CN101406517A - Use of pharmaceutical composition in preparing medicament for preventing and treating osteoporosis - Google Patents
Use of pharmaceutical composition in preparing medicament for preventing and treating osteoporosis Download PDFInfo
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Abstract
The invention relates to novel application of a medical composition to the preparation of a medicine for preventing and treating osteoporosis. The formula consists of 750 portions of radix salviae miltiorrhizae and 250 portions of safflower. The preparation formulations comprise injection, pills, granules, hard capsules, soft capsules, tablets, dripping pills or orally taken liquid preparation. The invention aims to provide the novel treating application of the medical composition, widen the clinical application scope of the medical composition, and avoid waste of good medicine resources.
Description
Technical field
The present invention relates to and belongs to field of medicaments, is specifically related to the application of a kind of pharmaceutical composition in preparation control medicine for treating osteoporosis.
Background technology
Osteoporosis is human a kind of common disease, in all ages and various group generation is arranged all, its sickness rate increased and increases along with the age, and especially prevalence is the highest in the old people of over-65s, wherein owing to other influence of hormones, the women suffers from the twice that osteoporosis is the male.The whole world has 200,000,000 people to suffer from osteoporosis approximately at present, its sickness rate has leapt to commonly encountered diseases, frequently-occurring disease the 7th, as the U.S. 2,500 ten thousand patients are arranged approximately, the annual fracture patient that is caused by osteoporosis is 1,500,000 examples down, just have 1/3 number to suffer from osteoporosis among 1,500 ten thousand old peoples of Japanese national over-65s approximately.All kinds of fracture that osteoporosis can cause, wherein also have quite a few various complication can occur, about 20% fracture patient concurrent pulmonary infarction, pneumonia and death in 1 year, the summation that surpasses mastocarcinoma, cervical cancer and uterus carcinoma at this type of mortality rate of women, 50% human action inconvenience is also arranged in the survivor, and it is many unfavorable to bring for family and patient.Therefore osteoporosis causes the miscellaneous fracture medical expense costly, and according to official statistics, the U.S. is used for directly and indirectly costing of osteoporosis aspect every year and reaches 10,000,000,000 dollars; The fund that the health of Britain and social security institution every year provide for osteoporosis is above 500,000,000 pounds; France only pays every year on average, and 30,000 femur and tibias folding patient's cost of hospitalization just reaches 13.5 hundred million French Francs.Huge social like this and financial burden that osteoporosis caused have constituted a serious global problem, have caused the very big concern of countries in the world.China is the maximum country of aging population in the world, sufferers of osteoporosis face has reached 6000-8000 ten thousand examples, developing country as maximum, the influence that such patient brings for family and society is heavier than developed country, therefore, preventing and treating osteoporosis is defying age, and life-saving guarantees the very urgent research topic of people's living standard.
According to defining of WHO tissue in 1994, osteoporosis is meant with the osseous tissue microstructure impaired, and bone ore deposit composition and bone matrix equal proportion ground constantly reduce the sclerotin attenuation, bone trabecula quantity reduces, the disease of a kind of whole body dysostosis that increase of bone fragility and risk of fractures degree raise.According to the disease characteristics, therapeutic strategy roughly has two classes at present, and one is the medicine of anti-bone resorption, and two for facilitating the bone medicine.As estrogen, calcitonin, diphosphate etc. is bone resorption inhibitor, and this type of medicine accounts for more than 90% in clinical use; Facilitate the bone medicine that bone mineralising promoter is arranged, as calcium preparation, vitamin D etc.These medicines are very limited, life-time service not only costs an arm and a leg, and has than significant side effects, along with the Chinese medicine development of modernization, more people turns to sight in the research and development of Chinese medicine, has applied for the Chinese medicine composition patent of invention of a lot of treatment osteoporosis in recent years.
After the DANHONG ZHUSHEYE listing in 2004, play an important role in cardiovascular and cerebrovascular diseases, this ingredient is simple relatively always, dosage form advanced person, and clinical efficacy is remarkable, and onset is rapid, is subjected to the favor of extensive patients deeply.We find advantages such as DANHONG ZHUSHEYE except curing mainly function, also have the good efficacy of protect against osteoporosis, and onset is rapid, and untoward reaction is few in a large amount of clinical uses.For many years, people never stopped for the research of two flavor principal agent Radix Salviae Miltiorrhizae and Flos Carthami in the DANHONG ZHUSHEYE, especially the research of their new therapeutic uses is flourish, be to disclose the effect that Radix Salviae Miltiorrhizae water extract or effective ingredient such as danshensu, TANSHINONES have protect against osteoporosis in 200310116281.9 the patent application as application number, disclosing in the application of application number 200710031802.9 with Radix Salviae Miltiorrhizae, Radix Notoginseng, Borneolum Syntheticum is that the FUFANG DANSHEN PIAN of principal agent is used for the treatment of new purposes of osteoporosis etc.Therefore, for the further new therapeutic use of exploitation DANHONG ZHUSHEYE, reduce the wasting of resources of medicine, on the basis of forefathers' research in conjunction with our clinical discovery, the present invention will carry out a series of dosage form and drug efficacy study to DANHONG ZHUSHEYE, for wider clinical application is taken a firm foundation.
