Traditional Chinese medicine composition for treating osteoporosis or climacteric syndrome

Abstract

The invention relates to a traditional Chinese medicine composition for treating osteoporosis or climacteric syndrome, which is prepared from the following components in parts by mass: 10 to 15 parts of radix rehmanniae recen, 9 to 15 parts of cortex lycii radicis, 6 to 12 parts of semen cuscutae, 5 to 12 parts of radix achyranthis bidentatae, 3 to 10 parts of rhizoma acori graminei and 3 to 10 parts of polygala tenuifolia. The traditional Chinese medicine composition can be used for effectively treating osteoporosis or climacteric syndrome, and particularly has obvious effects of regulating related hormone level, sleep quality, emotion, hypothalamus neurotransmitter, water intake, increasing maximum tibia load and the like.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition for treating osteoporosis or menopausal syndrome. Background Art

[0002] Menopausal syndrome mostly occurs in women aged 45 - 55. Most women may experience symptoms of varying degrees. Some women may start to show symptoms during the perimenopausal transition period, which persist for 2 - 3 years after menopause. In a small number of people, the symptoms may continue for 5 - 10 years after menopause before gradually alleviating or disappearing. Women with artificial menopause often develop perimenopausal syndrome 2 weeks after surgery, reaching a peak 2 months after surgery and lasting for up to 2 years. According to investigations, the most common symptoms of female menopausal syndrome are insomnia (50%), fatigue (48.2%), depression (46.9%), and hot flashes and sweating (23.9%) in sequence.

[0003] Osteoporosis is the main complication of women's menopausal syndrome. With the decline of ovarian function and the decrease of estrogen levels in the body, intestinal calcium absorption decreases, and bone calcium release is greater than bone calcium deposition. Bone mass gradually decreases, and the possibility of developing osteoporosis increases accordingly. The main pathogenesis is that the lack of sex hormones induces changes in the cytokine network system that generates osteoclasts, activates the activity of osteoclasts, inhibits the activity of osteoblasts, and the bone resorption rate exceeds the bone formation rate.

[0004] Currently, the western medicine treatment of menopausal syndrome still mainly relies on hormone therapy supplemented by symptomatic treatment. However, the adverse reaction rate of hormone therapy is relatively high. Especially in the long - term use of hormones, it increases the risks of uterine fibroids, cholelithiasis, epilepsy, migraine, asthma, breast cancer, cardiovascular and cerebrovascular diseases in patients. Moreover, patients generally have fears and misunderstandings about hormone preparations, thus reducing the compliance of hormone treatment (see non - patent literature: Menopause Group of the Obstetrics and Gynecology Society of the Chinese Medical Association. Guidelines for Menopause Management and Menopausal Hormone Therapy in China 2023 Edition [J]. Chinese Journal of Obstetrics and Gynecology, 2023, 58(1): 4 - 21.).

[0005] However, there have been reports of using traditional Chinese medicine compositions to treat osteoporosis or menopausal syndrome: Patent CN110179919A (publication date: 2019-08-30) discloses a traditional Chinese medicine composition including dendrobium, raw rehmannia, Morinda officinalis, Eucommia ulmoides, epimedium, moutan bark, angelica sinensis, gardenia, white peony root, julibrissin bark, tortoise shell, lily, polygonatum, poria, ophiopogon japonicus, codonopsis pilosula, bupleurum, costus root, cinnamon twig, tribulus terrestris, astragalus, and lithospermum officinale, which can be used to treat menopausal syndrome. However, no specific data on the improvement of water intake, serum hormone levels, hypothalamic neurotransmitters, mood and sleep conditions after administration are provided. Patent CN103041306B (publication date: 2013-04-17) discloses a traditional Chinese medicine composition for treating menopausal syndrome in women. The traditional Chinese medicine composition comprises Nigella Sativa seeds, Curculigo orchioides, Rosa laevigata fruits, Platycladus chinensis seeds, Polygala tenuifolia, Cistanche deserticola, Prunella vulgaris, Atractylodes macrocephala seeds, Black sesame seeds, Ecliptae macrophylla, Phellodendron amurense, Tortoise shell glue, Curcuma zedoaria, Pollen Typhae, Dalbergia odorifera, Dioscorea batatas, Acanthopanax senticosus, Japonica ginseng, White peony root, Salvia miltiorrhiza, Apocynum venetum leaves, Uncaria rhynchophylla, Adzuki bean, Rhizoma bambusae, Oyster, Achyranthes bidentata, Codonopsis pilosula, Tangerine peel, Coix lachryma-jobi seeds, and Licorice root. In the examples, only serum estrogen levels, hypothalamic neurotransmitter levels, and acute toxicity were verified. Data on sleep status, water intake, and mood-related indicators were not provided. Patent CN119524090A (publication date: 2025-02-28) discloses a traditional Chinese medicine composition for treating or preventing osteoporosis, which is composed of medicinal materials such as bullwhip, cinnamon, and alfalfa seeds. Summary of the Invention

[0006] The present invention provides a Chinese medicine composition for treating osteoporosis or menopausal syndrome, which can effectively improve the patient's relevant hormone levels, sleep quality, mood indicators, and maximum tibial load. The specific scheme is as follows:

[0007] The first aspect of the present invention provides a use of a traditional Chinese medicine composition in preparing a product for treating osteoporosis or menopausal syndrome, wherein the traditional Chinese medicine composition comprises, by weight:

[0008] 10-15 parts of Radix Rehmanniae, for example, 10, 11, 12, 13, 14 or 15 parts;

[0009] 9-15 parts of Lycium bark, for example, 9, 10, 11, 12, 13, 14 or 15 parts;

[0010] 3-10 parts of Acorus calamus, for example, 3, 4, 5, 6, 7, 8, 9 or 10 parts;

[0011] 6-12 parts of Cuscuta seeds, 6, 7, 8, 9, 10, 11 or 12 parts, etc.;

[0012] 5-12 parts of Achyranthes bidentata, such as 5, 6, 7, 8, 9, 10, 11 or 12 parts; and

[0013] 3 - 10 parts of Polygala tenuifolia, such as 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.

