Composition containing pinoresinol diglucoside for anti-osteoporosis and application thereof

Abstract

The present invention provides a composition containing pinoresinol diglucoside for resisting osteoporosis and its application, wherein the composition is composed of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol components; the mass ratio of the pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol is 1:0.2-0.4:0.05-0.25. The composition provided by the present invention has stable quality and high safety, is suitable for long-term use, has good effect in treating osteoporosis, can be used for senile osteoporosis, and has a more significant effect of inhibiting the reduction of bone density in an osteoporosis model of ovariectomized female rats.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to an anti-osteoporosis composition containing pinoresinol diglucoside and application thereof. Background Art

[0002] Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and damage to bone microstructure, which leads to increased bone fragility and fractures. The World Health Organization defines osteoporosis as a progressive systemic bone disease characterized by low bone mass and deterioration of bone microstructure, which in turn increases bone fragility and susceptibility to fractures. The main pathological features are damage to bone microstructure, with thinning of trabecular structure, widening of gaps, and reduction in number as the main manifestations.

[0003] At present, the main clinical anti-osteoporosis drugs include estrogens, calcitonins, bisphosphonates, and macromolecular monoclonal antibodies. Among them, long-term use of estrogens will increase the incidence of breast cancer and endometrial hyperplasia; bisphosphonates are first-line anti-osteoporosis drugs that can specifically bind to hydroxyphospholipids in bones, inhibit osteoclast activity, and thus inhibit bone resorption. These drugs are used to treat osteoporosis, especially osteoporosis characterized by "bone loss and bone structure destruction, leading to increased bone fragility and fracture rate."

[0004] The main active ingredients for anti-osteoporosis are lignans, including oleagin, eugenol diglucoside, pinoresinol diglucoside and other compounds. Studies have shown that lignans have a certain effect in treating osteoporosis, among which pinoresinol diglucoside has anti-osteoporosis and blood pressure lowering effects.

[0005] The inventor disclosed an extract of Eucommia ulmoides and its application in treating osteoporosis in patent CN111686147A. The patent disclosed an extract of Eucommia ulmoides, which includes 20-50 parts of Eucommia ulmoides petroleum ether extract and 10-30 parts of Eucommia ulmoides ethanol extract by weight. In the implementation process of the patent, different extraction methods are used to extract the effective components of Eucommia ulmoides, which can improve the effective components of the medicine to different degrees. Since the solubility of different effective components in the solvent is different, the content of the effective components can be effectively adjusted. The extraction method used in the invention is simple and easy, has significant therapeutic effect in treating osteoporosis, and the long-term safety of the composition is excellent, but the active ingredients are still not fully understood, the quality control is difficult, and the stability between batches is not easy to monitor.

[0006] Therefore, there is an urgent need for a composition with stable quality, high safety, clear active ingredients and better anti-osteoporosis effect. Summary of the invention

[0007] The present invention aims at the problems existing in the prior art and provides an anti-osteoporosis composition containing pinoresinol diglucoside and its application. The composition comprises three components, namely pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol. When the composition is composed according to a certain proportion, the composition has a more significant effect of preventing or treating osteoporosis.

[0008] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0009] The invention provides an anti-osteoporosis composition containing pinoresinol diglucoside, which consists of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol components.

[0010] Preferably, the mass ratio of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol is 1:0.2-0.4:0.05-0.25.

[0011] More preferably, the mass ratio of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol is 1:0.2-0.4:0.08-0.2.

[0012] The present invention also provides a method for preparing the composition, which comprises mixing pinoresinol diglucoside, pinoresinol monoglucoside and a pinoresinol component to obtain a composition containing pinoresinol diglucoside.

[0013] The present invention also provides use of the above composition or the composition prepared by the above preparation method in preparing a drug for preventing or treating osteoporosis.

[0014] Preferably, the osteoporosis includes postmenopausal osteoporosis and senile osteoporosis.