Summary of the invention
The object of the present invention is to provide the new therapeutic use of a kind of pharmaceutical composition, be specifically related to the application of a kind of pharmaceutical composition in preparation control medicine for treating osteoporosis.
Drug regimen raw material of the present invention is made up of Radix Salviae Miltiorrhizae, Flos Carthami two flavor medical materials, wherein 750 parts of Radix Salviae Miltiorrhizaes, 250 parts on Flos Carthami.Pharmaceutical composition of the present invention has the effect of blood circulation promoting and blood stasis dispelling, TONGMAI SHULUO, the at present clinical thoracic obstruction and the apoplexy that is usually used in due to the blood stasis impatency.
Technical scheme of the present invention is achieved in that 750 parts of Radix Salviae Miltiorrhizaes, 250 part of two flavor of Flos Carthami medical material, decocts with water twice, each 1 hour, merge decocting liquid, and filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, and cold preservation filters, and adjust pH is to 8-9, and cold preservation filters, and filtrate recycling ethanol adds proper auxiliary materials and makes different dosage form to there not being the alcohol flavor.
Preparation of drug combination adjuvant of the present invention can be acceptable any excipient or a carrier on the pharmaceutics.
The application of pharmaceutical composition of the present invention can be an acceptable forms on the pharmaceutics, comprises injection, pill, granule, hard capsule, soft capsule, tablet, drop pill or oral liquid, optimizing injection.
When we are widely used in the clinical treatment cardiovascular and cerebrovascular disease with intravenous formulations of the present invention, chance on the phenomenon that it also has the effect of treatment osteoporosis, in order further to develop its therapeutic use, therefore the clinical research by small sample, roll over luxuriant PMD diagnostic criteria of starting proposition with the professor of Tokyo Univ Japan, screened 100 routine patients, single at random blind method is divided into treatment and organizes 50 examples, matched group 50 examples are with biochemical markers of bone metabolism, bone density, hematuria E
2Situation of change etc. for monitoring index carries out preliminary clinical research, found that the present invention and matched group relatively have apparent in view therapeutic effect, therefore, for research of the present invention is deeply promoted, now details are as follows with main effect experiment:
Experiment 1: the present invention causes the influence of rats with osteoporosis preventive effect to retinoic acid
1. test material
1.1 be subjected to the reagent thing:
Get Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials, add 10 times of amounts of water and decoct twice, each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, add ethanol to containing the alcohol amount more than 80%, cold preservation filters, and adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol adds an amount of dissolved in distilled water concentrated solution to there not being the alcohol flavor, it is centrifugal to leave standstill the back, separation of supernatant and to be prepared into an amount of concentration standby.Positive control drug: hydroxyethyl sodium phosphate, commercially available.
1.2 animal subject: the SD rat, male and female half and half, laboratory animal portion of Xian Medical Univ provides.
1.3 reagent: retinoic acid, commercially available, it is standby to be made into suspension with 0.5%CMC; Calcium, Shanghai Vaccine and Serum Institute provides; The phosphorus test kit, the prompt pupil's thing in Shanghai technology company.
1.4 instrument: DPX-L type dual intensity X line bone densitometry instrument, U.S. LunAR company produces; Muffle furnace, the PVG glad scientific instrument factory that jumps; The 722S spectrophotometer, Shanghai science precision instrument company limited.
2. test method and result
2.1.1 set up model
Rat is divided into 6 groups at random, be respectively the normal control group, model control group, height of the present invention, in, low dose group, positive controls, except that the normal control group, each organizes the equal gastric infusion retinoic acid of rat 70mg/kg, dose 1ml/100g rat, every day 1 time, continuous 14 days, respectively organize rat every day simultaneously and irritate the long-pending distilled water of stomach consubstantiality (normal control group) successively, 0.5%CMC solvent (retinoic acid group), high dose 2ml/kg of the present invention, dosage 1ml/kg among the present invention, low dose group 0.5ml/kg of the present invention, hydroxyethyl sodium phosphate 50mg/kg (positive control drug), every day 1 time, continuous 28 days, weigh weekly during this time 1 time, adjust the administration consumption with body weight.
