CN1539427A - Icariin in application of preparing medication for treating and preventing osteoporosis - Google Patents
Icariin in application of preparing medication for treating and preventing osteoporosis Download PDFInfo
- Publication number
- CN1539427A CN1539427A CNA031279171A CN03127917A CN1539427A CN 1539427 A CN1539427 A CN 1539427A CN A031279171 A CNA031279171 A CN A031279171A CN 03127917 A CN03127917 A CN 03127917A CN 1539427 A CN1539427 A CN 1539427A
- Authority
- CN
- China
- Prior art keywords
- icariin
- osteoporosis
- group
- rat
- bone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
An application of icariin in preparing the medicines for preventing and treating osteoporosis is disclosed.
Description
Technical field
The present invention relates to the application of icariin in preparation treatment or prevention of osteoporosis medicine.
Background technology
Osteoporosis is geratologous heat subject, along with wearing out of world population, suffering from osteoporotic crowd is increasing year by year, the old people of the present over-65s of China has reached 1.2 hundred million according to statistics, account for 90% and suffer from osteoporotic patient in these crowds, therefore preventing and treating osteoporosis is a very urgent research topic that guarantees people's living standard.
Producing osteoporotic basic reason is exactly that bone resorption and bone formation effect are unbalance, and a large amount of bone resorption makes the minimizing of bone amount, downgrade.The therapy of present used treatment osteoporosis (as vitamin D, hormone replacement, bisphosphonates medicine) can only prevent that all bone is absorbed and can not impels bone formation.Controversies in hormone replacement in the elderly is because of it has potential carcinogenic risk and untoward reaction, so clinical practice is restricted; Though parathyroid hormone can stimulate bone formation, one of shortcoming is necessary drug administration by injection; Fluoride can work by the activity of stimulating osteoblast, but usually cause that serious gastrointestinal reaction, bone mineralising are bad, the frequency increase of hip fracture and vertebral fracture etc.; Calcitonin can short-term improve the pain of sufferers of osteoporosis face, but is preventing losing with the Hip Fracture effect of Compact bone bad.
The Chinese medicine Herba Epimedii is traditional kidney-nourishing yang-strengthening medicine, and saying of " mending the gate of vitality, beneficial vital essence, hard muscles and bones " arranged in " herbal outline ".Herba Epimedii promptly is applied to treating in the herbal mixture of osteoporosis very early, but its function of resisting osteoporosis just causes people's great attention up in recent years, and has carried out a large amount of infrastests and clinical application research.The testis method that spends Li Qingnan etc. causes the osteoporosis model of SD rat, gavages Herba Epimedii decocting extracting solution to rat model then, 6 times weekly.Continue the back discovery of 7 weeks, the bone trabecular bone absorption rate of perfusion group proximal tibia obviously reduces, and bone formation rate and mineralising deposition then obviously increase, and finds that simultaneously this medical instrument has the synthetic effect of the medullary cell DNA of promotion, see [Li Qingnan, Wu Tie, Xie Hua, Deng. Chinese herbal medicine,, the 12nd phase in 1993].Herba Epimedii is rich in flavone compound, has been proved to be the main effective ingredient of Herba Epimedii pharmacological action.Ji Hui etc. hang down the function of resisting osteoporosis of verifying Herba Epimedii total flavones on the inductive osteoporosis rat model of calcium feedstuff respectively at tretinoin in conjunction with low inductive osteoporosis rat model of calcium feedstuff and removal ovary combination, found that Herba Epimedii total flavones can obviously improve apparent surface density of osteoporosis rat femur and bone density, reduce bone trabecula sorbent surface percentage rate and form surperficial percentage rate, rising Trabecula Bone Volume percentage rate (TBV%), and have and improve bone Ca, the trend of bone P, see [Ji Hui, Liu Kang, Gong Xiaojian, Deng. Herba Epimedii total flavones is to extracing the preventive and therapeutic effect of ovary rats with osteoporosis. Chinese osteoporosis magazine, calendar year 2001, the 1st phase] and [Ji Hui, Liu Kang, Li Shaoping, Deng. Herba Epimedii total flavones is induced the preventive and therapeutic effect of rats with osteoporosis to tretinoin. China Medicine University's journal,, the 3rd phase in 2000].
Though the function of resisting osteoporosis of Herba Epimedii and Herba Epimedii total flavones has obtained the extensive approval of the world of medicine, but owing to the capacity of scientific research is limit and reason such as fund, technology barriers, which kind of composition what really work in Herba Epimedii and the Herba Epimedii total flavones is, conclusion is not arranged so far as yet.Have prevention or therapeutic dysfunction and vasoconstrictive effect although disclose icariin among the open text CN1282584A of Chinese patent, but about icariin have the prevention or treat osteoporotic effect and do not appear in the newspapers, Given this, the inventor is by a large amount of experimentatioies, being surprised to find the composition that has the effect of treatment osteoporosis in the Herba Epimedii total flavones is icariin, and promptly icariin has prevention or treats osteoporotic medical usage.