[0015] The present invention also provides an anti-osteoporosis drug, comprising the above composition and a pharmaceutically acceptable carrier.

[0016] Preferably, the composition accounts for 0.1-70% by weight of the drug.

[0017] More preferably, the weight percentage of the composition to the drug is 0.1-50%.

[0018] Preferably, the daily dosage of the composition is 1.0-10 mg / kg body weight.

[0019] Wherein, the dosage object is an oral dosage for humans.

[0020] More preferably, the daily dosage of the composition is 2.0-8 mg / kg body weight.

[0021] Preferably, the dosage form of the drug includes tablets, capsules, powders, syrups, adhesives, suspensions, injections, capsules, and granules.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The composition containing pinoresinol diglucoside of the present invention has a more significant therapeutic effect on senile osteoporosis and osteoporosis in ovariectomized female rats, can significantly improve bone density, increase the number of trabeculae, and reduce the separation of trabeculae. The composition containing pinoresinol diglucoside has good safety, is suitable for long-term use, has clear ingredients, and is controllable in quality, and can meet the needs of clinical application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The μCT scanned trabecular structure diagram of the osteoporosis rat model in Example 1; wherein, A: sham operation group; B: model control group; C: positive control group; D: A group; E: B group; F: C group; G: D group; H: E group; I: F group; J: G group; K: H group; L: I group. DETAILED DESCRIPTION

[0025] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of protection claimed in this application, and those skilled in the art can make various changes and modifications to the invention of this application based on the disclosed content, which should also fall within the scope of protection claimed in this application.

[0026] It is worth noting that the raw materials used in the present invention are all common commercial products, and their sources are not specifically limited. The following raw material sources are for illustrative purposes:

[0027] The CAS number of alendronate sodium is 121268-17-5;

[0028] The CAS number of pinoresinol diglucoside is 63902-38-5;

[0029] The CAS number of pinoresinol monoglucoside is 69251-96-3;

[0030] The CAS number of pinoresinol is 487-36-5.

[0031] The structural formula of pinoresinol diglucoside described in the present invention is:

[0032]

[0033] The structural formula of the pinoresinol monoglucoside is:

[0034]

[0035] The structural formula of the pinoresinol is:

[0036]

[0037] Example 1: Study on the efficacy of the composition

[0038] 1. Experimental Animals

[0039] 160 SPF female SD rats, 7-8 weeks old, weighing 200±20g.

[0040] 2. Establishment of osteoporosis model

[0041] SPF female SD rats, 7-8 weeks old, were selected and 10 were randomly selected as the sham operation group. The rats were anesthetized by intraperitoneal injection of 4% chloral hydrate. Except for the sham operation group, which only had an abdominal opening without removing the ovaries, the remaining 150 rats were bilaterally ovariectomized. After surgery, 800,000 IU / kg of penicillin potassium was intraperitoneally injected once a day for 7 consecutive days to prevent postoperative infection. At the 5th week, the bone mineral density (BMD) of the lumbar spine and femur of each rat was measured by a small animal dual-energy X-ray bone density body composition analyzer (iNSiGHT VET DX). 40 rats with no significant decrease in bone density were eliminated, and the remaining 110 SD rats (10 rats in the sham operation group were not included) were randomly divided into groups, with 10 rats in each group (n=10) and fed with ordinary complete feed.

[0042] 3. Grouping and Dosage

[0043] Sham operation group: given normal diet, n = 10;

[0044] Model control group: given normal diet, n = 10;

[0045] Positive control group: alendronate sodium, gavage once a week, dose of 6 mg / kg, n = 10;

[0046] Group A (pinoresinol diglucoside, 70 mg / kg, n=10)

[0047] Group B (pinoresinol monoglucoside, 70 mg / kg, n=10)

[0048] Group C (pinoresinol, 70 mg / kg, n=10)

[0049] Group D (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.2:0.25, 63 mg / kg, n=10)

[0050] Group E (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.4:0.2, 63 mg / kg, n=10)

[0051] Group F (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.2:0.08, 63 mg / kg, n=10)

[0052] Group G (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.25:0.05, 63 mg / kg, n=10)

[0053] Group H (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.3:0.5, 63 mg / kg, n=10)

[0054] Group I (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:1:1, 63 mg / kg, n=10)

[0055] All groups were mixed according to the proportion of each group to obtain the corresponding composition. Each group of drugs was orally administered by gavage once a day for 16 consecutive weeks, and the positive control group was given once a week.

