Pharmaceutical composition for preventing and treating osteoporosis

Abstract

A kind of pharmaceutical composition related to treatment and / or prevention of osteoporosis, including 2-8 parts by weight of ligustrum lucidum, 2-8 parts by weight of eclipta, 1-5 parts by weight of caesalpinia, 1-5 parts by weight of cyathula. The pharmaceutical composition can effectively prevent and treat osteoporosis, perimenstrual syndrome, constipation or obesity and reduce blood lipids, and the effect is better than that of Erzhi Decoction.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of traditional Chinese medicine, and relates to a pharmaceutical composition, in particular, to a pharmaceutical composition for treating and / or preventing osteoporosis. BACKGROUND

[0002] Osteoporosis (OP) is a systemic bone metabolic disease characterized by bone mass reduction in unit volume and microstructure destruction of bone tissue, thus leading to increased bone fragility and bone fracture. The National Institutes of Health defines osteoporosis as a skeletal disease with impaired bone strength, degenerated microstructure of bone tissue (thinning and breaking of bone trabeculae in cancellous bone and reduced number) and increased risk of fracture. Bone strength is a comprehensive reflection of bone density and bone mass. Osteoporosis can be divided into two categories: primary OP and secondary OP. Postmenopausal OP and senile OP belong to primary OP. Patients with osteoporosis generally have no special clinical manifestations, but hip, vertebral or distal radius fractures often occur when it is severe. Currently, commonly used OP treatment drugs include estrogen, bone resorption inhibitors, bone formation promoters and bone mineralization substances, etc.

[0003] Perimenopausal period is a special stage that women must go through. During this period, women's ovarian function decreases and estrogen levels decrease, causing functional disorders of multiple systems such as endocrine system, cardiovascular system and nervous system, and causing a series of symptoms of varying degrees collectively known as perimenopausal syndrome (PS). The specific manifestations of perimenopausal syndrome vary from person to person, and most symptoms can be improved through self-regulation and psychological counseling [1] . However, perimenopausal osteoporosis, as a very serious complication of perimenopausal syndrome, not only causes great harm to women's psychology and physiology, but also endangers the patient's life [2] .

[0004] According to statistics, the number of women with osteoporosis during perimenopausal period accounts for about 25% of the total number of perimenopausal women. The disease has the characteristics of long course and early detection difficulty. It will not be taken seriously until serious bone pain, vertebral degeneration or even fracture occurs, and the prognosis is poor, which can easily cause lifelong disability or even death of the patient [3,4] .

[0005] Currently, hormone replacement therapy (HRT) is commonly used in clinical treatment of perimenopausal osteoporosis, and the efficacy is still good but the adverse reactions are quite a lot. Research results show that long-term estrogen treatment can increase the incidence of breast cancer and endometrial cancer, and increase the risk of stroke, coronary sclerosis, pulmonary embolism and deep vein thrombosis [5-7]In addition, other types of drugs for treating osteoporosis are also reported to cause different types of adverse reactions, which are even life-threatening. Therefore, traditional Chinese medicine has gradually entered the sight of people due to its good therapeutic effect, small side effects and good compliance, and the research on traditional Chinese medicine for treating perimenopausal symptoms has been increasingly valued.

[0006] Erzhi Decoction is composed of Ligustri Lucidi Fructus and Herba Ecliptae, etc. Ligustri Lucidi Fructus is used as fruit for medicine, which is collected in winter solstice, while Herba Ecliptae is used as whole herb for medicine, which is collected in summer solstice. Erzhi Decoction is made into pills, which is called Erzhi Pills. In Erzhi Pills, Ligustri Lucidi Fructus is often used as Jiu Nvzhenzi, which is a processed product of Ligustri Lucidi Fructus. Erzhi Decoction has the functions of tonifying liver and kidney and nourishing yin and stopping bleeding. Modern studies have shown that the pharmacological effects of Erzhi Decoction mainly include immune regulation, antioxidant and anti-aging effects, liver protection, anti-osteoporosis effects, anti-inflammatory effects, anti-tumor effects, and hormone-like effects, etc. [8] .

[0007] In the prescription, Ligustri Lucidi Fructus is the fruit of Ligustri Lucidi Fructus, which is sweet in taste and cool in nature, and belongs to the liver and kidney channels. It has the functions of nourishing liver and kidney and benefiting the eyes and hair, and is often used for the treatment of liver and kidney yin deficiency, dizziness and tinnitus, soreness of the waist and knees, early graying of hair, and dim eyesight. Modern studies have shown that Ligustri Lucidi Fructus contains a large amount of effective substances, mainly including triterpenoids, iridoid glycosides, phenylethanoid glycosides, flavonoids, and Ligustri Lucidi Fructus polysaccharides. The iridoid glycoside speciosa was selected as the quality control component of Ligustri Lucidi Fructus in the 2015 edition of Chinese Pharmacopoeia [9] .

[0008] In the prescription, Herba Ecliptae (commonly known as Eclipta) is the whole herb of Eclipta prostrata, which is sweet and sour in taste and cool in nature, and belongs to the liver and kidney channels. It has the functions of nourishing liver and kidney and cooling blood to stop bleeding, and is often used for the treatment of blood-cooling, blood-stopping, kidney-nourishing, and yin-nourishing. Modern studies have shown that its effective substances mainly include flavonoids, triterpenes and their derivatives, verbenaceae compounds, thiophene compounds, steroids, and volatile oils. The verbenaceae compound wedelolactone was selected as the quality control component of Herba Ecliptae in the 2015 edition of Chinese Pharmacopoeia

[10] .

[0009] Caulis Spatholobi is a commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis, which belongs to the liver and kidney channels and has the effects of relaxing the tendons and collaterals, promoting blood circulation and tonifying blood, and regulating menstruation and relieving pain. The Bencao Biyao points out that “Caulis Spatholobi promotes blood circulation and relaxes tendons, and is used for treating blood deficiency and labor injury in men and women, and all kinds of deficiency and injury … …”. It is mainly used for irregular menstruation, blood deficiency and emaciation, numbness and paralysis, and rheumatic arthralgia. Modern studies have found that Caulis Spatholobi contains more than ten types of compounds, including flavanoids (such as catechin), terpenes (such as lupine alcohol), sterols (β-sitosterol), and anthraquinones (such as emodin).

[0010] Radix Achyranthis Bidentatae is the root of Achyranthes bidentata Blume of Chenopodiaceae. It is bitter, sour and flat in nature, and belongs to the liver and kidney channels. It has the functions of tonifying liver and kidney, strengthening bones and muscles, promoting blood circulation and unblocking channels, guiding qi and blood downward, and promoting urination and removing stones. It was first recorded in Shennong's Herbal Classic: "It is used for cold and dampness arthralgia, flaccidity, and knee pain, and can expel blood and qi, treat hot and sore skin, and prolong life and resist aging."