2.1.2 observation index
Administration finishes, and the sacrificed by decapitation rat is got blood system from serum, presses kit method and surveys S-Ca, S-P content, gets rat bilateral femur, peels meat and other tissue off, and wherein a side femur is done rat femur scanning on borne densitometers, measures bone density (g/cm
2), claim bone heavy (W), survey bone long (L), bone diameter (d) calculates bone lines of expression density (W/L), apparent surface density (W/L.d), dried 1 hour for 110 ℃ then, place interior 200,400,600,800 ℃ of each ashing of muffle furnace 2 hours again, after ashing finishes cooling, claim ash to weigh (Wash.g), extract the back with 6N HCL and survey bone ash Ca, bone ash P content, the gram numerical table that contains Ca or P with the 100g bone ash shows.
Opposite side femoral head 3%HNO
3Do paraffin section after the decalcification, HE dyeing, microscopically is surveyed the bone trabecula width.
2.2 result of the test:
2.2.1 rat body weight changes:
The results are shown in Table 1.
Table 1 the present invention causes the body weight change influence of rats with osteoporosis preventive effect to retinoic acid
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Result of the test shows, the equal no significant difference of each treated animal body weight in the test same day and the 1st week, and 2,4 all model group weight ratio normal group body weight all have obviously and alleviate (P＜0.05, P＜0.01) after the administration, show experiment modeling success.After 2 weeks of medication, each administration group and model group relatively, the high, medium and low dosage group of the present invention all has the effect that increases rat body weight, height wherein of the present invention, middle dosage group weight increase there were significant differences (P＜0.05, P＜0.01), and curative effect suitable with the positive controls hydroxyethyl sodium phosphate.
2.2.2 the influence of rat femur bone density and S-Ca, S-P
The results are shown in Table 2.
When table 2 the present invention causes the rats with osteoporosis preventive effect to retinoic acid
The influence of femoral bmd, Sca, Sp (x ± SD)
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Result of the test shows that model group rat femur bone density, serum Ca content obviously reduce (P＜0.01 or P＜0.05) than normal control group, and serum paraoxonase content has reduction trend, but changes not quite, whole situation explanation modeling success.After the medication, each administration group and model group are relatively, bone density, serum calcium levels, serum paraoxonase content all have rising by a relatively large margin, and height wherein of the present invention, three indexs of middle dosage group all have significant difference (P＜0.01 or P＜0.05), and curative effect and positive controls are suitable.
2.2.3 the present invention is to the exponential effect of Induced by Retinoic Acid rats with osteoporosis preventive effect bone
The results are shown in Table 3.(number of animals is 10)
Table 3 the present invention causes the exponential effect of rats with osteoporosis preventive effect bone (x ± SD) to retinoic acid
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Result of the test shows that model group and matched group compare, and the W of model group, L, d, W/L, W/Ld all have obvious reduction, shows the modeling success.After the administration, each administration group and model group more all have the exponential effect of rising experimental rat bone, and middle and high dosage group curative effect wherein of the present invention is (P＜0.01 or P＜0.05) significantly, compare therapeutic equivalence with positive controls.
2.2.4 influence to femur ash, bone Ca and bone P
The results are shown in Table 4.(number of animals is 10)
Table 4 the present invention causes the rats with osteoporosis preventive effect to retinoic acid
The influence of femur ash, bone Ca, bone P (x ± SD)
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Experimental result shows that model group and matched group compare, and bone Ca, bone P content all significantly reduce (P＜0.01 or P＜0.05) in the bone ash weight of model group, the bone ash, and the modeling success is described.After the administration, administration group and model group more all have the effect of bone Ca, bone P content in various degree rising bone ash weight, the bone ash, and middle and high dosage group curative effect wherein of the present invention is best, and suitable with the positive controls therapeutic effect.
Experiment 2: the present invention causes the influence of rats with osteoporosis therapeutical effect to retinoic acid
1. test material
1.1 be subjected to the reagent thing: with experiment 1.
1.2 animal subject: the SD rat, male and female half and half, laboratory animal portion of Xian Medical Univ provides.
1.3 reagent: with experiment 1.
1.4 instrument: with experiment 1.
2. test method and result
2.1.1 set up model
Rat is divided into 6 groups at random, be respectively normal control group, model control group, the high, medium and low dosage group of the present invention, positive controls, except that the normal control group, each organizes the equal gastric infusion retinoic acid of rat 70mg/kg, dose 1ml/100g rat, every day 1 time, continuous 14 days, finish each administration group of back by each dosage group gastric infusion, every day 1 time, continuous 28 days, normal control group and model group gave isopyknic solvent, during adjust dosage according to body weight.