[0056] 4. Evaluation of bone density, trabecular structure and other indicators:

[0057] After the 16-week administration period, the femur and lumbar bone density of the rats were measured under anesthesia; blood was collected from the eye sockets to measure serum biochemical indicators; the rats were killed, the femurs were removed, and the trabecular structure was measured using Micro-CT. The above indicators were used to evaluate the efficacy of the composition against osteoporosis.

[0058] The instrument used to measure the femur and lumbar spine bone density of rats was an iNSiGHT VET DXA dual-energy X-ray absorptiometry instrument produced by OsteoSys, South Korea; the kits for measuring serum biochemical indicators ALP, blood phosphorus and blood calcium were purchased from Nanjing Jiancheng Bioengineering Institute, with item numbers A059-2-2, C006-1-1 and C004-2-1, respectively; the instrument for measuring trabecular bone structure was named: Skyscan1174 X-Ray Microtomograph (μCT), produced by Bruker, Belgium; the detection conditions were as follows: sample scanning parameters: voltage 50 kV, current 800 μA, rat femur was scanned with a scanning resolution of 12 μm and a field of view size of 1304×1024.

[0059] 5. Results

[0060] Table 1 Results of bone mineral density measurement of femur and lumbar vertebrae in rats of each group after 16 weeks of administration (χ±SD, n=10)

[0061] Group <![CDATA[Lumbar bone mineral density (g / cm 2 )]]> <![CDATA[Femoral bone density (g / cm 2 )]]> Sham operation group 0.231±0.014 0.282±0.014 Model control group <![CDATA[0.163±0.015 ## ]]> <![CDATA[0.253±0.012 ## ]]> Positive control group 0.198±0.011* 0.272±0.010* Group A 0.196±0.010* 0.273±0.011* Group B 0.201±0.010* 0.269±0.012* Group C 0.205±0.012* 0.271±0.013* Group D <![CDATA[0.232±0.008** ▲ ]]> 0.285±0.010**▲ Group E <![CDATA[0.231±0.011** ▲ ]]> <![CDATA[0.288±0.009** ▲ ]]> Group F 0.229±0.012**▲ <![CDATA[0.286±0.013** ▲ ]]> Group G <![CDATA[0.230±0.012** ▲ ]]> <![CDATA[0.284±0.015** ▲ ]]> Group H 0.198±0.015* 0.272±0.019 Group I 0.201±0.014* 0.268±0.014*

[0062] Note: * indicates P<0.05 compared with the model control group; ** indicates P<0.01 compared with the model control group; ## Compared with the sham operation group, P < 0.01 ▲ Indicates P < 0.05 compared with the positive control group.

[0063] As can be seen from Table 1, after castration, the bone density of female rats was significantly reduced. The bone density of lumbar vertebrae and femur of rats in the model control group were 0.163±0.015 and 0.253±0.012, respectively, which were significantly lower than 0.231±0.014 and 0.282±0.014 of the sham operation group, respectively, indicating that the osteoporosis rat model was successfully established.