Summary of the invention
The invention provides the application of icariin in the medicine of preparation treatment or prevention of osteoporosis.
The invention provides the osteoporotic pharmaceutical composition of the treatment that contains icariin.
Icariin of the present invention draws by Herba Epimedii total flavones and icariin are carried out comparative study in the effect of treatment osteoporosis at treatment or the medical usage of prevention of osteoporosis disease.
The inventor has confirmed that by following test icariin has the effect of treatment or prevention of osteoporosis disease, but is not limited to this test.Test used " Herba Epimedii total flavones " and mainly comprise epimedin A, hexandraside A, epimedin B, epimedin and icariin, wherein icariin content is 20%; " icariin " contains icariin 90%.Press document [Wang Changli respectively, Song Xiaomei, military Xinhua, etc. the research of Herba Epimedii total flavones extraction and separation process. Chinese patent medicine, 1996, the 5th phase] and [Xin Zhongcheng, Euy Kyung Kim, Tian Zhenji, etc. icariin is to the relaxation effect and the mechanism of action thereof of cavernous body of penis. Science Bulletin, calendar year 2001, the 6th phase] described in the preparation of method extraction separation.
By test, the inventor finds that icariin can improve osteoporosis rat autonomic activities ability, femur, tibia peak load and structural strength; Increase femur and vertebra bone density, improve bone exponential sum femur ash separate index number." icariin " and " Herba Epimedii total flavones " dosage calculates by pure icariin amount, when dosage equates (as " icariin " 20mg/kg and " Herba Epimedii total flavones " 90mg/kg; " icariin " 40mg/kg and " Herba Epimedii total flavones " 180mg/kg), basic identical to osteoporotic therapeutical effect.Proved that thus icariin is the osteoporotic effective ingredient of treatment in the Herba Epimedii total flavones.
Icariin molecular formula: C
33H
40O
15, molecular weight: 676.67, fusing point: 225～230 ℃, chemical structural formula:
Icariin is used for the treatment of or during prevention of osteoporosis, its dosage is 10mg～1000mg, is preferably 100mg～500mg.
Icariin of the present invention is being used for the treatment of or during the prevention of osteoporosis disease, can use separately or use with the form of the pharmaceutical composition that contains icariin.
Pharmaceutical composition provided by the invention can be by means known in the art preparation and can be by administrations such as oral, Sublingual, percutaneous, muscle or subcutaneous, mucocutaneous, urethra, vagina or veins.Oral formulations can be made as tablet, capsule, granule, chewing agent, pill, suspension, solution etc., non-intestinal drug delivery agent can be made dosage forms such as injection, freeze-dried powder, and topical can be made as cream, ointment, patch, spray etc.But be not limited to this.
The specific embodiment:
Test example 1: icariin is to the therapeutical effect of female rats osteoporosis due to the retinoic acid
1. material:
Herba Epimedii total flavones (containing icariin 20%), press document [military Xinhua is etc. the research of. Herba Epimedii total flavones extraction and separation process for Wang Changli, Song Xiaomei. Chinese patent medicine, 1996 the 5th phases] preparation.
Icariin (containing icariin 90%) press document [Xin Zhongcheng, Euy Kyung Kim, etc. icariin is to the relaxation effect and the mechanism of action thereof of cavernous body of penis. Science Bulletin, the 6th phase of calendar year 2001] described in method extraction separation preparation.
The retinoic acid capsule, Hua Bang drugmaker in Chongqing produces, lot number 990701;
Low calcium feedstuff, Chinese Academy of Medical Sciences animal produces.
Regular grade Wistar rat, female, at 3～4 monthly ages, body weight 150～210g is provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106005, Shandong kinoplaszm word.
SX-2.5-10 type muffle furnace (production of Tianjin medium ring experimental electric furnace company limited);
BP210S type electronic analytical balance (German sartorius company produce);
QDR-4000 type dual intensity line bone densitometry instrument (production of U.S. HOLOGIC company);
CSS-1101C electronic universal tester (Changchun Inst of Testing Machine's production).
2. method
2.1 osteoporosis rat Preparation of model, animal grouping and medication
Get healthy 3～4 month female rats, be divided into 6 groups at random: the normal control group, the osteoporosis model group, icariin small dose group (20mg/kg), the heavy dose of group of icariin (40mg/kg), Herba Epimedii total flavones small dose group (90mg/kg), the heavy dose of group of Herba Epimedii total flavones (180mg/kg).Except that the normal control group, each organizes rat all with retinoic acid 70mg/kg dosage gastric infusion, 1 time/day, continuous three weeks.After three weeks of modeling, withdraw retinoic acid, each treated animal is respectively by said medicine dosage gastric infusion.1 time/day, successive administration one month.Normal control group and osteoporosis model group give the normal saline (10ml/kg) with capacity such as administration groups.22 ℃～25 ℃ of receptacle temperature, humidity 50%～70% is fed with low calcium feedstuff (calcium content＜0.3%), freely drinks water.
