CN1234371C - Application of nano copper powder for preparing medicine for prophylaxis of osteoporosis and bone fracture - Google Patents
Application of nano copper powder for preparing medicine for prophylaxis of osteoporosis and bone fracture Download PDFInfo
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- CN1234371C CN1234371C CNB031109551A CN03110955A CN1234371C CN 1234371 C CN1234371 C CN 1234371C CN B031109551 A CNB031109551 A CN B031109551A CN 03110955 A CN03110955 A CN 03110955A CN 1234371 C CN1234371 C CN 1234371C
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
Abstract
The present invention relates to the application of nanometer copper powder for preparing medicines for preventing and treating osteoporosis and fracture, which has the essential technology that commercial nanometer copper powder of which the particle diameter is from 0.1 to 1000 nm is used as raw materials, and the proportion by weight of the nanometer copper powder as the raw materials of prepared medicines to preparations is from 0.00025 to 0.0125: 1. The effects of the nanometer copper powder on resisting osteoporosis and promoting fracture healing are fully used so as to effectively overcome problems existing in the prior art. The medicines are ideal medicines for preventing and treating osteoporosis, primary osteoporosis, secondary osteoporosis and fracture caused by osteoporosis, and has the advantages of outstanding curative effect and low toxic side effect.
Description
Technical field
The present invention is the application of a kind of copper nanoparticle as preparation prophylactic treatment osteoporosis, fracture medicine.
Background technology
At present, osteoporosis be with the bone amount reduce, the microstructure degeneration of bone is feature, a kind of general skeletal diseases that causes the fragility of bone to increase and be easy to fracture.Along with the increase of population at advanced age, may become majority's healthy formidable enemy in following osteoporosis, so one of difficult problem that this frequently-occurring, metabolic osteopathy is present medical circle is studying tackling key problem.Osteoporosis mainly is divided into constitutional and Secondary cases two big classes, and primary osteoporosis is because the age increases a kind of physiological that osseous tissue takes place behind aging or the postmenopausal women changes.Because of some disease (as endocrine regulation, chronic diseases such as kidney, liver and gastrointestinal calcium absorption obstacles), malnutrition and drug-induced osteoporosis are called secondary osteoporosis.
The treatment osteoporosis adopts calcium preparation or controversies in hormone replacement in the elderly usually both at home and abroad.But the at present clinical medicine of replenishing the calcium absorbs bad mostly or absorbs back calcium phosphorus and can not deposit in skeleton.Estrogen replacement therapy can directly improve postmenopausal women's bone metabolism, prevents that effectively the carrying out property of several leading year bone after the menopause from losing, but short-term is taken, its curative effect is difficult to take the generation that is easy to cause various complication for a long time, as severe complications such as breast carcinoma, carcinomas of endometrium lastingly.
Summary of the invention
The purpose of this invention is to provide of the application of a kind of copper nanoparticle as preparation prophylactic treatment osteoporosis, fracture medicine, promptly make full use of osteoporosis, the accelerating union of bone fracture effect of copper nanoparticle, it effectively overcomes the problem that prior art exists, as prevention and treatment osteoporosis, the ideal medicament of the fracture that causes to constitutional and secondary osteoporosis and by osteoporosis, determined curative effect, toxic and side effects is little.
The object of the present invention is achieved like this: this copper nanoparticle is as the application of preparation prophylactic treatment osteoporosis, fracture medicine, its technical essential is: adopting commercially available particle diameter is that the copper nanoparticle of 0.1-1000nm is a raw material, and the weight ratio of raw materials used copper nanoparticle of the medicine of making and preparation is 0.00025～0.0125: 1.
Above-mentioned copper nanoparticle can be made dosage forms such as tablet, capsule, granule as the application of medicine.
Copper nanoparticle of the present invention can be obeyed secondary as the application of preparation prophylactic treatment osteoporosis, fracture medicine day, and a day dosing is advisable to be no more than 2～8mg.Its Main Ingredients and Appearance copper nanoparticle market is on sale, and corresponding report also disclosed copper nanoparticle can adopt method preparations such as laser method, chemical method, physics method, low-temperature freezing.But the report with preparation prophylactic treatment osteoporosis, fracture medicine is seen at the end.
By pharmacodynamic study to copper nanoparticle, measure copper nanoparticle to experimental prevention of osteoporosis, therapeutical effect due to the dexamethasone, copper nanoparticle causes tests such as experimental prevention of osteoporosis, therapeutical effect to retinoic acid, the result shows: copper nanoparticle has the formation that promotes bone collagen, collagen protein and elastin laminin and crosslinked, keep and recovery connective tissue effect, can be used for prophylactic treatment osteoporosis and fracture.For containing copper nanoparticle pharmaceutical preparation in clinical practice, opened up new purposes as preparation prophylactic treatment osteoporosis, fracture medicine.In this test method:
Experiment material:
1, be subjected to the reagent thing: copper nanoparticle, the black powder shape, 21st century Nanosolutions GmbH provides by Shenyang, faces the time spent and uses with the suspension that 0.5%CMC.Na liquid is made into desired concn.GUSHUKANG, the 10g/ bag, available from the Kang Chen of Donggang City pharmaceutical Co. Ltd, lot number: 020101, dissolved in distilled water uses.
2, laboratory animal: the Wistar rat, Kunming mouse, male and female half and half are provided by Shenyang Pharmaceutical University's animal center, the quality certification number: 033.
Experimental technique:
1, copper nanoparticle is to experimental prevention of osteoporosis effect due to the dexamethasone
Rat 250-300g, male and female half and half, totally 48.Be divided into 6 groups at random: normal control group, model control group, GUSHUKANG group (1.8g/kg).Copper nanoparticle 0.842g/kg, 2.5272mg/kg, three dosage groups of 7.5816mg/kg.Except that the normal control group, other respectively organize intramuscular injection dexamethasone 2.5mg/kg weekly twice, and in continuous 6 weeks, according to set dosage gastric infusion 1ml/100g, once a day, the normal control group gives the equivalent solvent simultaneously in modeling.Next day after the last administration, big rathole posterior vein blood sampling, centrifugal 10 minutes separation of serum of 2500 commentaries on classics/min are measured inorganic ions and every biochemical indicators such as serum calcium, phosphorus, copper, zinc, magnesium.Take off cervical vertebra after the blood sampling and put to death rat, get left and right sides femur and remove the soft tissue that adheres to, right femur is measured bone mineral density with the dual-energy x-ray borne densitometers, uses universal material machine three point bending test then, the record breaking load.Get fl with ten thousand/electronic balance weighing weight in wet base,, measure its volume according to Archimedes principle, subsequently with 2 parts of chloroform+1 part methyl alcohol mixed liquor defat 72 hours with vernier caliper measurement length and diameter.Put in the baking oven 120 ℃ of bakings 6 hours to constant weight, cooling back weighing gets dry weight.Dried bone was put 800 ℃ of luxuriant good fortune in-furnace dustizations 6 hours again, taken by weighing ash after the cooling and weigh.Experimental result is learned processing by statistics, does the t check and judges significance.
