Composition for preventing and treating osteoporosis as well as preparation method and application thereof

Abstract

The invention discloses a composition for preventing and treating osteoporosis as well as a preparation method and application thereof, and belongs to the field of biological pharmacy. The method comprises the following steps: uniformly spraying a sodium bicarbonate aqueous solution onto eucommia ulmoides powder, sealing and infiltrating, stir-frying with slow fire, spraying rice vinegar in the stir-frying process, turning off the fire after filament breaking, spreading and cooling, and performing reflux extraction with ethanol to obtain eucommia ulmoides extract; adding water into the rhizoma drynariae powder for high-temperature sterilization, cooling, adding lactobacillus plantarum for sealed fermentation, and performing reflux extraction by adopting ethanol to obtain a rhizoma drynariae extract; d-glucosamine hydrochloride, sodium chondroitin sulfate, herba epimedii extract and oyster powder are added into the extracted eucommia ulmoides extract and rhizoma drynariae extract and mixed uniformly, and the composition for preventing and treating osteoporosis is obtained. Eucommia ulmoides is processed through a sodium bicarbonate salt roasting and vinegar roasting method, rhizoma drynariae is subjected to fermentation treatment, the warm and dry property of an original composition can be neutralized, the internal heat side effects of constipation, dry mouth, swelling and aching of gum or throat pain are reduced, and the safety and tolerance of the composition are improved.

Description

Technical Field

[0001] The present invention relates to the field of biopharmaceuticals, and in particular to a composition for preventing and treating osteoporosis, and a preparation method and application thereof. Background Art

[0002] Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, microarchitectural disruption, increased bone fragility, and susceptibility to fracture. While it can occur in both sexes and at any age, it is more common in postmenopausal women and elderly men. Clinical manifestations include bone fragility and susceptibility to fracture, as well as potential symptoms such as low back pain, decreased height, and hunchback.

[0003] With the aging of the population, the incidence of osteoporosis continues to rise, becoming a major factor affecting the quality of life of middle-aged and elderly people. Currently, the main Western medications for treating this disease include estrogen, calcium supplements, calcitonin, bisphosphonates, and fluoride preparations. These drugs are generally expensive and have significant side effects after long-term use.

[0004] In the prior art, there are pharmaceutical compositions that improve osteoporosis by adding natural medicines. For example, prior art CN106165898A discloses a health-care composition and preparation method that increases bone density and promotes joint function. The health-care composition is made from the following raw materials: chondroitin sulfate, glucosamine, hyaluronic acid, mycelium of Paecilomyces hyssopus, Eucommia ulmoides, Cyathula capitata, Epimedium, Rhizoma Smilacis Glabrae, Dendrobium officinale, and Rhizoma Drynariae. The composition, with its kidney-tonifying and bone-strengthening properties and joint-promoting properties, synergistically acts to better increase bone density and promote joint function, and has the effect of preventing and improving osteoporosis. However, clinically, long-term use has found that symptoms of getting angry, such as constipation, swollen and sore gums, and sore throat, are prone to occur. Especially for the elderly and those with yin deficiency and hyperactivity of fire, it is more likely to cause dry stools and side effects such as difficulty in defecation.

[0005] The reasons for this may be: Eucommia ulmoides is warm in nature and sweet in taste. For those with yin deficiency and excessive fire, excessive consumption may aggravate internal heat and dryness, leading to symptoms such as dry mouth, sore throat, constipation, restlessness, and insomnia. Epimedium is warm in nature, and long-term or excessive use may lead to excessive yang energy in the body, causing symptoms such as dry mouth and hard stools. Drynaria fortunei is bitter and warm in nature, and long-term or excessive use can deplete the body's yin fluid, leading to intestinal dryness and constipation. Calcium supplements combine with oxalic acid and phosphoric acid to form insoluble calcium salts, which absorb water from the intestines and harden the stool. The combined use of these three traditional Chinese medicines and calcium supplements further depletes intestinal moisture and exacerbates side effects such as constipation.

[0006] Therefore, there is an urgent need to develop a new osteoporosis prevention and treatment composition that can not only effectively prevent and treat osteoporosis but also avoid adverse reactions such as constipation, so as to improve the safety and tolerability of patients' long-term medication and enhance patient compliance. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a method for preparing a composition for preventing and treating osteoporosis. By improving the method for extracting raw materials in the composition, the composition can not only prevent and treat osteoporosis, but also avoid the occurrence of adverse reactions such as constipation, so as to improve the safety and tolerability of patients' long-term medication and enhance patient compliance, thereby overcoming the problem that existing compositions for preventing and treating osteoporosis have obvious side effects.