[0011] There is still a need to develop more effective drugs for preventing and treating osteoporosis and other diseases. SUMMARY

[0012] The present inventors have developed a pharmaceutical composition for preventing and treating osteoporosis and other diseases, and an extract thereof. The present inventors have surprisingly found that the pharmaceutical composition or the extract thereof can effectively prevent and treat osteoporosis, particularly perimenopausal osteoporosis, prevent constipation, and / or lower blood lipids. The effects of the pharmaceutical composition or the extract of the present invention are superior to those of Erzhi Decoction (Erzhi Pills), and the long-term use is safe. Thus, the following invention is provided:

[0013] One aspect of the present invention relates to a pharmaceutical composition, comprising:

[0014] Ligustrum lucidum Ait. 2-8 parts by weight

[0015] Eclipta prostrata L. 2-8 parts by weight

[0016] Spatholobus suberectus Dunn 1-5 parts by weight

[0017] Radix Achyranthis Bidentatae 1-5 parts by weight

[0018] In some embodiments of the present invention, the pharmaceutical composition comprises:

[0019] Ligustrum lucidum Ait. 2-8 parts by weight

[0020] Eclipta prostrata L. 2-8 parts by weight

[0021] Spatholobus suberectus Dunn 2-4 parts by weight

[0022] Radix Achyranthis Bidentatae 1-3 parts by weight

[0023] Preferably, it comprises:

[0024] Ligustrum lucidum Ait. 4-6 parts by weight

[0025] Eclipta prostrata L. 4-6 parts by weight

[0026] Spatholobus suberectus Dunn 2-4 parts by weight

[0027] Radix Achyranthis Bidentatae 1-3 parts by weight

[0028] More preferably, it comprises:

[0029] Ligustrum lucidum Ait. 4.5-5.5 parts by weight

[0030] Eclipta 4.5-5.5 parts by weight

[0031] Spatholobus suberectus 2.5-3.5 parts by weight

[0032] Cyathula 1.5-2.5 parts by weight;

[0033] Further preferably, comprising:

[0034] Ligustrum lucidum 4.8-5.2 parts by weight

[0035] Eclipta 4.8-5.2 parts by weight

[0036] Spatholobus suberectus 2.8-3.2 parts by weight

[0037] Cyathula 1.8-2.2 parts by weight;

[0038] Particularly preferably, comprising:

[0039] Ligustrum lucidum 5 parts by weight

[0040] Eclipta 5 parts by weight

[0041] Spatholobus suberectus 3 parts by weight

[0042] Cyathula 2 parts by weight.

[0043] In some embodiments of the present application, the pharmaceutical composition has a unit dosage of 10-60 g, preferably 15-40 g, 20-30 g, 22-28 g or 24-26 g, more preferably 25 g.

[0044] In the pharmaceutical composition of the present application, each medicinal material (for example, 2, 3 or 4 of them) can be mixed or relatively independent (not mixed).

[0045] In some embodiments of the present application, the pharmaceutical composition consists of the above-mentioned 4 medicinal materials.

[0046] In some embodiments of the present application, the pharmaceutical composition consists of the above-mentioned 4 medicinal materials and pharmaceutically acceptable excipients.

[0047] Another aspect of the present application relates to an extract prepared from any of the pharmaceutical compositions of the present application.

[0048] In some embodiments of the present application, the extract is prepared by a preparation method comprising the following steps:

[0049] (1) extracting the Ligustrum lucidum, Eclipta, Spatholobus suberectus and Cyathula in any of the above-mentioned parts by weight with water or an ethanol solution to obtain an extract;

[0050] (2) concentrating the extract solution to obtain a concentrate, which is the extract.

[0051] In some embodiments of the present application, the extract is characterized by any one or more of the following ①-⑧:

[0052] ① in step (1), the extraction is performed once or multiple times, and when performed multiple times, the extract solutions of the multiple times are combined;

[0053] ② in step (1), the mixture of the Schisandra chinensis, the Euphorbia humifusa, the Spatholobus suberectus and the Achyranthes bidentata is extracted; or any one of them and the mixture of the remaining three are extracted respectively to obtain extract solutions, which are combined or not combined; or any two of them and the mixture of the remaining two are extracted respectively to obtain extract solutions, which are combined or not combined; or any one of them, another one and the mixture of the remaining two are extracted respectively to obtain extract solutions, which are combined or not combined; or the four medicinal materials are extracted respectively to obtain extract solutions, which are combined or not combined;

[0054] ③ in step (1), the concentration of the ethanol is 10%-99%, 20%-90%, 30%-80%, 40%-80%, 50%-80%, 50%-70% or 60%-80%;

[0055] ④ in step (1), the extraction is reflux extraction or decocting;

[0056] ⑤ in step (1), the extraction time is at least 0.5 hour, at least 1 hour, at least 2 hours or 1-5 hours;

[0057] ⑥ in step (1), the amount of water or ethanol solution is 5-20 times (ml / g), preferably 8-16 times;

[0058] ⑦ in step (2), the concentration is reduced pressure concentration;

[0059] ⑧ in step (2), the concentrate is an extractum.

[0060] In some embodiments of the present application, the extract, wherein in step (2), the concentrate is one or several (for example, 2, 3 or 4). In the case of not combining the extract solutions in the second item, several extract solutions will result in several concentrates; at this time, the several concentrates are the extract.

[0061] In some embodiments of the application, the extract, wherein, the extract of Fructus Ligustri Lucidi and Herba Ecliptae are extracted respectively to obtain a Fructus Ligustri Lucidi concentrate and a Herba Ecliptae concentrate; the mixture of Fructus Ligustri Lucidi, Caesalpinia japonica and Radix Achyranthis Bidentatae is extracted to obtain a Fructus Ligustri Lucidi Caesalpinia japonica Radix Achyranthis Bidentatae concentrate; and the three concentrates are the extract of the application.

[0062] In some embodiments of the application, the extract, wherein,

[0063] Step (1) comprises the following steps:

[0064] The Fructus Ligustri Lucidi and Herba Ecliptae are extracted respectively to obtain a Fructus Ligustri Lucidi extract and a Herba Ecliptae extract; the mixture of Fructus Ligustri Lucidi, Caesalpinia japonica and Radix Achyranthis Bidentatae is extracted to obtain a Fructus Ligustri Lucidi Caesalpinia japonica Radix Achyranthis Bidentatae extract;

[0065] Preferably, step (2) comprises the following steps:

[0066] The Fructus Ligustri Lucidi extract, the Herba Ecliptae extract and the Fructus Ligustri Lucidi Caesalpinia japonica Radix Achyranthis Bidentatae extract are concentrated respectively, or the extracts are combined and then concentrated, to obtain the extract.

[0067] In another aspect of the application, there is provided a pharmaceutical preparation comprising the extract of any one of the application, and one or more pharmaceutically acceptable excipients.

[0068] Preferably, the unit dose of the pharmaceutical preparation is 10-60g, preferably 15-40g or 20-30g, more preferably 25g, calculated as the mass of crude drug.

[0069] In some embodiments of the application, the pharmaceutical preparation, wherein the extract is the only active ingredient.

[0070] In some embodiments of the application, the pharmaceutical preparation consists of the extract and one or more pharmaceutically acceptable excipients.

[0071] In some embodiments of the application, the pharmaceutical preparation is a pill, a tablet, a granule, a capsule, a tincture or a suspension.

