CN105168272A - Application of pharmaceutical composition to preparation of drug for treating osteoporosis - Google Patents

Abstract

The invention belongs to the field of traditional Chinese medicines and particularly relates to an application of pharmaceutical composition to preparation of a drug for treating osteoporosis. The pharmaceutical composition comprises raw preparation materials in parts by weight as follows: 50-80 parts of purslane herbs, 5-12 parts of stilbene glucoside, 4-10 parts of kaempferol and 4-12 parts of quercetin. The drug formula is reasonable, the synergistic effect is high, the drug is used for treating the osteoporosis in a compatible manner, and clinical tests prove that the drug has the very significant effect.

Description

A kind of pharmaceutical composition is for the preparation of the purposes in treatment medicine for treating osteoporosis

Technical field

The invention belongs to the field of Chinese medicines, particularly relate to a kind of pharmaceutical composition for the preparation of the purposes in treatment medicine for treating osteoporosis.

Background technology

Osteoporosis is a kind of with bone amount minimizing, and the fine structure of bone destroys as feature, and the fragility causing bone increases, and is easy to a kind of general osteopathia of fracturing.Osteoporosis can be divided into three major types: primary osteoporosis, secondary osteoporosis and idiopathic osteoporosis.First kind primary osteoporosis can be divided into again osteoporosis (I type) and the senile osteoporosis (II type) of menopausal women; Equations of The Second Kind is secondary osteoporosis, and it is by other diseases (as renal failure, excess thyroid hormone or leukemia), or some factors such as medicine (as steroid) the osteoporosis of being brought out; 3rd class is idiopathic osteoporosis, and be more common in teenager or the adult in 8-14 year, mostly have hereditary family history, women is more than male, and the osteoporosis that forepart pregnant women and age of sucking occur also can list idiopathic osteoporosis in.

Chinese invention patent 200810198306 discloses a kind of compositions of the Effective Component of Chinese Medicine for preventing and treating diseased associated with cerebral ischemia injury, but openly not may be used for treating other diseases.

Chinese patent application 201410797516.3 discloses a kind of medicine being used for the treatment of osteoporosis, and this Chinese medicine composition is obtained by following raw material: Ramulus et Folium Psychotriae Serpentis 24-48 part, Carnis Coturnicis japonicae 22-47 part, Radix calophylli membranacei 20-44 part, Radix seu Caulis Verntilaginis Leiocarpae 20-44 part, Herba Thesii 17-42 part, Mytilus 16-40 part, Herba Sambuci Adnatae 16-40 part, Radix Flemingiae Philippinensis 15-35 part, Parmelia saxatilis Ach. 15-35 part, Herba Hoyae lancilimbae 14-32 part, Radix Angelicae Sinensis 14-32 part, Caulis Piperis Boehmeriaefolii 12-30 part.This Chinese medicine composition has keeps fit effect of strong bone, blood yiqi, but this traditional Chinese medicine composite not easily obtains, and preparation technology is more complicated, is unfavorable for batch, produces fast.

Chinese patent application 200910230776.1 discloses a kind of Chinese medicine composition for the treatment of osteoporosis, this Chinese medicine composition is obtained by following raw material: Herba Epimedii 15-20g, Cortex Eucommiae 10-15g, Radix Notoginseng 5-10g, Radix Astragali 10-15g, Ramulus Cinnamomi 10-15g, Rhizoma Chuanxiong 5-10g, Radix Rehmanniae Preparata 5-10g, Radix Angelicae Sinensis 10-15g, Rhizoma Drynariae 10-15g, Radix Angelicae Dahuricae 10-15g.It is simple, reasonable that this Chinese medicine composition has preparation, the advantages such as good effect, but strengthening the tendons and bones, blood nourishing and calcium replenishing aspect effect are not very remarkable.