[0064] After 16 weeks of continuous administration, alendronate sodium in the positive group significantly increased the bone density of the lumbar vertebrae and femur of rats to 0.198±0.011 and 0.272±0.010, which was significantly different from the corresponding bone density of the model control group (P<0.05). Group A, Group B and Group C were single-administration groups of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol, respectively. From the results of bone density measurement, the three active ingredients could significantly increase the bone density of lumbar vertebrae and femur of the tested rats, among which the bone density of lumbar vertebrae increased to 0.196±0.010, 0.201±0.010 and 0.205±0.012, respectively, which was comparable to the positive control drug alendronate sodium, while the bone density of femur increased to 0.273±0.011, 0.273±0.011 and 0.269±0.012, which was significantly different from the femur bone density of the model control group (P<0.05), indicating that the three monomer active ingredients all had a certain anti-osteoporosis effect, and the activity intensity was comparable to that of the positive control drug alendronate sodium. The three components were further used in a certain mass ratio to form a composition, such as the test drugs in groups D, E, F and G. After 16 weeks of administration, the bone density measurement results showed that the lumbar vertebrae bone density of the rats in the four groups was 0.232±0.008, 0.231±0.011, 0.229±0.012 and 0.230±0.012, respectively, which were significantly higher than those in the model control group (P<0.01) and higher than those in the positive control group (P<0.05); and the femoral bone density measurement results were also significantly improved. The results are shown in Table 1. The femoral bone density of groups D, E, F and G was 0.285±0.010, 0.288±0.009, 0.286±0.013 and 0.284±0.015, respectively, which were higher than the femoral bone density of rats in the model control group and the positive control group, indicating that these four groups have good anti-osteoporosis effects. In this experiment, the ratios of pinoresinol diglucoside: pinoresinol monoglucoside: pinoresinol in the compositions of groups H and I were 1:0.3:0.5 and 1:1:1, respectively. After 16 weeks of administration, the bone density of the lumbar vertebrae and femur of the rats was significantly increased compared with the corresponding bone density of the model control group, with significant statistical differences (P<0.05). However, the lumbar vertebrae bone density of rats in groups H and I was 0.198±0.015 and 0.201±0.014, which were significantly lower than those in groups D, E, F and G, while the femoral bone density of rats in groups H and I was 0.272±0.019 and 0.268±0.014, which were also lower than those in groups D, E, F and G, indicating that when the combination ratio of the three active ingredients was 1:0.3:0.5 or 1:1:1, the anti-osteoporosis efficacy was not significantly improved.

[0065] The above results show that the composition containing pinoresinol diglucoside significantly improves the reduction in bone density of castrated rats within the ratio range of pinoresinol diglucoside: pinoresinol monoglucoside: pinoresinol = 1: 0.2-0.4: 0.05-0.25, especially in groups D, E, F and G, and has a stronger therapeutic effect than the positive drug alendronate sodium.

[0066] Table 2 Changes in trabecular structure of femur in rats of each group after 16 weeks of administration (χ±SD, n=10)

[0067]

[0068]

[0069] Note: *Compared with the model group, P < 0.05; **Compared with the model group, P < 0.01; ## Compared with the sham operation group, P<0.01;★Compared with the positive control group, P<0.05.

[0070] After castration, the femoral microstructure of rats was destroyed, the number of trabeculae per unit size was significantly reduced, the separation of trabeculae increased, and the bone volume fraction decreased significantly. As shown in Table 2, the bone volume fraction BV / TV of the model control group decreased to 17.8±2.4%, which was significantly lower than 35.6±6.8% of the sham operation group, the number of trabeculae Tb.N in the model group decreased to 1.58±0.33 (1 / mm), which was significantly lower than 4.64±0.57 (1 / mm) in the sham operation group, and the separation of trabeculae increased significantly (0.81±0.11, compared with 0.34±0.04 in the model group, P<0.01), indicating that the osteoporosis model of rats was successfully established in this experiment.