[0072] In some embodiments of the application, the pharmaceutical preparation further comprises one or more of the following drugs:

[0073] Calcium agents, vitamin D, bisphosphonates, estrogens such as estradiol, estrogen receptor modulators, calcitonin, parathyroid hormone and osteoprotegerin.

[0074] The pharmaceutical composition according to any one of the present application, the extract according to any one of the present application or the pharmaceutical preparation according to any one of the present application for use in the treatment and / or prevention of osteoporosis, perimenopausal syndrome, constipation or obesity or for use in lowering blood lipid;

[0075] Preferably, the osteoporosis is primary osteoporosis or secondary osteoporosis.

[0076] Preferably, the osteoporosis is postmenopausal osteoporosis or senile osteoporosis.

[0077] Preferably, the osteoporosis is perimenopausal osteoporosis.

[0078] Preferably, the obesity is menopausal obesity.

[0079] Still another aspect of the present application relates to a combination pharmaceutical product comprising a first product and a second product packaged separately,

[0080] wherein,

[0081] the first product comprises the pharmaceutical composition according to any one of the present application, the extract according to any one of the present application or the pharmaceutical preparation according to any one of the present application;

[0082] the second product comprises one or more selected from the group consisting of:

[0083] calcium agents, vitamin D, bisphosphonates, estrogens such as estradiol, estrogen receptor modulators, calcitonin, parathyroid hormone and osteoprotegerin;

[0084] Preferably, the second product further comprises one or more pharmaceutically acceptable excipients.

[0085] Preferably, the unit dose of the first product is 10-60 g, preferably 15-40 g or 20-30 g, more preferably 25 g, in terms of the mass of crude drug.

[0086] The "first" or "second" in the "first product" or "second product" is merely for the purpose of distinguishing or referring clearly, and does not have the meaning of sequence.

[0087] Still another aspect of the present application relates to the use of the pharmaceutical composition according to any one of the present application, the extract according to any one of the present application or the pharmaceutical preparation according to any one of the present application in the preparation of a medicament for the treatment and / or prevention of osteoporosis, perimenopausal syndrome, constipation or obesity, or a medicament for lowering blood lipid;

[0088] Preferably, the osteoporosis is primary osteoporosis or secondary osteoporosis.

[0089] Preferably, the osteoporosis is postmenopausal osteoporosis or senile osteoporosis.

[0090] Preferably, the osteoporosis is perimenopausal osteoporosis.

[0091] Preferably, the obesity is menopausal obesity.

[0092] In some embodiments of the present application, the use, wherein the daily dosage per kilogram of body weight is 0.1g-2g, 0.2g-1g or 0.4g-0.8g, preferably 0.5g.

[0093] Still another aspect of the present application relates to a method for preparing the extract, comprising the following steps:

[0094] (1) extracting the female privet fruit, the euphorbia humifusa, the caulis acanthopanacis and the cyathula root in any one of the weight parts claimed in the present application with water or an ethanol solution to obtain an extract solution;

[0095] (2) concentrating the extract solution to obtain a concentrate, which is the extract.

[0096] In some embodiments of the present application, the method for preparing, characterized by any one or more of the following ①-⑧:

[0097] ① in step (1), the extraction is one or more times, and when it is more than one time, the extract solutions of each time are combined;

[0098] ② in step (1), the mixture of the female privet fruit, the euphorbia humifusa, the caulis acanthopanacis and the cyathula root is extracted; or the mixture of any one of them and the mixture of the remaining three are extracted respectively to obtain each extract solution, which is combined or not combined; or the mixture of any two of them and the mixture of the remaining two are extracted respectively to obtain each extract solution, which is combined or not combined; or the mixture of any one of them, the mixture of the other one and the mixture of the remaining two are extracted respectively to obtain each extract solution, which is combined or not combined; or the four medicinal materials are extracted respectively to obtain each extract solution, which is combined or not combined;

[0099] ③ in step (1), the concentration of the ethanol is 10%-99%, 20%-90%, 30%-80%, 40%-80%, 50%-80%, 50%-70% or 60%-80%;

[0100] ④ in step (1), the extraction is reflux extraction or decocting;

[0101] ⑤ in step (1), the extraction time is at least 0.5 hours, at least 1 hour, at least 2 hours or 1-5 hours;

[0102] In step (1), the amount of water or ethanol solution is 5-20 times (ml / g), preferably 8-16 times;

[0103] In step (2), the concentration is under reduced pressure.

[0104] In step (2), the concentrate is extract.

[0105] In some embodiments of the present application, the preparation method, wherein,

[0106] Step (1) comprises the following steps:

[0107] Separately extract the Schisandra chinensis and Eclipta prostrata to obtain Schisandra chinensis extract and Eclipta prostrata extract; extract the mixture of Schisandra chinensis residue after extraction, Millettia nitida and Achyranthes bidentata to obtain Schisandra chinensis, Millettia nitida and Achyranthes bidentata extract;

[0108] Preferably, step (2) comprises the following steps:

[0109] Separately concentrate the Schisandra chinensis extract, Eclipta prostrata extract and Schisandra chinensis, Millettia nitida and Achyranthes bidentata extract, or concentrate the combined extracts to obtain the extract.

[0110] In the present application, the ethanol solution, if not otherwise specified, refers to the aqueous solution of ethanol.

[0111] In the present application, the concentration of ethanol or the concentration of ethanol solution, if not otherwise specified, refers to the volume percentage concentration (v / v) %.

[0112] In the present application, the term "Erzhi prescription" refers to the prescription of Schisandra chinensis and Eclipta prostrata (commonly known as Eclipta alba), and the term "Erzhi pill" refers to the preparation obtained through industrial production, if not otherwise specified.

[0113] In the present application, the pharmaceutical composition or extract of the present application is also sometimes referred to as the flavored Erzhi prescription.

[0114] Generally, the pharmaceutical preparation of the present application contains 0.1% to 90% by weight of the extract of the present application as the main drug. The pharmaceutical preparation can be prepared according to the methods known in the art. For this purpose, the main drug can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants, if necessary, to form a suitable administration form or dosage form for human use.

[0115] The term "adjuvant" as used herein refers to an excipient or vehicle used to administer the principal drug, which includes but is not limited to diluents, disintegrants, precipitation inhibitors, surfactants, glidants, binders, lubricants, coating materials, etc. Adjuvants are generally described in "Remington's Pharmaceutical Sciences" by E. W. Martin. Examples of adjuvants include, but are not limited to, aluminum monostearate, aluminum stearate, carboxymethylcellulose, carboxymethylcellulose sodium, crospovidone, glyceryl isostearate, glyceryl monostearate, hydroxyethylcellulose, hydroxymethylcellulose, hydroxyoctacosyl hydroxystearate, hydroxypropylcellulose, hydroxypropylmethylcellulose, lactose, lactose monohydrate, magnesium stearate, mannitol, microcrystalline cellulose, etc.