2.1.2 observation index
Administration finishes, and the sacrificed by decapitation rat is got blood system from serum, presses kit method and surveys S-Ca, S-P content, gets rat bilateral femur, peels meat and other tissue off, and wherein a side femur is done rat femur scanning on borne densitometers, measures bone density (g/cm
2), claim bone heavy (W), survey bone long (L), bone diameter (d) calculates bone lines of expression density (W/L), apparent surface density (W/L.d), dried 1 hour for 110 ℃ then, place interior 200,400,600,800 ℃ of each ashing of muffle furnace 2 hours again, after ashing finishes cooling, claim ash to weigh (Wash.g), extract the back with 6N HCL and survey bone ash Ca, bone ash P content, the gram numerical table that contains Ca or P with the 100g bone ash shows.
Opposite side femoral head 3%HNO
3Do paraffin section after the decalcification, HE dyeing, microscopically is surveyed the bone trabecula width.
2.2 result of the test:
2.2.1 rat body weight changes:
The results are shown in Table 5.
Table 5 the present invention causes the body weight change influence of rats with osteoporosis therapeutical effect to retinoic acid
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Result of the test shows, the equal no significant difference of each treated animal body weight in the test same day and the 1st week, and 3,6 all model group weight ratio normal group body weight all have obviously and alleviate (P＜0.05, P＜0.01) after the administration, show experiment modeling success.After 3 weeks of medication, each administration group and model group relatively, the high, medium and low dosage group of the present invention all has the effect that increases rat body weight, height wherein of the present invention, middle dosage group weight increase there were significant differences (P＜0.05, P＜0.01), and curative effect suitable with the positive controls hydroxyethyl sodium phosphate.
2.2.2 influence to rat femur bone density and Sca, SP
The results are shown in Table in 6.(number of animals is 10)
When table 6 the present invention causes the rats with osteoporosis therapeutical effect to retinoic acid
Femur density and SCa, SP variable effect (x ± SD)
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Experimental result shows that model group and matched group compare, and bone Ca, bone P content all significantly reduce (P＜0.01 or P＜0.05) in the bone density of model group, the bone ash, and the modeling success is described.After the administration, administration group and model group more all have the effect of bone Ca, bone P content in various degree rising bone density, the bone ash, and middle and high dosage group curative effect wherein of the present invention is best, and suitable with the positive controls therapeutic effect.
2.2.3 the present invention is to the influence of Induced by Retinoic Acid rats with osteoporosis therapeutical effect bone index variation
The results are shown in Table in 7.(every treated animal number average is 10)
Table 7 the present invention causes the influence (x ± SD) of rats with osteoporosis therapeutical effect bone index variation to retinoic acid
* and blank group compare, P＜0.01; * compare P＜0.05 with the blank group.## and model control group compare, P＜0.01; # and model control group compare, P＜0.05.
Result of the test shows that model group and matched group compare, and the W of model group, L, d, W/L, W/Ld all have obvious reduction (P＜0.01 or P＜0.05), shows the modeling success.After the administration, each administration group and model group more all have the exponential effect of rising experimental rat bone, and middle and high dosage group curative effect wherein of the present invention is (P＜0.01 or P＜0.05) significantly, compare therapeutic equivalence with positive controls.
Experiment 3: the present invention is to the influence of castrated rats osteoporosis experimental model
1. test material
1.1 be subjected to the reagent thing:
With experiment 1.Positive control drug: GUSHUKANG KELI, commercially available.
1.2 animal subject: the SD rat, male and female half and half, laboratory animal portion of Xian Medical Univ provides.
1.3 reagent: chloral hydrate, commercially available, 10% concentration is standby with before being made into; Tetracycline, commercially available; Toluidine blue, commercially available; Serum calcium, phosphorus, alkaline phosphatase enzyme reagent kit, Beijing Zhongsheng Biological Engineering High Technology Company; The hydroxyproline standard substance, the biochemical institute in Chinese Academy of Sciences Shanghai; The creatinine reagent box, Beijing Zhongsheng Biological Engineering High Technology Company; The estradiol radioimmunological kit, Depew, Tianjin biotechnology and medical product company limited; Calcitonin is put and is exempted from medicine box, and Science and Technology Development Center of Chinese People's Liberation Army General Hospital puts and exempts from Research Institute; Bone Gla protein is put and is exempted from medicine box, and Science and Technology Development Center of Chinese People's Liberation Army General Hospital puts and exempts from Research Institute.