[0008] To solve the above technical problems, the present invention provides a method for preparing a composition for preventing and treating osteoporosis, comprising the following steps:

[0009] (1) Preparation of Eucommia ulmoides extract: spray sodium bicarbonate aqueous solution evenly onto Eucommia ulmoides powder, stir and seal for 1 hour, stir-fry at 100-120°C, and evenly spray 60-80°C rice vinegar during the stir-frying process. Stir-fry until the powder breaks, turn off the heat, spread out to cool, and extract the cooled Eucommia ulmoides powder twice with 70% ethanol reflux, filter, and concentrate the supernatant to dry and crush to obtain Eucommia ulmoides extract;

[0010] (2) Preparation of Drynaria extract: Add drynaria powder to a fermentation tank, add water, sterilize at high temperature, cool, add Lactobacillus plantarum, mix well, and ferment at 35°C for 3 days. Then, extract twice with 75% ethanol under reflux, filter, and concentrate the supernatant, dry it, and grind it to obtain drynaria extract;

[0011] (3) Preparation of a composition: Weigh 75-85 g of the Eucommia ulmoides extract prepared in step (1), 50-60 g of the Drynaria fortunei extract prepared in step (2), 140-180 g of D-glucosamine hydrochloride, 60-100 g of sodium chondroitin sulfate, 50 g of Epimedium extract and 55 g of oyster powder, and mix them evenly to obtain the composition for preventing and treating osteoporosis.

[0012] Further improvement: in step (1), the Eucommia ulmoides powder is passed through a 20-mesh sieve, the amount of sodium bicarbonate in the sodium bicarbonate aqueous solution used is 2% of the weight of the Eucommia ulmoides powder, the volume ratio of the sprayed rice vinegar to the weight of the Eucommia ulmoides powder is 0.2 ml / g, the acetic acid concentration in the rice vinegar is 9%, and the slow fire frying time is 8 to 10 min.

[0013] Further improvement: in step (2), the Rhizoma Drynariae powder is passed through an 80-mesh sieve, the volume ratio of water added to the Rhizoma Drynariae powder is 0.4 ml / g, the high-temperature sterilization condition is heating at 100°C for 20 min, the plantarum Lactobacillus is plantarum Lactobacillus ATCC 8014, and the number of viable plantarum Lactobacillus added is 8×10 8 ~ 1×10 9 CFU / ml.

[0014] Further improvement, the step (3) is prepared by the following steps: weighing the extract of eucommia ulmoides obtained in step (1) 80g, the extract of rhizoma drynariae obtained in step (2) 55g, D-glucosamine hydrochloride 160g, chondroitin sulfate sodium 80g, epimedium extract 50g and oyster shell powder 55g, and mixing uniformly, thereby obtaining the composition for preventing and treating osteoporosis.

[0015] In the above preparation method, the aqueous solution of sodium bicarbonate is sprayed on the surface of eucommia ulmoides powder before frying, so that the permeability of the plant cells is changed and the permeability of sodium bicarbonate is improved. The alkalinity of sodium bicarbonate can destroy the hydrogen bond structure of the gum silk and reduce its viscosity. At the same time, in the process of sodium bicarbonate salt frying of eucommia ulmoides, rice vinegar with a temperature of 60-80 DEG C is sprayed, and CO2 gas is generated by the reaction of rice vinegar and sodium bicarbonate permeated into the eucommia ulmoides gum during frying. The tiny bubbles play a physical destruction role on the eucommia ulmoides gum with intestinal viscosity, thereby improving the dissolution of the active ingredients. The rice vinegar can also reduce the astringency of alkaloids and tannins and reduce the intestinal viscosity. The preparation method uses sodium bicarbonate salt frying and vinegar frying to reduce the breaking temperature of eucommia ulmoides gum silk, reduce the processing time from 20-30 min to 8-10 min, avoid the loss of heat-sensitive active ingredients, reduce energy consumption, and improve the content of active ingredients. Moreover, rapid airing and cooling after sodium bicarbonate salt frying and vinegar frying can further avoid the loss of heat-sensitive ingredients and the re-aggregation of gum silk. The sodium bicarbonate salt frying and vinegar frying processing method can moderate the eucommia ulmoides warm dryness, help to reduce the warm dryness, reduce the risk of heatiness, and is more suitable for people with yin deficiency, which can reduce the symptoms of heatiness such as dry mouth and throat, sore throat, constipation, irritability and insomnia.

[0016] In the preparation method, the plant lactobacillus fermentation of rhizoma drynariae can secrete carbohydrate hydrolase to decompose naringin in rhizoma drynariae into naringenin, reduce the astringency, promote intestinal peristalsis, and significantly reduce the risk of constipation, thereby improving the patient's compliance.

[0017] In the preparation method, the content of icariin in epimedium extract is 2.5%.

[0018] The application also provides a composition for preventing and treating osteoporosis, which is prepared by the above-mentioned preparation method of the composition for preventing and treating osteoporosis.

[0019] The present invention also provides an oral preparation for preventing and treating osteoporosis, which comprises the above-mentioned composition for preventing and treating osteoporosis and pharmaceutically acceptable excipients.

[0020] The oral preparation is a tablet, granule or capsule.

[0021] The oral preparation is a tablet, and the preparation method is as follows: weigh 80g of the Eucommia ulmoides extract and 55g of the Drynaria fortunei extract, add 160g of D-glucosamine hydrochloride, 80g of sodium chondroitin sulfate, 50g of epimedium extract, 55g of oyster powder and 115g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5g of magnesium stearate, mix for 30 minutes, and then tablet, to obtain a composition tablet for preventing and treating osteoporosis.