2, copper nanoparticle is to experimental osteoporotic therapeutical effect due to the dexamethasone
Rat 250-300g, male and female half and half, totally 48.Be divided into 6 groups at random: normal control group, model control group, GUSHUKANG group (1.8g/kg), copper nanoparticle 0.842g/kg, 2.5272mg/kg, three dosage groups of 7.5816mg/kg.Except that the normal control group, other respectively organize intramuscular injection dexamethasone 2.5mg/kg weekly twice, and in continuous 6 weeks, experimental osteoporosis rat model causes.After the modeling success, each administration group is according to set dosage gastric infusion 1ml/100g, and once a day, the normal control group gives the equivalent solvent, continuous 4 weeks.Next day after the last administration, big rathole posterior vein blood sampling, centrifugal 10 minutes separation of serum of 2500 commentaries on classics/min are measured inorganic ions and every biochemical indicators such as serum calcium, phosphorus, copper, zinc, magnesium.Take off cervical vertebra after the blood sampling and put to death rat, get left and right sides femur and remove the soft tissue that adheres to, right femur is measured bone mineral density with the dual-energy x-ray borne densitometers, fl is with ten thousand/electronic balance weighing weight in wet base, with vernier caliper measurement length and diameter, measure its volume according to Archimedes principle.Experimental result is learned processing by statistics, does the t check and judges significance.
3, copper nanoparticle to oophorectomize after the preventive effect of rat bone loss
3 month female rats, body weight 300--350g, totally 48.Be divided into 6 groups at random: sham operated rats, model control group, GUSHUKANG group (1.8g/kg), copper nanoparticle 0.842g/kg, 2.5272mg/kg, three dosage groups of 7.5816mg/kg.Except that sham operated rats, other rat is all with 4 pentobarbital sodium intraperitoneal injection of anesthesia, and is fixing, open back, bilateral spay, tubal ligation, sew up wound, sterilization.The sham operated rats rat opens behind the abdomen not spay, and all the other steps are with the operation group.One week of postoperative, each administration group began according to set dosage gastric infusion 1ml/100g, and once a day, sham operated rats gives the equivalent solvent, and model control group is normally raised, continuous three months.Next day after the last administration, big rathole posterior vein blood sampling, centrifugal 10 minutes separation of serum of 2500 commentaries on classics/min are measured serum estradiol, calcitonin, Bone Gla protein.Take off cervical vertebra after the blood sampling and put to death rat, get left and right sides femur and remove the soft tissue that adheres to, right femur is measured bone mineral density with the dual-energy x-ray borne densitometers, uses universal material machine three point bending test then, the record breaking load.Get fl with ten thousand/electronic balance weighing weight in wet base,, measure its volume, simultaneously, open the abdominal cavity, peel off the uterus according to Archimedes principle with vernier caliper measurement length and diameter, weighing uterus weight on ten thousand/electronic balance, and calculate the uterus index.Experimental result is learned processing by statistics, does the t check and judges significance.
4, copper nanoparticle causes experimental prevention of osteoporosis effect to retinoic acid
Rat 180-260g, male and female half and half, totally 48.Be divided into 6 groups at random: normal control group, model control group, GUSHUKANG group (1.8g/kg), copper nanoparticle 0.842g/kg, 2.5272mg/kg, three dosage groups of 7.5816mg/kg.Except that the normal control group, other each groups all gavage retinoic acid 70mg/kg, once a day, and continuous 2 weeks.Each administration group is according to set dosage gastric infusion 1ml/100g simultaneously in modeling, and once a day, the empty map group gives the equivalent solvent, and model control group is normally raised, continuous 4 weeks.Next day after the last administration, big rathole posterior vein blood sampling, centrifugal 10 minutes separation of serum of 2500 commentaries on classics/min are measured inorganic ions and every biochemical indicators such as serum calcium, phosphorus, copper, zinc, magnesium.Take off cervical vertebra after the blood sampling and put to death rat, get left and right sides femur and remove the soft tissue that adheres to, right femur is measured bone mineral density with the dual-energy x-ray borne densitometers, uses universal material machine three point bending test then, the record breaking load.Get fl with ten thousand/electronic balance weighing weight in wet base,, measure its volume according to Archimedes principle, subsequently with 2 parts of chloroform+1 part methyl alcohol mixed liquor defat 72 hours with vernier caliper measurement length and diameter.Put in the baking oven 120 ℃ of bakings 6 hours to constant weight, cooling back weighing gets dry weight.Dried bone was put 800 ℃ of luxuriant good fortune in-furnace dustizations 6 hours again, taken by weighing ash after the cooling and weigh.Experimental result is learned processing by statistics, does the t check and judges significance.
5, copper nanoparticle causes experimental osteoporotic therapeutical effect to retinoic acid
Rat 180-260g, male and female half and half, totally 48.Be divided into 6 groups at random: normal control group, model control group, GUSHUKANG group (1.8g/kg), copper nanoparticle 0.842g/kg, 2.5272mg/kg, three dosage groups of 7.5816mg/kg.Except that the normal control group, other each groups all gavage retinoic acid 70mg/kg, once a day, and continuous 2 weeks.After the modeling success, each administration group begins according to set dosage gastric infusion 1ml/100g, and once a day, the blank group gives the equivalent solvent, and model control group is normally raised, continuous 4 weeks.Next day after the last administration, take off cervical vertebra and put to death rat, get left and right sides femur and remove the soft tissue that adheres to, right femur is measured bone mineral density with the dual-energy x-ray borne densitometers, fl is with ten thousand/electronic balance weighing weight in wet base, with vernier caliper measurement length and diameter, measure its volume according to Archimedes principle.Experimental result is learned processing by statistics, does the t check and judges significance.
6, acute toxicity test
Kunming mouse, body weight 18-22g, male and female half and half, totally 50, fasting is 12 hours before the test, is divided into 5 groups at random by body weight, 10 every group, dosage difference gastric infusion by the various dose group, agent is apart from being 1: 0.8, and the administration volume is a 0.2ml/10g mice body weight, observes 14 days continuously after the administration, reaction and the death condition of record animal are calculated LD with the Bliss method
50And 95% fiducial limit.
