola, Astragalus, Carapax tricolor, Phyllanthus urinaria, Paeonia lactiflora, and Salvia miltiorrhiza in a decoction vessel, adding water, soaking for 0.5 to 2 hours, boiling over high heat, then decocting over low heat for 30 to 60 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated Bifidobacterium bifidum and Lactobacillus plantarum LP45 into a culture medium at a ratio of 2 to 3:1 to obtain a mixed bacterial solution, centrifuging, and collecting the supernatant to obtain a fermentation agent; Step S4: preparing a fermentation active drug: uniformly mixing the Chinese medicine decoction and the millet paste, inoculating the fermentation bacteria into the mixture, culturing at 30-40° C. for 48-72 hours, mixing, and freeze-drying to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, and drying to obtain a granule.

[0019] Preferably, the mixing mass ratio of the Chinese herbal decoction to the millet paste is 1:0.8-1.6, and the inoculation volume ratio of the fermentation bacteria agent is 2-5%.

[0020] Compared with the prior art, the present invention has the following technical effects: (1) The present invention obtains a fermentation active drug for improving and treating idiopathic asthenozoospermia by mixing the Chinese medicinal ingredients of epimedium, Morinda officinalis, lily, Astragalus complanatus, Cuscuta australis, Cistanche deserticola and Astragalus membranaceus with millet paste, and fermenting the mixture with Bifidobacterium bifida. The fermentation active drug obtained by the Chinese medicinal ingredients of the present invention is fermented with a specific fermentation substrate and a fermentation strain, and has a good effect on treating idiopathic asthenozoospermia. The Chinese medicinal ingredients of the present invention, after being mixed and fermented with millet paste and Bifidobacterium bifida, unexpectedly have a good improvement in the effect of treating idiopathic asthenozoospermia.

[0021] (2) In the Chinese medicine prescription of the present invention, Epimedium nourishes the kidney and strengthens yang, Morinda officinalis nourishes kidney yang and benefits kidney essence, and the two are both monarch drugs; Lilium can strengthen the effect of nourishing the kidney and benefiting essence by clearing lung heat and calming the mind, and is used as a minister drug; Astragalus, Cuscuta, Cistanche and Astragalus are used together to nourish qi and raise yang, and are together adjuvant drugs. In this Chinese medicine prescription, it is special that a specific proportion of lily, a minister drug, is added. Lily belongs to the lung meridian, has the effects of nourishing yin and moistening the lungs, clearing the heart and calming the mind, and is often used to treat symptoms such as yin deficiency and dry cough, restlessness and palpitations, insomnia and dreaminess, and mental confusion. The inventors found that in this Chinese medicine prescription, adding lily as a minister drug can strengthen the effect of the monarch drug in nourishing the kidney and benefiting essence. The present invention provides measures to strengthen the effect of nourishing the kidney and benefiting essence by clearing the lung meridian. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the testicular tissue morphology section of the rats in the blank group; Figure 2 This is the section image of the testicular tissue morphology of rats in the model group; Figure 3 This is a section diagram of the testicular tissue morphology of rats in Example 1 group. DETAILED DESCRIPTION

[0023] One of the general implementation schemes of the present invention is to provide a Chinese medicine composition for treating idiopathic asthenozoospermia, which comprises the following components: epimedium, Morinda officinalis, lily, Astragalus membranaceus, Cuscuta australis, Cistanche deserticola, and Astragalus membranaceus; the Chinese medicine composition is mixed with millet paste and fermented to prepare an active drug for treating idiopathic asthenozoospermia.