[0022] The present invention also provides a use of the above-mentioned composition for preventing and treating osteoporosis in the preparation of a drug for preventing and treating osteoporosis.

[0023] The composition in the above application can reduce the side effects of internal heat caused by constipation, dry mouth, swollen and sore gums or sore throat in the process of preventing and treating osteoporosis.

[0024] After adopting such a design, the present invention has at least the following advantages:

[0025] The preparation method of the composition for preventing and treating osteoporosis of the present invention comprises the following steps: preparing Eucommia ulmoides by roasting Eucommia ulmoides with sodium bicarbonate salt and vinegar, which not only destroys Eucommia ulmoides gum, reduces its viscosity to the intestine, reduces the wrapping of active ingredients by the gum, and improves the dissolution of the active ingredients, but also alleviates the warming and dryness of Eucommia ulmoides, making it suitable for people with yin deficiency constitution, and reducing the side effects of internal heat such as dry mouth and tongue, sore throat, constipation, irritability and insomnia caused by dryness and heat; and further, fermenting Drynaria rhizome with Lactobacillus plantarum, decomposing naringin in Drynaria rhizome into naringenin, reducing the astringency of naringin, and metabolizing the polysaccharide components in Drynaria rhizome into small molecule polysaccharides suitable for intestinal absorption, strong water-holding capacity and lubricating effect on the intestine, thereby promoting intestinal peristalsis, significantly reducing the risk of constipation, and improving patient compliance with medication. The composition obtained by the preparation method of the present invention not only has the function of preventing osteoporosis of the original composition, but also has the function of reducing side effects of internal heat such as constipation, dry mouth, swollen and painful gums or sore throat. It has better therapeutic effect, higher safety and better compliance when taken for a long time. DETAILED DESCRIPTION

[0026] The present invention is described in detail below with reference to the embodiments.

[0027] Example 1

[0028] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 110°C. During the stir-frying process, 150 mL of 70°C rice vinegar was sprayed on the mixture. The mixture was stir-fried until the fibers broke, then turned off the heat and spread to cool. The mixture was extracted with 70% ethanol under reflux twice. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the Eucommia ulmoides extract was filtered, concentrated, dried, and crushed. The stir-frying time was 10 minutes.

[0029] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The mixture was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract of Drynaria rhizome was filtered, concentrated, dried, and crushed to obtain the extract of Drynaria rhizome.

[0030] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 9×10 8 CFU / ml.

[0031] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes, and then tablet to obtain a composition tablet 1 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0032] The epimedium extract was prepared using an existing method, specifically: the epimedium was crushed, extracted twice with 10-fold the amount of 70% ethanol under reflux, each time for 1.5 hours. The extract was concentrated, dried at -0.1 MPa and 80°C, crushed, and passed through an 80-mesh sieve to obtain the epimedium extract. The icariin content was 2.5%.

[0033] Example 2

[0034] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 120°C over a slow fire. During the stir-frying process, 150 mL of 60°C rice vinegar was sprayed on the mixture. The mixture was stir-fried until the fibers broke, then turned off the heat and spread out to cool. The mixture was extracted twice with 70% ethanol under reflux. The solid-liquid ratio for the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio for the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the Eucommia ulmoides extract was filtered, concentrated, dried, and crushed. The slow fire stir-frying time was 8 minutes.

[0035] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The mixture was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract of Drynaria rhizome was filtered, concentrated, dried, and crushed to obtain the extract of Drynaria rhizome.

[0036] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 1×10 9 CFU / ml.

[0037] (3) Weigh 75 g of the Eucommia ulmoides extract and 60 g of the Drynaria fortunei extract prepared in the above step, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet to obtain the composition tablet 2 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0038] Wherein, the epimedium extract is the same as that in Example 1.

[0039] Example 3

[0040] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 100°C. During the stir-frying process, 150 mL of 80°C rice vinegar was sprayed. The mixture was stir-fried until the fibers broke, then turned off the heat and spread out to cool. The mixture was extracted twice with 70% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the Eucommia ulmoides extract was filtered, concentrated, dried, and crushed. The stir-frying time was 10 minutes.

[0041] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The mixture was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract of Drynaria rhizome was filtered, concentrated, dried, and crushed to obtain the extract of Drynaria rhizome.

[0042] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 8×10 8 CFU / ml.

[0043] (3) Weigh 85 g of the Eucommia ulmoides extract and 50 g of the Drynaria fortunei extract prepared in the above step, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet to obtain the composition tablet 3 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0044] Wherein, the epimedium extract is the same as that in Example 1.

[0045] Example 4

[0046] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 110°C. During the stir-frying process, 150 mL of 70°C rice vinegar was sprayed on the mixture. The mixture was stir-fried until the fibers broke, then turned off the heat and spread to cool. The mixture was extracted twice with 70% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the Eucommia ulmoides extract was filtered, concentrated, dried, and crushed. The stir-frying time was 9 minutes.