[0014] Preferably, the active ingredients in the traditional Chinese medicine composition, by mass parts, include:

[0015] 10 - 15 parts of Rehmannia glutinosa, such as 10, 11, 12, 13, 14 or 15 parts, etc.;

[0016] 9 - 15 parts of Cortex Lycii, such as 9, 10, 11, 12, 13, 14 or 15 parts, etc.;

[0017] 3 - 10 parts of Acorus tatarinowii, such as 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.;

[0018] 6 - 12 parts of Cuscuta chinensis, 6, 7, 8, 9, 10, 11 or 12 parts, etc.;

[0019] 5 - 12 parts of Achyranthes bidentata, such as 5, 6, 7, 8, 9, 10, 11 or 12 parts, etc.; and

[0020] 3 - 10 parts of Polygala tenuifolia, such as 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.

[0021] In a specific embodiment of the present invention, the traditional Chinese medicine composition, by mass parts, includes 10 parts of Rehmannia glutinosa, 10 parts of Cortex Lycii, 10 parts of Acorus tatarinowii, 10 parts of Cuscuta chinensis, 10 parts of Achyranthes bidentata and 10 parts of Polygala tenuifolia.

[0022] In a specific embodiment of the present invention, the active ingredients in the traditional Chinese medicine composition, by mass parts, include 10 parts of Rehmannia glutinosa, 10 parts of Cortex Lycii, 10 parts of Acorus tatarinowii, 10 parts of Cuscuta chinensis, 10 parts of Achyranthes bidentata and 10 parts of Polygala tenuifolia.

[0023] Preferably, the menopausal syndrome is female menopausal syndrome.

[0024] Preferably, the osteoporosis is menopausal osteoporosis.

[0025] The Rehmannia glutinosa is derived from the fresh or dried tubers of the plant Rehmannia glutinosa Libosch. of the family Scrophulariaceae. The Rehmannia glutinosa clears heat and cools blood, nourishes yin and promotes the production of body fluid, and is an important herb for tonifying kidney yin.

[0026] The Cortex Lycii is derived from the dried root bark of the plant Lycium chinense Mill. or Lycium barbarum L. of the family Solanaceae. The Cortex Lycii clears deficiency - heat, reduces bone steaming, and is good at treating tidal fever and night sweating due to yin - deficiency and fire - hyperactivity.

[0027] The dodder seed is derived from the dried ripe seeds of the Convolvulaceae plants Cuscuta australis R.Br. or Cuscuta chinensis Lam. Preferably, the dodder seed is the processed dodder seed with yellow rice wine, for example, the dodder seed is processed with yellow rice wine. The dodder seed supplements the liver and kidney, arrests seminal emission and urinary frequency, prevents miscarriage, improves eyesight, and can be used for symptoms such as deficiency of the liver and kidney, soreness and weakness of the waist and knees, etc.

[0028] The achyranthes root is derived from the dried root of the Amaranthaceae plant Achyranthes bidentata Bl. Preferably, the achyranthes root is the processed achyranthes root with yellow rice wine, for example, the achyranthes root is processed with yellow rice wine. The achyranthes root supplements the liver and kidney, strengthens the tendons and bones, and guides fire downward to relieve the flaring-up of deficient fire.

[0029] The acorus tatarinowii rhizome is derived from the dried rhizome of the Araceae plant Acorus tatarinowii Schott. The acorus tatarinowii rhizome awakens the mind and improves intelligence, and can be used for symptoms such as coma, epilepsy, amnesia, insomnia, tinnitus, and deafness, etc.

[0030] The polygala root is derived from the dried root of the Polygalaceae plants Polygala tenuifolia Willd. or Polygala sibirica L. The polygala root tranquilizes the mind and improves intelligence, and connects the heart and kidney, and can be used for symptoms such as insomnia, dreaminess, amnesia, palpitations, trance, etc. caused by disharmony between the heart and kidney.

[0031] Preferably, the dosage forms of the traditional Chinese medicine composition include tablets, capsules, powders, pills, pellets, granules, injections, decoctions, medicated wines, plasters or pastes.

[0032] The traditional Chinese medicine composition also includes excipients.

[0033] Preferably, the excipients include one or more of diluents, disintegrants, lubricants, excipients, binders, glidants, fillers or surfactants.

[0034] More preferably, the diluents include, but are not limited to, one or more of lactose, starch, pregelatinized starch, microcrystalline cellulose, sorbitol, mannitol or inorganic calcium salts.

[0035] More preferably, the disintegrants include, but are not limited to, one or more of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, alginic acid, microcrystalline cellulose.

[0036] More preferably, the lubricants include, but are not limited to, one or more of stearic acid, sodium stearate, magnesium stearate, calcium stearate, polyethylene glycol, talc powder, hydrogenated vegetable oil.

[0037] More preferably, the excipient includes one or more of fructose, galactose, mannitol, polyvinyl alcohol, sodium carboxymethyl cellulose, erythritol or cyclodextrin.

[0038] More preferably, the binder includes one or more of starch paste, hydroxypropyl methylcellulose, polyvinylpyrrolidone, etc.

[0039] More preferably, the glidant includes one or more of colloidal silicon dioxide, talc or magnesium trisilicate, etc.

[0040] More preferably, the filler includes one or more of sucrose, disaccharide, maltodextrin, silicon dioxide, calcium carbonate, magnesium carbonate, aluminum powder or phenolic resin.

[0041] More preferably, the surfactant includes one or more of Tween-80, cetyltrimethylammonium bromide, sodium stearyl alcohol sulfonate or sodium dodecyl sulfate.

[0042] The product is a drug.