Summary of the invention

The technical problem to be solved in the present invention is to provide a kind of pharmaceutical composition for the preparation of the purposes in treatment medicine for treating osteoporosis, this pharmaceutical composition has effect of invigorating the kidney and strengthening the bones, blood circulation promoting and blood stasis dispelling and replenishing QI to invigorate the spleen, also there is good effect, cost is low, preparation technology is simple, the advantages such as cure rate is high, taking convenience.Described pharmaceutical composition can utilize modern pharmaceutical technology to make to facilitate easy-to-use finished product preparation.

Prove through the test of pesticide effectiveness, pharmaceutical composition of the present invention can also treat osteoporosis, and therapeutic effect is obvious, toxic and side effects is little, the therapeutic effect persistent period is long, slow down the misery of patients with osteoporosis greatly, significantly improve the compliance of sufferers of osteoporosis face, and improve the quality of life of patient.

This pharmaceutical composition comprises the raw materials of following parts by weight: Herba Portulacae 50-80 part, stilbene glucoside 5-12 part, kaempferol 4-10 part and Quercetin 4-12 part.

Preferably, described pharmaceutical composition comprises the raw materials of following parts by weight: Herba Portulacae 50 parts, stilbene glucoside 5 parts, kaempferol 4 parts and Quercetin 4 parts.

Preferably, described pharmaceutical composition comprises the raw materials of following parts by weight: Herba Portulacae 80 parts, stilbene glucoside 12 parts, kaempferol 10 parts and Quercetin 12 parts.

Preferably, described pharmaceutical composition comprises the raw materials of following parts by weight: Herba Portulacae 60 parts, stilbene glucoside 8 parts, kaempferol 8 parts and Quercetin 10 parts.

Preferably, described pharmaceutical composition is made into capsule, tablet, granule or pill.

Accordingly, the preparation technology of pharmaceutical composition of the present invention comprises the following steps:

A) Herba Portulacae is got, wash away impurity, crushed after being dried, cross 60-80 mesh sieve, adding medical material gross weight 8-10 times amount volume fraction is the ethanol of 60-80%, microwave extraction 8-15 minute, microwave power is 240-300W, and Extracting temperature is 40-60 DEG C, filters and retains Herba Portulacae medicinal residues, the extractum that relative density is 1.20-1.25 is surveyed, obtained Herba portulacae extract at filtrate reduced in volume to 60 DEG C;

B) take stilbene glucoside, kaempferol and Quercetin, add described Herba Portulacae residue, be ground into fine powder, after mixing, obtain fine powder compositions;

C) described fine powder compositions is added in described Herba portulacae extract, mixing, drying under reduced pressure, pulverize, cross 80-100 mesh sieve, to obtain final product.

Found the impact of rat bone density experiment by pharmaceutical composition of the present invention, pharmaceutical composition of the present invention has and improves osteoporosis, improves effect of bone density.This experiment adopts QIANGGU JIAONANG as a control group, the main component of QIANGGU JIAONANG comprises Process of Total Flavonoids in Drynaria Fortunei, there is effect of the kidney invigorating, bone strengthening, strong muscle, pain relieving, be used for the treatment of the Kidney-Yang Deficiency Syndrome of primary osteoporosis, bone amount minimizing patient, by treating comparing of the therapeutic effect in osteoporosis with pharmaceutical composition of the present invention, embodying the curative effect of pharmaceutical composition of the present invention in treatment osteoporosis.In addition, to rat oral gavage retinoic acid, retinoic acid is the growth of the metabolic intermediate of vitamin A in human body, major effect bone, passes through injectable drug, and measure the bone density of rat, can find out medicine for treatment osteoporosis rat effect, another inventor surprisingly, the femur volume of the rat of medicine group of the present invention is compared with model group, have the difference of remarkable shape, femur dry weight, ash weight, bone calcium and bone density then have extremely significant difference compared with model group; In addition, the femur volume of the rat of BUSHEN JIANGU JIAONANG matched group and medicine group of the present invention, dry weight, ash is heavy, bone calcium is suitable with bone density.Visible, the rat bone loss that pharmaceutical composition of the present invention can obviously suppress retinoic acid to cause, improves osteoporosis, improves bone density.