[0047] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The mixture was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract of Drynaria rhizome was filtered, concentrated, dried, and crushed to obtain the extract of Drynaria rhizome.

[0048] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 9×10 8CFU / ml.

[0049] (3) Take 85 g of the extract of Eucommia ulmoides prepared in the above step, 50 g of the extract of Drynariae Rhizoma, 140 g of D-glucosamine hydrochloride, 100 g of chondroitin sulfate sodium, 50 g of the extract of Herba Epimedii, 55 g of oyster shell powder and 115 g of microcrystalline cellulose, mix them evenly, add 95% ethanol to make soft material, granulate with 18 mesh sieve, dry at 55-60°C, sieve with 16 mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes, and then press into tablets to obtain the composition tablet 4 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0050] The extract of Herba Epimedii is the same as in Example 1.

[0051] Example 5

[0052] (1) The raw material Eucommia ulmoides is crushed, the powder is passed through a 20 mesh sieve, 15 g of sodium bicarbonate is dissolved in 35 ml of water and sprayed onto 750 g of the powder of Eucommia ulmoides, stirred and sealed for 1 h of soaking, and then slowly fried at 110°C. During the frying process, 150 ml of rice vinegar at 70°C is sprayed. After frying to the point of breaking, the fire is turned off and the temperature is lowered by spreading and airing. The Eucommia ulmoides extract is obtained by reflux extraction with 70% ethanol twice, with a solid-liquid ratio of 1:10 for the first extraction for 2 h and a solid-liquid ratio of 1:8 for the second extraction for 2 h. After extraction, filtration, concentration, drying and crushing, the Eucommia ulmoides extract is obtained. The slow frying time is 10 min.

[0053] (2) The raw material Drynariae Rhizoma is crushed, the powder is passed through an 80 mesh sieve, 670 g of the powder of Drynariae Rhizoma is added to a fermentation tank, 270 ml of water is added, high temperature sterilization is performed at 100°C for 20 min, and then cooled to 35°C. 20 ml of Lactobacillus plantarum is added and mixed evenly. The temperature is 35°C, the fermentation is sealed for 3 days, and then extracted twice with 75% ethanol, with a solid-liquid ratio of 1:8 for the first extraction for 2 h and a solid-liquid ratio of 1:6 for the second extraction for 2 h. After extraction, filtration, concentration, drying and crushing, the Drynariae Rhizoma extract is obtained.

[0054] The Lactobacillus plantarum is Lactobacillus plantarum ATCC 8014, and the number of viable bacteria is 9×10 8 CFU / ml.

[0055] (3) Take 85 g of the extract of Eucommia ulmoides prepared in the above step, 50 g of the extract of Drynariae Rhizoma, 150 g of D-glucosamine hydrochloride, 90 g of chondroitin sulfate sodium, 50 g of the extract of Herba Epimedii, 55 g of oyster shell powder and 115 g of microcrystalline cellulose, mix them evenly, add 95% ethanol to make soft material, granulate with 18 mesh sieve, dry at 55-60°C, sieve with 16 mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes, and then press into tablets to obtain the composition tablet 5 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0056] The extract of Herba Epimedii is the same as in Example 1.

[0057] Comparative Example 1

[0058] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 750 g of Eucommia ulmoides powder was extracted twice with 70% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 h. After extraction, the Eucommia ulmoides extract was obtained by filtering, concentrating, drying and crushing.

[0059] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The extract was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction was carried out for 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction was carried out for 2 h. After extraction, the extract was filtered, concentrated, dried, and crushed to obtain the Drynaria rhizome extract.

[0060] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 9×10 8 CFU / ml.

[0061] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet to obtain the composition tablet 6 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0062] Wherein, the epimedium extract is the same as that in Example 1.

[0063] Comparative Example 2

[0064] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 750 g of Eucommia ulmoides powder was extracted twice with 70% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 h. After extraction, the Eucommia ulmoides extract was obtained by filtering, concentrating, drying and crushing.

[0065] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was extracted twice with 75% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract was filtered, concentrated, dried, and crushed to obtain the Drynaria rhizome extract.

[0066] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet to obtain the composition tablet 6 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0067] Wherein, the epimedium extract is the same as that in Example 1.

[0068] Comparative Example 3

[0069] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 110°C over low heat until the fibers broke, then turned off the heat and spread out to cool. The mixture was extracted with 70% ethanol under reflux twice. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the mixture was filtered, concentrated, dried, and crushed to obtain the Eucommia ulmoides extract. The slow-frying time was 20 minutes.

[0070] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at high temperature. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The extract was extracted twice with 75% ethanol under reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction time was 2 h. After extraction, the extract was filtered, concentrated, dried, and crushed to obtain the Drynaria rhizome extract.

[0071] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 9×10 8 CFU / ml.

[0072] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet to obtain the composition tablet 8 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0073] Wherein, the epimedium extract is the same as that in Example 1.