[0043] Preferably, the preparation method of the traditional Chinese medicine composition includes powdering, water decocting, stir-frying, macerating, percolating, supercritical extraction or reflux extraction; preferably water decocting, direct powdering or powdering after ethanol infiltration.

[0044] In a specific embodiment of the present invention, each component of the traditional Chinese medicine composition is decocted with water and then concentrated into extract powder.

[0045] In another specific embodiment of the present invention, each component in the traditional Chinese medicine composition is infiltrated in ethanol, then dried and pulverized.

[0046] Preferably, before the infiltration, each component can be crushed or cut into pieces.

[0047] Preferably, the infiltration is appropriate when it is infiltrated thoroughly.

[0048] Preferably, the ethanol is 10-30% ethanol.

[0049] Preferably, the infiltration time is 1-7 days. More preferably, the infiltration time is 5-7 days.

[0050] The infiltration temperature is 20-30°C. Preferably, the infiltration temperature is room temperature.

[0051] Preferably, the treatment of osteoporosis or menopausal syndrome includes administering an effective amount of the traditional Chinese medicine composition to a subject in need.

[0052] Preferably, the traditional Chinese medicine composition can regulate serum hormone levels, enhance the maximum tibial load, hypothalamic neurotransmitters, sleep quality, water intake, mood, etc.

[0053] In a specific embodiment of the present invention, the traditional Chinese medicine composition treats menopausal syndrome by regulating one or more of serum hormone levels, hypothalamic neurotransmitters, sleep quality, water intake or mood.

[0054] In a specific embodiment of the present invention, the traditional Chinese medicine composition treats osteoporosis (especially menopausal osteoporosis) by regulating serum hormone levels and / or enhancing the maximum tibial load.

[0055] More preferably, the serum hormones include estradiol (E2), follicle-stimulating hormone (FSH) and / or luteinizing hormone (LH).

[0056] More preferably, the hypothalamic neurotransmitters include serotonin, norepinephrine and / or dopamine.

[0057] More preferably, the sleep quality includes sleep latency and sleep duration indicators.

[0058] Preferably, the treatment of osteoporosis or menopausal syndrome includes taking 2 - 100 (such as 2, 3, 4, 4.5, 5, 5.46, 5.5, 6, 6.5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100, etc.) g of the raw drug amount per day, and taking the traditional Chinese medicine composition for 1 - 24 (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24, etc., preferably 2 - 12 or 2 - 6) months.

[0059] In the second aspect of the present invention, there is provided a traditional Chinese medicine composition for treating osteoporosis or menopausal syndrome, which, by mass fraction, comprises:

[0060] 10 - 15 parts of Rehmannia glutinosa, such as 10, 11, 12, 13, 14 or 15 parts, etc.;

[0061] 9 - 15 parts of Cortex Lycii, such as 9, 10, 11, 12, 13, 14 or 15 parts, etc.;

[0062] 3 - 10 parts of Acorus tatarinowii, such as 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.;

[0063] [[ID=3३]]6 - 12 parts of Cuscuta chinensis, 6, 7, 8, 9, 10, 11 or 12 parts, etc.;

[0064] 5-12 parts of Achyranthes bidentata, such as 5, 6, 7, 8, 9, 10, 11 or 12 parts; and

[0065] 3-10 parts of Polygala tenuifolia, for example 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.

[0066] Preferably, the active ingredients in the traditional Chinese medicine composition, calculated by weight, include:

[0067] 10-15 parts of Radix Rehmanniae, for example, 10, 11, 12, 13, 14 or 15 parts;

[0068] 9-15 parts of Lycium bark, for example, 9, 10, 11, 12, 13, 14 or 15 parts;

[0069] 3-10 parts of Acorus calamus, for example, 3, 4, 5, 6, 7, 8, 9 or 10 parts;

[0070] 6-12 parts of Cuscuta seeds, 6, 7, 8, 9, 10, 11 or 12 parts, etc.;

[0071] 5-12 parts of Achyranthes bidentata, such as 5, 6, 7, 8, 9, 10, 11 or 12 parts; and

[0072] 3-10 parts of Polygala tenuifolia, for example 3, 4, 5, 6, 7, 8, 9 or 10 parts, etc.

[0073] In a specific embodiment of the present invention, the traditional Chinese medicine composition comprises, by mass, 10 parts of raw rehmannia root, 10 parts of lycium bark, 10 parts of calamus, 10 parts of dodder seed, 10 parts of achyranthes bidentata and 10 parts of polygala tenuifolia.

[0074] In a specific embodiment of the present invention, the active ingredients in the traditional Chinese medicine composition, calculated by mass, include 10 parts of raw rehmannia root, 10 parts of lycium bark, 10 parts of calamus, 10 parts of dodder seed, 10 parts of achyranthes bidentata and 10 parts of polygala tenuifolia.

[0075] Preferably, the dodder seed is wine dodder seed. Further preferably, the wine dodder seed is dodder seed processed with yellow rice wine.

[0076] Preferably, the Achyranthes Bidentata is Achyranthes Bidentata prepared with wine. Further preferably, the Achyranthes Bidentata prepared with wine is Achyranthes Bidentata prepared with yellow rice wine.

[0077] Preferably, the dosage form of the Chinese medicine composition includes tablets, capsules, powders, pills, pills, granules, injections, decoctions, wines, ointments or pastes.

[0078] The traditional Chinese medicine composition also includes auxiliary materials.

[0079] Preferably, the adjuvants include one or more of diluents, disintegrants, lubricants, excipients, binders, glidants, fillers or surfactants.

[0080] More preferably, the diluents include one or more of lactose, starch, pregelatinized starch, microcrystalline cellulose, sorbitol, mannitol or inorganic calcium salts.

[0081] More preferably, the disintegrants include one or more of crosslinked polyvinylpyrrolidone, croscarmellose sodium, alginic acid, microcrystalline cellulose.