[0116] The extract of the present application can be formulated into a pharmaceutical preparation, including a dosage form suitable for oral administration, a dosage form suitable for parenteral injection (e.g., intravenous injection, subcutaneous injection) (e.g., as a solution), a dosage form suitable for topical administration (e.g., as an ointment, a patch, or a cream), and a dosage form suitable for rectal administration (e.g., as a suppository), etc.

[0117] Still another aspect of the present application relates to a method of treating and / or preventing osteoporosis, perimenopausal syndrome, constipation, or obesity, or reducing blood lipid, comprising the step of administering to a subject in need thereof an effective amount of the pharmaceutical composition according to any one of the present application, the extract according to any one of the present application, or the pharmaceutical preparation according to any one of the present application;

[0118] Preferably, the osteoporosis is primary osteoporosis or secondary osteoporosis.

[0119] Preferably, the osteoporosis is postmenopausal osteoporosis or senile osteoporosis.

[0120] Preferably, the osteoporosis is perimenopausal osteoporosis.

[0121] Preferably, the obesity is menopausal obesity.

[0122] In some embodiments of the present application, the method, wherein the administration dosage is 0.1 g to 2 g, 0.2 g to 1 g, or 0.4 g to 0.8 g per kg of body weight per day, preferably 0.5 g per kg of body weight per day.

[0123] The pharmaceutical preparation of the present application can be administered once or more times daily in different dosages depending on the disease to be treated and the patient as well as the route of administration. The dosage to be administered depends on many factors, such as the severity of the osteoporosis to be treated or prevented, the gender, age, body weight and individual response of the patient, the route of administration and the number of administrations, etc. The above-mentioned dosage can be administered in a single dosage form or divided into several, for example two, three or four, dosage forms.

[0124] Actual dosage levels of the active pharmaceutical agent (extract) of the present application can be varied depending on the particular patient, composition, and mode of administration desired. Dosage levels should be selected in accordance with a regimen selected to achieve the desired therapeutic response. Generally, the dose administered to a patient is the dosage which will produce therapeutic or prophylactic effects in the patient, without causing substantial harmful or deleterious effects.

[0125] The term "effective amount" means an amount which is effective to achieve a therapeutic, prophylactic, palliative and / or alleviative effect on the disease or condition described herein.

[0126] Advantages of the Invention

[0127] The present application achieves any one or more of the following technical effects (1) to (6):

[0128] (1) The pharmaceutical composition or extract of the present application can effectively treat or prevent osteoporosis.

[0129] (2) The pharmaceutical composition or extract of the present application can effectively treat or prevent constipation.

[0130] (3) The pharmaceutical composition or extract of the present application can effectively lower blood lipid, treat or prevent hyperlipidemia.

[0131] (4) The pharmaceutical composition or extract of the present application has a better effect on treating or preventing osteoporosis than Ershifang (Ershipian).

[0132] (5) The pharmaceutical composition or extract of the present application has good safety for long-term use.

[0133] (6) The preparation method of the present application is superior to the conventional preparation process of Ershifang (Ershipian), for example, under the same prescription, the extract prepared by the preparation method of the present application has a better anti-osteoporosis effect, for example, can better improve bone density. BRIEF DESCRIPTION OF DRAWINGS

[0134] FIG. 1 Fig. 1 is a graph showing the change of body weight of animals in each group over time.

[0135] FIG. 2: Bar graph of body weight of each group of animals before sampling (before animal sacrifice).

[0136] FIG. 3 : Bar graph of liver weight index of each group of animals.

[0137] FIG. 4 : Bar graph of spleen index of each group of animals.

[0138] FIG. 5 : Bar graph of kidney index of each group of animals.

[0139] FIG. 6 : Bar graph of uterus index of each group of animals.

[0140] FIG. 7 : Representative uterus graph of each group of animals.

[0141] FIG. 8 : Bar graph of fat index of each group of animals.

[0142] FIG. 9 : Bar graph of white fat index of each group of animals.

[0143] FIG. 10 : Bar graph of serum LDL-C level of each group of animals.

[0144] FIG. 11 : Bar graph of bone density of each group of animals. DETAILED DESCRIPTION

[0145] The embodiments of the present application will be described in detail with examples, but those skilled in the art will understand that the following examples are only for illustration of the present application and should not be regarded as limiting the scope of the present application. The specific conditions not noted in the examples are carried out according to the conventional conditions or the conditions suggested by the manufacturer. The reagents or instruments not noted for the manufacturer are all the conventional products which can be obtained by purchase in the market.

[0146] Preparation Example 1: Preparation process example (1) of flavored extract of Erzhi Decoction

[0147] 1. Preparation and analysis of extract of Ligustrum lucidum Ait.

[0148] 1.1 Preparation of extract of Ligustrum lucidum Ait.

[0149] Experimental instruments: vacuum drying oven, heating jacket, rotary evaporator.

[0150] Experimental procedure:

[0151] Take 300g of female privet fruit medicinal materials, put them into a 20L round-bottom flask, add 10L of 80% (v / v) ethanol, and place it on a heating jacket for heating reflux extraction. From the time of liquid micro-boiling, after 2 hours, turn off the heating jacket and cool it down. Filter out the liquid in the flask with gauze, add 10L of 80% ethanol for extraction again, combine the two extraction liquids, and concentrate to thick extract at 50°C under reduced pressure. Dry it in a 45°C vacuum drying oven and weigh it.

[0152] Experimental results: a total of 72.0g of dried sample was obtained, with an extract yield of 24%.

[0153] 1.2 Test method and single-factor test results

[0154] 1.2.1 HPLC conditions: instrument: waters2695, column: Agilent 4.6x250mm, 5μm, temperature: 25°C, mobile phase: A: water, B: methanol, detection wavelength: 224nm.

[0155] 1.2.2 Liquid phase method:

[0156] As shown in Table 1 below.

[0157] Table 1

[0158]

[0159] Preparation of control solution: accurately weigh the speciosin control sample, dissolve it with methanol to prepare the control solution.

[0160] Inject 10μl of the control solution and sample liquid respectively, calculate the content of the index component, and count. The female privet fruit extract contains 19.82mg / g of speciosin.

[0161] 2. Preparation and analysis of Jinyanhuanlian extract

[0162] 2.1 Jinyanhuanlian 60% ethanol heating reflux extraction

[0163] Experimental instruments: vacuum drying oven, heating jacket, rotary evaporator.

[0164] Experimental process:

[0165] Take 300g of Jinyanhuanlian medicinal materials, put them into a 20L round-bottom flask, add 10L of 60% ethanol, and place it on a heating jacket for heating reflux extraction. From the time of liquid micro-boiling, after 2 hours, turn off the heating jacket and cool it down. Filter out the liquid in the flask with gauze, add 10L of 60% ethanol for extraction again, combine the two extraction liquids, and concentrate to thick extract at 55°C under reduced pressure. Dry it in a 45°C vacuum drying oven and weigh it.

[0166] Experimental results: a total of 53.25g of dried sample was obtained, with an extract yield of 17.75%.

[0167] 2.2 Detection method and single factor test results

[0168] 2.2.1 HPLC conditions: instrument: waters2695, column: Agilent 4.6x250mm, 5μm, temperature: 25℃, mobile phase: A: 0.5% acetic acid water, B: methanol, detection wavelength 351nm.