Experimental result
1, copper nanoparticle is to experimental prevention of osteoporosis effect experimental result due to the dexamethasone
Experimental result shows, model control group is compared bone density and is obviously reduced (P＜0.01) with the normal control group, copper nanoparticle can obviously improve the bone mineral density of osteoporosis rat, compares P＜0.05 and P＜0.0l with model control group, comparing with the GUSHUKANG group does not have significant difference, the results are shown in Table 1; The model control group breaking load is starkly lower than blank group (P＜0.01), and each dosage group of GUSHUKANG group and copper nanoparticle all can significantly improve breaking load P＜0.05 or P＜0.01 of rat model, the results are shown in Table 2; Copper nanoparticle to dexamethasone cause osteoporosis rat fl weight in wet base, dry weight, the heavy influence of ash sees Table 3, model control group femur weight in wet base, dry weight, grey weight average significantly are lower than blank group P＜0.01, and the heavy dose of group of GUSHUKANG group and copper nanoparticle can significantly improve the heavy P of rat model femur weight in wet base, dry weight and ash＜0.05 or P＜0.01; Model group rat femur volume, length and diameter are compared remarkable reduction P＜0.05 or P＜0.01 with the normal control group, the heavy dose of group of GUSHUKANG group and copper nanoparticle can significantly improve rat model femur volume and length P＜0.05, the femur diameter of each administration group is compared with model group does not have significant difference, the results are shown in Table 4; Model group rat blood serum Ca, P, Mg, Zn concentration significantly is lower than normal control group P＜0.05 or P＜0.01, copper nanoparticle can significantly improve the rat model serum Ca, P, the horizontal P of Mg＜0.05 or P＜0.01, its effect is better than the GUSHUKANG group, each administration group serum Zn concentration and model group difference are not remarkable, model group rat blood serum Cu level is significantly higher than blank group (P＜0.01), the GUSHUKANG group, the big small dose group levels of serum cu of copper nanoparticle is higher than model group, difference is not remarkable, the dosage group is compared significant difference P＜0.05 in the copper nanoparticle with model group, the results are shown in Table 5-6; Model control group serum alkaline phosphatase level is apparently higher than normal control group P＜0.01, in the copper nanoparticle, heavy dose of group can significantly reduce the horizontal P of rat model serum levels of ALP＜0.05 or P＜0.01 with the GUSHUKANG group, the results are shown in Table 7; Compare with the normal control group, model group rat blood serum hydroxyprolin levels P＜0.05 that significantly raises, creatinine level obviously reduces P＜0.01, hydroxyproline and creatinine ratio P＜0.01 that raises greatly, copper nanoparticle can obviously reduce the horizontal P of serum HOP＜0.05, rising creatinine level P＜0.01, corresponding reduction hydroxyproline and creatinine ratio P＜0.05 or P＜0.01, its effect is better than the GUSHUKANG group, the results are shown in Table 8.Above experimental result shows: copper nanoparticle has the good preventing effect to the inductive osteoporosis of dexamethasone, can reduce the caused bone loss of long-term heavy dose of glucocorticoid, and effect is certain dose dependent.
Table 1 copper nanoparticle causes the influence (x ± SD) of the right femur bone mineral density of osteoporosis rat to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | BMD (g/cm 2) |
| The normal control group | -- | 8 | 0.1224±0.004** |
| Model control group | -- | 8 | 0.1100±0.005 |
| The GUSHUKANG group | 1800 | 8 | 0.1194±0.008* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.1156±0.004* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.1182±0.006* |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.1217±0.009** |
Compare with model control group
*P＜0.05
*P＜0.01
Table 2 copper nanoparticle causes the influence (x ± SD) of the right femur breaking load of osteoporosis rat to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | Breaking load (N) |
| The normal control group | -- | 8 | 102.195±6.334** |
| Model control group | -- | 9 | 84.604±12.595 |
| The GUSHUKANG group | 1800 | 8 | 99.356±7.045** |
| The copper nanoparticle small dose group | 0.8424 | 8 | 97.101±10.425* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 100.555±11.363* |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 100.628±14.462* |
Compare with matched group
*P＜0.05
*P＜0.01
Table 3 copper nanoparticle to dexamethasone cause osteoporosis rat fl weight in wet base, dry weight, influence that ash is heavy (x ± SD, n=8)
| Group | Bone weight in wet base (g) | Key heavy (g) | Bone ash heavy (g) |
| The normal control group | 0.988±0.071** | 0.697±0.053** | 0.433±0.027** |
| Model control group | 0.874±0.044 | 0.592±0.033 | 0.378±0.032 |
| The GUSHUKANG group | 0.971±0.064** | 0.653±0.037** | 0.409±0.024* |
| The copper nanoparticle small dose group | 0.903±0.057 | 0.619±0.035 | 0.398±0.030 |
| Dosage group in the copper nanoparticle | 0.920±0.091 | 0.624±0.041 | 0.402±0.029 |
| The heavy dose of group of copper nanoparticle | 0.951±0.054** | 0.638±0.031* | 0.412±0.019* |
Compare with matched group
*P＜0.05
*P＜0.01
Table 4 copper nanoparticle to dexamethasone cause osteoporosis rat fl volume, length, diameter influence (x ± SD, n=8)
| Group | Bone volume (cm) | Bone length (cm) | Bone diameter (cm) |
| The normal control group | 0.641±0.044** | 3.824±0.098* | 0.333±0.015** |
| Model control group | 0.566±0.039 | 3.700±0.073 | 0.312±0.012 |
| The GUSHUKANG group | 0.631±0.052* | 3.803±0.102* | 0.321±0.013 |
| The copper nanoparticle small dose group | 0.552±0.047 | 3.742±0.113 | 0.316±0.006 |
| Dosage group in the copper nanoparticle | 0.600±0.064 | 3.750±0.071 | 0.323±0.010 |
| The heavy dose of group of copper nanoparticle | 0.609±0.038* | 3.796±0.010* | 0.322±0.011 |
Compare with matched group
*P＜0.05
*P＜0.01
Table 5 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum Ca, P to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | Ca (mmol/L) | P (mmol/L) |
| The normal control group | -- | 8 | 2.818±0.182** | 3.351±0.867** |
| Model control group | -- | 8 | 2.500±0.189 | 1.743±0.304 |