Found the clinical observation on the therapeutic effect of osteoporosis clinical volunteers patient by pharmaceutical composition of the present invention, pharmaceutical composition of the present invention has good effect, obvious effective rate advantages of higher.The patient of this clinical trial be 20-80 year patient, because osteoporosis can occur in all age group, so the larger patient of the range of choice is as subjects, at present, the drug main for the treatment of osteoporosis will comprise calcium preparation, chemical drugs and Chinese patent medicine, this test adopts BUSHEN JIANGU JIAONANG as a control group, and the main component of BUSHEN JIANGU JIAONANG comprises Radix Rehmanniae Preparata, Fructus Corni, Rhizoma Dioscoreae, Rhizoma Cibotii, Herba Epimedii, Radix Angelicae Sinensis, Rhizoma Alismatis, Cortex Moutan, Poria and Concha Ostreae, have nourishing the liver and kidney, effect of strengthening the tendons and bones, for the symptom such as deficiency of the liver and kindey of primary osteoporosis, by comparing with medicine composite for curing effect of the present invention, embody the curative effect of pharmaceutical composition of the present invention in treatment osteoporosis, make inventor surprisingly, the obvious effective rate of pharmaceutical composition of the present invention is 80%, and total effective rate is 92%, far above matched group, visible, pharmaceutical composition good effect of the present invention, obvious effective rate is high, can as the drug use for the treatment of osteoporosis.

Compared with prior art, the present invention has following technical advantage:

1, pharmaceutical composition of the present invention is in treatment osteoporosis, and have increase bone density, the effect of bone calcium, the patient of each age group all can use;

2, pharmaceutical composition of the present invention is natural pure Chinese medicinal preparation, and toxic and side effects is little;

3, pharmaceutical composition of the present invention has effect of invigorating the kidney and strengthening the bones, blood circulation promoting and blood stasis dispelling and replenishing QI to invigorate the spleen, also has good effect, and cost is low, and preparation technology is simple, the advantages such as obvious effective rate is high, taking convenience.

Detailed description of the invention

It will be understood by those skilled in the art that technology disclosed in following examples represents the technology playing good action in the practice of the invention of the present inventor's discovery.But, many changes can be made in disclosed specific embodiments, and still obtain same or analogous result, and not depart from the spirit and scope of the present invention.

Part I drug combination preparation of the present invention and preparation method thereof

Embodiment 1

Raw material is taken: Herba Portulacae 50 parts, stilbene glucoside 5 parts, kaempferol 4 parts and Quercetin 4 parts by following parts by weight.

Preparation method:

A) Herba Portulacae is got, wash away impurity, crushed after being dried, cross 60 mesh sieves, adding medical material gross weight 8 times amount volume fraction is the ethanol of 60%, microwave extraction 8 minutes, microwave power is 240W, and Extracting temperature is 40 DEG C, filters and retains Herba Portulacae medicinal residues, the extractum that relative density is 1.20 is surveyed, obtained Herba portulacae extract at filtrate reduced in volume to 60 DEG C;

B) take stilbene glucoside, kaempferol and Quercetin, add described Herba Portulacae residue, be ground into fine powder, after mixing, obtain fine powder compositions;

C) described fine powder compositions is added in described Herba portulacae extract, mixing, drying under reduced pressure, pulverize, cross 80 mesh sieves, to obtain final product.

Add starch, 5% gelatin solution and distilled water, be pressed into thin slice, be ground into granule, obtain the granule of pharmaceutical composition.

Embodiment 2

Raw material is taken: Herba Portulacae 80 parts, stilbene glucoside 12 parts, kaempferol 10 parts and Quercetin 12 parts by following parts by weight.

Preparation method:

A) Herba Portulacae is got, wash away impurity, crushed after being dried, cross 80 mesh sieves, adding medical material gross weight 10 times amount volume fraction is the ethanol of 80%, microwave extraction 15 minutes, microwave power is 300W, and Extracting temperature is 60 DEG C, filters and retains Herba Portulacae medicinal residues, the extractum that relative density is 1.25 is surveyed, obtained Herba portulacae extract at filtrate reduced in volume to 60 DEG C;

B) take stilbene glucoside, kaempferol and Quercetin, add described Herba Portulacae residue, be ground into fine powder, after mixing, obtain fine powder compositions;

C) described fine powder compositions is added in described Herba portulacae extract, mixing, drying under reduced pressure, pulverize, cross 100 mesh sieves, to obtain final product.

