CN104116868A - Compound medicine for treating osteoporosis and preparation method thereof - Google Patents

Compound medicine for treating osteoporosis and preparation method thereof Download PDF

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CN104116868A
CN104116868A CN201410399566.6A CN201410399566A CN104116868A CN 104116868 A CN104116868 A CN 104116868A CN 201410399566 A CN201410399566 A CN 201410399566A CN 104116868 A CN104116868 A CN 104116868A
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bone
radix
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CN104116868B (en
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赖祥林
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Yulin City Integrated Traditional Chinese And Western Medicine Orthopaedic Hospital
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Abstract

The invention discloses a compound medicine for treating osteoporosis and a preparation method thereof and aims to provide the compound medicine which has small side effects and has a good effect for treating the osteoporosis and lubar intervertebral disc protrusion of old people. According to the technical scheme, the compound medicine is prepared from the following components in parts by weight: 70-90 parts of herba epimedii, 40-60 parts of herba cistanche, 70-90 parts of polygonum multiflorum, 70-90 parts of the roots of red-rooted salvia, 40-60 parts of semen cuscutae, 40-60 parts of medlar, 25-35 parts of rhizoma curculiginis, 25-35 parts of morinda officinalis, 25-35 parts of dogwood, 25-35 parts of silkworm larva, 40-60 parts of prepared rehmannia roots, 25-35 parts of angelica sinensis and 7-13 parts of centipede. The compound medicine belongs to the technical field of traditional Chinese medicines.

Description

Compound medicines that treatment bone is thin and preparation method thereof
Technical field
The invention discloses a kind of compound medicines, specifically, is a kind of thin compound medicines of bone for the treatment of, and the present invention also discloses the polypharmaceutic preparation method that this treatment bone is dredged, and belongs to technical field of Chinese medicines.
Background technology
Osteoporosis and prolapse of lumbar intervertebral disc are the common metabolic osteopathy of old people, have a strong impact on old people's physical and mental health, have become the major issue of the public health of World Focusing, and osteoporosis is one of old people's three large diseases.Because the medicine of current western medical treatment osteoporosis is often only for osteoporotic a certain link medicines such as () bone resorption inhibitor, bone formation-promoter classes, and there is certain toxic and side effects.Therefore researching and developing new type of safe effectively preventing osteoporosis agents is the focus of world medicine worker research.
Chinese medicine is China people experience in several thousand and crystallization of wisdom, and the bone of Chinese medicine prevention and the similar clinical symptoms of osteoporosis withers, the rheumatism involving the bone card history of existing over thousands of year.Chinese medicine has original opinion to osteoporosis and prolapse of lumbar intervertebral disc, day by day comes into one's own in recent years, has become one of sight focus of medicine for treating osteoporosis researcher.
The mechanism of Chinese medicine osteoporosis and prolapse of lumbar intervertebral disc had both been different from the bone resorption inhibitor of Western medicine, also be different from bone formation-promoter, but focus on the adjusting to animal economy, act on multiple links, thereby improve hormone imbalances and the negative calcium balance of body, reach the effect for the treatment of both the principal and secondary aspects of a disease.And find in the clinical and pharmacological research of Chinese herb prevention osteoporosis and prolapse of lumbar intervertebral disc, Chinese medicine, compared with Western medicine, has the advantage of obvious safe, low toxic and side effects.
Summary of the invention
For above-mentioned deficiency, previous object of the present invention is to provide a kind of side effect little, treatment senile osteoporosis and the respond well compound medicines of prolapse of lumbar intervertebral disc, and the present invention also provides this polypharmaceutic preparation method.
For this reason, previous technical scheme provided by the invention is such: the compound medicines that this treatment bone is thin, made by the component of following weight parts: Herba Epimedii 70-90 part, Herba Cistanches 40-60 part, Radix Polygoni Multiflori 70-90 part, red three 70-90 part, Semen Cuscutae 40-60 part, Fructus Lycii 40-60 part, Rhizoma Curculiginis 25-35 part, Radix Morindae Officinalis 25-35 part, Fructus Corni 25-35 part, Bombyx Batryticatus 25-35 part, Radix Rehmanniae Preparata 40-60 part, Radix Angelicae Sinensis 25-35 part, Scolopendra 7-13 part.
Further, made by the component of following weight parts: Herba Epimedii 75-85 part, Herba Cistanches 45-55 part, Radix Polygoni Multiflori 75-85 part, Radix Salviae Miltiorrhizae 75-85 part, Semen Cuscutae 45-55 part, Fructus Lycii 45-55 part, Rhizoma Curculiginis 28-32 part, Radix Morindae Officinalis 28-32 part, Fructus Corni 28-32 part, Bombyx Batryticatus 28-32 part, Radix Rehmanniae Preparata 45-55 part, Radix Angelicae Sinensis 28-32 part, Scolopendra 9-11 part.
Further, made by the component of following weight parts: 80 parts of Herba Epimedii, 50 parts of Herba Cistanches, 80 parts of Radix Polygoni Multiflori, 80 parts of Radix Salviae Miltiorrhizaes, 50 parts of Semen Cuscutae, 50 parts of Fructus Lyciis, 30 parts of Rhizoma Curculiginises, 30 parts of Radix Morindae Officinaliss, 30 parts of Fructus Corni, 30 parts of Bombyx Batryticatus, 50 parts of Radix Rehmanniae Preparata, 30 parts of Radix Angelicae Sinensis, 10 parts of Scolopendras.
The present invention also has a technical scheme to be to provide this polypharmaceutic preparation method, and the method comprises the steps: successively
1) take each component by above-mentioned weight portion;
2) by step 1) Bombyx Batryticatus, Radix Salviae Miltiorrhizae, the powder of Fructus Corni that take be broken into fine powder;
3) by step 1) take by Herba Epimedii, Herba Cistanches, Radix Polygoni Multiflori, Semen Cuscutae, Fructus Lycii, Rhizoma Curculiginis, Radix Morindae Officinalis, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Scolopendra mix, and add gross mass 2-10 water doubly, decoct secondary; Collecting decoction, collects filtrate after filtering, and is condensed into filtrate the thick paste that relative density is 1.05-1.5, and temperature is 50C °-70C °;
4) to step 3) described thick paste adds step 1) described fine powder, mix rear dryly, be again ground into fine powder, granulate, compressed tablet, sugar coating, to obtain final product.
Further, described fine powder particle diameter is 60-100 order.
Compared with prior art, technical scheme tool provided by the invention has the following advantages:
1, technical scheme provided by the invention, through demonstration, science screening repeatedly, Long-term Clinical Observation, from the Chinese medicine of hundreds of invigorating kidney, promoting blood circulations, dredging collateral, from effect, performance, the abnormal smells from the patient of medicine, cure mainly, the aspects such as Gui Jing, compatibility, toxic and side effects comprehensively analyzes, the therefrom pure Chinese medicine of selected 13 taste, and carry out after the research of feasibility, science, creativeness, practicality, filled a prescription by expert group of Pharmacy department result of study.
2, technical scheme provided by the invention, treatment senile osteoporosis and prolapse of lumbar intervertebral disc carried out to screening study through proved recipe medicine, have that tonifying YIN is supporing yang, effect of invigorating the kidney and strengthening the bones, promoting blood circulation and stopping pain is as the specific prescription and medication for the treatment of senile osteoporosis and prolapse of lumbar intervertebral disc, and further it is carried out to Pharmacodynamics research and clinical efficacy checking, evaluate its safety, for the herbal mixture of exploitation treatment senile osteoporosis and prolapse of lumbar intervertebral disc provides theoretical and clinical foundation.