2.2 the mensuration of activities in rats ability
Behind the last administration 24h, get rat and place the experiment box, rat autonomic activities number of times in the record 5min.
2.3 rat bone density is measured
Behind the last administration 24h with 10% chloral hydrate (350mg/kg, i.p.) anesthetized rat, place under the QDR-4000 type dual intensity line bone densitometry instrument probe, facing upward the position is fixed on the monitor station, head and health are linearly, ray tube is aimed at the long axis of body mid point, selects osteoporosis rat sensitizing range one-sided (left side) femur mid point (F
50) cortical bone and third lumbar vertebra bone measure bone density.
2.4 the mensuration of rat bone index, bone ore deposit composition (bone Ca, P)
Behind the last administration 24h, get rat right side femur dry 2h in 120 ℃ of baking ovens, electronic balance is measured bone weight (W), slide gauge is measured bone long (L), bone diameter (D), calculates apparent line density (W/L), apparent surface density (W/LD).Above-mentioned femur is placed 800 ℃ of muffle furnace ashing 8h, and it is Powdered that bone is white in color, and claims ash heavy (Wash), and its ash heavily is inorganic substances weight.Measure the content of elements such as calcium, phosphorus in the bone ash with the plasma quantometer, and calculate ash lines of expression density (Wash/L) and the apparent surface density of ash (Wash/LD) that bone ash divides.
2.5 the mensuration of rat bone biomechanics
Behind the last administration 24h, left side femur, tibia are rejected muscle and surrounding tissue, put into and measure its biomechanical characterization within the liquid paraffin 7 days, do 3 breakdown tests with electronic universal tester, parameter is for demarcating 1/50, loading velocity 6mm/min, peak load 200 newton (N), span 20mm traces load-deformation curve, calculate peak load and structural strength (cause the load that the 1mm distortion needs, be equivalent to the slope on the curve).
3 results
3.1 icariin is to the influence of osteoporosis rat autonomic activities number of times
By table 1 as seen, compare with normal group, model group rat autonomic activities number of times significantly descends; The big small dose group of icariin all can significantly improve osteoporosis rat autonomic activities number of times, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).Table 1 icariin is to the influence of osteoporosis rat autonomic activities number of times (n=10, X ± s)
Group dosage (mg/kg) autonomic activities number of times
Normal group NS 214.8 ± 36.7
Model group NS 115.4 ± 29.3
*
Icariin is big by 40 191.6 ± 21.8
The Δ Δ
Icariin is little by 20 159.5 ± 31.0
Δ
Herba Epimedii total flavones is big by 180 180.8 ± 32.4
Δ
Herba Epimedii total flavones is little by 90 161.2 ± 34.1
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.2 icariin is to the influence of osteoporosis rat bone density
By table 2 as seen, compare model group rat femur density with normal group and vertebra density significantly descends, the big small dose group of icariin all can significantly improve osteoporosis rat femur density and vertebra density, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 2 icariin is to the influence of osteoporosis rat bone density (n=10, X ± s)
Group dosage (mg/kg) femur density (g/cm
2) vertebra density (g/cm
2)
Normal group NS 0.77 ± 0.08 0.75 ± 0.03
Model group NS 0.52 ± 0.06
*0.50 ± 0.05
*
Icariin is big by 40 0.70 ± 0.02
The Δ Δ0.68 ± 0.02
The Δ Δ
Icariin is little by 20 0.61 ± 0.04
Δ0.62 ± 0.03
Δ
Herba Epimedii total flavones is big by 180 0.72 ± 0.03
The Δ Δ0.69 ± 0.02
The Δ Δ
Herba Epimedii total flavones is little by 90 0.63 ± 0.07
Δ0.64 ± 0.06
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.3 icariin is to the exponential influence of osteoporosis rat bone
By table 3 as seen, compare model group rat femur weight, length, lines of expression density, apparent surface density all obviously descends with normal group, the big small dose group of icariin all can significantly improve osteoporosis rat femur density and vertebra density, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 3 icariin is to the exponential influence of osteoporosis rat femur ash (n=10, X ± s)
The apparent surface density of group dosage bone ash weight (g) the close ash of ash lines of expression