1.4 instrument: NORLAND X2-36 type dual intensity X line bone densitometry instrument, U.S. LunAR company produces; The WD-1 type electronic universal tester, Xi'an Ming Kesi checkout equipment company limited; Jarrell-Ash ICAP9000 type inductively coupled plasma spectrogrph, Shanghai science precision instrument company limited; LEICA 2163 type microtomes, German Leica company; Olympus BH-2 microscope, Nanjing power scientific instrument difficult to understand company limited.
2. test method and result
2.1.1 set up model
Each organizes rat with 10% chloral hydrate 350mg/kg intraperitoneal injection of anesthesia, cuts the otch of 1.5cm size over against the position of ovary in the spinal column both sides, separates muscle of back, exposes posterior peritoneum, takes out bilateral ovaries after cutting off peritoneum.Sham operated rats is left intact and puts back to the abdominal cavity after ovary is taken out, and sews up wound, sterilization; The operation group is excised after with the bilateral ovaries ligation, sews up wound, sterilization.Sham operated rats is given normal feedstuff, and all the other each groups are given low calcium feedstuff, freely drink water.Raise after 3 months and put to death.
2.1.2 grouping and administration
Get 60 of female sd inbred rats, be divided into 6 groups at random, every group of 10 rats.Sham operated rats keeps ovary, dosage group, low dose group of the present invention etc. are respectively organized rat and are done ovariectomy after 5 days among osteoporosis model group, positive controls (GUSHUKANG KELI), the heavy dose of group of the present invention, the present invention, sham operated rats, model group rat give certain water gaging every day, all the other respectively organize administration according to dosage, every day gastric infusion once, successive administration 3 months.
2.1.3 observation index
After administration finishes, draw materials after each treated animal anesthesia, measure following index respectively:
(1) blood calcium, serium inorganic phosphorus and blood alkali phosphatase:
The common carotid artery intubate is got blood, preserved 4 hours for 4 ℃, 4000 rev/mins centrifugal 10 minutes, separation of serum.The OCPC method is adopted in blood calcium determination, and serium inorganic phosphorus is measured the molybdic acid method that adopts, and King's method is adopted in serum alkaline phosphatase determination, all by the procedure operation of test kit description, measures with the MD-100 automatic biochemical analyzer.
(2) urine hydroxyproline (HOP), creatinine:
Rat is put to death and goes into metabolic cage the previous day, fasting, and normal drinking-water is collected its twenty-four-hour urine liquid.Measure and adopt improvement chloramine-T oxidizing process to measure; Picric acid method is adopted in creatinine assay, presses the operation of test kit description, measures with the MD-100 automatic biochemistry analyzer.
(3) serum hormone (estradiol, calcitonin, Bone Gla protein):
The common carotid artery intubate is got blood, preserved 4 hours for 4 ℃, 4000 rev/mins centrifugal 10 minutes, separation of serum.Estradiol uses the operation of estradiol radioimmunological kit by specification; Calcitonin uses calcitonin to put and exempts from the operation of medicine box by specification; Bone Gla protein uses Bone Gla protein to put and exempts from the operation of medicine box by specification.
(4) bone density:
After rat is put to death, strip its left side femur, pick os purum muscle and soft tissue on every side, use the normal saline scrub, wrap up respectively with the normal saline gauze, bone density and biomechanics of bone intensity are surveyed in-40 ℃ of preservations fully.Survey femoral bmd with the bone densitometry instrument, the left side femur is faced upward placed the enterprising line scanning of poly (methyl methacrylate) plate, step pitch 0.5*0.5mm; Scanning speed 30mm/s; Sweep length 6.55cm.After bone densitometry finishes, will femur-40 ℃ preservation, send and survey biomechanics of bone intensity.
(5) biomechanics of bone intensity:
Place the WD-1 type electronic universal tester to make the three-point bending mechanical test femur, span 25mm, loading velocity 2mm/min, record load-deflection curve.Calculate maximum load, maximum oar degree, bending rigidity, energy absorption from curve.
(6) bone inorganic element content:
Rat strips its right side femur after putting to death, and picks os purum muscle and soft tissue on every side, uses the normal saline scrub.Measure the content of inorganic elementss such as bone calcium, bone phosphorus, bone magnesium, bone zinc, bone aluminum.