3, technical scheme provided by the invention, to mitigating osteoporosis disease and patients with prolapse of lumbar intervertebral disc misery, prevent fracture, health level and the quality of life of improving old people are significant, by the experience to succession Chinese medicine osteoporosis and prolapse of lumbar intervertebral disc, the new drug of exploitation Prevention and Treatment of Osteoporosis and prolapse of lumbar intervertebral disc provides scientific basis.
Detailed description of the invention
In order better to understand, implement claim of the present invention, below in conjunction with specific embodiment, claim of the present invention is described in further detail, but the present invention is not limited to following embodiment, but is limited with claim.
Embodiment 1
A kind of thin compound medicines of bone for the treatment of provided by the invention, is made up of following component: Herba Epimedii 70g, Herba Cistanches 60g, Radix Polygoni Multiflori 70g, red three 90g, Semen Cuscutae 40g, Fructus Lycii 60g, Rhizoma Curculiginis 25g, Radix Morindae Officinalis 25g, Fructus Corni 35g, Bombyx Batryticatus 25g, Radix Rehmanniae Preparata 40g, Radix Angelicae Sinensis 35g, Scolopendra 13g.
Embodiment 2
The thin compound medicines of another kind for the treatment of bone provided by the invention, is made up of following component: Herba Epimedii 90g, Herba Cistanches 40g, Radix Polygoni Multiflori 90g, red three 70g, Semen Cuscutae 60g, Fructus Lycii 40, Rhizoma Curculiginis 35g, Radix Morindae Officinalis 35g, Fructus Corni 25g, Bombyx Batryticatus 25g, Radix Rehmanniae Preparata 60g, Radix Angelicae Sinensis 25g, Scolopendra 7g.
Embodiment 3
The thin compound medicines of another kind for the treatment of bone provided by the invention, is made up of following component: Herba Epimedii 85g, Herba Cistanches 45g, Radix Polygoni Multiflori 85g, Radix Salviae Miltiorrhizae 75g, Semen Cuscutae 55g, Fructus Lycii 45g, Rhizoma Curculiginis 32g, Radix Morindae Officinalis 22g, Fructus Corni 28g, Bombyx Batryticatus 32g, Radix Rehmanniae Preparata 55g, Radix Angelicae Sinensis 28g, Scolopendra 9g.
Embodiment 4
The thin compound medicines of another kind for the treatment of bone provided by the invention, is made up of following component: Herba Epimedii 75g, Herba Cistanches 55g, Radix Polygoni Multiflori 75g, Radix Salviae Miltiorrhizae 85g, Semen Cuscutae 45g, Fructus Lycii 55g, Rhizoma Curculiginis 28g, Radix Morindae Officinalis 28g, Fructus Corni 32g, Bombyx Batryticatus 28g, Radix Rehmanniae Preparata 45g, Radix Angelicae Sinensis 32g, Scolopendra 11g.
Embodiment 5
The thin compound medicines of another kind for the treatment of bone provided by the invention, is made up of following component: Herba Epimedii 80g, Herba Cistanches 50g, Radix Polygoni Multiflori 80g, Radix Salviae Miltiorrhizae 80g, Semen Cuscutae 50g, Fructus Lycii 50g, Rhizoma Curculiginis 30g, Radix Morindae Officinalis 30g, Fructus Corni 30g, Bombyx Batryticatus 30g, Radix Rehmanniae Preparata 50g, Radix Angelicae Sinensis 30g, Scolopendra 10g.
The thin compound medicines of any one treatment bone in embodiment 1 to 5, its preparation method is as follows:
1) take each component by any one group of mass number of embodiment 1 to 5;
2) by step 1) Bombyx Batryticatus, Radix Salviae Miltiorrhizae, the powder of Fructus Corni that take be broken into 80 order fine powders;
3) by step 1) take by Herba Epimedii, Herba Cistanches, Radix Polygoni Multiflori, Semen Cuscutae, Fructus Lycii, Rhizoma Curculiginis, Radix Morindae Officinalis, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Scolopendra mix, and add the water of 7 times of gross masses, decoct secondary, wherein, decocting time is 2 hours for the first time, and decocting time is 1.5 hours for the second time; Collecting decoction, collects filtrate after filtering, and is condensed into filtrate the thick paste that relative density is 1.35 (55 DEG C);
To step 3) described thick paste adds step 1) described fine powder, after mixing, dry, be again ground into 80 order fine powders, granulate, compressed tablet, sugar coating, to obtain final product.
Step 4) described granulation, compressed tablet, sugar coating, all carries out according to this area routine techniques means.
For product provided by the invention is better described, provide the experiment such as discriminating, toxicology and the result thereof of the product providing of the present invention below:
This product is coated tablet, removes after sugar-coat, aobvious pitchy; Mildly bitter flavor.
One, differentiate
Get 10 of this product, remove sugar-coat, porphyrize, the 30ml that adds diethyl ether, reflux 30 minutes, filters, filtrate evaporate to dryness, residue adds dehydrated alcohol 1ml to be made to dissolve, as need testing solution.Separately get ursolic acid reference substance, add dehydrated alcohol and make the solution of every 1ml containing 0.5mg, product solution in contrast.Test according to thin layer chromatography (annex VIB of Chinese Pharmacopoeia version in 2000), draw need testing solution 10 μ l, put respectively on same silica gel g thin-layer plate, taking cyclohexane extraction-chloroform-ethyl acetate-formic acid (20:5:8:0.1) as developing solvent, launch, take out, dry, spray is with 10% ethanol solution of sulfuric acid, and it is clear to strengthen to speckle colour developing at 105 DEG C.For in pilot chromatograph, with the corresponding position of reference substance chromatograph on, the speckle of aobvious same color.
Illustrate and meet every regulation relevant under tablet item (annex ID of Chinese Pharmacopoeia version in 2000).
Two, toxicological study is summed up
The thin compound medicines for the treatment of bone is carried out to acute toxicity test (LD 50).Undertaken by Wang Beiying, Li Yikui chief editor " new Chinese medicine development technology and method ".
1 experimental technique
Animal grouping: get 50 of Kunming kind white mice, body weight 20 ± 2g.Test front fasting, can't help water 16 hours.Be divided at random 5 groups by body weight, 10 every group, male and female half and half.
Medicine preparation: according to the result of preliminary experiment, get the thin compound medicines of a certain amount for the treatment of bone, be diluted to respectively 5 administration group desired concns with distilled water by 1:0.85 group distance: 100.00g/kg, 85.00g/kg, 72.25g/kg, 61.41g/kg, 52.20g/kg.
Medication: after 16 hours, each group is respectively by gastric infusion of above-mentioned dosage by above-mentioned 5 treated animal fasting (can't help water), and administration volume is 40ml/kg.
Outcome record and statistics: observed and recorded animal dead situation and main poisoning symptom after administration.Continuous Observation 7 days, not dead animal execution in the 8th day, anatomic observation.Calculate the LD of medicine with Sun Shi synthetic method 50and 95% fiducial limit.