[0074] Comparative Example 4

[0075] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 750 g of Eucommia ulmoides powder was stir-fried at 110 °C. During the stir-frying process, 150 mL of 70 °C rice vinegar was sprayed. After the Eucommia ulmoides was stir-fried until the fibers broke, the heat was turned off and the mixture was spread out to cool. The mixture was extracted with 70% ethanol under reflux twice. The solid-liquid ratio of the first extraction was 1:10 and the extraction time was 2 h. The solid-liquid ratio of the second extraction was 1:8 and the extraction time was 2 h. After extraction, the Eucommia ulmoides extract was obtained by filtering, concentrating, drying and crushing. The slow-frying time was 30 min.

[0076] (2) The raw material Drynaria rhizome was crushed and the powder was passed through an 80-mesh sieve. 670 g of Drynaria rhizome powder was added to a fermentation tank, 270 mL of water was added, and the mixture was sterilized at 100 °C for 20 min. The mixture was cooled to 35 °C and 20 mL of Lactobacillus plantarum was added and mixed evenly. The mixture was sealed and fermented at 35 °C for 3 days. The extract was extracted twice with 75% ethanol reflux. The solid-liquid ratio of the first extraction was 1:8 and the extraction was carried out for 2 h. The solid-liquid ratio of the second extraction was 1:6 and the extraction was carried out for 2 h. After extraction, the extract was filtered, concentrated, dried, and crushed to obtain the Drynaria rhizome extract.

[0077] Among them, Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the viable cell count was 9×10 8 CFU / ml.

[0078] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes and then tablet, to obtain a composition tablet 9 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0079] Wherein, the epimedium extract is the same as that in Example 1.

[0080] Comparative Example 5

[0081] (1) The raw material Eucommia ulmoides was crushed and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of Eucommia ulmoides powder. After stirring, the mixture was sealed and soaked for 1 hour. The mixture was stir-fried at 110°C over a slow fire. During the stir-frying process, 150 mL of 70°C rice vinegar was sprayed on the mixture. The mixture was stir-fried until the fibers broke, then turned off the heat and spread out to cool. The mixture was extracted twice with 70% ethanol under reflux. The solid-liquid ratio for the first extraction was 1:10 and the extraction time was 2 hours. The solid-liquid ratio for the second extraction was 1:8 and the extraction time was 2 hours. After extraction, the mixture was filtered, concentrated, dried, and crushed to obtain the Eucommia ulmoides extract. The slow fire stir-frying time was 10 minutes.

[0082] (2) The raw material Drynariae Rhizoma was crushed, and the powder was passed through an 80-mesh sieve. 670 g of the Drynariae Rhizoma powder was extracted twice by reflux extraction using 75% ethanol. The solid-liquid ratio was 1:8 for the first extraction, and the extraction was performed for 2 h. The solid-liquid ratio was 1:6 for the second extraction, and the extraction was performed for 2 h. After the extraction, the mixture was filtered, concentrated, dried, and crushed to obtain the Drynariae Rhizoma extract.

[0083] (3) 80 g of the Eucommiae Cortex extract prepared in the above step, 55 g of the Drynariae Rhizoma extract, 160 g of D-glucosamine hydrochloride, 80 g of chondroitin sulfate sodium, 50 g of the Herba Epimedii extract, 55 g of oyster shell powder, and 115 g of microcrystalline cellulose were uniformly mixed, and the mixture was made into soft material using 95% ethanol. The granules were prepared using a 18-mesh sieve, dried at 55-60°C, and sieved using a 16-mesh sieve. 5 g of magnesium stearate was added, and the mixture was mixed for 30 min before being compressed into tablets to obtain the composition tablet 11 for preventing and treating osteoporosis. The specification was 0.6 g / tablet.

[0084] In the above step, the Herba Epimedii extract was the same as in Example 1.

[0085] Comparative Example 6

[0086] (1) The raw material Eucommiae Cortex was crushed, and the powder was passed through a 20-mesh sieve. 15 g of sodium bicarbonate was dissolved in 35 ml of water and sprayed onto 750 g of the Eucommiae Cortex powder. After stirring, the mixture was sealed and soaked for 1 h. The mixture was slowly fried at 110°C. During the frying process, 150 ml of rice vinegar at 25°C was sprayed. After the mixture was fried until the silk was broken, the fire was turned off, and the mixture was spread and cooled. The mixture was extracted twice by reflux extraction using 70% ethanol. The solid-liquid ratio was 1:10 for the first extraction, and the extraction was performed for 2 h. The solid-liquid ratio was 1:8 for the second extraction, and the extraction was performed for 2 h. After the extraction, the mixture was filtered, concentrated, dried, and crushed to obtain the Eucommiae Cortex extract. The slow frying time was 10 min.