[0024] In the above Chinese medicine prescription, Epimedium nourishes the kidney and strengthens yang, Morinda officinalis nourishes kidney yang and benefits kidney essence, and the two are the main medicines; Lilium, by clearing lung heat and calming the mind, can strengthen the effect of nourishing the kidney and benefiting essence, and is the minister medicine; Astragalus, Cuscuta, Cistanche and Astragalus are used together to nourish qi and raise yang, and are the adjuvant medicines. In this Chinese medicine prescription, the special thing is that the specific proportion of the minister medicine lily is added. Lily belongs to the lung meridian, has the effect of nourishing yin and moistening the lungs, clearing the heart and calming the mind, and is often used to treat symptoms such as yin deficiency and dry cough, restlessness and palpitations, insomnia and dreaminess, and mental confusion. In this Chinese medicine prescription, adding lily as a minister medicine can strengthen the effect of the main medicine of nourishing the kidney and benefiting essence.

[0025] Preferably, in the mixed fermentation, fermentation is carried out by adding Bifidobacterium bifidum.

[0026] More preferably, in the mixed fermentation, fermentation is carried out by adding Bifidobacterium bifidum and Lactobacillus plantarum LP45.

[0027] The invention discloses a fermentation active drug for improving and treating idiopathic asthenozoospermia by mixing the Chinese medicinal ingredients of epimedium, Morinda officinalis, lily, Astragalus compatibility, Cuscuta australis, Cistanche deserticola and Astragalus membranaceus with millet paste and fermenting the mixture with Bifidobacterium bifida. The fermentation active drug obtained by the Chinese medicinal ingredients of the invention with the specific fermentation substrate millet paste and fermentation strain has a good effect on treating idiopathic asthenozoospermia. The fermentation strain is preferably Bifidobacterium bifida, or a double strain of Bifidobacterium bifida and Lactobacillus plantarum LP45.

[0028] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 8-12 parts of Epimedium, 10-20 parts of Morinda officinalis, 7-14 parts of Lilium, 10-20 parts of Astragalus membranaceus, 10-17 parts of Cuscuta australis, 5-15 parts of Cistanche deserticola, and 15-20 parts of Astragalus membranaceus.

[0029] Although Epimedium and Morinda officinalis are common Chinese medicinal ingredients used for strengthening yang and benefiting the kidney, and the "Epimedium" therein is also used in Chinese medicinal compositions for asthenozoospermia in the prior art. However, the present invention wants to emphasize that the effects of Epimedium and Morinda officinalis on benefiting the kidney and replenishing essence are limited. The addition of other components of the present invention, especially the ministerial drugs, and the specific proportions of other components have a great effect on the effect of treating idiopathic asthenozoospermia. In the Chinese medicinal prescription of the present invention, in addition to exerting their respective effects, each medicine has an additional effect on the whole after being combined, which has a good effect on improving asthenozoospermia. The present invention combines 8 to 12 parts of Epimedium, 10 to 20 parts of Morinda officinalis, 7 to 14 parts of Lilium, 10 to 20 parts of Astragalus, 10 to 17 parts of Cuscuta, 5 to 15 parts of Cistanche deserticola, and 15 to 20 parts of Astragalus, which has an unexpected effect of treating asthenozoospermia.

[0030] More preferably, the Chinese medicine composition comprises the following components in parts by weight: 10 parts of Epimedium, 18 parts of Morinda officinalis, 12 parts of Astragalus membranaceus, 16 parts of Cuscuta australis, 10 parts of Cistanche deserticola, 20 parts of Astragalus membranaceus, and 11 parts of Lilium.

[0031] Preferably, the Chinese medicine composition comprises the following components in parts by weight: 6-10 parts of turtle shell, 2-5 parts of Phyllanthus urinaria, 5-10 parts of red peony root, and 10-15 parts of Salvia miltiorrhiza.

[0032] Biejia belongs to the liver and kidney meridians, and has the effects of nourishing yin and suppressing yang, softening and dispersing nodules; Phyllanthus urinaria can remove pathogenic heat in the body and has the effect of eliminating accumulation; Red peony root helps to relieve the symptoms of liver qi stagnation, and can be used to relieve emotional instability and mental tension; Salvia miltiorrhiza can clear the heart and relieve troubles, and improve restlessness and insomnia. By adding a specific ratio of Biejia, Phyllanthus urinaria, Red peony root, and Salvia miltiorrhiza, the effect of the Chinese medicine prescription of the present invention on the treatment of idiopathic asthenospermia can be further improved, and the effect of strengthening the effect can be played.