(mg/kg) degree (g/cm) (g/cm
2)
Normal group NS 0.36 ± 0.03 0.10 ± 0.00 0.26 ± 0.01
Model group NS 0.22 ± 0.02
*0.06 ± 0.00
*0.20 ± 0.01
*
Icariin is big by 40 0.33 ± 0.03
The Δ Δ0.08 ± 0.01
The Δ Δ0.24 ± 0.01
The Δ Δ
Icariin is little by 20 0.26 ± 0.03
Δ0.07 ± 0.02
Δ0.23 ± 0.01
Δ
Herba Epimedii total flavones is big by 180 0.34 ± 0.05
The Δ Δ0.08 ± 0.01
The Δ Δ0.24 ± 0.01
The Δ Δ
Herba Epimedii total flavones is little by 90 0.27 ± 0.03
Δ0.07 ± 0.01
Δ0.23 ± 0.02
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.4 icariin is to the influence of osteoporosis rat bone ore deposit component content
By table 4 as seen, compare model group rat femur Ca with normal group, P content significantly reduces, the big small dose group of icariin all can significantly improve osteoporosis rat femur Ca, P content, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 4 icariin is to the exponential influence of osteoporosis rat femur ash (n=10, X ± s)
Group dosage calcium (mg/g) phosphorus (mg/g)
(mg/kg)
Normal group NS 34.39 ± 2.13 15.44 ± 0.75
Model group NS 21.41 ± 2.51
*9.62 ± 0.56
*
Icariin is big by 40 30.36 ± 3.52
The Δ Δ13.28 ± 1.54
The Δ Δ
Icariin is little by 20 26.45 ± 3.22
Δ12.67 ± 1.21
Δ
Herba Epimedii total flavones is big by 180 31.33 ± 3.64
The Δ Δ13.62 ± 1.10
The Δ Δ
Herba Epimedii total flavones is little by 90 27.69 ± 3.58
Δ12.36 ± 1.38
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.5 icariin is to the mensuration of osteoporosis rat femur, tibia biomechanics
By table 5 as seen, peak load, the structural strength of comparing model group rat femur and tibia with normal group significantly reduce, the big small dose group of icariin all can significantly improve peak load, the structural strength of osteoporosis rat femur and tibia, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 5 icariin is to the influence of osteoporosis rat femur, tibia biomechanics (n=10, X ± s)
Group dosage femur peak load femur structure intensity tibia peak load tibia structural strength
(mg/kg) (N) (N/mm) (N) (N/mm)
Normal group NS 108.5 ± 5.7 357.6 ± 22.2 71.8 ± 12.8 511.3 ± 134.9
Model group NS 71.6 ± 8.7
*250.7 ± 18.9
*48.2 ± 13.1
*369.6 ± 86.5
*
Icariin is big by 40 98.7 ± 6.4
The Δ Δ315.4 ± 26.9
The Δ Δ67.2 ± 10.4
The Δ Δ464.8 ± 65.3
*
Icariin is little by 20 83.6 ± 9.6
Δ278.6 ± 25.7
Δ61.8 ± 10.6
Δ449.6 ± 74.4
Δ
Herba Epimedii total flavones is big by 180 101.5 ± 6.2
The Δ Δ318.6 ± 33.4
The Δ Δ68.6 ± 15.3
The Δ Δ473.6 ± 101.9
The Δ Δ
Herba Epimedii total flavones is little by 90 85.6 ± 9.1
Δ281.7 ± 35.9
Δ62.8 ± 14.9
Δ452.9 ± 80.5
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
4 conclusions
Above result of the test shows, give the isodose icariin of osteoporosis rat (contain Herba Epimedii total flavones 90mg/kg, the 180mg/kg of 20% icariin or contain icariin 20mg/kg, the 40mg/kg of icariin 90%), therapeutical effect to osteoporosis rat is basic identical, and promptly to treat osteoporotic effective ingredient be icariin to Herba Epimedii total flavones.
Test example 2: icariin is to the therapeutical effect of rat kidney weak osteoporosis due to the excision testis
1. material:
Herba Epimedii total flavones (containing icariin 20%), press document [military Xinhua is etc. the research of. Herba Epimedii total flavones extraction and separation process for Wang Changli, Song Xiaomei. Chinese patent medicine,, the 5th phase in 1996] preparation.
Icariin (containing icariin 90%) press document [Xin Zhongcheng, Euy Kyung Kim, etc. icariin is to the relaxation effect and the mechanism of action thereof of cavernous body of penis. Science Bulletin, calendar year 2001, the 6th phase] described in method extraction separation preparation.
The retinoic acid capsule, Hua Bang drugmaker in Chongqing produces, lot number 990701;
Low calcium feedstuff, Chinese Academy of Medical Sciences animal produces.
Regular grade Wistar rat, male, at 3～4 monthly ages, body weight 150～210g is provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106005, Shandong kinoplaszm word.
SX-2.5-10 type muffle furnace (production of Tianjin medium ring experimental electric furnace company limited); BP210S type electronic analytical balance (German sartorius company produce); QDR-4000 type dual intensity line bone densitometry instrument (production of U.S. HOLOGIC company); CSS-1101C electronic universal tester (Changchun Inst of Testing Machine's production).