[0169] 2.2.2 Liquid phase method:

[0170] As shown in Table 2 below.

[0171] Table 2

[0172]

[0173] Preparation of control solution: accurately weigh the control sample of pinoresinol, dissolve it with methanol to prepare the control solution.

[0174] 10μl of the control solution and sample solution were injected respectively, the content of the index component was calculated and counted. The content of pinoresinol in the extract of Euphorbia humifusa was 0.8mg / g.

[0175] 3. Preparation and analysis of Spatholobus suberectus extract

[0176] 3.1 Spatholobus suberectus 60% ethanol heating reflux

[0177] Experimental instruments: vacuum drying oven, heating jacket, rotary evaporator.

[0178] Experimental process:

[0179] Take 300g of Spatholobus suberectus medicinal materials and put them into a 5L round-bottom flask, add 3000ml of 60% ethanol, and place it on a heating jacket for heating reflux extraction. From the liquid micro-boiling time, turn off the heating jacket after 2 hours and cool it down. Filter out the liquid in the flask with gauze, add 3000ml of 60% ethanol for extraction again, combine the two extraction liquids, and concentrate to thick extract at 55℃ under reduced pressure. Dry it in a 45℃ vacuum drying oven and weigh it.

[0180] Experimental results: dry solid 60.24g, extract yield 20.08%.

[0181] 4. Preparation and analysis of Achyranthes bidentata extract

[0182] 4.1 Achyranthes bidentata 60% ethanol extraction

[0183] Chickweed 250g, add 8 times the amount of 60% ethanol 2000ml reflux extraction 2h, pour out the extract, the residue is added 2000ml 60% ethanol reflux extraction 2h, the two extract combined, concentrated to dryness of the extract 126.4g, the extract rate 50.6%.

[0184] Preparation Example 2: Preparation process example (2) of flavored extract of Erzhi Decoction

[0185] 1. Take 200g of Ligusticum lucidum, placed in a round bottom flask, add 2400ml of 60% ethanol, heated reflux extraction 2 hours, pour out the filtrate Ligusticum lucidum first extract, add 2400ml of 60% ethanol, heated reflux extraction 2 hours, pour out the filtrate Ligusticum lucidum second extract, Ligusticum lucidum residue for use, combined two extract, concentrated to dryness Ligusticum lucidum extract 48.78g.

[0186] 2. Take 200g of Eclipta prostrata L. medicinal materials, placed in a round bottom flask, add 2000ml of 70% ethanol, heated reflux extraction 3 hours, pour out the filtrate Eclipta prostrata L. first extract, add 2000ml of 70% ethanol, heated reflux extraction 3 hours, pour out the filtrate Eclipta prostrata L. second extract, combined two extract, concentrated to dryness Eclipta prostrata L. extract 28.52g.

[0187] 3. Take the Ligusticum lucidum residue prepared in the previous step 1, add 120g of Broussonetia papyrifera, 80g of Achyranthes bidentata, placed in a round bottom flask, add 3200ml of water, heated reflux extraction 2 hours, pour out the solution to get the first extract, add 3200ml of water, heated reflux extraction 2 hours, pour out the solution to get the second extract, combined two extract concentrated to dryness Ligusticum lucidum Broussonetia papyrifera Achyranthes bidentata extract 67.56g.

[0188] The Ligusticum lucidum extract 48.78g, Eclipta prostrata L. extract 28.52g and Ligusticum lucidum Broussonetia papyrifera Achyranthes bidentata extract 67.56g prepared above are mixed to obtain the extract of the present application, code XGY.

[0189] Without being limited by theory, the present inventors found that the sample prepared by the preparation method of Preparation Example 2 is beneficial to the preparation of the preparation, the content of the possible effective ingredients (Ligusticum lucidum polysaccharide, verbascoside and / or clerodendrin A, etc.) is higher, and the efficacy is better.

[0190] In addition, any two or any three of the four medicinal materials can also be mixed for extraction.

[0191] Preparation Example 3: Preparation process example (3) of flavored extract of Erzhi Decoction

[0192] Take 200g Ligustrum lucidum Ait medicinal materials, 200g Eclipta prostrata L medicinal materials, 120g Spatholobus suberectus Dunn and 80g Achyranthes bidentata Blume, place them in a round-bottom flask, add 6000 milliliters of 70% ethanol, heat and reflux to extract, extract twice, 2 hours each time, combine the two extraction solutions, concentrate and dry to obtain 140.58g of modified Sisheng Decoction extract, code XF.

[0193] Experimental Example 1: Anti-osteoporosis experiment

[0194] 1. Materials and methods

[0195] 1.1 Experimental animals

[0196] SPF level female C57BL / 6 mice, 8 weeks old, weighing 19-20g. Purchased from Spafas (Beijing) Biotechnology Co., Ltd., license number SCXK (Jing) 2016-0002. Raising in Tianjin Institute of Radiation Medicine, Chinese Academy of Medical Sciences, raising temperature 23-25℃, humidity 50%-60%, light 12 hours light-dark cycle.

[0197] 1.2 Drugs

[0198] Modified Sisheng Decoction group: Ligustrum lucidum Ait extract, Eclipta prostrata L extract, Spatholobus suberectus Dunn extract, and Achyranthes bidentata Blume extract were all prepared according to the method of Preparation Example 1.

[0199] Preparation method: take 14.4g of Ligustrum lucidum Ait extract, 10.65g of Eclipta prostrata L extract, 7.23g of Spatholobus suberectus Dunn extract, and 12.14g of Achyranthes bidentata Blume extract, dissolve them with 0.2% CMCNa, and make up to 100mL, as the administration solution of modified Sisheng Decoction group. Store at 4℃.

[0200] 1.3 Preparation of ovariectomized animal model

[0201] After one week of adaptive feeding, the mice were randomly divided into sham operation group (sham) and operation group (OVX) according to body weight. During the operation, the animals were anesthetized with tribromoethanol, the mice were fixed on the operation board, the middle and lower 1 / 3 of the back of the mice were depilated and prepared, iodophor was used for disinfection, a 2cm incision was made longitudinally in the center of the back, the skin layer and muscle layer were separated, the ovaries were gently pulled out with sterile ophthalmic forceps, the ovaries were completely removed with ophthalmic scissors, and finally the uterus was slowly inserted into the abdominal cavity. The same method was used to remove the bilateral ovaries, and the muscle layer and skin layer were sutured. The sham operation group was operated in the same way, but only the adipose tissue around the ovary was removed, without removing the ovary. After the operation, penicillin sodium (0.1mL / each, 200,000 units / mL) was continuously injected intraperitoneally for three days to prevent infection in the body caused by the operation.

[0202] 1.4 Experimental grouping and administration

[0203] As shown in Table 3 below.

[0204] Table 3

[0205]

[0206] The experimental animals were administered by gavage at 0.1 mL / 10 g / d for 8 weeks, and the growth of the mice was observed during the administration period. The mice were weighed and recorded every week, and were fed with standard feed throughout the process, with free access to food and water.