Add starch, lactose, 20% gelatin solution, dried starch and distilled water, add lubricant after combination drying, tabletting, coating, obtain the tablet of pharmaceutical composition.

Embodiment 3

Raw material is taken: Herba Portulacae 60 parts, stilbene glucoside 8 parts, kaempferol 8 parts and Quercetin 10 parts by following parts by weight.

Preparation method:

A) Herba Portulacae is got, wash away impurity, crushed after being dried, cross 80 mesh sieves, adding medical material gross weight 9 times amount volume fraction is the ethanol of 70%, microwave extraction 10 minutes, microwave power is 280W, and Extracting temperature is 50 DEG C, filters and retains Herba Portulacae medicinal residues, the extractum that relative density is 1.25 is surveyed, obtained Herba portulacae extract at filtrate reduced in volume to 60 DEG C;

B) take stilbene glucoside, kaempferol and Quercetin, add described Herba Portulacae residue, be ground into fine powder, after mixing, obtain fine powder compositions;

C) described fine powder compositions is added in described Herba portulacae extract, mixing, drying under reduced pressure, pulverize, cross 100 mesh sieves, to obtain final product.

Add starch, lactose, 5% gelatin solution, dried starch and distilled water, mixing, dry, pulverize into fine powder, incapsulates in shell, obtain the capsule preparations of pharmaceutical composition.

Part II pharmaceutical composition pharmacodynamic study of the present invention

Pharmaceutical composition of the present invention is tested the impact of rat bone density

1, experiment material:

(1) laboratory animal: SD rat, 180 ~ 220g, male and female half and half, are provided by Zhongshan University's Experimental Animal Center.

(2) Experimental agents: the pharmaceutical composition that the embodiment of the present invention 1 ~ 3 prepares; QIANGGU JIAONANG (Beijing Chinese medicine pharmaceutical Co. Ltd, accurate word Z20030007, the 0.25*30 grain/bottle of traditional Chinese medicines).

(3) experimental apparatus: UMSP-30 type microscope spectrophotometer, VIDAS Image analysis system.

2, experimental technique:

Get SD rat 60, be divided into 6 groups at random, often organize 10, be respectively blank group, model group (isometric(al) normal saline), medicine A group (embodiment 1 pharmaceutical composition 2.28g/kgd), medicine B group (embodiment 2 pharmaceutical composition 2.28g/kgd), medicine C group (embodiment 3 pharmaceutical composition 2.28g/kgd) and QIANGGU JIAONANG matched group (0.9g/kgd); Except blank group, the retinoic acid of rats difference gavage 0.06g/kg that every day is respectively organized to other, stop using after two weeks, and the simultaneously corresponding medicine of gavage, blank group and model group be gavage isometric(al) normal saline then, continuous use surrounding (retinoic acid stop using after, continue medication two weeks), after surrounding, by rat sacrificed by decapitation, take a blood sample, get bone, under fluorescence irradiates, with microscope spectrophotometer, tibia sectioning image is all inputted Image analysis system, in computer, carry out data and image procossing.

3, experimental result

Table 1 respectively group rat femur meterological change

Note: compare with blank group, ^△p < 0.05, ^{△ △}p < 0.01; Compare with model group, ^▲p < 0.05, ^{▲ ▲}p < 0.01.