[0033] The addition of 6-10 parts of turtle shell, 2-5 parts of Phyllanthus urinaria, 5-10 parts of red peony root, and 10-15 parts of Salvia miltiorrhiza can help lily strengthen the effect of the main medicine in nourishing the kidney and replenishing essence, thereby further improving the effect of treating idiopathic asthenozoospermia.

[0034] The second general implementation scheme of the present invention is to provide a method for preparing granules for treating idiopathic asthenozoospermia, comprising the following steps: Step S1: preparing millet paste: mixing millet with pure water, heating and soaking the millet for a period of time to soften the millet, crushing and homogenizing the millet, and then high-temperature steaming to gelatinize the millet paste to obtain millet paste; Step S2: preparing a Chinese herbal decoction: placing epimedium, Morinda officinalis, lily, Astragalus complanatus, Cuscuta australis, Cistanche deserticola, Astragalus, Carapax tricolor, Phyllanthus urinaria, Paeonia lactiflora, and Salvia miltiorrhiza in a decoction vessel, adding water, soaking for 0.5 to 2 hours, boiling over high heat, then decocting over low heat for 30 to 60 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated Bifidobacterium bifidum and Lactobacillus plantarum LP45 into a culture medium at a ratio of 2 to 3:1 to obtain a mixed bacterial solution, centrifuging, and collecting the supernatant to obtain a fermentation agent; Step S4: preparing a fermentation active drug: uniformly mixing the Chinese medicine decoction and the millet paste, inoculating the fermentation bacteria into the mixture, culturing at 30-40° C. for 48-72 hours, mixing, and freeze-drying to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, and drying to obtain a granule.

[0035] Preferably, when decocting Chinese medicine to prepare a decoction, water is added in an amount such that the water level is 2 to 3 cm higher than the medicine surface.

[0036] Preferably, the mixing mass ratio of the Chinese medicine decoction to the millet paste is 1:0.8-1.6. After the mixture is inoculated, it needs to be fermented at 30-40°C, which is the suitable temperature for the fermentation of Bifidobacterium bifidum and Lactobacillus plantarum LP45. If the temperature is lower or higher than this, the fermentation effect of the strain is poor.

[0037] Preferably, the inoculation volume ratio of the fermentation bacteria is 2 to 5%.

[0038] The present invention will be further described below in conjunction with embodiments. Those of ordinary skill in the art will be able to implement the present invention based on these descriptions. In addition, the embodiments of the present invention involved in the following description are generally only embodiments of a part of the present invention, rather than all embodiments. Therefore, based on the embodiments in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work should belong to the scope of protection of the present invention.

[0039] The Chinese medicine formula involved in the embodiment of the present invention is prepared by weight.

[0040] The adhesive used in the embodiment of the present invention is dextrin; the wetting agent used in the embodiment of the present invention is a 5% PVP K30 ethanol solution (v / v); the bifidobacterium used in the embodiment of the present invention is ATCC29521 Bifidobacterium bifidum, which is derived from Wuhan Warner Biotechnology Co., Ltd.; the plant lactobacillus used in the embodiment of the present invention is plant lactobacillus LP45, which is derived from Hebei Yiran Biotechnology Co., Ltd.; the cyclophosphamide for injection in the embodiment of the present invention (specification: 0.2 grams per vial) is derived from Jiangsu Hengrui Medicine Co., Ltd.