[0071] After 16 weeks of administration, the rats in the positive group were given alendronate intervention, and the bone volume fraction BV / TV and the number of trabeculae Tb.N (1 / mm) increased to 27.4±5.3% and 2.64±0.42 (1 / mm), respectively. Both values ​​were statistically different from the corresponding values ​​in the model control group, P<0.05, indicating that alendronate can significantly increase the number of trabeculae per unit size; trabecular separation is an important parameter for measuring the health of bone microstructure. After 16 weeks of alendronate administration, the Tb.Sp of the positive control group decreased from 0.81±0.11 in the model control group to 0.52±0.12, and the difference was statistically significant (P<0.05). After 16 weeks of administration, the rat femoral bone volume fraction and the number of trabeculae in the administration groups D, E, F and G, in which the composition containing pinoresinol diglucoside provided by the present invention is the test drug, are significantly higher than those in the model control group (P<0.01), and higher than those in the group A, B and C, in which the three active ingredients in the composition are used alone, and the difference is biologically significant; the trabecular separation of rats in the groups D, E, F and G containing pinoresinol diglucoside composition is significantly lower than that in the model control group, and the difference is statistically significant. Compared with the positive drug sodium alendronate, the groups D, E, F and G containing pinoresinol diglucoside composition are better than the positive control group, and the difference is statistically significant (P<0.05). When the mass ratio of pinoresinol diglucoside:pinoresinol monoglucoside:pinoresinol was 1:0.3:0.5 or 1:1:1, corresponding to group H and group I in this experiment, it can be seen that after 16 weeks of administration, the femoral bone volume fraction, the number of trabeculae and the degree of bone separation of the rats were significantly improved compared with the model control group (P<0.01), but the efficacy was equivalent to that of the positive control drug alendronate sodium, and the intensity of action was not as good as that of groups D, E, F and G at the same dose, indicating that the composition containing pinoresinol diglucoside can only significantly increase the trabecular volume fraction and the number of trabeculae per unit length of the femur of osteoporotic rats at a certain combination ratio, and reduce the degree of trabecular separation.

[0072] Table 3 Changes of serum biochemical indexes in rats in each group after 16 weeks of administration

[0073]

[0074]

[0075] Note: *P<0.05 compared with the model group, # Compared with the sham operation group, P<0.05.

[0076] As shown in Table 3, after 16 weeks of administration, compared with the model control group, the activity of alkaline phosphatase ALP of rats in the positive control group, D, E, F, and G groups of the composition containing pinoresinol diglucoside was significantly reduced, indicating that both the tested drug and the positive drug alendronate sodium can reduce the ALP of osteoporotic rats. No significant differences were found in the blood phosphorus and blood calcium of rats in each test group.

[0077] The composition containing pinoresinol diglucoside has the effect of significantly increasing the bone density of castrated female rats, showing that it has a significant anti-osteoporosis effect, increasing the number and thickness of trabeculae and reducing the separation degree, showing that it has a significant effect of treating osteoporosis.

[0078] Example 2: Drug efficacy test for anti-bone density reduction in aged male rats

[0079] 1. Experimental Animals

[0080] 180 SPF male SD rats, aged 7-8 weeks, weighing (200±20) g.

[0081] 2. Establishment of osteoporosis model

[0082] Male SD rats, 7-8 weeks old, were selected and fed with normal feed until 18 months old. The bone mineral density (BMD) of the lumbar spine and femur of the rats was measured using a small animal dual-energy X-ray bone density body composition analyzer (iNSiGHT VET DX). 60 rats with no significant decrease in bone density were eliminated, and the remaining 120 SD rats were randomly divided into groups, 10 rats in each group, and fed with ordinary full-price feed. Before the end of the experiment, 10 male SD rats, 8 weeks old, were purchased as a normal control group.