2 experimental results (in table 1)
Jing Sunshi synthetic method calculates: LD 50for 63.95g/kg, LD 50the 95% credible 63.95 ± 5.66g/kg that is limited to.Death time of animal concentrated on after administration in 1 hour.Poisoning manifestations starts as animal rolls up, peace and quiet, and, there is rapid spring, twitch in vomiting, dead rapidly after half an hour.Postmortem naked eyes show no obvious abnormalities.Not dead mice is put to death and cuts open the each internal organs naked eyes no abnormality seen of inspection on the 8th day.
Table 1 is treated the thin compound medicines LD of bone 50initial data and the calculating chart of experiment
Dm: estimate maximum lethal dose; The logarithm value of Xm:Dm; N: every treated animal number; K: group number; I: the logarithm of dose ratio between group
Three, Pharmacodynamics research
(1) treat the impact of the thin compound medicines of bone on castration (rat of Bilateral oophorectomy) osteoporosis rat
1 experiment material
1.1 laboratory animal
6 84 of monthly age SD rats, SPF level, body weight 250 ± 20g, female.Purchased from Guangxi Medical University's Experimental Animal Center, the quality certification number: SCXK osmanthus 2003-0003.
1.2 medicines and reagent
The thin compound medicines for the treatment of bone of the present invention, every gram containing crude drug amount 3.583g.Provided by Yulin City of Guangxi Zhuang Autonomous combination of Chinese and Western medicine urgent disorder in orthopaedics hospital, in institute, preparation is criticized code: osmanthus medicine word (2004) 800034 processed.XIANLING GUBAO JIAONANG (Guizhou Tongjitang Pharmaceutical Co., Ltd, lot number: 060342), Nilestriol Tablets (Shanghai Pharmaceutical Group company limited, lot number: 050831), alkali phosphatase (AKP) test kit (French Yi Jie company), inorganic calcium test kit (French Yi Jie company), inorganic phosphorus reagent box (French Yi Jie company).
1.3 experiment equipment
XR-36 dual energy X-ray absorptiometry measuring instrument (production of Norland company of the U.S.); JN-2 type precision torsion balance (Shanghai Second Balance Factory); 78X-2 matrix agent four-function analyzer (Shanghai Huanghai Sea medicine inspection instrument plant); JY6001 electronic balance (Shanghai balance equipment head factory); 721 spectrophotometers (Shanghai the 3rd analytical tool factory), 7060 type automatic biochemistry analyzers (HIT).
2 experimental techniques
84 of female sd inbred rats, are divided into 7 groups at random: normal group, sham operated rats, model group, XIANLING GUBAO JIAONANG group, Nilestriol Tablets group, product high and low dose group provided by the invention, 12 every group.Modeling: model group, XIANLING GUBAO JIAONANG group, Nilestriol Tablets group, product high and low dose group experimental rat provided by the invention are done to intraperitoneal injection anesthesia with 3% pentobarbital sodium by per kilogram of body weight 40mg, ventricumbent position is fixed on rat clamping plate, routine disinfection, get spinal column both sides otch, under sterile working, enter abdominal cavity, bilateral ovaries is dissociated and excise, hemostatic suture, wound is wiped prevention infection outward with Ma Yinglong ointment for treating hemorrhoid, and postoperative rat all freely drinks water.Rats in sham-operated group is under the anesthesia identical with modeling and otch condition, and the each fat in excision intraperitoneal left and right is done sham-operation.
Normal group is blank group, under the same terms, feeds, and does not do special handling.Within postoperative the 91st day, start gastric infusion.Product high and low dose group provided by the invention is pressed respectively the granule dosage administration of 3.2g/kg, 0.8g/kg; XIANLING GUBAO JIAONANG group is pressed 0.246g/kg dosed administration (by people Mus body weight conversion dosage); Nilestriol Tablets group is pressed 0.001g/kg dosed administration (by people Mus body weight conversion dosage).When use, with distilled water, treatment bone thin compound medicines is made into respectively to 0.32g/ml, 0.08g/ml suspension, every day gavage 1 time; XIANLING GUBAO JIAONANG is made into 0.0246g/ml, every day gavage 1 time; Nilestriol Tablets is made into 0.0001g/ml, gavage 1 time weekly, and all the other give distilled water for 6 days and replace; Normal group, model group and sham operated rats give respectively distilled water gavage, every day 1 time.Each group gavage capacity is 10ml/kg body weight.Treat after 90 days in medication for each group, fasting (can't help water) 12h, weighs, and through 1% pentobarbital anesthesia, after eye socket venous blood collection, puts to death, and cuts open and gets both sides femur.
3 observation index and assay method
The detection of 3.1 blood serum samples
Laboratory animal eye socket venous blood sampling, separation of serum ,-20 DEG C of preservations.Measure the content of serum calcium, phosphorus, alkali phosphatase with automatic biochemical analyzer.
3.2 femur weight in wet bases, dry weight are measured
Peel off rat right side femur and weigh rapidly its weight in wet base, then immerse in normal saline ,-20 DEG C of preservations, for measuring bone density.Dry 8h at 120 DEG C, take out and weigh its dry weight.
3.3 bone densitometries (Dual X-ray absorbs (DEXA) method) application XR-36 type dual energy X-ray absorptiometry instrument, the bone density of mensuration rat right side femur.
3.4 biomechanical properties in bones are measured
According to the principle of three-point bending test, improve the assay method of bone biomechanical, with tablet four-function analyzer, loading velocity is 12mm/min, span 26mm.Measure the maximum load hardness of right side femur.
3.5 histopathologic examination
Peel off rats with left femur and put into rapidly 10% formalin and fix, Alchlor process decalcification, paraffin section, HE dyeing, om observation.
4 statistical methods
All data acquisitions carry out statistical analysis with SPSS11.0 statistical package, respectively organize sample average and relatively adopt F inspection.
5 experimental results
5.1 on the impact of ovariectomized female rats overall condition in table 2.
After model group ovariectomized rats, dietary amount obviously reduces, and therebetween, rat fear of cold, cold extremities, bradykinesia, mobility obviously reduce, and occur the performance such as hogback, the withered original text of hypotrichosis in experiment.Two dosage group rat ordinary circumstances of product provided by the invention are all good compared with model group.Before experiment, each group weight ratio is compared with difference not statistically significant (F=2.1191, P>0.05); After experiment, each treated animal weight ratio has statistical significance (F=8.1685 compared with difference, P<0.05), after model group ovariectomized rats, body weight gain is obviously not so good as normal group and sham operated rats (P<0.05), and the each dosage group of product provided by the invention body weight gain is better than model group (P<0.05).
The body weight change of table 2 experimental rat ( )
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.2 on the impact of ovariectomized female rats right lateral thigh bone length and weight in wet base, dry weight in table 3.
The length of model group rat femur and weight in wet base and normal group be difference not statistically significant (P>0.05) relatively; Product high dose provided by the invention can significantly increase femur weight in wet base, has statistical significance (P<0.05) with model group comparison difference.The dry weight of model group rat femur and normal group significantly decline (P<0.05); Two dosage of product provided by the invention all can increase the dry weight of femur, have statistical significance (P<0.05) with model group comparison difference.