[0041] Example 1 The Chinese medicine formula is as follows: The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated bifidobacterium and Lactobacillus plantarum LP45 in an MRS medium at a ratio of 2.5:1, culturing at 40°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: mixing a Chinese medicine decoction and millet paste at a mass ratio of 1:1.2, inoculating the fermentation agent into the mixture at a volume ratio of 3%, culturing at 40°C for 60 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0042] Example 2 The Chinese medicine formula is as follows: The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated bifidobacterium and Lactobacillus plantarum LP45 in a ratio of 3:1 into an MRS medium, culturing at 40°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: mixing a Chinese medicine decoction and millet paste at a mass ratio of 1:1.2, inoculating the fermentation agent into the mixture at a volume ratio of 3%, culturing at 40°C for 60 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0043] Example 3 The Chinese medicine formula is as follows: The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated bifidobacterium and Lactobacillus plantarum LP45 in a ratio of 2:1 into an MRS medium, culturing at 40°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: mixing a Chinese medicine decoction and millet paste at a mass ratio of 1:1.2, inoculating the fermentation agent into the mixture at a volume ratio of 3%, culturing at 40°C for 60 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0044] Example 4 The Chinese medicine formula is as follows: The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated Bifidobacterium bifidum into an MRS medium, culturing at 40° C. for 12 hours, collecting the fermentation liquid, centrifuging it, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: uniformly mixing the Chinese medicine decoction and the millet paste at a mass ratio of 1:1.2, inoculating the fermentation bacteria into the mixture at a volume ratio of 3%, culturing at 40° C. for 60 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0045] Example 5 The Chinese medicine formula is as follows: Epimedium Morinda officinalis lily Astragalus complanatus Cuscuta Cistanche deserticola Astragalus 8 servings 10 servings 7 servings 10 servings 10 servings 5 servings 15 servings The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating activated bifidobacteria and Lactobacillus plantarum LP45 in a ratio of 2.5:1 into an MRS culture medium, culturing at 30°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: mixing a Chinese medicine decoction and millet paste at a mass ratio of 1:0.8, inoculating the fermentation agent into the mixture, culturing at 30°C for 48 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0046] Example 6 The Chinese medicine formula is as follows: Epimedium Morinda officinalis lily Astragalus complanatus Cuscuta Cistanche deserticola Astragalus 12 servings 20 servings 14 servings 20 servings 17 servings 15 servings 20 servings The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing millet paste: soaking millet in pure water at a material-liquid ratio of 1:20, heating to 80° C. and soaking for 20 minutes to soften the millet, stirring evenly, pouring into a colloid mill, homogenizing for 3 minutes, then pouring out, and high-temperature steaming at 90° C. for 20 minutes to obtain millet paste, sterilizing the millet paste at 120° C. for 10 minutes, and then transferring to a sterile environment for standby use; Step S2: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating activated bifidobacteria and Lactobacillus plantarum LP45 in a ratio of 2.5:1 into an MRS culture medium, culturing at 40°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S4: preparing a fermentation active drug: mixing a Chinese medicine decoction and millet paste at a mass ratio of 1:0.8-1.6, inoculating the fermentation agent into the mixture, culturing at 40°C for 72 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0047] Comparative Example 1 Compared with Example 1, the only difference is that step S1 is not performed, and millet paste is not added for fermentation in step S4. Other differences are the same as Example 1. This comparative example is carried out according to the following method: The Chinese medicine formula is as follows: The fermented product of the above Chinese medicine formula is used to prepare a granule, and the method is as follows: Step S1: preparing a Chinese herbal decoction: taking Chinese herbal medicines according to the above formula, placing them in a decoction vessel, adding water to submerge the herbs, with the water level being 3 cm higher than the herbs, soaking for 1 hour, boiling over high heat, then decocting over low heat for 40 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S2: preparing a fermentation agent: inoculating the activated Bifidobacterium bifidum and Lactobacillus plantarum LP45 into an MRS medium at a ratio of 2.5:1, culturing at 40°C for 12 hours, collecting the fermentation liquid, centrifuging, taking the supernatant, and obtaining a fermentation agent; Step S3: preparing a fermentation active drug: inoculating the fermentation agent into a traditional Chinese medicine decoction at a volume ratio of 3%, culturing at 40°C for 60 hours, mixing, freeze-drying, and crushing into fine powder to obtain a fermentation active drug; Step S4: adding a wetting agent and a binder to the fermentation active drug, granulating, drying, granulating, and packaging to obtain a granule.