[0083] 3. Grouping and Dosage

[0084] Normal control group: given normal diet, n = 10;

[0085] Model control group: given normal diet, n = 10;

[0086] Positive control group: alendronate sodium, oral gavage once a week, dose of 6 mg / kg, n = 10;

[0087] Group Ⅰ (pinoresinol diglucoside, 60 mg / kg, n=10)

[0088] Group II (pinoresinol monoglucoside, 60 mg / kg, n=10)

[0089] Group III (pinoresinol, 60 mg / kg, n=10)

[0090] Group IV (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.2:0.25, 50.4 mg / kg, n=10)

[0091] Group V (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.4:0.2, 50.4 mg / kg, n=10)

[0092] Group VI (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.2:0.08, 50.4 mg / kg, n=10)

[0093] Group VII (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.25:0.05, 50.4 mg / kg, n=10)

[0094] Group VIII (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:0.3:0.5, 50.4 mg / kg, n=10)

[0095] Group IX (pinoresinol diglucoside + pinoresinol monoglucoside + pinoresinol, 1:1:1, 50.4 mg / kg, n=10)

[0096] Group X (eucommia petroleum ether extract-eucommia ethanol extract described in Example 1 of CN111686147A, 2:1, 90 mg / kg, n=10)

[0097] All groups were mixed according to the proportions of each group to obtain the corresponding composition, and each group of drugs was orally administered by gavage for 12 consecutive months, once a day, with the same administration time each time.

[0098] 4. Bone density measurement and results

[0099] After 12 months of administration, the femur and lumbar spine bone density of the rats were measured under anesthesia to evaluate the anti-osteoporosis efficacy of the composition.

[0100] The instrument used to measure the femur and lumbar spine bone density of rats was the iNSiGHT VET DXA dual-energy X-ray absorptiometry produced by OsteoSys, South Korea.

[0101] Table 4 Bone mineral density of femur and lumbar vertebrae of rats in each group after 12 months of administration (χ±SD, n=10)

[0102]

[0103]

[0104] Note: * indicates P<0.05 compared with the model control group; ** indicates P<0.01 compared with the model control group; #Indicates P < 0.05 compared with the normal control group; ## Compared with the normal control group, P < 0.01.

[0105] As can be seen from Table 4, after castration, the lumbar vertebrae bone density and femoral bone density of rats were significantly lower than those of the normal control group (P<0.01), indicating that the osteoporosis model of rats was successfully established.

[0106] After 12 months of continuous administration, the positive group rats were given alendronate sodium intervention, and the lumbar vertebrae bone density and femoral bone density increased to 0.235±0.015 and 0.288±0.014, respectively, which were higher than the lumbar vertebrae bone density of 0.214±0.014 and femoral bone density of 0.254±0.018 in the model group. The difference was statistically significant (P<0.05), indicating that alendronate sodium can reverse the decreased bone density in the model rats. Groups Ⅰ, Ⅱ and Ⅲ were single-dose groups of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol, respectively. After 12 months of administration, the lumbar vertebrae and femoral bone density of the rats were improved to a certain extent compared with the model control group, indicating that the three lignan components alone have a certain anti-osteoporosis effect. Compared with the positive drug alendronate sodium, the three compounds have a slightly weaker degree of improving the bone density of the lumbar vertebrae and femur of rats, and are biologically less effective than alendronate sodium, but there is no statistically significant difference. The tested drugs in groups IV, V, VI and VII were pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol, respectively. The three components were combined in a certain ratio, and the combination ratio was 1:0.2:0.25, 1:0.4:0.2, 1:0.2:0.08 and 1:0.25:0.05. After 12 months of continuous administration, the lumbar bone density of the four groups of rats was 0.234±0.010, 0.237±0. The bone mineral density of group I, group II and group III were 0.014, 0.233±0.012 and 0.238±0.019, and the femoral bone mineral density were 0.294±0.017, 0.292±0.019, 0.298±0.016 and 0.296±0.014, respectively, which were significantly higher than those of the model control group. Compared with the positive control group, the anti-osteoporosis effect was equivalent. Compared with the corresponding bone mineral density values ​​of group I, group II and group III, the bone density increased by about 10%, which was of biological significance.