| The GUSHUKANG group | 1800 | 8 | 2.646±0.167 | 1.886±0.112 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 2.523±0.223 | 2.379±0.549** |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 2.743±0.140* | 2.789±0.791** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 2.853±0.336** | 3.462±0.924** |
Compare with model control group
*P＜0.05
*P＜0.01
Table 6 copper nanoparticle to dexamethasone cause osteoporosis rat serum Mg, Cu, Zn influence (x ± SD, n=8)
| Group | Mg (mmol/L) | Cu (g/dl) | Zn (g/dl) |
| The normal control group | 1.568±0.250* | 36.10±12.02** | 59.92±9.79** |
| Model control group | 1.295±0.270 | 56.49±18.41 | 38.64±14.44 |
| The GUSHUKANG group | 1.356±0.375 | 66.66±15.54 | 42.15±13.56 |
| The copper nanoparticle small dose group | 1.440±0.267 | 66.93±17.99 | 31.47±9.61 |
| Dosage group in the copper nanoparticle | 1.539±0.167* | 77.04±12.51* | 29.59±12.46 |
| The heavy dose of group of copper nanoparticle | 1.690±0.251** | 58.65±13.73 | 34.22±9.22 |
Compare with matched group
*P＜0.05
*P＜0.01
Table 7 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum alkaline phosphatase to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | ALP (U/L) |
| The normal control group | -- | 8 | 133.44±82.69** |
| Model control group | -- | 8 | 278.89±90.65 |
| The GUSHUKANG group | 1800 | 8 | 190.89±49.22* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 245.70±63.28 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 171.27±62.55** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 190.78±66.65* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 8 copper nanoparticle to dexamethasone cause osteoporosis rat serum HOP, Cre influence (x ± SD, n=8)
| Group | HOP (g/ml) | Cre mmol/L | HOP/Cre |
| The normal control group | 1.324±0.501* | 108.90±15.64** | 0.014±0.006** |
| Model control group | 1.851±0.464 | 62.27±7.85 | 0.028±0.008 |
| The GUSHUKANG group | 1.614±0.274 | 63.00±4.29 | 0.027±0.006 |
| The copper nanoparticle small dose group | 1.709±0.279 | 57.00±8.51 | 0.030±0.006 |
| Dosage group in the copper nanoparticle | 1.656±0.214 | 87.78±16.15** | 0.022±0.005* |
| The heavy dose of group of copper nanoparticle | 1.233±0.742* | 93.12±16.48** | 0.016±0.010** |
Compare with model control group
*P＜0.05
*P＜0.01
2, copper nanoparticle is to experimental osteoporotic therapeutical effect experimental result due to the dexamethasone
Experimental result shows that model control group is compared bone density and obviously reduced (P＜0.01) with the normal control group, and the heavy dose of group of copper nanoparticle can obviously improve the bone mineral density (P＜0.01) of osteoporosis rat, and is similar with the effect of GUSHUKANG group, the results are shown in Table 9; Copper nanoparticle sees Table 10 to the influence that dexamethasone causes osteoporosis rat fl weight in wet base, volume, model control group femur weight in wet base significantly is lower than blank group P＜0.01, the heavy dose of group of copper nanoparticle can significantly improve rat model femur weight in wet base P＜0.05, effect is better than the GUSHUKANG matched group, each administration group femur volume has been compared with model group and has been increased trend, but does not have significant difference between each group; Model group rat femur length is compared remarkable reduction P＜0.05 or P＜0.01 with diameter with the normal control group, copper nanoparticle can significantly improve rat model femur length and diameter P＜0.05, the results are shown in Table 11; Each organizes rat blood serum Ca, Cu, Zn concentration does not have significant difference, model group rat blood serum P, Mg concentration significantly are lower than normal control group P＜0.05 or P＜0.01, copper nanoparticle can obviously improve the horizontal P of rat model blood-serum P＜0.05, its effect is better than the GUSHUKANG group, serum Mg concentration simultaneously raises, but do not have significant difference, the results are shown in Table 12-13; Model control group serum alkaline phosphatase level is apparently higher than normal control group P＜0.05, and copper nanoparticle and GUSHUKANG the results are shown in Table 14 to not obviously influence of serum levels of ALP; Compare with the normal control group, model group rat blood serum hydroxyprolin levels P＜0.01 that significantly raises, creatinine level obviously reduces P＜0.05, hydroxyproline and creatinine ratio rising P＜0.01, copper nanoparticle can obviously reduce the horizontal P of rat model serum HOP＜0.05 or P＜0.01, corresponding reduction hydroxyproline and creatinine ratio P＜0.05 or P＜0.01, its effect is better than the GUSHUKANG group, the results are shown in Table 15.Above experimental result shows: copper nanoparticle has the good curing effect to the inductive osteoporosis of dexamethasone, can increase the rat model bone mass, and its effect is consistent with the prevention administration.
Table 9 copper nanoparticle causes the influence (x ± SD) of the right femur bone mineral density of osteoporosis rat to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | BMD (g/cm 2) |
| The normal control group | -- | 8 | 0.1214±0.005** |
| Model control group | -- | 8 | 0.1090±0.006 |
| The GUSHUKANG group | 1800 | 8 | 0.1167±0.006* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.1091±0.007 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.1106±0.004 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.1154±0.004* |
Compare with model control group
*P＜0.05
*P＜0
Table 10 copper nanoparticle to dexamethasone cause that osteoporosis rat fl bone is heavy, the influence of bone volume (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Bone heavy (g) | Bone volume (cm 3) |
| The normal control group | -- | 8 | 0.975±0.053** | 0.654±0.038 |
| Model control group | -- | 8 | 0.853±0.042 | 0.598±0.066 |
| The GUSHUKANG group | 1800 | 8 | 0.892±0.096 | 0.619±0.083 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.869±0.057 | 0.618±0.076 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.908±0.066 | 0.620±0.031 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.939±0.076* | 0.611±0.066 |
Compare with model control group
*P＜0.05
*P＜0.01
Table 11 copper nanoparticle to dexamethasone cause that osteoporosis rat fl bone is long, the influence of bone diameter (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Bone length (cm) | Bone diameter (cm) |