[0082] More preferably, the lubricants include one or more of stearic acid, sodium stearate, magnesium stearate, calcium stearate, polyethylene glycol, talc powder, hydrogenated vegetable oil.

[0083] More preferably, the excipients include one or more of fructose, galactose, mannitol, polyvinyl alcohol, sodium carboxymethylcellulose, erythritol or cyclodextrin.

[0084] More preferably, the binders include one or more of starch paste, hydroxypropyl methylcellulose, polyvinylpyrrolidone.

[0085] More preferably, the glidants include one or more of colloidal silicon dioxide, talc powder or magnesium trisilicate.

[0086] More preferably, the fillers include one or more of sucrose, trehalose, maltodextrin, silicon dioxide, calcium carbonate, magnesium carbonate, aluminum powder or phenolic resin.

[0087] More preferably, the surfactants include one or more of Tween-80, cetyltrimethylammonium bromide, sodium stearyl sulfonate or sodium dodecyl sulfate.

[0088] In the third aspect of the present invention, a preparation method of the traditional Chinese medicine composition described in the second aspect is provided. The preparation method includes powdering, decocting with water, stir-frying, macerating, percolating, supercritical extraction or reflux extraction; preferably decocting with water, directly powdering or powdering after ethanol infiltration.

[0089] In a specific embodiment of the present invention, each component of the traditional Chinese medicine composition is decocted with water and then concentrated into extract powder.

[0090] In a specific embodiment of the present invention, each component in the traditional Chinese medicine composition is infiltrated in ethanol and then dried and pulverized.

[0091] Preferably, before the infiltration, each component can be crushed or cut into pieces.

[0092] Preferably, the infiltration should be thorough.

[0093] Preferably, the ethanol is 10 - 30% ethanol.

[0094] Preferably, the infiltration time is 1 - 7 days. More preferably, the infiltration time is 5 - 7 days.

[0095] The infiltration temperature is 20 - 30°C. Preferably, the infiltration temperature is room temperature.

[0096] In a specific embodiment of the present invention, the preparation method includes: crushing or cutting each component in the traditional Chinese medicine composition, then infiltrating at room temperature in ethanol for 1 - 7 days until all components are just thoroughly infiltrated; then drying in an oven; further, after returning to room temperature, freezing, and pulverizing and sieving.

[0097] In the fourth aspect of the present invention, there is provided an application of the traditional Chinese medicine composition described in the second aspect or the traditional Chinese medicine composition obtained by the preparation method described in the third aspect, and the application includes:

[0098] A) Application in the preparation of products for treating insomnia, anxiety, and / or depression;

[0099] B) Application in the preparation of products for treating sequelae of ovariectomy;

[0100] C) Application in the preparation of products for treating serum hormone disorders;

[0101] D) Application in the preparation of products for treating hypothalamic neurotransmitter disorders; or,

[0102] E) Application in the preparation of products for enhancing the maximum load of the tibia.

[0103] Preferably, the serum hormones include estradiol (E2), follicle-stimulating hormone (FSH), and / or luteinizing hormone (LH).

[0104] Preferably, the hypothalamic neurotransmitters include serotonin, norepinephrine, and / or dopamine.

[0105] Preferably, the sequelae of ovariectomy include serum hormone disorders, hypothalamic neurotransmitter disorders, insomnia, anxiety, and / or depression caused by ovariectomy.

[0106] In the fifth aspect of the present invention, there is provided a method for treating osteoporosis or menopausal syndrome, and the method includes administering an effective amount of the traditional Chinese medicine composition described in the second aspect or the traditional Chinese medicine composition obtained by the preparation method described in the third aspect to a subject in need.

[0107] Preferably, the menopausal syndrome is female menopausal syndrome.

[0108] Preferably, the osteoporosis is menopausal osteoporosis.

[0109] Preferably, the traditional Chinese medicine composition can regulate the serum hormone levels of the subjects, enhance the maximum load of the tibia, hypothalamic neurotransmitters, sleep quality, water intake, mood, etc.

[0110] More preferably, the serum hormones include estradiol (E2), follicle-stimulating hormone (FSH) and / or luteinizing hormone (LH).

[0111] More preferably, the hypothalamic neurotransmitters include serotonin, norepinephrine and / or dopamine.

[0112] More preferably, the sleep quality includes sleep latency and sleep duration indicators.

[0113] Preferably, the treatment of osteoporosis or menopausal syndrome includes taking 2 - 100 (such as 2, 3, 4, 4.5, 5, 5.46, 5.5, 6, 6.5, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100, etc.) g of the crude drug amount per day, and taking the traditional Chinese medicine composition for 1 - 24 (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24, etc., preferably 2 - 12 or 2 - 6) months.

[0114] In the sixth aspect of the present invention, a method for improving sleep is provided, and the method includes administering the traditional Chinese medicine composition described in the second aspect or the traditional Chinese medicine composition obtained by the preparation method described in the third aspect.

[0115] In the seventh aspect of the present invention, a method for regulating serum hormones is provided, and the method includes administering the traditional Chinese medicine composition described in the second aspect or the traditional Chinese medicine composition obtained by the preparation method described in the third aspect.

[0116] The present invention has the following beneficial effects:

[0117] (1) The traditional Chinese medicine composition of the present application has few medicinal flavors and a simple process, and has obvious pharmacoeconomic advantages.

[0118] (2) The present application uses the traditional Chinese medicine composition to treat osteoporosis or female menopausal syndrome, avoiding the dependence, drug resistance and side effects generated during the treatment with western medicine.

[0119] (3) The traditional Chinese medicine composition of the present application significantly improves the relevant hormone levels, sleep, mood of patients, and enhances the maximum load of the tibia, etc.