(7) vertebra osseous tissue morphometry:
Rat was put to death preceding the 14th day, irritated stomach tetracycline 35-40mg/kg, continuous 2 days.After being separated by 10 days, 2 days tetracyclines of continuous irrigation stomach in kind again.After the execution, get third and fourth lumbar vertebra, after fixing, dehydration, embedding etc. are handled, with the machine-processed vertical undecalcified bone slice that is equipped with 5 μ m of bone slice, Toluidine blue staining.Toluidine blue staining is not made in the section that is used for Fluirescence observation.With microscope, the observation of JVCPK-C1380 image pick-up card, adopt bone histomorphometry's analysis software that observation index is measured and analyzes.The parameters that adopts is: bone trabecula surface percentage, bone formation surface percentage, bone resorption surface percentage, average bone wall thickness and or mineralising deposition.
2.2 experimental result
2.2.1 the situation of change of rat blood calcium, serium inorganic phosphorus and blood alkali phosphatase:
The results are shown in Table in 8.
Table 8 the present invention is to the influence of rat model blood calcium, phosphorus, alkali phosphatase and urine proline/creatinine (x ± SD)
Compare * * P＜0.01 with sham operated rats; Compare #P＜0.05, ##P＜0.01 with model group.
Show by table 8 result, the serum alkaline phosphatase of model group rat (ALP) and urine hydroxyproline/creatinine (HOP/Cr) are all than the obvious rising (P＜0.01) of sham operated rats, show that bone formation and bone resorption that castration causes strengthen simultaneously, but bone resorption is relatively greater than bone formation, thereby the bone amount can not be kept the generation that balance can cause rats with osteoporosis well, i.e. modeling success.After giving medicine, each dosage group of the present invention and positive controls all can make ALP activity and HOP/Cr ratio significantly reduce (P＜0.05 or P＜0.01), and wherein the present invention's middle and high dosage group curative effect is suitable with positive controls.Illustrate that the present invention can significantly improve the alkali phosphatase that the castrated rats osteoporosis causes and the unusual rising of urine hydroxyproline/creatinine ratio.
2.2.2 serum hormone variable effect
The results are shown in Table in 9.
The influence that table 9 the present invention changes the rat hormonal readiness (x ± SD)
Compare * * P＜0.01 with sham operated rats; Compare #P＜0.05, ##P＜0.01 with model group; Compare ， ﹠amp with positive controls; P＜0.05.
Show by table 9 result, three serum hormone of model group rat are all than the remarkable reduction of sham operated rats (P＜0.01), after giving medicine, each administration group all can obviously improve hormone serum level (P＜0.05 or P＜0.01), wherein the middle and high dosage group of the present invention curative effect is the most remarkable, compare with positive controls, have significant difference (P＜0.05) on changing, illustrate that the present invention can improve the hormone serum level of osteoporosis model rat very effectively in calcitonin, Bone Gla protein level.
2.2.3 femoral bmd variable effect
The results are shown in Table in 10.
The situation that influences that table 10 the present invention changes the rat femur bone density (x ± SD)
Compare * * P＜0.01 with sham operated rats; Compare ##P＜0.01 with model group; Compare ， ﹠amp with positive controls; P＜0.05.
Can cause after the rat castration that bone density significantly reduces, form osteoporosis, give medicine after, each administration group can obviously increase rat bone density, high dose group curative effect wherein of the present invention is the most remarkable, compares with positive controls, and high dose group of the present invention has significant difference (P＜0.05).This shows that the present invention can obviously increase the bone density of castration Osteoporosis Rats.
2.2.4 the variable effect of femur inorganic elements
The influence that table 11 the present invention changes castrated rats femur inorganic element content (x ± SD)
Compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare #P＜0.05, ##P＜0.01 with model group.
There is table 11 result to show, the content of calcium, magnesium, zinc significantly reduces in the castrated rats osseous tissue, give medicine after, each administration group all can obviously improve the content (P＜0.05 or P＜0.01) of above-mentioned inorganic elements, high dose group wherein of the present invention and positive controls curative effect the best, and quite.
2.2.5 the influence of femur biomechanics
The results are shown in Table in 12.
Table 12 the present invention is to the situation that influences of rat femur biomechanical strength (x ± SD)
Compare * P＜0.05, * * P＜0.01 with sham operated rats; Compare #P＜0.05, ##P＜0.01 with model group.
Show that by table 12 result every index of model group rat all is starkly lower than sham operated rats, promptly less external force and energy can be fractured, rat had suffered from osteoporosis after the excision ovary was described, bone structure changes, flexibility decrease, and fracture risk improves.After giving Drug therapy, each administration group can obviously improve indexs (P＜0.05 or P＜0.01) such as maximum load, maximum oar degree, bending rigidity, energy absorption, wherein middle and high dosage group of the present invention and positive controls curative effect are good, and quite, illustrate that the present invention can significantly improve the mechanical property of osteoporosis rat osseous tissue, reduce the danger of fracture, may with the present invention's bone density that raises, increase bone mineral content content and increase the bone amount relevant.