[0048] Comparative Example 2 Compared with Example 1, the only difference is that the weight portion of Morinda officinalis in the traditional Chinese medicine formula is 7. Other parts are the same as Example 1.

[0049] Comparative Example 3 Compared with Example 1, the only difference is that the weight portion of Morinda officinalis in the traditional Chinese medicine formula is 23. Other parts are the same as Example 1.

[0050] Comparative Example 4 Compared with Example 1, the only difference is that the weight portion of lily in the traditional Chinese medicine formula is 5. The rest is the same as Example 1.

[0051] Comparative Example 5 Compared with Example 1, the only difference is that the weight portion of lily in the traditional Chinese medicine formula is 16. The rest is the same as Example 1.

[0052] Comparative Example 6 Compared with Example 1, the only difference is that the weight portion of Astragalus membranaceus in the traditional Chinese medicine formula is 8. The rest is the same as Example 1.

[0053] Comparative Example 7 Compared with Example 1, the only difference is that the weight portion of Astragalus membranaceus in the traditional Chinese medicine formula is 20 parts. The rest is the same as Example 1.

[0054] Comparative Example 8 Compared with Example 1, the only difference is that the Chinese medicine formula does not contain Phyllanthus urinaria. Others are the same as Example 1.

[0055] Comparative Example 9 Compared with Example 1, the only difference is that the weight portion of Phyllanthus urinaria in the traditional Chinese medicine formula is 8. The rest is the same as Example 1.

[0056] Effect Evaluation The granules prepared in the examples and comparative examples were evaluated for their efficacy using asthenozoospermia model rats. The results are shown in Table 1. The method is: 1. Grouping and modeling: 114 10-week-old SPF SD male rats with an average body weight of 250±30g were randomly divided into 19 groups, with 6 rats in each group. After 1 week of adaptive feeding, rats in each group, except the blank group, were intraperitoneally injected with cyclophosphamide once a day at a dose of 35 mg / kg for 7 consecutive days. The blank group was intraperitoneally injected with an equal amount of normal saline.

[0057] 2. After the model was successfully established, each group of rats was given the drug once a day for 30 consecutive days in the following manner: Model group: given normal saline 10mL / kg by gavage; For each example group: 1.12 g of the granules prepared in the corresponding example group was mixed and dissolved with 10 mL of normal saline (for example, the granules prepared in Example 1 were taken in Example 1 group, the granules prepared in Example 2 were taken in Example 2 group, and so on), and the mixture was intragastrically administered at a dosage volume of 10 mL / kg; For each comparative example group: 1.12 g of the granules prepared in the corresponding comparative example group was mixed and dissolved with 10 mL of normal saline (for example, comparative example group 1 was mixed with the granules prepared in comparative example 1, comparative example group 2 was mixed with the granules prepared in comparative example 2, and so on), and the mixture was intragastrically administered at a dosage volume of 10 mL / kg; Blank group: 10 mL / kg normal saline was given by intragastric administration.

[0058] 3. Sampling and analysis: fast for 24 hours after the last administration, anesthetize with 10% chloral hydrate intraperitoneally, quickly remove the left epididymis, cut into pieces, dissolve in 2 mL of normal saline, and continue incubating at 37°C for 15 minutes until the sperm completely swims out to obtain a sperm suspension, then take the sperm suspension and mix it, drop it onto a sperm counting plate, and perform sperm concentration and total sperm motility tests. For routine semen analysis, refer to the human sperm analysis method to analyze indicators such as rat sperm motility and sperm density.