4, conclusion

This experiment adopts QIANGGU JIAONANG as a control group, the main component of QIANGGU JIAONANG comprises Process of Total Flavonoids in Drynaria Fortunei, there is effect of the kidney invigorating, bone strengthening, strong muscle, pain relieving, be used for the treatment of the Kidney-Yang Deficiency Syndrome of primary osteoporosis, bone amount minimizing patient, by treating comparing of the therapeutic effect in osteoporosis with pharmaceutical composition of the present invention, embodying the curative effect of pharmaceutical composition of the present invention in treatment osteoporosis.In addition, to rat oral gavage retinoic acid, retinoic acid is the growth of the metabolic intermediate of vitamin A in human body, major effect bone, passes through injectable drug, and measure the bone density of rat, can find out medicine for treatment osteoporosis rat effect, another inventor surprisingly, the femur volume of the rat of medicine A, B, C group of the present invention is compared with model group, have the difference of significance, femur dry weight, ash weight, bone calcium and bone density then have extremely significant difference compared with model group; In addition, model group, compared with blank group, all has the difference of significance in femur volume, dry weight, ash weight, bone calcium and bone density; In addition, the femur volume of the rat of BUSHEN JIANGU JIAONANG matched group and medicine A, B, C group of the present invention, dry weight, ash is heavy, bone calcium is suitable with bone density.Visible, the rat bone loss that pharmaceutical composition of the present invention can obviously suppress retinoic acid to cause, improves osteoporosis, improves bone density.

Pharmaceutical composition of the present invention is to the clinical observation on the therapeutic effect of osteoporosis clinical volunteers patient

(1) case and diagnostic criteria

1, Western medicine diagnose standard:

With reference to " Chinese's osteoporosis suggestion diagnostic criteria " (the second original text) and " new Chinese medicine guideline of clinical investigations ", determining that the diagnostic criteria of this test is as follows: possess overall pain, is main mainly with lumbar and back pain, aching and limp unable, increase the weight of gradually, microtrauma can cause fracture; Scheuermann kyphosis deformity; Bone density reduces by 2 above persons of standard deviation.

Note: (1) bone density refers to measures the meansigma methods of lumbar vertebra 2-4 vertebral bone density or the bone density value of hip with Dual-energy X-rays absorptionmetry (DEXA), as long as one of them reaches lower than 2 above persons of standard deviation.

(2) pain is modal, the topmost symptom of osteoporosis.Clinical the most common with lumbago and backache, for spinous process or have tenderness and percussion pain, with whole body skeleton pain.

(3) be suitable for lumbar vertebra by the diagnostic index that standard deviation represents, hip position can refer to execution.When standard deviation inconvenience application, available lumbar vertebra Percentage of bone loss (%) diagnostic index.

2, tcm diagnosis standard:

Evaluation with reference to " guideline of clinical investigations of new Chinese medicine treatment osteoporosis " of " new Chinese medicine guideline of clinical investigations " (2002) requires to formulate.Diagnostic criteria is: lumbar vertebrae pain, aching and limp few power, walk with difficulty, the vertigo, can not be prudent, body of the tongue or partially red or light, thin lingual fur or thin white, deep-thready pulse etc.

3, Excluded cases standard: 1) have secondary osteoporosis and other serious complication persons such as hyperparathyroidism, osteomalacia, rheumatoid arthritis, multiple myeloma; Or late deformity, maimed person, disability person; 2) severe primary such as cardiovascular and hemopoietic system disease patient is associated with; 3) liver function ALT is more than 1.5 times of upper limits of normal; Renal function serum creatinine > 133umol/L; 4) psychosis or old dementia patients; 5) adopt hormone replacement therapy (HRT) in nearly three months and take calcitonin (as Calcitonin and elcatonin), having continuous 15 days in nearly six months and apply Diphosphonate person.

Two, clinical trial

1, physical data

Clinical volunteers patient of all selected fracture being loosened is divided into two groups at random, treatment group 100 example, wherein male patient 50 example, female patient 30 example; Matched group 100 example, wherein male patient 54 example, female patient 46 example.Age is 20 ~ 80 years old, 49 years old mean age.Two groups of influence factors such as age, symptom, through statistical procedures, there was no significant difference, meets a point set condition.

2, Therapeutic Method

Treatment group: take the capsule (0.3g*100 grain/bottle) that embodiment 3 prepares, every day 3 times, each 4, serve on 3 months;

Matched group: take BUSHEN JIANGU JIAONANG (Wuhan JianMin Pharmaceutical Group Co., Ltd, accurate word Z20020056, the 0.58g*36 grain/box of traditional Chinese medicines), each 4,3 times on the one, serve on 3 months.