2. method
2.1 osteoporosis rat Preparation of model, animal grouping and medication
Animal is divided into sham operated rats at random, osteoporosis model group, icariin small dose group (20mg/kg), the heavy dose of group of icariin (40mg/kg), Herba Epimedii total flavones small dose group (90mg/kg), the heavy dose of group of Herba Epimedii total flavones (180mg/kg).The rat chloral hydrate (face upward the position and fix iodine disinfection scrotum portion by 350mg/kg, i.p.) anesthesia, along scrotum center longitudinal incision one osculum, separate otch, the oval testis promptly exposes, the silk thread ligation, between ligature and testis, cut testis, sew up the incision, sterilize with 75% cotton ball soaked in alcohol.The sham operated rats animal is used with method and separates testis, but does not extract, and puts back to stitching.Three week of operation, each treated animal of back was respectively by said medicine dosage gastric infusion.1 time/day, successive administration one month.Normal control group and osteoporosis model group give the normal saline (10ml/kg) with capacity such as administration groups.22 ℃～25 ℃ of receptacle temperature, humidity 50%～70% is fed with low calcium feedstuff (calcium content＜0.3%), freely drinks water.
2.2 the mensuration of activities in rats ability
Behind the last administration 24h, get rat and place the experiment box, rat autonomic activities number of times in the record 5min.
2.3 rat bone density is measured
Behind the last administration 24h with 10% chloral hydrate (350mg/kg, i.p.) anesthetized rat, place under the QDR-4000 type dual intensity line bone densitometry instrument probe, facing upward the position is fixed on the monitor station, head and health are linearly, ray tube is aimed at the long axis of body mid point, selects osteoporosis rat sensitizing range one-sided (left side) femur mid point (F
50) cortical bone and third lumbar vertebra bone measure bone density.
2.4 the mensuration of rat bone index, bone ore deposit composition (bone Ca, P)
Behind the last administration 24h, get rat right side femur dry 2h in 120 ℃ of baking ovens, electronic balance is measured bone weight (W), slide gauge is measured bone long (L), bone diameter (D), calculates apparent line density (W/L), apparent surface density (W/LD).Above-mentioned femur is placed 800 ℃ of muffle furnace ashing 8h, and it is Powdered that bone is white in color, and claims ash heavy (Wash), and its ash heavily is inorganic substances weight.Measure the content of elements such as calcium, phosphorus in the bone ash with the plasma quantometer, and calculate ash lines of expression density (Wash/L) and the apparent surface density of ash (Wash/LD) that bone ash divides.
2.5 the mensuration of rat bone biomechanics
Behind the last administration 24h, left side femur, tibia are rejected muscle and surrounding tissue, put into and measure its biomechanical characterization within the liquid paraffin 7 days, do 3 breakdown tests with electronic universal tester, parameter is for demarcating 1/50, loading velocity 6mm/min, peak load 200 newton (N), span 20mm traces load-deformation curve, calculate peak load and structural strength (cause the load that the 1mm distortion needs, be equivalent to the slope on the curve).
3. result
3.1 icariin is to the influence of osteoporosis rat autonomic activities number of times
By table 1 as seen, compare with normal group, model group rat autonomic activities number of times significantly descends; The big small dose group of icariin all can significantly improve osteoporosis rat autonomic activities number of times, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 1 icariin is to the influence of osteoporosis rat autonomic activities number of times (n=10, X ± s)
Group dosage (mg/kg) autonomic activities number of times
Normal group NS 232.5 ± 32.7
Model group NS 126.1 ± 35.4
*
Icariin is big by 40 205.0 ± 34.6
The Δ Δ
Icariin is little by 20 167.5 ± 33.5
Δ
Herba Epimedii total flavones is big by 180 215.8 ± 32.6
The Δ Δ
Herba Epimedii total flavones is little by 90 168.2 ± 38.1
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.2 icariin is to the influence of osteoporosis rat bone density
By table 2 as seen, compare model group rat femur density with normal group and vertebra density significantly descends, the big small dose group of icariin all can significantly improve osteoporosis rat femur density and vertebra density, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 2 icariin is to the influence of osteoporosis rat bone density (n=10, X ± s)
Group dosage (mg/kg) femur density (g/cm
2) vertebra density (g/cm
2)
Normal group NS 0.78 ± 0.02 0.75 ± 0.02
Model group NS 0.53 ± 0.07
*0.49 ± 0.05