[0207] 2. Experimental results

[0208] 2.1 Effect of the administration of the Modified Erzhi Formula on the body weight and organs of the ovariectomized mice

[0209] Gavage was performed once a day for 8 consecutive weeks, and the changes in the body weight and organs of the mice in each group were observed. The results showed that the body weight of the mice in the Model group increased significantly, and the Modified Erzhi Formula group could significantly reduce the increase in the body weight of the ovariectomized mice (P<0.05). There was no significant change in the organs in the mice in each group.

[0210] 2.2 Effect of the administration of the Modified Erzhi Formula on the uterus of the ovariectomized mice

[0211] The weight of the uterus of the ovariectomized mice decreased significantly (P<0.01), and the uterus showed atrophy. The Modified Erzhi Formula improved the atrophy of the uterus.

[0212] 2.3 Effect of the administration of the Modified Erzhi Formula on the fat content of the ovariectomized mice

[0213] The results showed that, compared with the Sham operation group, there was no significant change in the back fat content of the ovariectomized mice, while the Modified Erzhi Formula could significantly increase the back fat content (P<0.01). The results of the abdominal fat content showed that the abdominal fat content of the ovariectomized mice increased significantly (P<0.01), and the Modified Erzhi Formula could significantly reduce the abdominal fat content (P<0.01).

[0214] 2.4 Effect of the administration of the Modified Erzhi Formula on the bone density of the ovariectomized mice

[0215] The bone mineral density of the tibia of the mice was detected by a dual-energy X-ray bone densitometer. The results showed that, compared with the Sham operation group, the bone mineral density (BMD) of the tibia of the mice in the Model group decreased significantly (P<0.01). The administration of the Modified Erzhi Formula increased the bone density of the tibia.

[0216] Experimental Example 2: Anti-osteoporosis experiment

[0217] 1. Materials and methods

[0218] 1.1 Experimental animals

[0219] SPF level female C57BL / 6 mice, 8 weeks old, body weight 19-20 g. Purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., license number SCXK (Jing) 2016-0006. Raising in the animal center of Tianjin University of Chinese Medicine, raising temperature 23-25℃, humidity 50%-60%, light 12 hours light-dark cycle.

[0220] 1.2 Drug

[0221] Xiaoyi Erzhi Decoction group (XGY): The extract of Ligustri Lucidi Fructus, the extract of Herba Ecliptae and the mixed extract of Ligustri Lucidi Fructus, Caulis Spatholobi and Radix Astragali were prepared according to the method of Preparation Example 2. Preparation method: 14.63 g of the extract of Ligustri Lucidi Fructus, 8.56 g of the extract of Herba Ecliptae and 20.27 g of the mixed extract of Ligustri Lucidi Fructus, Caulis Spatholobi and Radix Astragali were weighed, dissolved with 0.2% CMCNa, and made up to 100 mL as the Xiaoyi Erzhi Decoction group (XGY) administration solution. Stored at 4℃.

[0222] Xiaoyi Erzhi Decoction group (XF): The mixed medicinal materials of Ligustri Lucidi Fructus, Herba Ecliptae, Caulis Spatholobi and Radix Astragali were prepared according to the method of Preparation Example 3. Preparation method: 42.2 g of the above XF extract was dissolved with 0.2% CMCNa, and made up to 100 mL as the Xiaoyi Erzhi Decoction group (XF) administration solution. Stored at 4℃.

[0223] Erzhi Decoction group (EZF): The extract of Ligustri Lucidi Fructus and the extract of Herba Ecliptae were prepared according to the method of Preparation Example 1. Preparation method: 14.4 g of the extract of Ligustri Lucidi Fructus and 10.65 g of the extract of Herba Ecliptae were weighed, dissolved with 0.2% CMCNa, and made up to 100 mL as the Erzhi Decoction group (EZF) administration solution. Stored at 4℃.

[0224] 1.3 Preparation of ovariectomized animal model

[0225] After one week of adaptive feeding, the mice were randomly divided into sham operation group (sham) and operation group (OVX) according to body weight. During the operation, the animals were anesthetized with tribromoethanol, and the mice were fixed on the operation board. The middle and lower 1 / 3 of the back of the mice was depilated and skinned, and iodophor was used for disinfection. A longitudinal incision of about 2 cm was made in the center of the bilateral back, and the skin layer and muscle layer were separated. The ovaries were gently pulled out with sterile ophthalmic forceps, and the end of the oviduct was ligated with surgical thread (to prevent postoperative bleeding). The ovaries were completely removed with ophthalmic scissors, and finally the uterus was slowly inserted into the abdominal cavity. The bilateral ovaries were removed in the same way, and the muscle layer and skin layer were sutured. The sham operation group was operated in the same way, but only the adipose tissue around the ovary was removed without removing the ovary. After the operation, penicillin sodium (0.1 mL per mouse, 200,000 units / mL) was continuously injected intraperitoneally for three days to prevent infection in the body caused by the operation.

[0226] 1.4 Experimental grouping and administration

[0227] As shown in Table 4 below.

[0228] Table 4

[0229]

[0230] The experimental animals were administered by gavage at 0.1 mL / 10 g / d for 8 weeks, and the growth of the mice was observed during the administration period. The mice were weighed and recorded every week, and were fed with standard feed throughout the process, with free access to food and water.

[0231] 1.5 Detection of LDL-C content in serum

[0232] Before detection, the mouse serum samples were taken out from the -80℃ refrigerator and equilibrated to room temperature. The LDL-C content in the mouse serum was detected using a full-automatic biochemical analyzer (model: BS-240VET, Shenzhen Mindray Biomedical Electronics Co., Ltd.) and a low-density lipoprotein cholesterol (LDL-C) detection kit (batch number: 142020006).

[0233] 2. Experimental results

[0234] 2.1 Effect of flavored Erzhi Decoction administration on the body weight and organs of ovariectomized mice

[0235] The gavage administration was performed once a day, and the gavage was continuously performed for 8 weeks. The changes in the body weight and organs of the mice in each group were observed, and the results are shown in Table 2. FIG. 1 to FIG. 5

[0236] The results showed that the body weight of the mice in the Model group was significantly increased, and the Erzhi Decoction group, the flavored Erzhi Decoction group (XGY), and the flavored Erzhi Decoction group (XF) could significantly reduce the phenomenon of body weight increase in ovariectomized mice (P<0.05). There was no significant change in the organs of the mice in each group. FIG. 1 FIG. 2 FIG. 3 to FIG. 5

[0237] 2.2 Effect of flavored Erzhi Decoction administration on the uterus of ovariectomized mice

[0238] The results are shown in Table 3 and Table 4. FIG. 6 FIG. 7

[0239] The results showed that the uterus weight of the ovariectomized mice was significantly reduced (P<0.01), and the uterus showed atrophy. The flavored Erzhi Decoction (XGY) and the flavored Erzhi Decoction (XF) had the phenomenon of improving uterine atrophy.