[0087] (2) The raw material Drynariae Rhizoma was crushed, and the powder was passed through an 80-mesh sieve. 670 g of the Drynariae Rhizoma powder was added to a fermentation tank, 270 ml of water was added, and the mixture was sterilized at 100°C for 20 min. After cooling to 35°C, 20 ml of Lactobacillus plantarum was added and uniformly mixed. The mixture was sealed and fermented at 35°C for 3 days. The mixture was extracted twice by reflux extraction using 75% ethanol. The solid-liquid ratio was 1:8 for the first extraction, and the extraction was performed for 2 h. The solid-liquid ratio was 1:6 for the second extraction, and the extraction was performed for 2 h. After the extraction, the mixture was filtered, concentrated, dried, and crushed to obtain the Drynariae Rhizoma extract.

[0088] In the above step, the Lactobacillus plantarum was Lactobacillus plantarum ATCC 8014, and the number of viable bacteria was 9 x 10 8 CFU / ml.

[0089] (3) Weigh 80 g of the Eucommia ulmoides extract and 55 g of the Drynaria fortunei extract prepared in the above steps, add 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of Epimedium brevicornum extract, 55 g of oyster powder and 115 g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5 g of magnesium stearate, mix for 30 minutes, and then tablet to obtain a composition tablet 1 for preventing and treating osteoporosis. The specification is 0.6 g / tablet.

[0090] Wherein, the epimedium extract is the same as that in Example 1.

[0091] Experimental Example 1: Detection of active ingredient content in tablets

[0092] Preparation of test solution:

[0093] Take 4 tablets prepared in Examples 1-5 and Comparative Examples 1-6 above, place them in round-bottom flasks respectively, add 30 mL of methanol respectively, heat and reflux for 3 h, cool, filter, and place the filtrate in a 50 mL volumetric flask respectively. Wash the container several times with a small amount of methanol, put the washing filtrate into the same volumetric flask, add methanol to the scale, shake well, and obtain the test solution.

[0094] The test solutions prepared in Examples 1-5 and Comparative Examples 1-6 were tested using high performance liquid chromatography (HPLC) to calculate the active ingredients icariin, naringin, naringenin, pinoresinol diglucoside, geniposide, and aucubin in each test solution. The test results are shown in Table 1 below.

[0095] Table 1: Test results of the active ingredient content in each test solution

[0096]

[0097] As shown in Table 1, the naringenin content in the composition tablets obtained in Examples 1-5 remained stable at 2.199-2.302 mg / g, while no naringenin was detected in Comparative Examples 2 and 5. This indicates that the naringenin content in the Drynaria extracts obtained by direct extraction without a fermentation step is low, falling below the detection limit. This result demonstrates that the β-glucosidase produced by Lactobacillus plantarum fermentation can indeed promote the deglycosylation of naringin to naringenin.

[0098] The contents of pinoresinol diglucoside, geniposide, and aucubin in the composition tablets obtained in Experimental Examples 1-5 were significantly higher than those in Comparative Examples 1-4 and 6, and comparable to those in Comparative Document 5, indicating that the sodium bicarbonate salt-roasted and vinegar-roasted method of preparing Eucommia ulmoides in the composition preparation method can effectively destroy Eucommia gum and improve the dissolution of the active ingredients in Eucommia ulmoides. Furthermore, from the comparison of the results of Comparative Examples 3-4 and 6 with Comparative Example 5 and Comparative Example 1-2, it can be seen that the contents of pinoresinol diglucoside, geniposide, and aucubin in the composition tablets obtained in Comparative Examples 3-4 and 6 are lower than those in the composition tablets obtained in Example 5, but significantly higher than those in the composition tablets obtained in Comparative Examples 1-2, indicating that the combined sodium bicarbonate salt-roasted and vinegar-roasted method for Eucommia ulmoides is significantly better than the sodium bicarbonate salt-roasted or vinegar-roasted method alone, and that the temperature control of the vinegar during the vinegar-roasting process also has a significant impact on the vinegar-roasting effect.

[0099] Example 2 Animal Experiment

[0100] Materials and groups:

[0101] 130 SPF-grade healthy female SD rats aged 33 weeks, weighing 300±20 g, were randomly divided into 13 groups, with 10 rats in each group. The groups were blank control group, model group, Example 1-5 groups, and Comparative Example 1-6 groups.

[0102] Animal housing conditions: Barrier system animal room, temperature 20-25°C, relative humidity 40-60%, controlled lighting 12 / 12h. One mouse per cage, separate cages, free access to water and food, timely replacement of bedding, and regular cleaning of cages.

[0103] Establishment of a rat model of osteoporosis due to Yin deficiency and hyperactivity of fire and drug administration: After 7 days of adaptive feeding, rats in the model group, Example 1-5 groups, and Comparative Example 1-6 groups underwent bilateral ovariectomy on the 8th day. A blank control group underwent sham surgery, with the surgical cavity opened and sutured. Penicillin (400,000 units / rat) was injected daily for 3 days postoperatively to prevent infection. Postoperatively, rats were gavaged daily with potassium retinoate and thyroxine at a dose of 70 mg / kg and 50 μg / kg, respectively, for 14 consecutive days. The blank control group was gavaged with normal saline for 29 consecutive days. After 29 days, the rats in the model group, Example 1-5 groups, and Comparative Example 1-6 groups showed a greater than 50% increase in water intake compared to the blank control group. Bone density testing revealed a greater than 15% decrease in bone mass, confirming the successful establishment of a rat model of osteoporosis due to Yin deficiency and hyperactivity of fire.