*
Icariin is big by 40 0.71 ± 0.03
The Δ Δ0.67 ± 0.02
The Δ Δ
Icariin is little by 20 0.62 ± 0.04
Δ0.61 ± 0.03
Δ
Herba Epimedii total flavones is big by 180 0.75 ± 0.03
The Δ Δ0.68 ± 0.02
The Δ Δ
Herba Epimedii total flavones is little by 90 0.63 ± 0.07
Δ0.61 ± 0.05
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.3 icariin is to the exponential influence of osteoporosis rat bone
By table 3 as seen, compare model group rat femur weight, length, lines of expression density, apparent surface density all obviously descends with normal group, the big small dose group of icariin all can significantly improve osteoporosis rat femur density and vertebra density, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 3 icariin is to the exponential influence of osteoporosis rat femur ash (n=10, X ± s)
The apparent surface density of group dosage bone ash weight (g) ash lines of expression density ash
(mg/kg) (g/cm) (g/cm
2)
Normal group NS 0.36 ± 0.02 0.14 ± 0.00 0.25 ± 0.01
Model group NS 0.24 ± 0.02
*0.08 ± 0.01
*0.21 ± 0.01
*
Icariin is big by 40 0.33 ± 0.03
The Δ Δ0.11 ± 0.01
The Δ Δ0.24 ± 0.01
The Δ Δ
Icariin is little by 20 0.28 ± 0.03
Δ0.09 ± 0.02
Δ0.23 ± 0.01
Δ
Herba Epimedii total flavones is big by 180 0.34 ± 0.05
The Δ Δ0.11 ± 0.03
The Δ Δ0.24 ± 0.01
The Δ Δ
Herba Epimedii total flavones is little by 90 0.28 ± 0.03
Δ0.09 ± 0.01
Δ0.23 ± 0.02
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.4 icariin is to the influence of osteoporosis rat bone ore deposit component content
By table 4 as seen, compare model group rat femur Ca with normal group, P content significantly reduces, the big small dose group of icariin all can significantly improve osteoporosis rat femur Ca, P content, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 4 icariin is to the exponential influence of osteoporosis rat femur ash (n=10, X ± s)
Group dosage (mg/kg) calcium (mg/g) phosphorus (mg/g)
Normal group NS 34.66 ± 3.51 14.64 ± 1.35
Model group NS 22.37 ± 2.63
*9.31 ± 0.87
*
Icariin is big by 40 31.38 ± 3.58
The Δ Δ13.16 ± 1.45
The Δ Δ
Icariin is little by 20 27.82 ± 3.55
Δ12.58 ± 1.07
Δ
Herba Epimedii total flavones is big by 180 32.36 ± 3.73
The Δ Δ13.39 ± 1.13
The Δ Δ
Herba Epimedii total flavones is little by 90 28.65 ± 3.22
Δ12.64 ± 1.32
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.5 icariin is to the mensuration of osteoporosis rat femur, tibia biomechanics
By table 5 as seen, peak load, the structural strength of comparing model group rat femur and tibia with normal group significantly reduce, the big small dose group of icariin all can significantly improve peak load, the structural strength of osteoporosis rat femur and tibia, and effect is basic identical with the Herba Epimedii total flavones of suitable dosage (by icariin).
Table 5 icariin is to the influence of osteoporosis rat femur, tibia biomechanics (n=10, X ± s)
Group dosage femur peak load femur structure intensity tibia peak load tibia structural strength
(mg/kg) (N) (N/mm) (N) (N/mm)
Normal group NS 118.8 ± 7.5 367.6 ± 22.8 79.2 ± 8.9 648.9 ± 138.8
Model group NS 87.4 ± 19.6
*255.8 ± 16.3
*53.2 ± 13.2
*468 ± 108.2
*
Icariin is big by 40 102.2 ± 9.3
The Δ Δ311.2 ± 25.4
The Δ Δ73.6 ± 10.5
The Δ Δ588.4 ± 84.7
The Δ Δ
Icariin is little by 20 99.6 ± 15.1
Δ279.4 ± 26.1
Δ64.7 ± 10.2
Δ509.6 ± 94.3
Δ
Herba Epimedii total flavones is big by 180 102.3 ± 7.9
The Δ Δ317.2 ± 34.5
The Δ Δ75.2 ± 15.4
The Δ Δ582.6 ± 123.9
The Δ Δ
Herba Epimedii total flavones is little by 90 97.6 ± 9.1
Δ283.3 ± 34.8
Δ66.5 ± 14.1
Δ512.9 ± 91.2
Δ
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
4 conclusions
Above result of the test shows, give the isodose icariin of osteoporosis rat (contain Herba Epimedii total flavones 90mg/kg, the 180mg/kg of 20% icariin or contain icariin 20mg/kg, the 40mg/kg of icariin 90%), therapeutical effect to osteoporosis rat is basic identical, and promptly to treat osteoporotic effective ingredient be icariin to Herba Epimedii total flavones.
Test example 3: the various dose icariin is to the therapeutical effect of female rats osteoporosis due to the retinoic acid
1. material:
Icariin (containing icariin 90%) press document [Xin Zhongcheng, Euy Kyung Kim, Tian Zhenji, etc. icariin is to the relaxation effect and the mechanism of action thereof of cavernous body of penis. Science Bulletin, calendar year 2001, the 6th phase] described in method extraction separation preparation.
The retinoic acid capsule, Hua Bang drugmaker in Chongqing produces, lot number 990701;
Low calcium feedstuff, Chinese Academy of Medical Sciences animal produces.
Regular grade Wistar rat, female, at 3～4 monthly ages, body weight 150～210g is provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106005, Shandong kinoplaszm word.