| The normal control group | -- | 8 | 3.804±0.077** | 0.326±0.015* |
| Model control group | -- | 8 | 3.638±0.052 | 0.312±0.008 |
| The GUSHUKANG group | 1800 | 8 | 3.794±0.167 | 0.322±0.018 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 3.789±0.140 | 0.318±0.010 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 3.787±0.118* | 0.320±0.016 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 3.791±0.143 | 0.323±0.010* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 12 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum Ca, P to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | Ca (mmol/L) | P (mmol/L) |
| The normal control group | -- | 8 | 2.397±0.191 | 2.692±0.550** |
| Model control group | -- | 8 | 2.260±0.108 | 1.821±0.252 |
| The GUSHUKANG group | 1800 | 8 | 2.242±0.092 | 2.100±0.193* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 2.247±0.084 | 2.012±0.338 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 2.239±0.086 | 2.116±0.405 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 2.264±0.086 | 2.193±0.315* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 13 copper nanoparticle to dexamethasone cause osteoporosis rat serum Mg, Cu, Zn influence (x ± SD, n=8)
| Group | Mg (mmol/L) | Cu (g/dl) | Zn (g/dl) |
| The normal control group | 1.328±0.264* | 60.49±25.54 | 37.43±12.14 |
| Model control group | 1.110±0.077 | 67.24±25.81 | 26.42±6.20 |
| The GUSHUKANG group | 1.113±0.109 | 72.80±17.32 | 33.58±14.66 |
| The copper nanoparticle small dose group | 1.094±0.126 | 67.19±26.40 | 23.61±7.71 |
| Dosage group in the copper nanoparticle | 1.142±0.132 | 65.93±34.64 | 26.56±8.51 |
| The heavy dose of group of copper nanoparticle | 1.139±0.106 | 72.15±26.10 | 24.68±9.11 |
Compare with matched group
*P＜0.05
*P＜0.01
Table 14 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum alkaline phosphatase to dexamethasone
| Group | Dosage mg/kg | Number of animals (only) | ALP (U/L) |
| The normal control group | -- | 8 | 147.33±50.44* |
| Model control group | -- | 8 | 273.00±93.20 |
| The GUSHUKANG group | 1800 | 8 | 208.00±90.30 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 266.28±86.87 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 280.11±96.95 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 265.89±103.11 |
Compare with model control group
*P＜0.05
*P＜0.01
Table 15 copper nanoparticle to dexamethasone cause osteoporosis rat serum HOP, Cre influence (x ± SD, n=8)
| Group | HOP (g/ml) | Cre mmol/L | HOP/Cre |
| The normal control group | 0.850±0.095** | 86.00±7.01* | 0.010±0.008** |
| Model control group | 1.204±0.279 | 54.18±5.21 | 0.022±0.006 |
| The GUSHUKANG group | 0.915±0.207 | 56.83±3.06 | 0.016±0.005 |
| The copper nanoparticle small dose group | 0.908±0.075** | 53.00±7.13 | 0.017±0.007 |
| Dosage group in the copper nanoparticle | 0.886±0.227* | 58.22±4.41 | 0.015±0.003** |
| The heavy dose of group of copper nanoparticle | 0.870±0.076* | 57.00±4.82 | 0.015±0.009* |
Compare with model control group
*P＜0.05
*P＜0.01
3, copper nanoparticle to oophorectomize after the preventive effect experimental result of rat bone loss
Experimental result shows, compare with the normal control group, the model control group bone density obviously reduces (P＜0.01), copper nanoparticle can obviously improve the bone mineral density of osteoporosis rat, compare P＜0.05 and P＜0.01 with model control group, comparing with the GUSHUKANG group does not have significant difference, the results are shown in Table 16; The model control group breaking load is starkly lower than blank group (P＜0.01), and each dosage group of GUSHUKANG group and copper nanoparticle all can significantly improve breaking load P＜0.05 or P＜0.01 of rat model, the results are shown in Table 17; Each administration group femur weight in wet base has been compared increase trend with model group, but difference is not remarkable, model group rat femur volume, length are compared remarkable reduction P＜0.01 with the normal control group, the heavy dose of group of GUSHUKANG group and copper nanoparticle can significantly improve rat model femur volume and length P＜0.05, the femur diameter of each administration group is compared with model group does not have significant difference, the results are shown in Table 18-19; Copper nanoparticle sees Table 20 to the influence of removal ovary rat uterus weight, and GUSHUKANG and copper nanoparticle heavy dose can obviously increase rat uterus weight and uterus indices P＜0.05; Compare with the normal control group, model group serum estradiol, calcitonin level obviously reduce P＜0.05 or P＜0.01, the Bone Gla protein level obviously increases P＜0.05, each administration group serum estradiol level does not have significant difference, in the copper nanoparticle, heavy dose of group can obviously increase the horizontal P of serum calcitonin＜0.05 or P＜0.01, its effect is better than GUSHUKANG, and the heavy dose of group of copper nanoparticle significantly reduces rat model serum osteocalcin level, the results are shown in Table 21.Above experimental result shows: copper nanoparticle has tangible preventive effect to the osteoporosis due to the spay, can reduce the caused bone loss of removal ovary, increases bone strength, and effect is certain dose dependent.
Table 16 copper nanoparticle is to the influence of the right femur bone mineral density of castrated rats (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | BMD (g/cm 2) |
| The normal control group | -- | 8 | 0.1307±0.009** |
| Model control group | -- | 8 | 0.1138±0.005 |
| The GUSHUKANG group | 1800 | 8 | 0.1207±0.003* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.1212±0.004* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.1215±0.003** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.1217±0.004** |
Compare with model control group
*P＜0.05
*P＜0.01
Table 17 copper nanoparticle is to the influence of the right femur breaking load of castrated rats (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Breaking load (N) |
| The normal control group | -- | 8 | 120.159±8.343** |
| Model control group | -- | 9 | 87.809±10.900 |
| The GUSHUKANG group | 1800 | 8 | 100.356±7.058** |
| The copper nanoparticle small dose group | 0.8424 | 8 | 99.002±9.415* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 102.557±10.361* |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 109.998±13.361** |