The impact of table 3 on ovariectomized female rats right lateral thigh bone length, weight in wet base and dry weight ( )
Group Dosage (g/kg) n Length (mm) Weight in wet base (mg) Dry weight (mg)
Normal group -- 12 35.12±1.03 0.79±0.08 0.57±0.05
Sham operated rats -- 12 34.85±0.86 0.74±0.09 0.61±0.04
Model group -- 12 35.41±0.48 0.75±0.07 0.46±0.03 ①
This product high dose group 3.2 12 35.22±1.10 0.88±0.07 ② 0.60±0.07 ②
This product low dose group 0.8 12 34.95±0.96 0.76±0.08 0.57±0.13 ②
XIANLING GUBAO JIAONANG group 0.246 12 35.97±0.67 0.76±1.10 0.56±0.11 ②
Nilestriol Tablets group 0.001 12 35.23±0.87 0.69±0.05 0.55±0.08 ②
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.3 on the impact of ovariectomized female rats right side femoral bmd and bone hardness in table 4.
Each group right side femoral bmd, bone hardness ratio have statistical significance (F compared with difference bone density=4.6931, F bone hardness=9.1364, P<0.05).Model group is femoral bmd and all significantly reductions (P<0.05) of bone hardness compared with normal group.Product high dose group bone density provided by the invention is apparently higher than model group (P<0.05), and effect approaches XIANLING GUBAO JIAONANG group (P>0.05).Two dosage of product provided by the invention on the hardness of right side femur without obvious impact.
The impact of table 4 on ovariectomized female rats right side femoral bmd and bone hardness ( )
Group Dosage (g/kg) n Bone density (g/cm 2) Bone hardness (kg)
Normal group -- 12 0.126±0.008 4.95±1.38
Sham operated rats -- 12 0.123±0.005 4.76±1.57
Model group -- 12 0.114±0.007 ① 3.32±0.98 ①
This product high dose group 3.2 12 0.124±0.009 ② 3.51±1.08 ①
This product low dose group 0.8 12 0.117±0.007 ① 3.46±1.64 ①
XIANLING GUBAO JIAONANG group 0.246 12 0.127±0.010 ② 6.89±2.55 ①②
Nilestriol Tablets group 0.001 12 0.121±0.006 ② 6.71±2.30 ①②
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.4 on the impact of ovariectomized female rats blood parameters in table 5
With normal group comparison, calcium ion concentration in model group rat blood serum is without significant change (P>0.05), phosphate ion concentration significantly declines (P<0.05), and the activity of serum alkaline phosphatase significantly increases (P<0.05).Two dosage of product provided by the invention to serum calcium without obvious effect.Product high dose provided by the invention can improve serum paraoxonase level, has statistical significance (P<0.05) with model group comparison difference, and effect approaches XIANLING GUBAO JIAONANG group (P>0.05).The activity of product high and low dose group alkali phosphatase provided by the invention slightly declines compared with model group, but difference not statistically significant (P>0.05).
The impact of table 5 on Ca, P, AKP content in ovariectomized female rats serum ( )
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.5 impacts on femur of mature ovariectomized rats pathological tissue
The dry marrow end of model group rat femur check pathological section shows that bone trabecula is sparse, fracture, arrangement disorder, and cortical bone is loose, is and nibbles sample and the change of Herba Alii fistulosi skin sample, and medullary cavity expands.A little nibbles sample change to product low dosage cortical bone provided by the invention as seen, and bone trabecula is thinner, arranges more consistent.Product high dose bone pathology section provided by the invention all shows that bone trabecula is thicker, marshalling, medullary cavity normal in size, cortical bone densification, neat in edge.Point out product high dose provided by the invention can obviously improve the microstructural pathological change of Ovariectomized Rats osseous tissue.
(2) the thin compound medicines for the treatment of bone causes the impact of osteoporosis rat on retinoic acid
1 experiment material
1.1 laboratory animal
6 84 of monthly age SD rats, SPF level, body weight 250 ± 20g, male.Purchased from Guangxi Medical University's Experimental Animal Center, the quality certification number: SCXK osmanthus 2003-0003.
1.2 medicines and reagent
The thin compound medicines for the treatment of bone of the present invention, every gram containing crude drug amount 3.583g.Provided by Yulin City of Guangxi Zhuang Autonomous combination of Chinese and Western medicine urgent disorder in orthopaedics hospital, in institute, preparation is criticized code: osmanthus medicine word (2004) 800034 processed.XIANLING GUBAO JIAONANG (Guizhou Tongjitang Pharmaceutical Co., Ltd, lot number: 060342); Nilestriol Tablets (Shanghai Pharmaceutical Group company limited, lot number: 050831); Retinoic acid sheet (Shandong pharmaceutical Co. Ltd of Liang Fu group, lot number: 060501); Alkali phosphatase (AKP) test kit (French Yi Jie company); Inorganic calcium test kit (French Yi Jie company), inorganic phosphorus reagent box (French Yi Jie company).
1.3 experiment equipment
XR-36 dual energy X-ray absorptiometry measuring instrument (production of Norland company of the U.S.); JN-2 type precision torsion balance (Shanghai Second Balance Factory); 78X-2 matrix agent four-function analyzer (Shanghai Huanghai Sea medicine inspection instrument plant); JY6001 electronic balance (Shanghai balance equipment head factory); 721 spectrophotometers (Shanghai the 3rd analytical tool factory), 7060 type automatic biochemistry analyzers (HIT).
2 experimental techniques
84 of male SD rats, are divided into 7 groups at random: normal group, model group, the high, medium and low dosage group of product provided by the invention, XIANLING GUBAO JIAONANG group, Nilestriol Tablets group, 12 every group.Except normal group, all the other groups gavage 7% retinoic acid solution (being made into retinoic acid sheet and normal saline) by the dosage of 70mg/kg body weight in the 1st day to the 14th day in experiment, and every day 1 time, gavage capacity is 10ml/kg body weight, 14 days inactive retinoic acid afterwards.From testing the 1st day to the 28th day high, medium and low dosage group of product provided by the invention respectively by the granule dosage administration of 3.2g/kg, 1.6g/kg, 0.8g/kg; XIANLING GUBAO JIAONANG group is pressed 0.246g/kg dosed administration (by people Mus body weight conversion dosage); Nilestriol Tablets group is pressed 0.001g/kg dosed administration (by people Mus body weight conversion dosage).When use, with distilled water, treatment bone thin compound medicines is made into respectively to 0.32g/ml, 0.16g/ml, 0.08g/ml suspension, every day gavage 1 time; XIANLING GUBAO JIAONANG is made into 0.0246g/ml, every day gavage 1 time; Nilestriol Tablets is made into 0.0001g/ml, gavage 1 time weekly, and all the other give distilled water for 6 days and replace; Normal group, model group give respectively distilled water gavage, every day 1 time.Each group gavage capacity is 10ml/kg body weight.Treat after 28 days in medication for each group, fasting (can't help water) 12h, weighs, and through 1% pentobarbital anesthesia, after eye socket venous blood collection, puts to death, and cuts open and gets both sides femur.
3 observation index and assay method
3.1 blood serum samples detect
Laboratory animal eye socket venous blood sampling, separation of serum ,-20 DEG C of preservations.Measure the content of serum calcium, phosphorus, alkali phosphatase with automatic biochemical analyzer.
3.2 femur weight in wet bases, dry weight are measured
Peel off rat right side femur and weigh rapidly its weight in wet base, then immerse in normal saline ,-20 DEG C of preservations, for measuring bone density.Dry 8h at 120 DEG C, take out and weigh its dry weight.
3.3 bone densitometries (Dual X-ray absorbs (DEXA) method)
Application XR-36 type dual energy X-ray absorptiometry instrument, the bone density of mensuration rat right side femur.