SX-2.5-10 type muffle furnace (production of Tianjin medium ring experimental electric furnace company limited);
BP210S type electronic analytical balance (German sartorius company produce);
QDR-4000 type dual intensity line bone densitometry instrument (production of U.S. HOLOGIC company);
CSS-1101C electronic universal tester (Changchun Inst of Testing Machine's production).
2. method
2.1 osteoporosis rat Preparation of model, animal grouping and medication
Get healthy 3～4 month female rats, be divided into 5 groups at random: normal control group, osteoporosis model group, the heavy dose of group of icariin (20mg/kg), dosage group (10mg/kg) in the icariin, icariin small dose group (5mg/kg).Except that the normal control group, each organizes rat all with retinoic acid 70mg/kg dosage gastric infusion, 1 time/day, continuous three weeks.After three weeks of modeling, withdraw retinoic acid, each treated animal is respectively by said medicine dosage gastric infusion.1 time/day, successive administration one month.Normal control group and osteoporosis model group give the normal saline (10ml/kg) with capacity such as administration groups.22 ℃～25 ℃ of receptacle temperature, humidity 50%～70% is fed with low calcium feedstuff (calcium content＜0.3%), freely drinks water.
2.2 rat bone density is measured
Behind the last administration 24h with 10% chloral hydrate (350mg/kg, i.p.) anesthetized rat, place under the QDR-4000 type dual intensity line bone densitometry instrument probe, facing upward the position is fixed on the monitor station, head and health are linearly, ray tube is aimed at the long axis of body mid point, selects osteoporosis rat sensitizing range one-sided (left side) femur mid point (F
50) cortical bone and third lumbar vertebra bone measure bone density.
2.3 the mensuration of rat bone biomechanics
Behind the last administration 24h, left side femur, tibia are rejected muscle and surrounding tissue, put into and measure its biomechanical characterization within the liquid paraffin 7 days, do 3 breakdown tests with electronic universal tester, parameter is for demarcating 1/50, loading velocity 6mm/min, peak load 200 newton (N), span 20mm traces load-deformation curve, calculate peak load and structural strength (cause the load that the 1mm distortion needs, be equivalent to the slope on the curve).
3 results
3.1 icariin is to the influence of osteoporosis rat bone density
By table 1 as seen, compare model group rat femur density with normal group and vertebra density significantly descends, the big or middle dosage of icariin all can significantly improve osteoporosis rat femur density and vertebra density, and icariin low dose (5mg/kg) does not have obviously influence to this.
Table 1 icariin is to the influence of osteoporosis rat bone density (n=10, X ± s)
Group dosage (mg/kg) femur density (g/cm
2) vertebra density (g/cm
2)
Normal control group NS 0.81 ± 0.02 0.79 ± 0.02
Model control group NS 0.51 ± 0.07
*0.47 ± 0.05
*
Icariin is big by 20 0.76 ± 0.03
The Δ Δ0.71 ± 0.02
The Δ Δ
In the icariin 10 0.64 ± 0.04
Δ0.63 ± 0.03
Δ
Icariin is little by 5 0.54 ± and 0.07 0.51 ± 0.05
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
3.2 icariin is to the mensuration of osteoporosis rat femur, tibia biomechanics
By table 2 as seen, peak load, the structural strength of comparing model group rat femur and tibia with normal group significantly reduce, the big or middle dosage of icariin all can significantly improve peak load, the structural strength of osteoporosis rat femur and tibia, and icariin low dose (5mg/kg) does not have obviously influence to this.
Table 2 icariin is to the influence of osteoporosis rat femur, tibia biomechanics (n=10, X ± s)
Group dosage femur peak load femur structure intensity tibia peak load tibia structural strength
(mg/kg) (N) (N/mm) (N) (N/mm)
Normal control group NS 119.8 ± 7.7 373.6 ± 22.8 81.3 ± 8.5 653.2 ± 133.1
Model control group NS 67.4 ± 19.3
*205.7 ± 16.3
*41.2 ± 12.2
*447 ± 99.2
*
Icariin is big by 20 103.2 ± 18.3
The Δ Δ321.2 ± 25.5
The Δ Δ76.6 ± 12.3
The Δ Δ581.4 ± 86.7
The Δ Δ
In the icariin 10 89.6 ± 15.1
Δ265.4 ± 29.1
Δ62.7 ± 10.2
Δ498.6 ± 94.5
Δ
Icariin is little by 5 73.6 ± and 12.3 231.3 ± 34.81 51.2 ± 14.8 459.9 ± 128.2
* P＜0.01 VS normal group;
ΔP＜0.05,
The Δ ΔP＜0.01 VS model group
Test example 4: icariin acute toxicity test
1 material:
Icariin (containing icariin 90%) press document [Xin Zhongcheng, Euy Kyung Kim, Tian Zhenji, etc. icariin is to the relaxation effect and the mechanism of action thereof of cavernous body of penis.Science Bulletin, calendar year 2001, the 6th phase] described in the preparation of method extraction separation.