Compare with matched group
*P＜0.05
*P＜0.01
Table 18 copper nanoparticle is heavy to castrated rats fl bone, the influence of bone volume (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Bone heavy (g) | Bone volume (cm1) |
| The normal control group | -- | 8 | 0.960±0.072 | 0.642±0.034** |
| Model control group | -- | 8 | 0.895±0.084 | 0.584±0.037 |
| The GUSHUKANG group | 1800 | 8 | 0.915±0.043 | 0.620±0.028* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.908±0.028 | 0.605±0.028 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.933±0.026 | 0.626±0.032* |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.945±0.031 | 0.636±0.039* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 19 copper nanoparticle is long to castrated rats fl bone, the influence of bone diameter (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Bone length (cm) | Bone diameter (cm) |
| The normal control group | -- | 8 | 3.826±0.062** | 0.321±0.024 |
| Model control group | -- | 8 | 3.726±0.070 | 0.311±0.016 |
| The GUSHUKANG group | 1800 | 8 | 3.834±0.084* | 0.315±0.015 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 3.793±0.090 | 0.311±0.006 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 3.790±0.074 | 0.318±0.013 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 3.801±0.040* | 0.324±0.009 |
Compare with model control group
*P＜0.05
*P＜0.01
Table 20 copper nanoparticle is to the influence of removal ovary rat uterus weight (x ± SD)
| Group | Dosage mg/kg | Number of animals (only) | Uterus weight (g) | Uterus index (%) |
| The normal control group | -- | 8 | 0.512±0.196* | 0.142±0.054* |
| Model control group | -- | 8 | 0.307±0.120 | 0.079±0.035 |
| The GUSHUKANG group | 1800 | 8 | 0.594±0.261* | 0.153±0.071* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.380±0.234 | 0.102±0.061 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.427±0.189 | 0.116±0.055 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.468±0.151* | 0.133±0.045* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 21 copper nanoparticle to the influence of removal ovary rat blood serum estradiol, calcitonin, Bone Gla protein (x ± SD, n=8)
| Group | E 2 (pg/ml) | CT (ng/L) | BGP (ng/ml) |
| The normal control group | 4.628±1.371* | 516.53±161.62* * | 0.684±0.191* |
| Model control group | 2.958±1.402 | 175.46±57.38 | 1.001±0.391 |
| The GUSHUKANG group | 4.103±0.963 | 265.39±95.45* | 0.873±0.296 |
| The copper nanoparticle small dose group | 2.580±1.047 | 218.67±68.16 | 1.002±0.409 |
| Dosage group in the copper nanoparticle | 3.684±1.083 | 380.25±260.68* | 0.914±0.438 |
| The heavy dose of group of copper nanoparticle | 2.788±1.564 | 406.67±258.59* | 0.703±0.117* |
Compare with matched group
*P＜0.05
*P＜0.01
4, copper nanoparticle is to experimental prevention of osteoporosis effect experimental result due to the retinoic acid
Experimental result shows, model control group is compared bone density and is obviously reduced (P＜0.01) with the normal control group, copper nanoparticle can obviously improve the bone mineral density of osteoporosis rat, compares P＜0.05 and P＜0.01 with model control group, comparing with the GUSHUKANG group does not have significant difference, the results are shown in Table 22; The model control group breaking load is starkly lower than blank group (P＜0.01), and each dosage group of GUSHUKANG group and copper nanoparticle all can significantly improve breaking load P＜0.05 and P＜0.01 of rat model, the results are shown in Table 23; Copper nanoparticle to retinoic acid cause osteoporosis rat fl weight in wet base, dry weight, the heavy influence of ash sees Table 24, model control group femur weight in wet base, dry weight, grey weight average significantly are lower than blank group P＜0.01, and GUSHUKANG group and copper nanoparticle all can significantly improve the heavy P of rat model femur weight in wet base, dry weight and ash＜0.05 or P＜0.01; Model group rat femur volume, length and diameter are compared remarkable reduction P＜0.01 with the normal control group, GUSHUKANG group and copper nanoparticle all can significantly improve rat model femur volume, length and diameter P＜0.05 or P＜0.01, the results are shown in Table 25; Each organizes rat blood serum Ca concentration does not have significant difference, model group rat blood serum P, Mg concentration significantly are lower than normal control group P＜0.01, GUSHUKANG and copper nanoparticle heavy dose can significantly improve rat model blood-serum P, the horizontal P of Mg＜0.05, model group rat blood serum Cu, Zn level are significantly higher than blank group P＜0.05 or P＜0.01, each administration group serum Cu level does not have difference, the heavy dose of group of copper nanoparticle blood Zn concentration is compared significant difference P＜0.01 with model group, near with blank winding, the results are shown in Table 26-27; Model control group serum alkaline phosphatase level is apparently higher than normal control group P＜0.01, and each dosage group of copper nanoparticle all can significantly reduce the horizontal P of rat model serum levels of ALP＜0.05 and P＜0.01, the results are shown in Table 28; Compare with the normal control group, model group rat blood serum hydroxyprolin levels P＜0.01 that significantly raises, creatinine level obviously reduces P＜0.01, hydroxyproline and creatinine ratio P＜0.01 that raises greatly, copper nanoparticle can obviously reduce the horizontal P of serum HOP＜0.05, rising creatinine level P＜0.05 and P＜0.01, corresponding reduction hydroxyproline and creatinine ratio P＜0.01, its effect is better than the GUSHUKANG group, the results are shown in Table 29.Above experimental result shows: copper nanoparticle has the good preventing effect to the osteoporosis of Induced by Retinoic Acid, can reduce the bone loss that long-term large dose oral administration retinoic acid causes, and effect is certain dose dependent.
Table 22 copper nanoparticle causes the influence (x ± SD) of the right femur bone mineral density of osteoporosis rat to retinoic acid
| Group | Dosage mg/kg | Number of animals (only) | BMD (g/cm 2) |
| The normal control group | -- | 8 | 0.1084±0.002** |
| Model control group | -- | 8 | 0.0918±0.003 |