3, evaluation of clinical curative effect standard

Osteoporosis bone density efficacy determination

First calculating bone density changing value=(after treatment the front bone density of bone density-treatment)/treat front bone density × 100%

Effective: bone density rate of change is more than or equal to the minimum significant change value of bone density;

Effective: bone density rate of change is between the minimum significant change value of positive and negative bone density;

Invalid: bone density rate of change is less than the minimum significant change value of negative bone density.

Wherein bone density minimum significant change value=2.77 × (%CV), the CV-coefficient of variation.

Total effective rate=(effective+effectively)/total case load × 100%

4, therapeutic outcome, as shown in table 2.

Table 2 therapeutic effect

Group	Number of cases	Effective (rate)	Effectively	Invalid	Total effective rate
						Treatment group	100	82(82％)	10	8	92％
Matched group	100	57(57％)	23	20	80％

5, conclusion

The patient of this clinical trial is the patient of 20 ~ 80 years old, because osteoporosis can occur in all age group, so the larger patient of the range of choice is as subjects, by comparing with medicine composite for curing effect of the present invention, embody the curative effect of pharmaceutical composition of the present invention in treatment osteoporosis, make inventor surprisingly, the obvious effective rate of pharmaceutical composition of the present invention is 82%, total effective rate is 92%, far above matched group, visible, pharmaceutical composition good effect of the present invention, obvious effective rate is high, can as the drug use for the treatment of osteoporosis.

Owing to describing the present invention by above preferred embodiment, in spirit of the present invention and/or scope, any for replacement/of the present invention or combination implement the present invention, be all apparent for a person skilled in the art, and be included among the present invention.

Claims (6)

1. pharmaceutical composition is for the preparation of the purposes in treatment medicine for treating osteoporosis, and it is characterized in that, described pharmaceutical composition comprises the raw materials of following parts by weight:

Herba Portulacae 50-80 part, stilbene glucoside 5-12 part, kaempferol 4-10 part and Quercetin 4-12 part.

2. purposes according to claim 1, is characterized in that, described pharmaceutical composition comprises the raw materials of following parts by weight:

Herba Portulacae 50 parts, stilbene glucoside 5 parts, kaempferol 4 parts and Quercetin 4 parts.

3. purposes according to claim 1, is characterized in that, described pharmaceutical composition comprises the raw materials of following parts by weight:

Herba Portulacae 80 parts, stilbene glucoside 12 parts, kaempferol 10 parts and Quercetin 12 parts.

4. purposes according to claim 1, is characterized in that, described pharmaceutical composition comprises the raw materials of following parts by weight:

Herba Portulacae 60 parts, stilbene glucoside 8 parts, kaempferol 8 parts and Quercetin 10 parts.

5., according to the arbitrary described purposes of claim 1-4, it is characterized in that, described pharmaceutical composition is made into capsule, tablet, granule or pill.

6., according to the arbitrary described purposes of claim 1-4, it is characterized in that, the preparation technology of described pharmaceutical composition comprises the following steps:

A) Herba Portulacae is got, wash away impurity, crushed after being dried, cross 60-80 mesh sieve, adding medical material gross weight 8-10 times amount volume fraction is the ethanol of 60-80%, microwave extraction 8-15 minute, microwave power is 240-300W, and Extracting temperature is 40-60 DEG C, filters and retains Herba Portulacae medicinal residues, the extractum that relative density is 1.20-1.25 is surveyed, obtained Herba portulacae extract at filtrate reduced in volume to 60 DEG C;

B) take stilbene glucoside, kaempferol and Quercetin, add described Herba Portulacae residue, be ground into fine powder, after mixing, obtain fine powder compositions;

C) described fine powder compositions is added in described Herba portulacae extract, mixing, drying under reduced pressure, pulverize, cross 80-100 mesh sieve, to obtain final product.