[0107] The combination of the three lignan components in a certain ratio can form a more effective anti-osteoporosis synergistic effect, and the mass ratio of pinoresinol diglucoside: pinoresinol monoglucoside: pinoresinol is 1:0.2-0.4:0.05-0.25. To further verify the ratio range, this experiment added groups VIII and IX, and the drugs given to them were the three lignan components in a ratio of 1:0.3:1 and 1:0.5:0.5, respectively. The data of lumbar vertebrae bone density and femoral bone density of rats after continuous administration for 12 months are shown in Table 4. It can be seen that the lumbar vertebrae and femoral bone density of rats in groups VIII and IX were significantly higher than the corresponding bone density of the model control group (except that the femoral bone density of group VIII did not show statistical difference compared with the model control group), indicating that The composition has an anti-osteoporosis effect, but compared with the positive control group, the anti-osteoporosis effect of the test drug in group VIII and group IX is not as good as that of alendronate sodium. Although there is no statistical difference, the bone density is biologically lower than that in the positive control group, and no good therapeutic advantage is shown. Compared with group IV, group V, group VI and group VII, the anti-bone density reduction effect of group VIII and group IX is significantly weakened, indicating that the significantly increased mass proportion of pinoresinol monoglucoside and pinoresinol in the composition is not beneficial to the anti-osteoporosis activity. This study also set up a X group, and the test drug used was a composition of Eucommia petroleum ether extract and Eucommia ethanol extract in a mass ratio of 2:1. The results showed that after 12 months of continuous gavage, the bone density of the lumbar vertebrae and femur of the rats in Group X were 0.220±0.016 and 0.257±0.013, respectively. Although both were significantly higher than the corresponding bone density values ​​of the model control group, they were not as good as the anti-osteoporosis effect of the pinoresinol diglucoside composition provided by the present invention. Even at a significantly increased dosage of 90 mg / kg, its therapeutic effect was still weaker than that of the composition provided by the present invention.

[0108] In conclusion, the composition provided by the present invention significantly improves the reduction of bone density in rats after castration within the ratio range of pinoresinol diglucoside: pinoresinol monoglucoside: pinoresinol = 1: 0.2-0.4: 0.05-0.25, and has a more significant therapeutic effect than the positive drug alendronate sodium.

[0109] The above composition can be made into tablets, capsules or granules. The specific method is: weigh 10g of the composition containing pinoresinol diglucoside, add 1.8g starch and 0.2g magnesium stearate, mix well, and make tablets, capsules or granules after granulation.

[0110] The above composition can be made into capsules, and the specific method is: weigh 10g of the composition containing pinoresinol diglucoside, add 4g of pre-melted starch, mix evenly, granulate, sieve, and fill capsules.

[0111] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. An anti-osteoporosis composition containing pinoresinol diglucoside, characterized in that: The invention is composed of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol components, wherein the mass ratio of the pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol is 1:0.2-0.4:0.05-0.

25.

2. The composition according to claim 1, characterized in that: The mass ratio of pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol is 1:0.2-0.4:0.08-0.

2.

3. A method for preparing the composition according to any one of claims 1 to 2, characterized in that: The preparation method comprises the steps of mixing pinoresinol diglucoside, pinoresinol monoglucoside and pinoresinol components to obtain a composition containing pinoresinol diglucoside.

4. Use of the composition according to any one of claims 1 to 2 or the composition prepared by the preparation method according to claim 3 in preparing a drug for preventing or treating osteoporosis.

5. The use according to claim 4, characterized in that: The osteoporosis includes postmenopausal osteoporosis and senile osteoporosis.

6. An anti-osteoporosis drug, characterized in that: The invention comprises the composition according to any one of claims 1 to 2 and a pharmaceutically acceptable carrier.

7. The drug according to claim 6, characterized in that: The weight percentage of the composition to the drug is 0.1-70%.

8. The drug according to claim 7, characterized in that: The dosage forms of the medicine include tablets, capsules, powders, syrups, suspensions, injections and granules.

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