| The GUSHUKANG group | 1800 | 8 | 0.0958±0.004* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 0.0983±0.006* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 0.0999±0.006** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 0.1024±0.005** |
Compare with model control group
*P＜0.05
*P＜0.01
Table 23 copper nanoparticle causes the influence (x ± SD) of the right femur breaking load of osteoporosis rat to retinoic acid
| Group | Dosage mg/kg | Number of animals (only) | Breaking load (N) |
| The normal control group | -- | 8 | 91.10±5.44** |
| Model control group | -- | 9 | 71.29±5.80 |
| The GUSHUKANG group | 1800 | 8 | 80.01±9.28* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 79.92±8.40* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 80.62±6.01** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 83.59±11.77* |
Compare with matched group
*P＜0.05
*P＜0.01
Table 24 copper nanoparticle to retinoic acid cause osteoporosis rat fl weight in wet base, dry weight, influence that ash is heavy (x ± SD, n=8)
| Group | Bone weight in wet base (g) | Key heavy (g) | Bone ash heavy (g) |
| The normal control group | 0.844±0.060** | 0.534±0.026** | 0.337±0.019** |
| Model control group | 0.640±0.050 | 0.409±0.026 | 0.259±0.016 |
| The GUSHUKANG group | 0.688±0.038* | 0.442±0.032* | 0.286±0.029* |
| The copper nanoparticle small dose group | 0.742±0.093* | 0.451±0.063 | 0.283±0.038 |
| Dosage group in the copper nanoparticle | 0.755±0.130* | 0.459±0.057* | 0.290±0.034* |
| The heavy dose of group of copper nanoparticle | 0.766±0.082** | 0.479±0.037** | 0.302±0.020** |
Compare with matched group
*P＜0.05
*P＜0.01
Table 25 copper nanoparticle to retinoic acid cause osteoporosis rat fl volume, length, diameter influence (x ± SD, n=8)
| Group | Bone volume (cm) | Bone length (cm) | Bone diameter (cm) |
| The normal control group | 0.569±0.055** | 3.547±0.097** | 0.311±0.014** |
| Model control group | 0.436±0.042 | 3.351±0.090 | 0.280±0.007 |
| The GUSHUKANG group | 0.486±0.047* | 3.440±0.056* | 0.291±0.012* |
| The copper nanoparticle small dose group | 0.500±0.075 | 3.411±0.196 | 0.297±0.014* |
| Dosage group in the copper nanoparticle | 0.511±0.080* | 3.468±0.105* | 0.302±0.015** |
| The heavy dose of group of copper nanoparticle | 0.524±0.062** | 3.475±0.107* | 0.296±0.018* |
Compare with matched group
*P＜0.05
*P＜0.01
Table 26 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum Ca, P to retinoic acid
| Group | Dosage mg/kg | Number of animals (only) | Ca (mmol/L) | P (mmol/L) |
| The normal control group | -- | 8 | 2.289±0.271 | 2.357±0.279** |
| Model control group | -- | 8 | 2.373±0.030 | 1.787±0.520 |
| The GUSHUKANG group | 1800 | 8 | 2.413±0.078 | 2.344±0.341* |
| The copper nanoparticle small dose group | 0.8424 | 8 | 2.230±0.344 | 1.903±0.496 |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 2.233±0.284 | 2.147±0.281 |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 2.281±0.356 | 2.242±0.137* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 27 copper nanoparticle to retinoic acid cause osteoporosis rat serum Mg, Cu, Zn influence (x ± SD, n=8)
| Group | Mg (mmol/L) | Cu (g/dl) | Zn (g/dl) |
| The normal control group | 0.924±0.064** | 38.19±19.14* | 25.68±7.65** |
| Model control group | 0.790±0.114 | 55.95±15.96 | 41.66±8.26 |
| The GUSHUKANG group | 0.886±0.073* | 60.53±12.09 | 36.31±6.22 |
| The copper nanoparticle small dose group | 0.826±0.078 | 49.42±10.80 | 41.63±9.52 |
| Dosage group in the copper nanoparticle | 0.879±0.071 | 47.74±18.57 | 29.32±6.89** |
| The heavy dose of group of copper nanoparticle | 0.894±0.076* | 49.58±19.16 | 26.70±5.01** |
Compare with matched group
*P＜0.05
*P＜0.01
Table 28 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat serum alkaline phosphatase to retinoic acid
| Group | Dosage mg/kg | Number of animals (only) | ALP (U/L) |
| The normal control group | -- | 8 | 124.90±61.89** |
| Model control group | -- | 8 | 236.90±86.04 |
| The GUSHUKANG group | 1800 | 8 | 194.25±68.32 |
| The copper nanoparticle small dose group | 0.8424 | 8 | 167.00±61.26* |
| Dosage group in the copper nanoparticle | 2.5272 | 8 | 138.36±66.45** |
| The heavy dose of group of copper nanoparticle | 7.5816 | 8 | 154.71±53.13* |
Compare with model control group
*P＜0.05
*P＜0.01
Table 29 copper nanoparticle to retinoic acid cause osteoporosis rat serum HOP, Cre influence (x ± SD, n=8)
| Group | HOP (g/ml) | Cre mmol/L | HOP/Cre |
| The normal control group | 1.835±0.625** | 64.90±6.71** | 0.029±0.005** |
| Model control group | 3.165±1.013 | 42.22±12.06 | 0.075±007 |
| The GUSHUKANG group | 2.295±0.732* | 54.54±9.47* | 0.042±0.006* |
| The copper nanoparticle small dose group | 2.522±0.952 | 53.73±12.50 | 0.047±0.008 |
| Dosage group in the copper nanoparticle | 2.375±0.835 | 56.86±8.13* | 0.042±0.004** |
| The heavy dose of group of copper nanoparticle | 2.306±0.308* | 61.56±6.60** | 0.038±0.003** |
Compare with model control group
*P＜0.05
*P＜0.01
5, copper nanoparticle is to experimental osteoporotic therapeutical effect experimental result due to the retinoic acid
Experimental result shows, model control group is compared bone density and is obviously reduced (P＜0.01) with the normal control group, copper nanoparticle can obviously improve the bone mineral density of osteoporosis rat, compares P＜0.05 and P＜0.01 with model control group, comparing with the GUSHUKANG group does not have significant difference, the results are shown in Table 30; Copper nanoparticle sees Table 31 to the influence that retinoic acid causes osteoporosis rat fl weight in wet base, dry weight, model control group femur weight in wet base, dry weight all significantly are lower than blank group P＜0.05 or P＜0.01, and the heavy dose of group of copper nanoparticle can significantly improve rat model femur weight in wet base and dry weight P＜0.05; Model group rat femur volume, length and diameter are compared remarkable reduction P＜0.05 or P＜0.01 with the normal control group, each dosage group of GUSHUKANG group and copper nanoparticle all can significantly improve rat model femur volume and diameter P＜0.05 or P＜0.01, the heavy dose of group of copper nanoparticle can obviously improve the rat model femur length, the results are shown in Table 32.Above experimental result shows: copper nanoparticle has the good curing effect to the osteoporosis of Induced by Retinoic Acid, and is consistent with the result of prevention administration.