3.4 biomechanical properties in bones are measured
According to the principle of three-point bending test, improve the assay method of bone biomechanical, with tablet four-function analyzer, loading velocity is 12mm/min, span is 26mm.Measure the maximum load hardness of right side femur.
3.5 histopathologic examination
Peel off rats with left femur and put into rapidly 10% formalin and fix, Alchlor process decalcification, paraffin section, HE dyeing, om observation.
4 statistical methods
All data acquisitions carry out statistical analysis with SPSS11.0 statistical package, respectively organize sample average and relatively adopt F inspection.
5 experimental results
5.1 impacts that retinoic acid is caused to male osteoporosis rat overall condition are in table 6.
Model group rat gives after retinoic acid gavage, and dietary amount obviously reduces, and therebetween, activities in rats degree obviously reduces in experiment, occurs the performances such as hogback, perpendicular hair, the withered original text of hair color, and sees that 2 rats walk lamely respectively at modeling the 9th day, appearance in the 13rd day.Three dosage group rat ordinary circumstances of product provided by the invention are all good compared with model group.Before experiment, each group weight ratio is compared with difference not statistically significant (F=1.5719, P>0.05); After experiment, each treated animal weight ratio has statistical significance (F=31.2206 compared with difference, P<0.05), retinoic acid has obvious inhibitory action to the growth of rat body weight, and that the each dosage of product provided by the invention all can resist the body weight gain of retinoic acid induced osteoporosis rat model is slow.
The body weight change of table 6 experimental rat ( )
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.2 impacts that retinoic acid is caused to male osteoporosis rat right side femoral bmd and bone hardness are in table 7.
Give bone density and the bone hardness of rat femur after retinoic acid and obviously reduce, there were significant differences compared with normal group (P<0.05).Between each group, femoral bmd comparison difference has statistical significance (F=10.0972, P<0.05).Product provided by the invention high, middle dosage group bone density and bone hardness and model group comparison difference have statistical significance (P<0.05), high, the middle dosage of product provided by the invention can significantly raise bone density and the bone hardness of osteoporosis rat femur are described, effect is close to XIANLING GUBAO JIAONANG group and Nilestriol Tablets group (P>0.05).
Table 7 on retinoic acid cause male osteoporosis rat right side femoral bmd and bone hardness impact ( )
Group Dosage (g/kg) n Bone density (g/cm 2) Bone hardness (kg)
Normal group -- 12 0.125±0.006 5.15±1.41
Model group -- 12 0.111±0.008 ① 3.63±1.57 ①
This product high dose group 3.2 12 0.131±0.006 ② 6.32±0.18 ①②
Dosage group in this product 1.6 12 0.126±0.009 ② 5.52±1.12 ②
This product low dose group 0.8 12 0.117±0.007 ① 3.41±1.64 ①
XIANLING GUBAO JIAONANG group 0.246 12 0.128±0.010 ② 6.96±2.65 ①②
Nilestriol Tablets group 0.001 12 0.123±0.005 ② 6.73±2.16 ①②
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.3 the impact that retinoic acid is caused to male osteoporosis rat right side femur length and weight in wet base, dry weight is in table 8.
Relatively difference not statistically significant (F=0.2022, P>0.05) of each group right side femur weight in wet base, the weight in wet base that three dosage of product provided by the invention cause osteoporosis rat right side femur to retinoic acid is without obvious impact.The growth of Femur of Rats Poured Retinoic Acid Down Throat length is suppressed, all has statistical significance (P<0.05) with normal group comparison difference; Femur dry weight compared with normal group significantly decline (P<0.05), high, the middle dosage of product provided by the invention can significantly increase the dry weight of osteoporosis rat right side femur, has statistical significance (P<0.05) with model group comparison difference.
Table 8 on retinoic acid cause male osteoporosis rat right side femur length, weight in wet base and dry weight impact ( )
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.4 impacts that retinoic acid is caused to male osteoporosis rat blood biochemical indicator are in table 9.
Compared with normal group, the calcium in model group rat blood serum, phosphate ion concentration there is no significant impact, alkaline phosphatase activities significantly decline (P<0.05).The high, medium and low dosage of the product provided by the invention blood calcium that all obviously raises, the high dose serium inorganic phosphorus that obviously raises, high dose improves alkaline phosphatase activities, all has statistical significance (P<0.05) with model group comparison difference.
Table 9 on retinoic acid cause Ca, P in male osteoporosis rat blood serum, AKP content impact ( )
Note: with more 1. P<0.05 of normal group, with more 2. P<0.05 of model group
5.5 cause the impact of male osteoporosis rat femur pathological tissue to retinoic acid
The dry marrow end of model group rat femur check pathological section shows that bone trabecula is sparse, fracture, arrangement disorder, osteoclast hypertrophy, indivedual focal acidophilia's degeneration of the visible hyaline cartilage of animal.High, middle dosage group is normal epiphysis tissue substantially, and the visible bone trabecula of indivedual animals reduces, and arranges and evacuates; Low dose group bone trabecula reduces, and arranges and evacuates, osteoclast hypertrophy.Point out high, the middle dosage of product provided by the invention can improve retinoic acid and cause the microstructural pathological change of osteoporosis rat osseous tissue.
Four, clinical application research
1 clinical data
1.1 diagnostic criteria
Western medicine diagnose standard specifies 639 pages of osteoporosis and Diagnosis of Lumber Disc Prolapse standard and in October, 1999 " diagnostic criteria (trying) of primary osteoporosis for Chinese people and prolapse of lumbar intervertebral disc ", 19 10 phases of volume of " Chinese combination of Chinese and Western medicine magazine " October in 1999 with reference to nineteen ninety-five WHO.Tcm diagnosis standard and differentiation of symptoms and signs for classification of syndrome are with reference to " the blood stasis symptom diagnostic criteria " of the 6th the 10th phase of volume " combination of Chinese and Western medicine magazine " in 1986, " the dialectical reference standard of Chinese medicine deficiency-syndrome " and Second China National blood circulation promoting and blood stasis dispelling research academic conference revision in 1986.
1.2 physical data
Meet case osteoporosis choice criteria person and amount to 150 examples, adopt parallel control, random method for designing, point treatment group 100 examples, matched group 50 examples.Wherein treatment group male 22 examples, women's 78 examples, matched group male 12 examples, women's 38 examples.45～86 years old treatment group age, average 64.5 years old.45～85 years old matched group age, average 64.35 years old.The treatment group course of disease 0.5～30 year, average 6.5 years, the matched group course of disease 0.6～29 year, average 6.3 years.Two groups of Genders, age, course of disease comparison, no significant difference, has comparability.
What meet prolapse of lumbar intervertebral disc is divided into treatment group and each 120 examples of matched group at random, wherein treatment group man 69 examples, female's 51 examples, 22～58 years old age; Average 40.5 years old; Average course for the treatment of 10.6 months.Matched group man 64 examples, female's 56 examples, 23～54 years old age, average 43.5 years old, average course of disease 12.5 months, two groups of patients, sex, age, the course of disease, the outstanding physical data of being in hospital are relatively all without obvious.
1.3 include case standard in
Meet Western medicine diagnose standard and tcm diagnosis standard person, for including observation case in.