[0120] The "menopausal syndrome" described in the present invention is also called perimenopausal syndrome, which is a series of syndrome groups mainly caused by the decline of ovarian function and accompanied by autonomic nervous system dysfunction and neuropsychological symptoms, including hot flashes and sweating, insomnia and forgetfulness, mental fatigue, anxiety and depression, dizziness and vertigo, tinnitus and palpitation, low back and back pain, feverish palms and soles, etc.

[0121] The "treatment" described in the present invention means to slow down, interrupt, prevent, control, stop, relieve, or reverse the progression or severity of a sign, symptom, disorder, disease condition, or disease after the disease has started to develop, but does not necessarily involve the complete elimination of all disease-related signs, symptoms, disease conditions, or disorders.

[0122] The "effective amount" described in the present invention refers to the amount or dose of the traditional Chinese medicine composition of the present invention that provides the desired treatment after being administered to a subject or an organ in a single or multiple doses.

[0123] The "subject" described in the present invention can be a human or non-human mammal, or can be a cell, tissue, or organ of a human or non-human mammal. The non-human mammal can be a wild animal, zoo animal, economic animal, pet, experimental animal, etc. Preferably, the non-human mammal includes but is not limited to pigs, cows, sheep, horses, donkeys, foxes, raccoons, minks, camels, dogs, cats, rabbits, rats (such as rats, mice, guinea pigs, hamsters, gerbils, chinchillas, squirrels), or monkeys, etc. Detailed implementation mode

[0124] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0125] It should be noted that the methods used in the present invention are all conventional methods unless otherwise specified, and the reagents used in the present invention are all commercially available products unless otherwise specified.

[0126] Progynova was purchased from Bayer Healthcare Co., Ltd. Guangzhou Branch; specification: 1 mg / tablet, 21 tablets / box; batch number: 762A.

[0127] Dizhen Granules was purchased from Tiansheng Pharmaceutical Group Co., Ltd.; specification: 5 g / bag, 18 bags / box; batch number: 2221001.

[0128] Radix Rehmanniae was derived from the dried tuber of Rehmannia glutinosa Libosch. of the family Scrophulariaceae.

[0129] The cortex lycii radicis is derived from the dried root bark of the Solanaceae plant Lycium chinense Mill.

[0130] The semen cuscutae is derived from the dried ripe seeds of the Convolvulaceae plant Cuscuta australis R.Br.

[0131] The radix achyranthis bidentatae is derived from the dried root of the Amaranthaceae plant Achyranthes bidentata Bl.

[0132] The rhizoma acori tatarinowii is derived from the dried rhizome of the Araceae plant Acorus tatarinowii Schott.

[0133] The radix polygalae is derived from the dried root of the Polygalaceae plant Polygala tenuifolia Willd.

[0134] Example 1: Preparation method of traditional Chinese medicine composition

[0135] After weighing the mass parts of each component in the traditional Chinese medicine composition according to Table 1, simply crush or cut them, and moisten them with an appropriate amount of 15% ethanol at room temperature for 6 days until all components are just thoroughly moistened. Then place the prescription in an 80°C oven to dry. After taking it out and restoring it to room temperature, place it at -80°C for freezing. The next day, pulverize it through a 200-mesh sieve and store it frozen in a -80°C refrigerator for standby.

[0136] Table 1: Mass parts of each component in the traditional Chinese medicine composition

[0137] Rehmannia glutinosa Cortex Lycii Radicis Acorus tatarinowii Cuscuta chinensis Lam. with wine Achyranthes bidentata Blume with wine Polygala tenuifolia Prescription 1 10 15 3 7 9 8 Prescription 2 10 12 6 6 12 6 Prescription 3 10 10 10 10 10 10 Prescription 4 12.5 10 10 8 5 10 Prescription 5 15 9 8 12 10 3

[0138] Example 2: The traditional Chinese medicine composition effectively regulates hormone levels

[0139] 1. Female castrated rat (ovariectomized) model and grouping

[0140] Sixty female SD rats were divided into a sham operation group (10 rats) and an ovariectomized group (50 rats). In the ovariectomized group, the bilateral ovaries of the rats were removed. In the sham operation group, except for not removing the ovaries, other operations were the same. Five days after the operation, vaginal smears were taken for each rat at the same time every day to examine the estrous cycle of the rats. Rats that did not show estrus for 4 consecutive days were considered to have successfully modeled. The results showed that a total of 40 rats successfully modeled. The successfully modeled rats were divided into a model group, a traditional Chinese medicine positive drug group (Dizhen Granules, 1.5 g / kg), a low-dose traditional Chinese medicine composition group (0.5 g / kg), and a high-dose traditional Chinese medicine composition group (1 g / kg), with 10 rats in each group. The traditional Chinese medicine positive drug group and the traditional Chinese medicine composition group were administered once a day, and the sham operation group and the model group were gavaged with an equal volume of drinking water, and continuously gavaged for 60 days.

[0141] 2. Detection of serum hormone levels (estradiol, follicle-stimulating hormone, luteinizing hormone)

[0142] After anesthetizing the rats in each group, blood was collected from the abdominal aorta. The blood was left standing at room temperature for 1 h, centrifuged at 1500 g for 10 min, the serum was separated and stored at -80 °C for later use. According to the ELISA kit instructions, the contents of estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in the serum were detected.

[0143] 3. Results

[0144] Taking Prescription 3 of Example 1 as an example, the results of the effects of the traditional Chinese medicine composition on the serum hormone levels of rats are shown in Table 2.