[0059] Table 1 Group <![CDATA[Sperm concentration (10 6 / mL)]]> Total sperm motility (%) Blank Group 50.23±4.26 67.89±4.17 Model Group 26.56±3.12 40.62±2.85 Example 1 46.71±4.02 61.50±4.11 Example 2 43.64±3.59 60.43±5.54 Example 3 44.87±2.12 61.01±3.66 Example 4 40.96±3.22 56.36±4.23 Example 5 39.14±3.06 54.65±2.23 Example 6 40.32±3.61 55.74±5.05 Comparative Example 1 32.40±3.06 44.07±3.56 Comparative Example 2 33.64±3.00 46.36±2.83 Comparative Example 3 36.01±2.32 47.07±2.44 Comparative Example 4 33.98±2.80 47.36±3.82 Comparative Example 5 34.56±3.59 46.48±2.40 Comparative Example 6 34.22±3.12 46.47±3.26 Comparative Example 7 35.68±1.99 48.10±2.26 Comparative Example 8 37.02±2.30 47.99±2.60 Comparative Example 9 38.08±3.12 47.21±3.18 From Table 1, we can see that: (1) After 30 days of medication, the sperm concentration and total sperm motility of the rats in the embodiment group of the present invention were significantly improved compared with the model group. This shows that the present invention, by mixing the Chinese medicinal ingredients of epimedium, Morinda officinalis, lily, Astragalus, Cuscuta australis, Cistanche deserticola, Astragalus, Carapax tricolor, Phyllanthus urinaria, Paeonia lactiflora, and Salvia miltiorrhiza with millet paste, and fermenting the fermented active drug with Bifidobacterium bifida, has a good effect on the treatment of idiopathic asthenospermia. And from the comparative analysis of Example 1 and Example 4, it can be seen that Example 4 is fermented with Bifidobacterium bifida alone, and the sperm concentration of the rats in Example 4 is reduced to a certain extent. Therefore, it can be seen that it is preferred that the two strains of Bifidobacterium bifida and Lactobacillus plantarum LP45 are added simultaneously during fermentation.

[0060] (2) By comparing and analyzing Comparative Example 1 with Example 1, it is found that in Comparative Example 1, no millet paste is added for fermentation, and the sperm concentration of the rats in Comparative Example 1 is significantly reduced. This shows the importance of mixed fermentation of millet paste and Chinese herbal medicine decoction. It is speculated that millet paste can promote the effect of the Chinese herbal medicine ingredients in this formula on nourishing the kidney and replenishing sperm after fermentation, or that the fermented ingredients of millet paste itself have a certain regulatory effect on the reproductive system.

[0061] (3) By comparing comparative examples 2 to 3 with Example 1, the number of Morinda officinalis added in comparative examples 2 and 3 is 7 parts and 23 parts respectively, and the sperm concentration of rats in comparative examples 2 and 3 is reduced to varying degrees, especially in comparative example 2. The reduction is obvious, which shows the importance of the specific ratio of Morinda officinalis ingredients in the formula of the present invention. Morinda officinalis is commonly used in the field of traditional Chinese medicine to tonify the kidney and strengthen yang, and is used to treat symptoms such as cold waist and knees, impotence and spermatorrhea, and premature ejaculation caused by kidney yang deficiency. However, in the present invention, in comparative example 3, the number of Morinda officinalis is increased to 23 parts, and its sperm concentration and total sperm motility do not increase but slightly decrease, indicating that in this formula, when Morinda officinalis is added in too many parts, it will bring certain "side effects", and this "side effect" may cause the effect of this prescription in treating asthenozoospermia to be weakened to a certain extent. Further analysis shows that Morinda officinalis can affect the digestive system and cause symptoms such as vomiting, nausea, and diarrhea. Therefore, excessive Morinda officinalis may affect the body's functions, resulting in poor absorption of the active ingredients of the drug, thereby partially affecting the efficacy of the drug. As a result, the sperm concentration in Example 3 decreased. This proves that the present invention is more effective in treating asthenozoospermia, which may be related to the fact that Bifidobacterium bifida is beneficial to intestinal health.