2 treatment and observational techniques
2.1 Therapeutic Method
2.1.1 osteoporosis
Treatment group is taken product provided by the invention and is produced by Yulin City of Guangxi Zhuang Autonomous combination of Chinese and Western medicine urgent disorder in orthopaedics hospital Drug Manufacturing Room, and every contains crude drug 1.23g, and oral, every day 3 times, each 5, serveing on 3 months was 1 course for the treatment of, generally used 2 courses for the treatment of.Matched group takes calcareacarbonica chewable tablet (deriving from Fei Hong pharmaceutcal corporation, Ltd of Nanchang City), and every day 3 times, each 2, taking 3 months was 1 course for the treatment of.Viewing duration, all Chinese-western medicine preparations identical with trial drug effect of stopping using.
2.1.2 prolapse of lumbar intervertebral disc
Treatment group is taken product provided by the invention every day 3 times, and each 3, taking 3 months was 1 course for the treatment of.Matched group: " Yaobitong Capsule" (Jiangsu Kang Yuan Pharmaceutical is produced), every day 3 times, each 3, taking 3 months was 1 course for the treatment of.
2.2 observation index and method
2.2.1 bone densitometry
Female age is more than 45 years old, and male, more than 50 years old, has back, skeleton arthralgia, normal companion's waist lower limb is weak, two lower limb knot, and bend over, stand up, squat down, fracture person occurs difficult or the limited and fracture patient of activity such as walking repeatedly, treat front and back and carry out bone densitometry.
2.2.2X line film making is measured
Clap lumbar vertebra and the positive side of sacroiliac joint position X-ray, observe vertebral bone cortical thickness and the bone trabecular density of vertical and horizontal.
2.2.3ASO, ESR, RF check: to get rid of the illness such as rheumatism, rheumatoid arthritis.
2.2.4 blood fat, blood sugar detection: to get rid of the Senile disease such as hyperlipemia, diabetes.
2.2.5 security inspection
The routine examinations such as blood, urine, feces routine, liver, renal function, electrocardiogram, each 1 time for the treatment of front and back.
3 therapeutic outcomes
3.1 criterion of therapeutical effect
3.1.1 osteoporosis
The efficacy evaluation of osteoporosis in conjunction with this area patient's practical situation, is divided into effective with reference to " clinical disease diagnosis is according to curing improvement standard " of " new Chinese medicine guideline of clinical investigations " [1] and the announcement of The General Logistics Department of PLA's Ministry of Public Health in June, 1987 first edition: transference cure, bone density are recovered normal or normal.Effective: symptom alleviates, bone density increases.Invalid: symptom and sign is not improved.
3.1.2 prolapse of lumbar intervertebral disc
Draft with reference to relevant criterion of therapeutical effect in " traditional Chinese medical science disease Standardization of diagnosis and curative effect " and " prolapse of lumbar intervertebral disc ": cure: lumbago and skelalgia disappears, more than straight lower limb is raised 70 degree, can recover normal work; Take a turn for the better: lumbago and skelalgia alleviates, waist movable function improves; Invalid: symptom, sign are without improvement.
The comparison of 3.2 liang of group curative effects
Effective 63 examples of osteoporosis therapy group, effective 32 examples, invalid 5 examples, total effective rate 95%; Matched group: effective 10 examples, effective 22 examples, invalid 18 examples, total effective rate 64%.Two groups of obvious effective rates and total effective rate more all have significant difference (P<0.01).
Treatment of lumbar disc herniation group total effective rate treatment group is 94.17%, and matched group is and 80.83%, two group of comparison, has statistical discrepancy.
Table 10 liang group therapeutic outcome and curative effect comparison (example)
Group n Cure Take a turn for the better Invalid Total effective rate %
Treatment group 120 53 60 7 94.17％
Matched group 120 39 58 23 80.83％
3.3 untoward reaction
During all cases medication treatment, do not find untoward reaction.
Five, result of study analysis
Osteoporosis and prolapse of lumbar intervertebral disc belong to " atrophic debility of bones, bone are withered, rheumatism involving the bone " category in motherland's medical science, and its morbidity is in close relations with kidney.The traditional Chinese medical science is thought, kidney storing essence, the raw marrow of main bone, the prosperity and decline of main growth promoter and reproductive function.The osteosis deficiency of suffering from a deficiency of the kidney, kidney plays an important role in the growth of bone with in rebuilding.Product provided by the invention develops through proved recipe medicine according to Yulin City of Guangxi Zhuang Autonomous combination of Chinese and Western medicine urgent disorder in orthopaedics hospital treatment osteoporosis and prolapse of lumbar intervertebral disc,, invigorating the kidney and strengthening the bones supporing yang taking tonifying YIN, promoting blood circulation and stopping pain are rule prescription, focus on the adjusting to animal economy, to reach the effect for the treatment of both the principal and secondary aspects of a disease, cure mainly the lumbago and skelalgia due to senile osteoporosis, sore neck shoulder is tired, general aching, limbs are weak, insomnia forgetfulness, night the disease such as many urine.
1 prescription analysis
Product provided by the invention is made up of Herba Epimedii, Herba Cistanches, Radix Polygoni Multiflori, Radix Salviae Miltiorrhizae, Semen Cuscutae, Fructus Lycii, Rhizoma Curculiginis, Radix Morindae Officinalis, Fructus Corni, Radix Angelicae Sinensis, Bombyx Batryticatus, Radix Rehmanniae Preparata, Scolopendra 13 taste Chinese medicines.
Herba Epimedii, Radix Rehmanniae Preparata are returned liver, kidney two warps, kidney invigorating and YANG supporting, beneficial blood are filled out marrow, bone and muscle strengthening, modern pharmacology confirms that Herba Epimedii has significantly short gonad function effect, the absorption that can suppress bone can stimulate again derivation hypertrophy osteoblast, the absorption function that suppresses osteoclast, produces more bone matrix, makes bone metabolism be converted into positive balance, in effectively maintaining disease bone bone amount, can also make the sclerotin having lost be able to recovery to a certain degree; Radix Rehmanniae Preparata is enriched blood and is invigorated blood circulation, and supports kidney pain relieving, increases blood flow, is beneficial to the deposition of calcium salt, thereby increases bone trabecular thickness; Herba Cistanches the kidney invigorating and essence nourishing, moisturize laxation, beneficial marrow tonifying YANG, control chills and pain of the waist and kness; Fructus Lycii enriching yin and nourishing kidney are the yang aspect of yin medicine, and resistance to old, the tonification muscles and bones of hard muscle, nourishing kidney lung moistening, tonifying liver improving eyesight, control deficiency of both the liver and kidney, the weak all diseases of waist knee joint; Semen Cuscutae kidney tonifying, essence replenishing; Rhizoma Curculiginis temperature male wind-supplying kidney; Radix Salviae Miltiorrhizae can QI invigorating be enriched blood, promoting blood circulation to disperse blood clots and relieves pain, and Radix Salviae Miltiorrhizae has again the warm inclined to one side Sheng effect of balance other drug; Radix Morindae Officinalis warming the kidney to invigorate YANG.
We are according to the pathogenesis of senile osteoporosis and prolapse of lumbar intervertebral disc, in the kidney invigorating, add and use bone strengthening blood circulation promoting medicine, the nephroyin and nephroyang source that can ensure gerontal patient is without cease, makes again blood vessels meridians unblocked, makes it extremity bones of the body collectively and obtains vital essence nourishing, warm, play altogether nourishing YIN supporing yang, kidney tonifying, essence replenishing, bone strengthening increases marrow, the merit of promoting blood circulation and stopping pain.