[0104] One day after successful modeling, the tablets of the compositions prepared in Examples 1-5 and Comparative Examples 1-6 were fully suspended into a 36 mg / mL suspension, and the rats in the Example 1-5 group and the Comparative Example 1-6 group were gavaged and administered, respectively. The suspensions prepared from the compositions of Examples 1-5 and Comparative Examples 1-6 were gavaged at a dose of 10 mL / kg, once a day for 8 consecutive weeks, and the blank control group was gavaged with an equal amount of normal saline.

[0105] After 56 consecutive days of gavage, rats were anesthetized with an intraperitoneal injection of 45 mg / kg sodium pentobarbital 1 hour after gavage administration, and blood was collected from the abdominal artery. After the blood was allowed to stand for 20 minutes, it was centrifuged at 2000 rpm, and the supernatant was collected and placed in an EP tube and stored at -20°C for later use.

[0106] (1) Bone density and bone calcium testing

[0107] After blood was drawn, the rats were sacrificed and the left femur was removed. Bone mineral density (BMD) of the left hind limb femur was measured using a biological X-ray small animal bone densitometer. The femur was dried to a constant weight and accurately weighed and recorded. The femur was then ashed, dissolved in acid, and the bone calcium content was measured by titration with EDTA. The results are shown in Table 2 below.

[0108] Table 2 Average values ​​of femoral bone density, femoral dry weight and bone calcium content in rats in each experimental group

[0109]

[0110] As can be seen from the results in Table 2, the composition tablets obtained from Example 1-5 and Comparative Example 1-6 groups have significant differences in the femoral bone density of rats in the rat Yin deficiency and fire excess type osteoporosis model compared with the model group rats, and the femoral bone density of the rats in Example 1-5 groups is significantly higher than that in Comparative Example 1-6 groups.

[0111] The composition tablets obtained from Examples 1-5 and Comparative Examples 1-6 showed significant differences in bone calcium content in rats in a rat model of Yin-deficiency-fire-excess osteoporosis compared to the model group. The bone calcium content in Examples 1-5 was higher than that in Comparative Examples 1-6. This demonstrates that the composition obtained by the preparation method described in Examples 1-5 has a significant ability to increase bone density and bone calcium content.

[0112] (2) Alternative serum testing

[0113] An automatic biochemical analyzer was used to measure the serum levels of osteocalcin (BGP), alkaline phosphatase (ALP), calcitonin (CT), interleukin-1 (IL-1), and interleukin-6 (IL-6) in the rat serum of each group at week 8 after oral administration. The results are shown in Table 3 below.

[0114] Table 3 Results of the levels of various indicators in the serum of rats in each experimental group.

[0115]

[0116] As shown in Table 3, the composition tablets obtained from Examples 1-5 and Comparative Examples 1-6 showed significant differences in osteocalcin, alkaline phosphatase, and calcitonin levels in a rat model of Yin-deficiency-fire-excess osteoporosis compared to the model group, and were similar to those in the blank control group. This indicates that the compositions obtained by the preparation methods described in Examples 1-5 and Comparative Examples 1-6 have a significant effect on regulating bone metabolism.

[0117] The tablet compositions obtained in Examples 1-5 significantly reduced interleukin-1 (IL-1) and interleukin-6 (IL-6) levels in rat serum compared to the model group, and were superior to the tablet compositions obtained in Comparative Examples 1-6. This indicates that the compositions prepared by the methods described in Examples 1-5 can promote osteoblast differentiation, thereby improving bone metabolism imbalance caused by estrogen deficiency.

[0118] (III) Detection of constipation indicators in rats:

[0119] On the 49th day after the rats were gavaged, the bedding and absorbent paper in the rat cages were replaced, and the feces were collected. The feces excreted by the rats within 6 hours were collected.

[0120] Measure the water content of rat feces. After oral administration, collect feces from rats and measure the wet weight using a precision electronic balance within 6 hours. Then, bake the feces in an electric constant-temperature incubator at 120°C for 8 hours. Measure the dry weight of the feces and calculate the percentage of water content in the feces.

[0121] Rat feces moisture percentage = (wet weight - dry weight) / wet weight × 100%. The results are shown in Table 4 below.

[0122] Table 4 Results of fecal wet weight, fecal dry weight and fecal water content of rats in each experimental group

[0123]

[0124] As shown in Table 4, the fecal moisture content of rats in Examples 1-5, the model group, and the blank control group ranged from 18.48% to 19.02%, which is within the range of fecal moisture content in healthy rats (15-25%). In contrast, the fecal moisture content of rats in Comparative Example Groups 1, 2, and 5 was 11.83%, 10.45%, and 11.29%, respectively, less than 12%, indicating constipation. Compared to Comparative Example 2, the original composition without the special preparation of Eucommia ulmoides and Drynariae rhizome, the control of constipation was particularly significant. The fecal moisture content of rats in Comparative Example Groups 3, 4, and 6 was 12.61%, 14.42%, and 12.46%, respectively, indicating pre-constipation or slowed intestinal motility, with a potential risk of constipation. This indicates that the composition tablets prepared by the preparation methods of Examples 1-5 can effectively overcome adverse reactions such as constipation caused by the use of the unprocessed original composition, improving the safety and tolerability of the composition and significantly enhancing patient compliance.