[0240] From the above results, it can be seen that the flavored Erzhi Decoction has the effects of reducing the body weight of ovariectomized mice and improving uterine atrophy. FIG. 6 to FIG. 7 ​​​​​​Results analysis, the uterus index of the Erzhi Decoction (XGY) group and the Erzhi Decoction (XF) group is more close to the normal group than the Erzhi Decoction (EZF) group, indicating that the Erzhi Decoction (XGY) group and the Erzhi Decoction (XF) group have stronger effects on nourishing the uterus than the Erzhi Decoction (EZF) group, and show stronger estrogen-like effects than the Erzhi Decoction (EZF) group.

[0241] 2.3 Effects of the Erzhi Decoction on the fat content of the ovariectomized mice

[0242] Results are shown in FIG. 8 and FIG. 9 .

[0243] Results show that the abdominal fat content of the ovariectomized mice is significantly higher than that of the sham operation group (P<0.01), and the Erzhi Decoction, the Erzhi Decoction (XGY) and the Erzhi Decoction (XF) can significantly reduce the abdominal fat content (P<0.01). Meanwhile, the body fat composition of the ovariectomized mice is significantly higher than that of the sham operation group (P<0.01), and the Erzhi Decoction, the Erzhi Decoction (XGY) and the Erzhi Decoction (XF) can significantly reduce the body fat composition of the ovariectomized mice (P<0.01). In addition, FIG. 8 Results show that the Erzhi Decoction (XF) has a stronger effect on preventing and treating menopausal obesity than the Erzhi Decoction (EZF), indicating that the Erzhi Decoction (XF) has a stronger effect on preventing and treating menopausal obesity.

[0244] 2.4 Effects of the Erzhi Decoction on the LDL-C level of the ovariectomized mice

[0245] Compared with the sham operation group, the serum LDL-C level of the model group is increased, and the Erzhi Decoction, the Erzhi Decoction (XGY) and the Erzhi Decoction (XF) all have the effect of reducing LDL-C FIG. 10 .

[0246] 2.5 Effects of the Erzhi Decoction on the bone mineral density of the ovariectomized mice

[0247] The bone mineral density of the femur of the mice was detected by a dual-energy X-ray bone densitometer, and the results are shown in FIG. 11 FIG. 1 FIG. 2 FIG. 3 to FIG. 5 FIG. 6 FIG. 7 FIG. 6 to FIG. 7 FIG. 8 FIG. 9 FIG. 8 FIG. 10 FIG. 11 .

[0248] Results show that the bone mineral density (BMD) of the femur of the mice in the model group is significantly lower than that of the sham operation group (P<0.01). The Erzhi Decoction, the Erzhi Decoction (XGY) and the Erzhi Decoction (XF) can all increase the bone mineral density of the femur (P<0.05 or P<0.01). Results also show that the Erzhi Decoction (XGY) has a more obvious effect on increasing the bone mineral density than the Erzhi Decoction (EZF) group; the effect of the Erzhi Decoction (XGY) is even better than that of the Erzhi Decoction (XF) which is extracted by a combined extraction process of 4 traditional Chinese medicines.

[0249] References

[0250] [1]Liu E, Zhou Y. Efficacy of estradiol drospirenone tablets in hormone replacement therapy for menopausal syndrome [J]. Chinese Journal of Gerontology, 2014, 26(19): 5566-5567.

[0251] [2] Chen W, Liu D, Jiang X. Clinical efficacy of Huayang acupuncture in the treatment of menopausal syndrome due to spleen-kidney yang deficiency [J]. Chinese Journal of Basic and Clinical Medicine of Traditional Chinese Medicine, 2016, 22(3): 401-403.

[0252] [3] Shen H, Xie Y. Risk factors of osteoporotic fracture and research status of risk assessment of TCM syndrome elements [J]. Chinese Journal of Orthopedics, 2014, 27(3): 261-265.

[0253] [4] Guo H, Yu Y, Chen W, Yu B, Qi Q. Analysis of risk factors for postmenopausal osteoporosis and discussion of preventive measures [J]. Chinese Journal of Rehabilitation Medicine, 2011, 26(5): 424-428.

[0254] [5] Huang J, Wang G, Li L. Effect observation of traditional Chinese and western medicine in the treatment of senile osteoporosis [J]. Chinese Journal of Osteoporosis, 2016, 22(12): 1573-1575+1584.

[0255] [6] Zhang J. Comparison of adverse reactions of traditional Chinese and western medicine in the treatment of depression [J]. Chinese Practical Medicine, 2010, 5(19): 130-131.

[0256] [7] Bai J. Clinical observation on hormone replacement therapy combined with alendronate sodium in the treatment of perimenopausal osteoporosis [J]. Clinical Medicine and Practice, 2017, 26(2): 107-109.

[0257] [8] Zou Y, Zuo Z, Zhao H, et al. Research progress on pharmacological effects of Erzhi pill [J]. Jiangxi Journal of Traditional Chinese Medicine, 2015, 46(03): 75-76+80.

[0258] [9] Liu T, Wang M. Research progress on chemical constituents and pharmacological effects of Ligustrum lucidum [J]. Chinese Journal of Experimental Prescriptions, 2014, 20(14): 228-234.

[0259]

[10] Fang Y, Li X, Zhang Z. Research progress on chemical constituents and pharmacological activities of Herba Ecliptae [J]. Strait Pharmaceutical Journal, 2015, 27(06): 1-3.

[0260] While the specific embodiments of the application have been described in detail, those skilled in the art will appreciate that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. The foregoing is intended to cover all modifications and alternatives within the scope of the present application. It is to be understood that the scope of the application fully encompasses other applications such as those that may arise to those who are skilled in the art. It is intended, therefore, that the scope of the application be limited only by the broadest interpretation of the appended claims to which they are fairly incident.

Claims

1. A pharmaceutical composition for preventing and treating osteoporosis, comprising the following components: 4-6 parts by weight of privet fruit 4-6 parts by weight of Eclipta prostrata 2-4 parts by weight of chicken blood vine, and Achyranthes bidentata 1-3 parts by weight.

2. The pharmaceutical composition according to claim 1, wherein the composition is as follows: Privet fruit 4.5-5.5 parts by weight Eclipta prostrata 4.5-5.5 parts by weight Chicken blood vine 2.5-3.5 parts by weight, and 1.5-2.5 parts by weight of Achyranthes bidentata.

3. The pharmaceutical composition according to claim 1, wherein the composition is as follows: Privet fruit 4.8-5.2 parts by weight Eclipta prostrata 4.8-5.2 parts by weight Chicken blood vine 2.8-3.2 parts by weight, and Achyranthes bidentata 1.8-2.2 parts by weight.

4. The pharmaceutical composition according to claim 1, wherein the composition is as follows: 5 parts by weight of privet fruit 5 parts by weight of Eclipta prostrata 3 parts by weight of chicken blood vine, and Two parts by weight of Achyranthes bidentata.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein the unit dose is 10-60g.

6. The pharmaceutical composition according to any one of claims 1 to 4, wherein the unit dose is 15-40g.

7. The pharmaceutical composition according to any one of claims 1 to 4, wherein the unit dose is 20-30g.

8. The pharmaceutical composition according to any one of claims 1 to 4, wherein the unit dose is 25g.

9. An extract for preventing and treating osteoporosis, prepared from the pharmaceutical composition according to any one of claims 1 to 8.