[0145] Table 2 Effects of the traditional Chinese medicine composition on the serum of rats

[0146] Grouping E2 (pg / ml) FSH (ng / ml) LH (pg / ml) Sham operation group 10.86±0.47 6.32±0.10 280.95±26.98 Model group <![CDATA[9.39±0.52 ## > <![CDATA[6.62±0.08 ## > <![CDATA[368.96±18.54 ## > Dizhen Granule group <![CDATA[9.93±0.44 * > 6.53±0.13 338.45±44.50 Low-dose traditional Chinese medicine composition group <![CDATA[9.85±0.28 * > 6.55±0.13 <![CDATA[339.94±27.58 * > High-dose traditional Chinese medicine composition group <![CDATA[9.93±0.61 * > <![CDATA[6.50±0.12 * > <![CDATA[327.31±34.36 ** >

[0147] The research results showed that the traditional Chinese medicine composition had significant regulatory effects on the three serum hormones of ovariectomized rats (P < 0.05 or P < 0.01), but the Dizhen Granule group only had a significant regulatory effect on one serum hormone (p < 0.05).

[0148] Example 3: The traditional Chinese medicine composition can relieve emotions and improve sleep

[0149] 1. Female castrated rat (ovariectomized) model and grouping

[0150] Seventy female SD rats were divided into a sham operation group (10 rats) and an ovariectomized group (60 rats). In the ovariectomized group, the bilateral ovaries of the rats were removed. In the sham operation group, except for not removing the ovaries, other operations were the same. Five days after the operation, vaginal smears were taken from each rat at the same time every day to examine the estrous cycle of the rats. Rats that did not show an estrous period for 4 consecutive days were considered to have successfully established the model. The results showed that a total of 50 rats had successfully established the model. The successfully modeled rats were divided into a model group, a western medicine positive group (Premarin, 0.09 mg / kg), a traditional Chinese medicine positive drug group (Dizhen Granule, 1.5 g / kg), a low-dose traditional Chinese medicine composition group (0.5 g / kg), and a high-dose traditional Chinese medicine composition group (1 g / kg), with 10 rats in each group. The positive drug and the traditional Chinese medicine composition group were administered once a day, and the sham operation group and the model group were gavaged with an equal volume of drinking water. Continuous gavage was performed for 60 days.

[0151] 2. Detection methods for related indicators

[0152] The hypothalamic neurotransmitters (serotonin, norepinephrine, dopamine), emotion indicators (swimming immobility time, sucrose preference index), sleep indicators (sleep latency, sleep duration), 24-hour water intake and other indicators were investigated. The detection methods are as follows:

[0153] (1) Water intake

[0154] Before the experiment, the rats were deprived of water but not food for 24 h. During the formal experiment, the rats were housed individually in cages, and the water intake within 24 h on the 60th day of the experiment was recorded.

[0155] (2) Mood indicators

[0156] ① Sucrose preference index

[0157] Before the experiment, the rats were housed individually in cages and underwent 48 h of sucrose drinking training. During the formal experiment, the rats were deprived of water but not food for 12 h. The initial weights of the sucrose solution and drinking water were recorded. The rats were given the sucrose solution and drinking water for 6 h, during which they were fasted. Then, the weights were measured again, and the weight differences of the sucrose solution and drinking water before and after were calculated to obtain the amounts of the sucrose solution and drinking water. Sucrose preference index (%) = sucrose solution consumption / (sucrose solution consumption + drinking water consumption).

[0158] ② Immobility time during swimming

[0159] Pour about 30 cm high of clear water at (25 ± 1) °C into a cylindrical plastic swimming bucket with a diameter of 30 cm and a height of 50 cm. The rats were vertically dropped into the water from a position about 15 cm directly above the swimming bucket and allowed to swim freely for 1 min. The cumulative immobility time of the rats within the next 5 min was recorded (the standard for immobility is that the rat floats on the water surface and stops swimming, or only has slight movements to maintain its floating). After the experiment, the water on the surface of the rats' bodies was dried with a dry towel.

[0160] (3) Effect on pentobarbital sodium-induced sleep

[0161] The rats were intraperitoneally injected with pentobarbital sodium (40 mg / kg). The injection time, the time of the rats falling asleep, and the awakening time were recorded, and the sleep duration and sleep latency of each rat were calculated. (Falling asleep time: the time point when the rat lies on its back for 30 s and the righting reflex disappears within 60 s; Awakening time: the time point when the rat lies on its back for more than 30 s and the righting reflex recovers; Sleep latency: the time period from drug administration to the time when the rat falls asleep; Sleep duration: the time period from the time when the rat falls asleep to the awakening time.)

[0162] (4) Hypothalamic neurotransmitter levels

[0163] After blood collection from the rats in each group, the skulls were quickly peeled off to obtain the brain tissues. The hypothalamus was isolated on ice and stored at -80 °C for later use. According to the instructions of the ELISA kit, the contents of 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA) in the hypothalamic tissues were examined.

[0164] 3. Test results

[0165] Taking Prescription 3 in Example 1 as an example, the results are as follows (the meanings of the data symbols in the table: compared with the sham operation group, ##P<0.01, #P<0.05; compared with the model group, *P<0.05, **P<0.01).

[0166] (1) Water intake

[0167] The detection results of the water intake of rats are shown in Table 3 as follows:

[0168] Table 3 Effects of the traditional Chinese medicine composition on the water intake of rats

[0169] Grouping Water intake (ml) Sham operation group 54.58±3.05 Model group <![CDATA[57.39±2.68 # > Premarin group 57.63±3.76 Dizhen Granule group <![CDATA[54.74±2.71 * > Low-dose traditional Chinese medicine composition group <![CDATA[53.54±4.91 * > High-dose traditional Chinese medicine composition group <![CDATA[54.84±2.29 * >

[0170] It can be seen from Table 3 that the water intake of rats in the model group increased significantly. The low and high dose groups of Dizhen Granules and the traditional Chinese medicine composition could significantly reduce the water intake of rats (P<0.05), while the Premarin group had no obvious effect on the water intake of rats.

[0171] (2) Emotional index

[0172] The effects of the traditional Chinese medicine composition on the emotional indexes of rats are shown in Table 4 as follows.