[0062] (4) Comparative Examples 4-5 and Example 1 show that the proportions of lily added in Comparative Examples 4-5 are 5 and 16 respectively, and the sperm concentration and total sperm motility of rats in Comparative Examples 4 and 5 decrease to a certain extent, which shows the importance of adding lily as the assistant drug in the formula of the present invention. Lily belongs to the lung meridian, which shows that a specific proportion of lily in this Chinese medicine prescription can enhance the effect of the main drug in tonifying the kidney and benefiting the essence.

[0063] (5) Comparative Examples 6 to 9 and Example 1 show that the adjustment of the ratio of Astragalus and Phyllanthus urinaria will have a certain impact on the efficacy of the present invention. Phyllanthus urinaria can remove the heat evil in the body, help eliminate food accumulation in the body, and relieve symptoms such as indigestion. It is speculated that Phyllanthus urinaria can promote the effect of the main drug to replenish the kidney and essence by adjusting the health of the digestive system.

[0064] Therefore, in combination with Comparative Examples 2 to 3, Comparative Examples 4 to 5, and by comparing Comparative Examples 6 to 9 with Example 1, it can be seen that the specific ratio of the components of the present invention has a great improvement effect on the effect of treating idiopathic asthenozoospermia. In the Chinese medicine prescription of the present invention, in addition to exerting their respective effects, each medicine has achieved additional effects as a whole after being combined together, which has a good effect on improving asthenozoospermia. The present invention mixes 8 to 12 parts of Epimedium, 10 to 20 parts of Morinda officinalis, 7 to 14 parts of Lilium, 10 to 20 parts of Astragalus, 10 to 17 parts of Cuscuta, 5 to 15 parts of Cistanche, and 15 to 20 parts of Astragalus, and adds 6 to 10 parts of Carapax Trichosanthis, 2 to 5 parts of Phyllanthus urinaria, 5 to 10 parts of Red Peony Root, and 10 to 15 parts of Salvia miltiorrhiza, so that the present formula has an unexpected effect of treating asthenozoospermia.

[0065] 4. Sampling and analysis: After the last administration, fast for 24 hours, anesthetize with 10% chloral hydrate intraperitoneally, quickly remove the testicular tissue, fix it with 4% paraformaldehyde fixative, and observe the testicular pathological sections. The results are shown in Figures 1 to 3 .in, Figure 1 The testicular tissue morphology of rats in the blank group (100×). Figure 2 The testicular tissue morphology of rats in the model group (100×). Figure 3 The testicular tissue morphology of rats in Example 1 group (100×).

[0066] Depend on Figures 1 to 3 It can be seen that: Figure 1 It showed that a large number of sperms were observed in the seminiferous tubules of the blank group rats, and the seminiferous epithelium and spermatogenic cells at all levels were arranged regularly; Figure 2 The results showed that the mature sperm in the testicular lumen of the rats in the model group were significantly reduced, the seminiferous tubules were more cavitary, the seminiferous epithelium was significantly thinned, and the number of spermatogenic cells was reduced and their arrangement was disordered; Figure 3 The results showed that the number of mature sperm in the testicular lumen of rats in Example 1 group increased significantly compared with that in the model group. In contrast, the number of spermatogenic epithelial layers in the testicular lumen of rats in Example 1 group increased, the number of spermatogenic cells at all levels in the lumen increased, and the arrangement of spermatogenic cells at all levels was regular. Figures 1 to 3 The comparative analysis shows that the formula of the present invention is an excellent effect in improving and treating idiopathic asthenospermia by mixing the Chinese medicinal ingredients of Epimedium, Morinda officinalis, Lilium, Astragalus, Cuscuta australis, Cistanche deserticola and millet paste with the fermentation product obtained by Bifidobacterium bifida.

[0067] The raw materials and equipment used in the present invention, unless otherwise specified, are all commonly used raw materials and equipment in the art; the methods used in the present invention, unless otherwise specified, are all conventional methods in the art.