Table 30 copper nanoparticle causes the influence (x ± SD) of the right femur bone mineral density of osteoporosis rat to retinoic acid
| Group | Dosage mg/kg | Number of animals (only) | BMD (g/cm 2) |
| The normal control group | -- | 10 | 0.1075±0.005** |
| Model control group | -- | 9 | 0.1006±0.005 |
| The GUSHUKANG group | 1800 | 9 | 0.1061±0.004* |
| The copper nanoparticle small dose group | 0.8424 | 10 | 0.1058±0.004* |
| Dosage group in the copper nanoparticle | 2.5272 | 10 | 0.1060±0.006* |
| The heavy dose of group of copper nanoparticle | 7.5816 | 9 | 0.1078±0.005** |
Compare with model control group
*P＜0.05
*P＜0.01
Table 31 copper nanoparticle causes the influence (x ± SD) of osteoporosis rat fl weight in wet base, dry weight to retinoic acid
| Group | Number of animals (only) | Bone weight in wet base (g) | Key heavy (g) |
| The normal control group | 10 | 0.869±0.089** | 0.546±0.057* |
| Model control group | 9 | 0.738±0.080 | 0.483±0.054 |
| The GUSHUKANG group | 9 | 0.790±0.075 | 0.510±0.040 |
| The copper nanoparticle small dose group | 10 | 0.780±0.069 | 0.509±0.033 |
| Dosage group in the copper nanoparticle | 10 | 0.810±0.112 | 0.524±0.063 |
| The heavy dose of group of copper nanoparticle | 9 | 0.829±0.096* | 0.540±0.055* |
Compare with matched group
*P＜0.05
*P＜0.01
Table 32 copper nanoparticle to retinoic acid cause osteoporosis rat fl volume, length, diameter influence (x ± SD, n=8)
| Group | Bone volume (cm) | Bone length (cm) | Bone diameter (cm) |
| The normal control group | 0.573±0.055** | 3.633±0.127* | 0.308±0.012** |
| Model control group | 0.461±0.061 | 3.493±0.141 | 0.280±0.015 |
| The GUSHUKANG group | 0.519±0.050* | 3.547±0.072 | 0.296±0.014* |
| The copper nanoparticle small dose group | 0.521±0.068* | 3.528±0.060 | 0.299±0.023* |
| Dosage group in the copper nanoparticle | 0.529±0.074* | 3.584±0.120 | 0.300±0.018* |
| The heavy dose of group of copper nanoparticle | 0.528±0.067* | 3.626±0.109* | 0.302±0.014** |
Compare with matched group
*P＜0.05
*P＜0.01
6, behind the The acute toxicity tests animals administer, being slow in action appears in the high dose mice, perpendicular hair, and rapid breathing, mouth and nose pastiness phenomenon, most of death occurred in 48 hours, and dead mice postmortem does not see that pathologic changes, and not dead mice recovers normal gradually.LD
50And 95% fiducial limit the results are shown in Table 33.
Table 33 copper nanoparticle gastric infusion LD
50And 95% fiducial limit
| Drug dose (mg/kg) | Log10 dose (X) | Number of animals (n) | Dead animal number (n) | Mortality rate (%) | Experiment probit (Y) | LD 50And 95% fiducial limit |
| 750.0 | 2.88 | 10 | 10 | 100 | 7.28 | 436.3mg/kg 378.8-493.7 mg/kg |
| 600.0 | 2.78 | 10 | 8 | 80 | 5.81 | |
| 480.0 | 2.68 | 10 | 6 | 60 | 5.25 | |
| 384.0 | 2.58 | 10 | 4 | 40 | 4.75 | |
| 307.2 | 2.49 | 10 | 1 | 10 | 3.72 |
The specific embodiment
Below in conjunction with implementation method the present invention is further described.
Embodiment one preparation tablet
Adopt following steps: get copper nanoparticle, adopt conventional film-making technology, add dry adhesive and lubricant, mix homogeneously, directly compacting is in blocks, and sugar coating promptly gets tablet, and making every, to contain copper nanoparticle be 2.5mg.
Usage and dosage: oral, an a slice, every day secondary.
Embodiment two preparation capsules
Adopt following steps: get copper nanoparticle, sieve, add the starch mix homogeneously, be sub-packed in the hard capsule, make capsule, it is 2.5mg that every capsules contains copper nanoparticle.
Usage and dosage: oral, one time one, every day secondary.
Embodiment three preparation granules
Adopt following steps: get copper nanoparticle, add excipient Icing Sugar, starch, sieve, make soft material, pelletize, cold drying, granulate is distributed into bag, promptly gets granule, and every bag contains copper nanoparticle is 2.5mg.Usage and dosage: warm boiled water, one time one bag, every day secondary.
Claims (1)
1, a kind of copper nanoparticle is as the application of preparation prophylactic treatment osteoporosis, fracture medicine, it is characterized in that: adopting commercially available particle diameter is that the copper nanoparticle of 0.1-1000nm is a raw material, and the weight ratio of raw materials used copper nanoparticle of the medicine of making and preparation is 0.00025～0.0125: 1.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031109551A CN1234371C (en) | 2003-01-28 | 2003-01-28 | Application of nano copper powder for preparing medicine for prophylaxis of osteoporosis and bone fracture |
| AU2003221272A AU2003221272A1 (en) | 2003-01-28 | 2003-01-29 | Use of a nano-copper powder in preparation of the medicaments in preventing and treating of osteoporosis and fracture |
| PCT/CN2003/000099 WO2004067016A1 (en) | 2003-01-28 | 2003-01-29 | Use of a nano-copper powder in preparation of the medicaments in preventing and treating of osteoporosis and fracture |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031109551A CN1234371C (en) | 2003-01-28 | 2003-01-28 | Application of nano copper powder for preparing medicine for prophylaxis of osteoporosis and bone fracture |
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| Publication Number | Publication Date |
|---|---|
| CN1430970A CN1430970A (en) | 2003-07-23 |
| CN1234371C true CN1234371C (en) | 2006-01-04 |
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| CNB031109551A Expired - Fee Related CN1234371C (en) | 2003-01-28 | 2003-01-28 | Application of nano copper powder for preparing medicine for prophylaxis of osteoporosis and bone fracture |
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| Country | Link |
|---|---|
| CN (1) | CN1234371C (en) |
| AU (1) | AU2003221272A1 (en) |
| WO (1) | WO2004067016A1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050053673A1 (en) * | 2003-09-05 | 2005-03-10 | Shrirang Netke | Composition and method for facilitating bone healing |
| CN112999433B (en) * | 2021-02-23 | 2022-07-05 | 吴江永元生物科技有限公司 | Cu-Zn composite material intrauterine device and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8702254D0 (en) * | 1987-05-29 | 1987-05-29 | Kabivitrum Ab | NOVEL HEPARIN DERIVATIVES |
| US5151274A (en) * | 1990-08-06 | 1992-09-29 | The Procter & Gamble Company | Calcium and trace mineral supplements |
| CN1065411C (en) * | 1995-06-18 | 2001-05-09 | 侯润安 | Healthful nutrition milk powder and production method |
| CN1299678A (en) * | 1999-12-15 | 2001-06-20 | 李全才 | Chinese medicine shennongjingguling |
-
2003
- 2003-01-28 CN CNB031109551A patent/CN1234371C/en not_active Expired - Fee Related
- 2003-01-29 WO PCT/CN2003/000099 patent/WO2004067016A1/en not_active Application Discontinuation
- 2003-01-29 AU AU2003221272A patent/AU2003221272A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU2003221272A1 (en) | 2004-08-23 |
| WO2004067016A1 (en) | 2004-08-12 |
| CN1430970A (en) | 2003-07-23 |
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