2 experimental studies results analyses
Technical scheme provided by the invention adopts castration, retinoic acid to cause rats with osteoporosis and model of lumbar intervertebral disc protrusion is that object of study is treated the thin compound medicines treatment osteoporosis of bone and prolapse of lumbar intervertebral disc research, inquires into drug effect, the Safety and effect mechanism of product treatment osteoporosis provided by the invention and prolapse of lumbar intervertebral disc.Ovariectomized rats and mankind's postmenopausal osteoporosis and prolapse of lumbar intervertebral disc, Cancellous bone loss be greater than cortical bone loss, processus styloideus radii transfevent feature, intestinal calcium absorption obstacle and vitamin D metabolism changes and to the reaction of various Drug therapys on have many similarities, therefore ovariectomized female rats is suitable for the evaluation of osteoporotic research and new drug.
After spay 3 months, model group animal bone density obviously declines, the alkali phosphatase relevant with bone formation significantly raises etc., shows that the model of high turnover forms, illustrate with the osteoporosis model of this method foundation of oophorectomize be successful.The osteoporosis of Induced by Retinoic Acid belongs to secondary osteoporosis.Retinoic acid is a kind of derivant of vitamin, be usually used in clinically the control of the dermatosiss such as psoriasis and Partial tumors, one of its side reaction is that body bone metabolism is had to stronger impact, often cause osteoporosis and prolapse of lumbar intervertebral disc, be applied to the experimentation of Experimental Osteoporosis and prolapse of lumbar intervertebral disc, it is short that retinoic acid model has the modeling cycle, and osteoporosis is clearly sure, is easy to the feature of repetition.
Retinoic acid model is selected in this experiment, from the result of experiment, when modeling finishes, model group bone density compared with normal matched group obviously decline (P<0.05), tectology aspect shows that bone trabecula is sparse, fracture, and medullary cavity expands, and model group has 2 rats to occur walking lamely in modeling process, after experiment finishes, draw materials and turn out to be due to spontaneous fracture, prove that osteoporosis model copies successfully.
Experimental result shows:
The thin compound medicines for the treatment of bone provided by the invention can resist removal ovary and retinoic acid and cause the weight loss of osteoporosis model rat, and it is all good compared with model group that product provided by the invention is respectively organized rat overall condition, and body weight increases apparently higher than model group; Treatment bone thin compound medicines can improve ovariectomized rats and occur " suffering from a deficiency of the kidney " symptom such as fear of cold, cold extremities, bradykinesia, few moving, hypotrichosis.
The femoral shaft representation work that removal ovary and retinoic acid cause osteoporosis model rat reduces, thin high and low two dosage of compound medicines for the treatment of bone all can significantly suppress the reduction of Ovariectomized Rats femur dry weight, treatment bone thin high, the middle dosage of compound medicines all can significantly suppress retinoic acid and cause the reduction of osteoporosis rat femur dry weight, illustrate that the thin compound medicines for the treatment of bone can increase the content (as collagen protein, inorganic mineral salt) of osseous tissue solid constituent.
Bone density be at present for osteoporosis and Diagnosis of Lumber Disc Prolapse and risk of fractures degree evaluate most important, the most objectively detect index, it is closely related with bone strength, and bone strength is the determiner of sensitivity of fracturing.Therefore, bone density is closely related with the danger that fracture occurs, and can be used for predicting the danger of osteoporosis and fracture.
Experimental result shows: the bone density compared with normal that removal ovary and retinoic acid cause osteoporosis model group rat obviously reduces (P<0.05), and prompting removal ovary and retinoic acid can obviously cause the generation of rats with osteoporosis and prolapse of lumbar intervertebral disc; And the thin compound medicines high dose for the treatment of bone can obviously increase the bone density (with relatively P<0.05 of model group) of Ovariectomized Rats femur, effect approaches (P>0.05) with XIANLING GUBAO JIAONANG group; High, middle dosage all can obviously increase the bone density (with relatively P<0.05 of model group) that retinoic acid causes osteoporosis rat femur, the thin compound medicines of prompting treatment bone can resist removal ovary and gavage the bone loss of the rat femur that retinoic acid causes, increase bone density, its mechanism of action may with the thin integrally-regulated body function of compound medicines for the treatment of bone, improve Abwehrkraft des Koepers, suppress bone resorption, promoting bone growing is relevant.Thin high, the middle dosage of compound medicines for the treatment of bone all can obviously increase rat bone hardness, the thin compound medicines of prompting treatment bone can increase the bearing capacity of osseous tissue, improve the impact capacity of skeleton opposing external force, avoid the generation of fracture, thereby control or delaying osteoporosis occur.
Blood calcium is regulated by multiple endocrine hormone and in poised state.Though the blood calcium of clinical examination menopausal women has the tendency of increase, how within normal range, to fluctuate, some experimentatioies also point out, and castration does not affect the level of blood calcium, and in this research, the calcium level of Ovariectomy model group rat is without significant change.Have literature research to show, retinoic acid causes that rat serum calcium concentration reduces, and causes the endocrine variation of appearance in body, Secondary cases causes that PTH increases, stimulated the activity of osteoclast, bone resorption is strengthened, this may be also the Another reason that retinoic acid causes bone loss.But the blood calcium concentration and the relatively also there was no significant difference of normal group that in this research, gavage retinoic acid group rat, its reason, also may be relevant with Calcium Content in Foodstuff except outside the Pass may having with animal species and age.The thin compound medicines for the treatment of bone can not significantly increase the blood calcium concentration of ovariectomized female rats, only has the trend that increases blood calcium, but the thin high, medium and low dosage of compound medicines for the treatment of bone all obviously raises, retinoic acid causes the blood calcium of osteoporosis rat.The raising of calcium level contributes to new bone formation and calcification, suppress bone calcium to blood transfer simultaneously, the thin compound medicines of the above results prompting treatment bone may cause by rising retinoic acid the blood calcium of osteoporosis rat, promote the absorption of bone to calcium, be conducive to the formation of bone mineral content, thereby reduce the loss of animal pattern bone amount.
In body, phosphorus 85% is present in bone, and its Main Function is to promote the synthetic of bone matrix and bone ore deposit deposition, the level affects bone resorption rate of blood plasma Phos, and the stable of serium inorganic phosphorus is the essential condition of osteogenesis and mineralising.The serum paraoxonase level (P<0.05) that after this experiment demonstration product high dose provided by the invention can improve removal ovary and gavage retinoic acid, osteoporosis rat declines.
Osteoblast contains abundant alkali phosphatase, a large amount of secreting alkaline phosphorus phytases of osteoblast when skeletonization enlivens, and a part participates in the calcification of bone, and one is discharged in blood, and enzymatic activity in blood is raise.In serum, approximately 50% AKP derives from bone, and therefore in blood, the variation of AKP content can roughly reflect the degree of the metabolic alterations of bone, is considered to the early sign thing of osteoblast differentiation, is an important indicator of reflection osteoblast activity.Have experimentation to prove, after castration, animal blood AKP is active raises.Rising that it is generally acknowledged this blood AKP is to be accompanied by bone resorption compensatory bone formation enhancing hyperfunction and that occur to cause.