[0068] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent transformation made to the above embodiment based on the technical essence of the present invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for treating idiopathic asthenozoospermia, characterized in that: The Chinese medicine composition comprises the following components: epimedium, Morinda officinalis, lily, Astragalus complanatus, Cuscuta australis, Cistanche deserticola, and Astragalus membranaceus; The Chinese medicine composition is mixed with millet paste and fermented to prepare an active medicine for treating idiopathic asthenozoospermia.

2. A Chinese medicine composition for treating idiopathic asthenozoospermia according to claim 1, characterized in that: In the mixed fermentation, fermentation is performed by adding Bifidobacterium bifidum.

3. A Chinese medicine composition for treating idiopathic asthenozoospermia according to claim 2, characterized in that: In the mixed fermentation, fermentation is performed by adding Bifidobacterium bifidum and Lactobacillus plantarum LP45.

4. A Chinese medicine composition for treating idiopathic asthenozoospermia according to claim 1, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 8-12 parts of epimedium, 10-20 parts of Morinda officinalis, 7-14 parts of lily, 10-20 parts of Astragalus membranaceus, 10-17 parts of Cuscuta australis, 5-15 parts of Cistanche deserticola and 15-20 parts of Astragalus membranaceus.

5. A Chinese medicine composition for treating idiopathic asthenozoospermia according to claim 4, characterized in that: The traditional Chinese medicine composition comprises the following components in parts by weight: 6-10 parts of turtle shell, 2-5 parts of Phyllanthus urinaria, 5-10 parts of red peony root, and 10-15 parts of Salvia miltiorrhiza.

6. A Chinese medicine composition for treating idiopathic asthenozoospermia according to claim 4 or 5, characterized in that: In the mixed fermentation, the mixing mass ratio of the traditional Chinese medicine composition to the millet paste is 1:0.8-1.

6.

7. Use of the traditional Chinese medicine composition according to any one of claims 1 to 6 in the treatment of idiopathic asthenozoospermia.

8. A pharmaceutical preparation comprising the Chinese medicine composition according to any one of claims 1 to 6, characterized in that: It is any one of granules, mixtures, pills, syrups, powders, pastes, capsules and tablets.

9. A method for preparing granules for treating idiopathic asthenozoospermia, characterized in that: The following steps are involved: Step S1: preparing millet paste: mixing millet with pure water, heating and soaking the millet for a period of time to soften the millet, crushing and homogenizing the millet, and then high-temperature steaming to gelatinize the rice paste to obtain millet paste; Step S2: preparing a Chinese herbal decoction: placing epimedium, Morinda officinalis, lily, Astragalus, Cuscuta australis, Cistanche deserticola, Astragalus, Phyllanthus urinaria, Paeonia lactiflora, and Salvia miltiorrhiza in a decoction vessel, adding water, soaking for 0.5 to 2 hours, boiling over high heat, then decocting over low heat for 30 to 60 minutes, removing the residue, and obtaining a Chinese herbal decoction; Step S3: preparing a fermentation agent: inoculating the activated Bifidobacterium bifidum and Lactobacillus plantarum LP45 into a culture medium at a ratio of 2 to 3:1 to obtain a mixed bacterial solution, centrifuging, and collecting the supernatant to obtain a fermentation agent; Step S4: preparing a fermentation active drug: uniformly mixing the Chinese medicine decoction and the millet paste, inoculating the fermentation bacteria into the mixture, culturing at 30-40° C. for 48-72 hours, mixing, and freeze-drying to obtain a fermentation active drug; Step S5: adding a wetting agent and a binder to the fermentation active drug, granulating, and drying to obtain a granule.

10. The preparation method according to claim 9, characterized in that: The mixing mass ratio of the Chinese medicine decoction and the millet paste is 1:0.8-1.6, and the inoculation volume ratio of the fermentation bacteria agent is 2-5%.

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