10. The extract according to claim 9, obtained by a preparation method comprising the following steps: (1) Extract the parts by weight of Ligustrum lucidum, Eclipta prostrata, Spatholobus suberectus and Achyranthes bidentata according to any one of claims 1 to 8 with water or ethanol solution to obtain an extract; (2) Concentrate the extract to obtain a concentrate, which is the extract.

11. The extract according to claim 10, characterized in that... Any one or more of the following items ①-⑧: ① In step (1), the extraction may be performed once or multiple times. When it is performed multiple times, the extracts from each extraction are combined. ② In step (1), the mixture of Ligustrum lucidum, Eclipta prostrata, Spatholobus suberectus and Achyranthes bidentata is extracted; or any one of the herbs and the mixture of the other three herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or any two herbs and the mixture of the other two herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or any one herb, another herb and the mixture of the other two herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or the four herbs are extracted separately to obtain each extract, and the extracts are combined or not combined. ③ In step (1), the concentration of ethanol is 10%-99%; ④ In step (1), the extraction is either reflux extraction or decoction; ⑤ In step (1), the extraction time is at least 0.5 hours; ⑥ In step (1), the amount of water or ethanol solution used is 5-20 times the amount calculated in mL / g; ⑦ In step (2), the concentration is reduced pressure concentration; ⑧ In step (2), the concentrate is an extract.

12. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 20%-90%.

13. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 30%-80%.

14. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 40%-80%.

15. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 50%-80%.

16. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 50%-70%.

17. The extract according to claim 10, wherein, In step (1), the concentration of ethanol is 60%-80%.

18. The extract according to claim 10, wherein, In step (1), the extraction time is at least 1 hour.

19. The extract according to claim 10, wherein, In step (1), the extraction time is at least 2 hours.

20. The extract according to claim 10, wherein, In step (1), the extraction time is 1-5 hours.

21. The extract according to claim 10, wherein, In step (1), the amount of water or ethanol solution used is 8-16 times the amount calculated in mL / g.

22. The extract according to any one of claims 10 to 21, wherein, Step (1) includes the following steps: Ligustrum lucidum and Eclipta prostrata were extracted separately to obtain Ligustrum lucidum extract and Eclipta prostrata extract respectively; the residue after Ligustrum lucidum extraction was extracted with a mixture of Spatholobus suberectus and Achyranthes bidentata to obtain Ligustrum lucidum, Spatholobus suberectus and Achyranthes bidentata extract.

23. The extract according to claim 22, wherein, Step (2) includes the following steps: The extracts of Ligustrum lucidum, Eclipta prostrata, and Ligustrum lucidum, Spatholobus suberectus, and Achyranthes bidentata were concentrated separately and then mixed or combined and concentrated to obtain the extract.

24. A pharmaceutical preparation for preventing and treating osteoporosis, comprising the extract as described in any one of claims 10 to 23, and one or more pharmaceutically acceptable excipients.

25. The pharmaceutical preparation according to claim 24, wherein, The unit dose of the pharmaceutical preparation is 10-60g, calculated based on the mass of the raw medicinal material.

26. The pharmaceutical preparation according to claim 24, wherein, The unit dose of the pharmaceutical preparation is 15-40g, calculated based on the mass of the raw medicinal material.

27. The pharmaceutical preparation according to claim 24, wherein, Based on the mass of the raw medicinal material, the unit dose of the pharmaceutical preparation is 20-30g.

28. The pharmaceutical preparation according to claim 24, wherein, Based on the mass of the raw medicinal material, the unit dose of the pharmaceutical preparation is 25g.

29. The pharmaceutical preparation according to any one of claims 24 to 28, wherein it is a pill, tablet, granule, capsule, tincture, or suspension.

30. Use of the pharmaceutical composition of any one of claims 1 to 8, the extract of any one of claims 9 to 23, or the pharmaceutical preparation of any one of claims 24 to 29 in the preparation of a medicament for treating and / or preventing osteoporosis.

31. The use according to claim 30, wherein, The osteoporosis referred to is either primary osteoporosis or secondary osteoporosis.

32. The use according to claim 30, wherein, The osteoporosis mentioned refers to postmenopausal osteoporosis.

33. The use according to claim 30, wherein, The osteoporosis mentioned refers to perimenopausal osteoporosis.

34. A method for preparing an extract for preventing and treating osteoporosis, comprising the following steps: (1) Extract the parts by weight of Ligustrum lucidum, Eclipta prostrata, Spatholobus suberectus and Achyranthes bidentata according to any one of claims 1 to 8 with water or ethanol solution to obtain an extract; (2) Concentrate the extract to obtain a concentrate, which is the extract.

35. The preparation method according to claim 34, characterized in that... Any one or more of the following items ①-⑧: ① In step (1), the extraction may be performed once or multiple times. When it is performed multiple times, the extracts from each extraction are combined. ② In step (1), the mixture of Ligustrum lucidum, Eclipta prostrata, Spatholobus suberectus and Achyranthes bidentata is extracted; or any one of the herbs and the mixture of the other three herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or any two herbs and the mixture of the other two herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or any one herb, another herb and the mixture of the other two herbs are extracted separately to obtain each extract, and the extracts are combined or not combined; or the four herbs are extracted separately to obtain each extract, and the extracts are combined or not combined. ③ In step (1), the concentration of ethanol is 10%-99%; ④ In step (1), the extraction is either reflux extraction or decoction; ⑤ In step (1), the extraction time is at least 0.5 hours; ⑥ In step (1), the amount of water or ethanol solution used is 5-20 times the amount calculated in mL / g; ⑦ In step (2), the concentration is reduced pressure concentration; ⑧ In step (2), the concentrate is an extract.

36. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 20%-90%.

37. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 30%-80%.

38. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 40%-80%.

39. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 50%-80%.

40. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 50%-70%.

41. The preparation method according to claim 34, wherein, In step (1), the concentration of ethanol is 60%-80%.

42. The preparation method according to claim 34, wherein, In step (1), the extraction time is at least 1 hour.

43. The preparation method according to claim 34, wherein, In step (1), the extraction time is at least 2 hours.

44. The preparation method according to claim 34, wherein, In step (1), the extraction time is 1-5 hours.

45. The preparation method according to claim 34, wherein, In step (1), the amount of water or ethanol solution used is 8-16 times the amount calculated in mL / g.

46. ​​The preparation method according to any one of claims 34 to 45, wherein, Step (1) includes the following steps: Ligustrum lucidum and Eclipta prostrata were extracted separately to obtain Ligustrum lucidum extract and Eclipta prostrata extract respectively; the residue after Ligustrum lucidum extraction was extracted with a mixture of Spatholobus suberectus and Achyranthes bidentata to obtain Ligustrum lucidum, Spatholobus suberectus and Achyranthes bidentata extract.

47. The preparation method according to claim 46, wherein, Step (2) includes the following steps: The extracts of Ligustrum lucidum, Eclipta prostrata, and Ligustrum lucidum, Spatholobus suberectus, and Achyranthes bidentata were concentrated separately and then mixed or combined and concentrated to obtain the extract.

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