2.2.6 the influence of osseous tissue morphometry
The results are shown in Table in 13.
Table 13 the present invention is to the situation that influences of rat bone tissue norphometry mathematic(al) parameter (x ± SD)
Compare * * P＜0.01 with sham operated rats; Compare #P＜0.05, ##P＜0.01 with model group; Compare ， ﹠amp with positive controls; P＜0.05.
Show by table 13 result, after rat is extractd ovary, bone trabecula and form generation significant change thereof, bone trabecula surface percentage, average bone wall thickness and mineralising deposition all are starkly lower than sham operated rats, and bone formation surface percentage, bone resorption surface percentage obviously increase, and bone trabecula decreased number, gap increase, after having shown the rat castration, bone formation and bone resorption are all hyperfunction, but bone resorption is relatively greater than bone formation, thereby cause bone loss to cause osteoporosis.After giving Drug therapy, each administration group all can significantly improve bone trabecula surface percentage, mineralising deposition, reduces bone formation surface percentage, bone resorption surface percentage, and average bone wall thickness is increased.High dose group curative effect wherein of the present invention is the most remarkable, compares with positive controls, and significant difference (P＜0.05) is being arranged aspect bone resorption surface percentage, bone formation surface percentage and the average bone wall thickness.Explanation thus, the present invention can obviously promote the formation and the mineralising of osteoporosis rat osteoid, and significantly suppresses bone resorption, osteoplastic abnormal conditions, can improve the microstructure of bone, weighs, improves bone structure thereby increase bone, promotes the mechanical property of bone to improve.
This shows that above results of pharmacodynamic test lays a solid foundation for the novel clinical use that the present invention treats osteoporosis.
The specific embodiment
Embodiment 1
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, and cold preservation filters, and adjust pH is to 8-9, cold preservation filters, and filtrate recycling ethanol adds water to 1000ml, cold preservation to there not being the alcohol flavor, filter, add water to ormal weight, packing, sterilization promptly gets injection.Usage and dosage: intramuscular injection, a 2-4ml, 1-2 time on the one; Intravenous injection, a 4ml adds the slowly injection of 50% glucose injection 20ml dilution back, 1-2 time on the one; Intravenous drip, a 20-40ml adds 5% glucose injection 100-500ml dilution back and slowly instils 1-2 time on the one; During with special circumstances such as diabetes, use 0.9% normal saline dilution back use instead; Or follow the doctor's advice.
Embodiment 2
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, cold preservation, filter, adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol adds appropriate amount of starch, sodium carboxymethyl cellulose, stevioside to there not being the alcohol flavor, mixing is crossed 80 mesh sieves, add suitable quantity of water and granulate 60 ℃ of drying under reduced pressure, granulate, the 1000g granule is made in packing.Usage and dosage: once take 20-40g, 1-2 time on the one.
Embodiment 3
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, cold preservation, filter, adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol is to not having alcohol flavor, drying under reduced pressure, crushing screening, add starch, mixing incapsulates after granulating, and makes the 1000g hard capsule.Usage and dosage: once take 20-40g, 1-2 time on the one.
Embodiment 4
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, and cold preservation filters, and adjust pH is to 8-9, and cold preservation filters, and filtrate recycling ethanol is not to there being the alcohol flavor, and drying under reduced pressure was pulverized 120～180 mesh sieves.With gelatin, water and glycerol (1: 1: 0.3-0.45) melt heat preservation for standby use behind the glue, medicated powder added an amount of vegetable oil (soybean oil or salad oil) and stirs evenly, and colloid mill grinds to form even heavy-gravity pastel, the decompression degasification, the 1000g soft capsule is made in compacting.Usage and dosage: once take 20-40g, 1-2 time on the one.
Embodiment 5
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, cold preservation, filter, adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol is to not having alcohol flavor, drying under reduced pressure, crushing screening, add appropriate amount of starch, micropowder silica gel and magnesium stearate, granulate, compacting in flakes, coating is made the 1000g tablet.Usage and dosage: once take 20-40g, 1-2 time on the one.
Embodiment 6
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, cold preservation, filter, adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol is to not having alcohol flavor, drying under reduced pressure, pulverized 120 mesh sieves, joined in 3: 1 the molten polyethylene glycol 4000-polyethylene glycol 6000 of 4 times of amounts, stirred, be transferred to the drop pill machine, drip and make ball, remove the dimethicone on surface, packing is made the 1000g drop pill.Usage and dosage: once take 20-40g, 1-2 time on the one.