[0173] Table 4 Effects of the traditional Chinese medicine composition on the emotional related indexes of rats

[0174] Grouping Swimming immobility time (s) Sucrose preference index (%) Sham operation group 324.33±21.23 93.39±7.45 Model group <![CDATA[288.50±19.49 ## > <![CDATA[83.78±5.50 ## > Premarin group 293.75±47.05 85.19±9.99 Dizhen Granule group 301.10±33.75 85.83±6.19 Low-dose traditional Chinese medicine composition group 292.78±23.27 <![CDATA[88.49±2.77 * > High-dose traditional Chinese medicine composition group <![CDATA[317.00±30.46 * > <![CDATA[89.51±4.13 * >

[0175] The results showed that in terms of regulating emotions, the high dose group of the traditional Chinese medicine composition could significantly prolong the immobile time of rats in swimming (P<0.05); the low and high dose groups could significantly improve the preference degree of model rats for sugar water (P<0.05). However, the Premarin group and the Dizhen Granules group had no significant improvement effect on the above two emotional indexes (p>0.05).

[0176] (3) Sleep

[0177] The detection results of the improvement of sleep by the traditional Chinese medicine composition are shown in Table 5 as follows:

[0178] Table 5 Effects of the traditional Chinese medicine composition on the sleep of rats

[0179]

[0180]

[0181] The results showed that in terms of improving sleep, the low and high dose groups of the Chinese medicine composition can significantly shorten the sleep latency time of sodium pentobarbital-assisted sleep and prolong the sleep duration (P<0.05 or P<0.01), and have a good sleep-aiding effect. However, the Bujiale group and the Dizhen Granule group had no significant improvement effect on the above two sleep indicators (p>0.05).

[0182] (4) Hypothalamic neurotransmitter levels

[0183] The results of the effect of the Chinese medicine composition on rat hypothalamic neurotransmitters are shown in Table 6.

[0184] Table 6 Effects of Chinese herbal composition on neurotransmitters in rat hypothalamus

[0185] Grouping 5-HT (ng / mg protein) NE (ng / mg protein) DA (ng / mg protein) Sham operation group 2.45±0.15 1.66±0.10 5.40±0.31 Model group <![CDATA[1.78±0.40 ## > <![CDATA[1.87±0.20 # > <![CDATA[4.64±0.46 ## > Premarin group 1.91±0.29 <![CDATA[1.70±0.06 * > 4.95±0.46 Dizhen Granule group 2.07±0.22 1.73±0.09 <![CDATA[5.12±0.41 * > Low-dose traditional Chinese medicine composition group <![CDATA[2.17±0.40 * > 1.83±0.19 <![CDATA[5.15±0.46 * > High-dose traditional Chinese medicine composition group <![CDATA[2.23±0.33 * > <![CDATA[1.71±0.10 * > <![CDATA[5.16±0.43 * >

[0186] The results of the study showed that the Chinese herbal composition had a significant regulatory effect on the three neurotransmitters in ovariectomized rats (P<0.05 or P<0.01).

[0187] Example 4: Traditional Chinese medicine composition for treating osteoporosis

[0188] 1 Establishment and grouping of osteoporosis model

[0189] 80 female SD rats were divided into a sham operation group (10 rats) and an ovariectomy group (60 rats). The ovariectomy group had both ovaries removed, and the sham operation group underwent the same operation except that the ovaries were not removed. Five days after the operation, vaginal smears were performed on each rat at the same time every day to examine the estrous cycle of the rats. Rats that did not show estrus for four consecutive days were considered to have successfully established a model. The results showed that a total of 50 rats were successfully established. The rats with successful modeling were divided into a model group, a Western medicine positive group (Bujiale, 0.09 mg / kg), a Chinese medicine positive group (Dizhen Granules, 1.5 g / kg), a low-dose Chinese medicine composition group (0.5 g / kg), and a high-dose Chinese medicine composition group (1 g / kg), with 10 rats in each group. The positive drug and Chinese medicine composition groups were administered once a day, and the sham operation group and the model group were gavaged with equal volumes of drinking water for 60 consecutive days.

[0190] 2. Detection Method

[0191] The left tibia of a rat was removed, the attached skin and muscle carefully removed, and then frozen at -80°C. The biomechanical properties were determined using a three-point bending test. The tibia was first removed from the -80°C freezer and allowed to return to room temperature. The tibia was then placed on the two support bars of the testing instrument, 20 mm apart, with the femur's physiological curvature pointing upward. The loading rod was positioned in the center of the femur and loaded uniformly at a rate of 2 mm / min until the femur fractured. Data were recorded and analyzed using the instrument's built-in software, with a sampling rate of 100 Hz.

[0192] 3. Results

[0193] The effects of the traditional Chinese medicine composition on the maximum load of the tibia of ovariectomized rats are shown in Table 7.

[0194] Table 7 Effects of the traditional Chinese medicine composition on the maximum load of the tibia of ovariectomized rats

[0195] Group Maximum load (N) Sham operation group 106.21±9.93 Model group <![CDATA[93.89±8.45 ## > Premarin group <![CDATA[101.01±8.57 * > Dizhen Granule group 99.09±8.84 Low-dose traditional Chinese medicine composition group <![CDATA[101.85±9.02 * > High-dose traditional Chinese medicine composition group <![CDATA[104.83±7.32 ** >

[0196] The research results show that the western medicine positive drug Progynova, and the low and high dose groups of the traditional Chinese medicine composition can significantly increase the maximum load of the tibia of ovariectomized rats (P<0.05 or P<0.01). However, the effect of Dizhen Granule group on the maximum load of the tibia of rats has no statistical significance.

[0197] Example 5: Safety verification

[0198] 1. Experimental method

[0199] According to the relevant requirements of the "Technical Guidelines for Single-dose Toxicity Studies of Drugs" and the "Technical Guidelines for Acute Toxicity Studies of Traditional Chinese Medicines and Natural Medicines", we adopted the maximum dose method to preliminarily investigate the acute toxicity of the traditional Chinese medicine composition prescription.