[0125] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Those skilled in the art can make some simple modifications, equivalent changes or modifications based on the technical content disclosed above, which all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a composition for preventing and treating osteoporosis, characterized in that: The steps include: (1) Preparation of Eucommia ulmoides extract: spray sodium bicarbonate aqueous solution evenly onto Eucommia ulmoides powder, stir and seal for 1 hour, stir-fry at 100-120°C, and evenly spray 60-80°C rice vinegar during the stir-frying process. Stir-fry until the powder breaks, turn off the heat, spread out to cool, and extract the cooled Eucommia ulmoides powder twice with 70% ethanol reflux, filter, and concentrate the supernatant to dry and crush to obtain Eucommia ulmoides extract; (2) Preparation of Drynaria extract: Add drynaria powder to a fermentation tank, add water, sterilize at high temperature, cool, add Lactobacillus plantarum, mix well, and ferment at 35°C for 3 days. Then, extract twice with 75% ethanol under reflux, filter, and concentrate the supernatant, dry it, and grind it to obtain drynaria extract; (3) Preparation of a composition: Weigh 75-85 g of the Eucommia ulmoides extract prepared in step (1), 50-60 g of the Drynaria fortunei extract prepared in step (2), 140-180 g of D-glucosamine hydrochloride, 60-100 g of sodium chondroitin sulfate, 50 g of Epimedium extract and 55 g of oyster powder, and mix them evenly to obtain the composition for preventing and treating osteoporosis.

2. The method for preparing the composition for preventing and treating osteoporosis according to claim 1, characterized in that: In step (1), the Eucommia ulmoides powder is passed through a 20-mesh sieve, the amount of sodium bicarbonate in the sodium bicarbonate aqueous solution used is 2% of the weight of the Eucommia ulmoides powder, the volume ratio of the sprayed rice vinegar to the weight ratio of the Eucommia ulmoides powder is 0.2 ml / g, the acetic acid concentration in the rice vinegar is 9%, and the slow fire frying time is 8 to 10 minutes.

3. The method for preparing the composition for preventing and treating osteoporosis according to claim 2, wherein: In step (2), the Rhizoma Drynariae powder was passed through an 80-mesh sieve, the volume of water added was 0.4 ml / g to the weight of the Rhizoma Drynariae powder, the high-temperature sterilization condition was heating at 100°C for 20 min, the plantarum Lactobacillus was plantarum Lactobacillus ATCC 8014, and the number of viable Lactobacillus plantarum added was 8×10 8 ~ 1×10 9 CFU / ml.

4. The method for preparing the composition for preventing and treating osteoporosis according to claim 3, wherein: The step of preparing the composition in step (3) is as follows: weighing 80 g of the Eucommia ulmoides extract prepared in step (1), 55 g of the Drynaria fortunei extract prepared in step (2), 160 g of D-glucosamine hydrochloride, 80 g of sodium chondroitin sulfate, 50 g of epimedium extract and 55 g of oyster powder, and mixing them evenly to obtain the composition for preventing and treating osteoporosis.

5. A composition for preventing and treating osteoporosis, characterized in that: The composition is prepared by the preparation method of the composition for preventing and treating osteoporosis according to any one of claims 1 to 4.

6. An oral preparation for preventing and treating osteoporosis, characterized in that: The composition comprises the composition for preventing and treating osteoporosis according to claim 5, and pharmaceutically acceptable excipients.

7. The oral preparation for preventing and treating osteoporosis according to claim 6, characterized in that: The oral preparation is in the form of tablets, granules, powders or capsules.

8. The oral preparation for preventing and treating osteoporosis according to claim 7, characterized in that: The oral preparation is a tablet, and the preparation method is as follows: weigh 80g of the Eucommia ulmoides extract and 55g of the Drynaria fortunei extract, add 160g of D-glucosamine hydrochloride, 80g of sodium chondroitin sulfate, 50g of epimedium extract, 55g of oyster powder and 115g of microcrystalline cellulose, mix evenly, add 95% ethanol to make a soft material, granulate with an 18-mesh sieve, dry at 55-60°C, sieve the whole granules with a 16-mesh sieve, add 5g of magnesium stearate, mix for 30 minutes, and then tablet, to obtain a composition tablet for preventing and treating osteoporosis.

9. Use of the composition for preventing and treating osteoporosis according to claim 5 in the preparation of a drug for preventing and treating osteoporosis.

10. Use of the composition for preventing and treating osteoporosis according to claim 9 in preparing a drug for preventing and treating osteoporosis, characterized in that: The composition can reduce the side effects of internal heat caused by constipation, dry mouth, swollen and sore gums or sore throat during the prevention and treatment of osteoporosis.

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