Embodiment 7
Radix Salviae Miltiorrhizae 750g, Flos Carthami 250g two flavor medical materials add 10 times of amounts of water and decoct twice, and each 1 hour, merge decocting liquid, filter, filter after the clarification cold preservation.Filtrate adds an amount of gelatin, and cold preservation filters.It is 1.10-1.20 (65 ℃) that filtrate is concentrated into relative density, adds ethanol to containing the alcohol amount more than 80%, cold preservation, filter, adjust pH is to 8-9, cold preservation, filter, filtrate recycling ethanol adds water and leaves standstill to there not being the alcohol flavor, filter, filtrate adds an amount of 1.2-propylene glycol, ethyl hydroxybenzoate, aspartame, and adding distil water more at last is after stirring, the 1000ml oral liquid is made in the embedding sterilization.Usage and dosage: once take 20-40ml, 1-2 time on the one.
Claims (6)
1, the application of a kind of pharmaceutical composition in preparation prevention and treatment medicine for treating osteoporosis is characterized in that according to the weight portion meter raw material of making this drug composition active component is: 750 parts of Radix Salviae Miltiorrhizaes, 250 parts on Flos Carthami.
2, the application in the preparation as claimed in claim 1 control medicine for treating osteoporosis is characterized in that: 250 parts of 750 parts of Radix Salviae Miltiorrhizaes, Flos Carthami become injection, pill, granule, hard capsule, soft capsule, tablet, drop pill or oral liquid for feedstock production.
3, the application in the preparation control medicine for treating osteoporosis as claimed in claim 2 is characterized in that described pharmaceutical composition is an injection.
4, as the application in claim 1, the 2 or 3 described preparation control medicine for treating osteoporosis, it is characterized in that described osteoporosis is primary osteoporosis and secondary osteoporosis.
5, the application in the preparation control medicine for treating osteoporosis as claimed in claim 4 is characterized in that described osteoporosis is a primary osteoporosis.
6, primary osteoporosis as claimed in claim 5 is the degeneration osteoporosis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008102324279A CN101406517A (en) | 2008-11-26 | 2008-11-26 | Use of pharmaceutical composition in preparing medicament for preventing and treating osteoporosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008102324279A CN101406517A (en) | 2008-11-26 | 2008-11-26 | Use of pharmaceutical composition in preparing medicament for preventing and treating osteoporosis |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240321A (en) * | 2010-05-14 | 2011-11-16 | 中国人民解放军第三军医大学第一附属医院 | Medicinal composition for treating bone infarction and preparation method and application thereof |
| CN104116868A (en) * | 2014-08-14 | 2014-10-29 | 赖祥林 | Compound medicine for treating osteoporosis and preparation method thereof |
| CN108578470A (en) * | 2018-05-23 | 2018-09-28 | 广东永青生物科技有限公司 | The pharmaceutical composition that the hyperthyroid high conversion hysteria bone loss of one group of improvement and bone biomechanical property decline |
-
2008
- 2008-11-26 CN CNA2008102324279A patent/CN101406517A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102240321A (en) * | 2010-05-14 | 2011-11-16 | 中国人民解放军第三军医大学第一附属医院 | Medicinal composition for treating bone infarction and preparation method and application thereof |
| CN104116868A (en) * | 2014-08-14 | 2014-10-29 | 赖祥林 | Compound medicine for treating osteoporosis and preparation method thereof |
| CN104116868B (en) * | 2014-08-14 | 2017-09-15 | 玉林市中西医结合骨科医院 | Treat thin compound medicine of bone and preparation method thereof |
| CN108578470A (en) * | 2018-05-23 | 2018-09-28 | 广东永青生物科技有限公司 | The pharmaceutical composition that the hyperthyroid high conversion hysteria bone loss of one group of improvement and bone biomechanical property decline |
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Owner name: HEZE BUCHANG PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: BUCHANG MEDICAL SCIENCE + TECHNOLOGY DEVELOPING CO., LTD., XIANYANG CITY Effective date: 20100108 |
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Effective date of registration: 20100108 Address after: 99, Kunming Road, peony Industrial Park, Shandong, Heze Province, China: 274000 Applicant after: Heze Buchang Pharmaceutical Co.,Ltd. Address before: The postcode of Western Yuquanlu Road, Shaanxi, Xianyang Province, 712000 Applicant before: Buchang Medical & Drug Science & Tech. Development Co., Ltd., Xianyang |
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Application publication date: 20090415 |