[0200] The test drug was prepared as in Example 1. The experiment was divided into two groups: a control group and a drug administration group, with 10 mice in each group (5 males and 5 females). The maximum dose administration method was used, with a gavage volume of 40 ml / kg, and gavage was performed once a day (at 7:00 and 19:00), and the maximum daily dose was 16 g / kg (205 times the clinical dose). The survival status, body weight, organ index, etc. of the animals were investigated, and continuous observation was carried out for 14 days.

[0201] 2. Experimental results

[0202] (1) Survival status

[0203] ① During the experimental period, no mouse death occurred in the drug administration group and the test group;

[0204] ② On the day of drug administration and the next day, loose stools occurred in the drug administration group and the test group, but this phenomenon disappeared on the 3rd - 14th days. For other indicators, such as respiration, body surface color, movement, eyelids, and salivary secretion, no obvious abnormalities were observed, and no convulsions, abnormal reflexes, dystonia, etc. occurred.

[0205] ③ After the experiment, all animals were sacrificed by cervical dislocation. After dissection, the main tissues and organs (brain, heart, liver, spleen, lung, kidney, stomach, large intestine, small intestine, bladder) were carefully observed, and no obvious abnormalities were found in the texture, color, shape, volume, etc. of the organs.

[0206] (2) Body weight change

[0207] On the 0th and 14th days of the observation period, all mice were weighed and counted respectively (Table 8). The results showed that the body weights of the mice in both groups increased, but the increased values had no significant difference.

[0208] Table 8 Effects of acute toxicity experiment of traditional Chinese medicine composition on body weight of mice

[0209]

[0210] (3) Organ index

[0211] The experiment investigated the organ indexes of the heart, liver, spleen, lung, kidney, thymus, etc. The results showed that there were no statistical differences in the organ indexes of each organ between the administration group and the control group. The results are shown in Table 9.

[0212] Table 9 Effects of traditional Chinese medicine composition on organ indexes of mice

[0213]

[0214]

[0215] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the technical concept of the present invention, various simple modifications can be made to the technical solutions of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a product for treating osteoporosis or menopausal syndrome, characterized in that, The traditional Chinese medicine composition, by mass parts, comprises 10 - 15 parts of Rehmannia glutinosa, 9 - 15 parts of Cortex Lycii Radicis, 3 - 10 parts of Acorus tatarinowii, 6 - 12 parts of Cuscuta chinensis, 5 - 12 parts of Achyranthes bidentata, and 3 - 10 parts of Polygala tenuifolia.

2. The application according to claim 1, characterized in that, The traditional Chinese medicine composition, by mass parts, comprises 10 parts of Rehmannia glutinosa, 10 parts of Cortex Lycii Radicis, 10 parts of Acorus tatarinowii, 10 parts of Cuscuta chinensis, 10 parts of Achyranthes bidentata, and 10 parts of Polygala tenuifolia.

3. The application according to claim 1 or 2, characterized in that, The Cuscuta chinensis is Cuscuta chinensis processed with yellow rice wine, and the Achyranthes bidentata is Achyranthes bidentata processed with yellow rice wine; Preferably, the Cuscuta chinensis processed with yellow rice wine is obtained by processing Cuscuta chinensis with yellow rice wine; Preferably, the Achyranthes bidentata processed with yellow rice wine is obtained by processing Achyranthes bidentata with yellow rice wine.

4. The application according to any one of claims 1-3, characterized in that The dosage form of the traditional Chinese medicine composition includes tablets, capsules, powders, pills, bolus, granules, injections, decoctions, medicated wines, ointments or pastes.

5. The application according to any one of claims 1-4, characterized in that, The traditional Chinese medicine composition further comprises excipients; preferably, the excipients include one or more of diluents, disintegrants, lubricants, excipients, binders, glidants, fillers or surfactants.

6. The application according to any one of claims 1-5, characterized in that, The preparation method of the traditional Chinese medicine composition includes powdering, water decocting, stir-frying, macerating, percolating, supercritical extraction or reflux extraction; preferably, it is water decocting, direct powdering or powdering after ethanol infiltration; Preferably, each component in the traditional Chinese medicine composition is infiltrated in ethanol, then dried and pulverized; Preferably, before infiltration, each component can be crushed or cut into pieces.

7. The application according to any one of claims 1-6, characterized in that, The menopausal syndrome is female menopausal syndrome; the osteoporosis is menopausal osteoporosis; Preferably, the treatment of menopausal syndrome includes regulating one or more of serum hormone levels, hypothalamic neurotransmitters, sleep quality, water intake or mood; Preferably, the treatment of osteoporosis includes regulating serum hormone levels and / or enhancing the maximum load of the tibia.

8. A traditional Chinese medicine composition for treating osteoporosis or menopausal syndrome, characterized in that, The traditional Chinese medicine composition, by mass parts, comprises 10 - 15 parts of Rehmannia glutinosa, 9 - 15 parts of Cortex Lycii Radicis, 3 - 10 parts of Acorus tatarinowii, 6 - 12 parts of Cuscuta chinensis, 5 - 12 parts of Achyranthes bidentata, and 3 - 10 parts of Polygala tenuifolia; Preferably, by mass parts, it comprises 10 parts of Rehmannia glutinosa, 10 parts of Cortex Lycii Radicis, 10 parts of Acorus tatarinowii, 10 parts of Cuscuta chinensis, 10 parts of Achyranthes bidentata, and 10 parts of Polygala tenuifolia; Preferably, the Cuscuta chinensis is Cuscuta chinensis processed with yellow rice wine, and the Achyranthes bidentata is Achyranthes bidentata processed with yellow rice wine.

9. A method for improving sleep, characterized in that, The method includes administering the traditional Chinese medicine composition as claimed in claim 8.

10. Use of the traditional Chinese medicine composition as claimed in claim 8 in the preparation of a product for treating insomnia, anxiety and / or depression.

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