In this experiment, removal ovary causes osteoporosis model group rat blood serum AKP and significantly raises, and disclosing bone turnover rate and bone formation obviously increases.Product high and low dose provided by the invention all has the tendency that reduces ovariectomized female rats serum AKP level activity, but not obvious.So, the thin compound medicines for the treatment of bone whether by reducing bone turnover rate, reduce mechanism that bone loss plays the effect of control osteoporosis in ovariectomized rats and need further research.Retinoic acid causes osteoporosis model group rat blood serum AKP significantly to be reduced, and the thin compound medicines high dose for the treatment of bone can improve retinoic acid and cause osteoporosis rat serum AKP level activity, illustrates that the thin compound medicines for the treatment of bone has the effect of promoting bone growing.
The pathological change of removal ovary rat bone tissue under light microscopic: due to the effect of bone resorption, finally make that bone trabecula attenuates, attenuation, so that fracture, bone trabecula is connected and destroyed, occur that the gap between bone trabecula becomes large, bone trabecula is sparse etc.Retinoic acid causes the pathological change of osteoporosis rat osseous tissue: bone trabecula is sparse, fracture, arrangement disorder, osteoclast hypertrophy, indivedual focal acidophilia's degeneration of the visible hyaline cartilage of animal.The thin compound medicines high dose group ovariectomized in rats tissue pathological slice for the treatment of bone all shows bone trabecula marshalling, medullary cavity normal in size, show that product high dose provided by the invention can improve the microstructural pathological change of ovariectomized female rats osseous tissue, may play a role to prevention of osteoporosis fracture.Thin high, the middle dosage group of the compound medicines retinoic acid for the treatment of bone causes the section of osteoporosis rat bone pathology and is shown as normal epiphysis tissue, the visible bone trabecula of indivedual animals reduces, arrange and evacuate, point out high, the middle dosage of product provided by the invention can improve retinoic acid and cause the microstructural pathological change of osteoporosis rat osseous tissue.
Conclusion: the thin compound medicines for the treatment of bone provided by the invention is in range of doses, there is the retinoic acid of increasing and cause osteoporosis rat bone density, improve bone biomechanical index, improve the microstructural pathological change of bone, the effect of rising blood calcium, serium inorganic phosphorus, alkali phosphatase; In range of doses, there is the retinoic acid of increasing and cause osteoporosis rat bone density, improve the microstructural pathological change of bone, the effect of rising serium inorganic phosphorus.Treatment bone thin compound medicines has certain antagonism removal ovary and causes the effect of rats with osteoporosis and prolapse of lumbar intervertebral disc.
3 clinical research interpretations of result
Adopt 100 examples of compound medicines treatment senile osteoporosis provided by the invention and prolapse of lumbar intervertebral disc, obvious effective rate 63%, total effective rate 95%, has statistical significance with calcareacarbonica chewable tablet group (obvious effective rate 20%, the total effective rate 64%) difference of making comparisons.Treatment of lumbar disc herniation 120 examples, total effective rate is 94.7%. matched group 120 examples, total effective rate 83.83%, therefore, two groups relatively have significant difference.
4 safety analysiss
Get Kunming kind white mice the thin compound medicines for the treatment of bone is carried out to acute toxicity test, LD50 is the credible 63.95 ± 5.66g/kg that is limited to of 63.95g/kg, LD5095%.In clinical application research, during all cases medication treatment, do not find untoward reaction.Before and after treatment, patient is done the routine examinations such as blood, urine, feces routine, liver, renal function, electrocardiogram, do not find because of take product provided by the invention cause the large routine of patient three and liver, renal function, electrocardiogram etc. extremely, proof oral product provided by the invention in this clinical research dosage range treats senile osteoporosis and prolapse of lumbar intervertebral disc does not find to exist obvious toxic and side effects, and clinical practice can be provided.

Claims (7)

1. treat the thin compound medicines of bone, it is characterized in that, made by the component of following weight parts: Herba Epimedii 70-90 part, Herba Cistanches 40-60 part, Radix Polygoni Multiflori 70-90 part, red three 70-90 part, Semen Cuscutae 40-60 part, Fructus Lycii 40-60 part, Rhizoma Curculiginis 25-35 part, Radix Morindae Officinalis 25-35 part, Fructus Corni 25-35 part, Bombyx Batryticatus 25-35 part, Radix Rehmanniae Preparata 40-60 part, Radix Angelicae Sinensis 25-35 part, Scolopendra 7-13 part.
2. the thin compound medicines for the treatment of bone according to claim 1, is characterized in that, is made up of the component of following weight parts: Herba Epimedii 75-85 part, Herba Cistanches 45-55 part, Radix Polygoni Multiflori 75-85 part, Radix Salviae Miltiorrhizae 75-85 part, Semen Cuscutae 45-55 part, Fructus Lycii 45-55 part, Rhizoma Curculiginis 28-32 part, Radix Morindae Officinalis 28-32 part, Fructus Corni 28-32 part, Bombyx Batryticatus 28-32 part, Radix Rehmanniae Preparata 45-55 part, Radix Angelicae Sinensis 28-32 part, Scolopendra 9-11 part.
3. according to the thin compound medicines for the treatment of bone described in claim 1 or 2, it is characterized in that, made by the component of following weight parts: 80 parts of Herba Epimedii, 50 parts of Herba Cistanches, 80 parts of Radix Polygoni Multiflori, 80 parts of Radix Salviae Miltiorrhizaes, 50 parts of Semen Cuscutae, 50 parts of Fructus Lyciis, 30 parts of Rhizoma Curculiginises, 30 parts of Radix Morindae Officinaliss, 30 parts of Fructus Corni, 30 parts of Bombyx Batryticatus, 50 parts of Radix Rehmanniae Preparata, 30 parts of Radix Angelicae Sinensis, 10 parts of Scolopendras.
4. according to the thin compound medicines for the treatment of bone described in claim 1 or 2, it is characterized in that, use photograph the thin layer chromatography of Chinese Pharmacopoeia version in a 2000 annex VIB, and with ursolic acid in contrast when product detection, this compound medicines manifests the speckle of same color on the corresponding position of described reference substance.
5. the polypharmaceutic method that preparation treatment bone claimed in claim 1 is dredged, is characterized in that, comprises the steps: successively
1) take each component by weight portion claimed in claim 1;
2) by step 1) Bombyx Batryticatus, Radix Salviae Miltiorrhizae, the powder of Fructus Corni that take be broken into fine powder;
3) by step 1) take by Herba Epimedii, Herba Cistanches, Radix Polygoni Multiflori, Semen Cuscutae, Fructus Lycii, Rhizoma Curculiginis, Radix Morindae Officinalis, Radix Rehmanniae Preparata, Radix Angelicae Sinensis and Scolopendra mix, and add gross mass 2-10 water doubly, decoct secondary; Collecting decoction, collects filtrate after filtering, and filtrate is condensed into the thick paste that relative density is 1.05-1.5, and temperature is 50C °-70C °;
4) to step 3) described thick paste adds step 1) described fine powder, mix rear dryly, be again ground into fine powder, granulate, compressed tablet, sugar coating, to obtain final product.
6. the polypharmaceutic method that preparation according to claim 5 treatment bone is dredged, is characterized in that step 1) described fine powder particle diameter is 60-100 order.
7. the polypharmaceutic method that preparation according to claim 5 treatment bone is dredged, is characterized in that step 4) decocting time is 2 hours for the first time when described decoction, decocting time is 1.5 hours for the second time.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105535709A (en) * 2015-12-29 2016-05-04 朱晓杰 Traditional Chinese medicine composition for treating senile osteoporosis

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