Cleaning level kunming mouse, 18～22g is provided by natural drug Engineering Technical Research Centre zoopery center, Shandong Province.The quality certification number: No. 200106003, Shandong kinoplaszm word.Feedstuff identifies that by Chinese pharmaceutical biological product check is provided.By SOP requirement one week of quarantine, reject defective animal.Test chamber and receptacle term harmonization.18～25 ℃ of room temperatures, humidity 40～60% is filtered air-supply, illumination 12 hours.Freely ingest and drink water, change the drinking-water bottle every day once.
2 methods
2.1 dosage design
The animal test of pesticide effectiveness shows that the oral 10mg/kg of rat promptly has the effect of tangible osteoporosis.The suspension that Gong the filling stomach that icariin can be prepared is used is 100mg/ml, and it is 1ml/ that the maximum of mouse stomach administration allows volume, so the design dosage is mice 5.0g/kg, and administration every day 1 time.
2.2 grouping, administration
Get 40 of healthy mices, male and female half and half.Be divided into normal saline group and icariin group at random, 20 every group.After weighing, press the dosage of 5.0g/kg, the administration volume filling stomach of 1ml/20g, matched group is irritated stomach equal-volume normal saline.Toxic reaction of close observation mice and death condition after the administration; After 4 hours, change into and observe once continuous 14 days every day.Measure body weight weekly 1 time.
3 results
After the filling stomach gives icariin, the movable no abnormality seen of mice.In 4 hours, do not see the change of site color such as ear, eyelid, four-footed, the urine color shows no obvious abnormalities.In 14 days, mice hair color light, diet, activity and body weight all do not have significant difference (table 1) with matched group.
The variation of the oral 5.0g/kg icariin of table 1 mice body weight (X ± s);
The weight of animals (g)
The group sex
Quantity test the preceding the 7th day the 14th day
Herba Epimedii ♀ 10 18.58 ± 0.65 25.45 ± 1.07 28.2 ± 1.53
Glycosides group ♂ 10 18.86 ± 0.52 29.15 ± 0.81 34.57 ± 1.80
Physiology salt ♀ 10 18.52 ± 0.63 26.04 ± 2.19 29.38 ± 3.19
Water group ♂ 10 18.59 ± 0.82 29.27 ± 1.77 34.87 ± 1.94
Claims (6)
1. the application of icariin in preparation treatment or prevention of osteoporosis medicine.
2. application according to claim 1, the using dosage scope that it is characterized in that icariin is 10mg～1000mg.
3. application according to claim 2 is characterized in that the using dosage of icariin is preferably 100mg～500mg.
4. contain being used for the treatment of or the pharmaceutical composition of prevention of osteoporosis of icariin.
5. pharmaceutical composition according to claim 4, said composition can be by oral, Sublingual, percutaneous, through muscle or subcutaneous, mucocutaneous, urethra, vagina or intravenous route administration.
6. according to claim 4 or 5 described pharmaceutical compositions, it is characterized in that compositions can exist with forms such as tablet, pill, granule, capsule, suspension, solution, syrup, injection, cream, ointment, spray, chewing agent or patches.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031279171A CN1539427A (en) | 2003-04-23 | 2003-04-23 | Icariin in application of preparing medication for treating and preventing osteoporosis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031279171A CN1539427A (en) | 2003-04-23 | 2003-04-23 | Icariin in application of preparing medication for treating and preventing osteoporosis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1539427A true CN1539427A (en) | 2004-10-27 |
Family
ID=34322084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA031279171A Pending CN1539427A (en) | 2003-04-23 | 2003-04-23 | Icariin in application of preparing medication for treating and preventing osteoporosis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1539427A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101843629A (en) * | 2010-06-11 | 2010-09-29 | 首都医科大学宣武医院 | New application of icariin and epimedium flavone containing icariin |
| CN1911103B (en) * | 2005-08-08 | 2011-07-27 | 天津丹溪国药研究所 | Health-care food for improving human body physical agility and endurance |
| CN101444552B (en) * | 2008-12-31 | 2011-08-31 | 重庆市中药研究院 | Chinese medicinal preparation for treating osteoporosis |
| CN105384786A (en) * | 2015-11-13 | 2016-03-09 | 江苏康缘药业股份有限公司 | Compound as well as preparation method and application thereof |
| CN112891366A (en) * | 2019-12-03 | 2021-06-04 | 暨南大学 | Traditional Chinese medicine active ingredient formula for treating postmenopausal osteoporosis and application thereof |
-
2003
- 2003-04-23 CN CNA031279171A patent/CN1539427A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1911103B (en) * | 2005-08-08 | 2011-07-27 | 天津丹溪国药研究所 | Health-care food for improving human body physical agility and endurance |
| CN101444552B (en) * | 2008-12-31 | 2011-08-31 | 重庆市中药研究院 | Chinese medicinal preparation for treating osteoporosis |
| CN101843629A (en) * | 2010-06-11 | 2010-09-29 | 首都医科大学宣武医院 | New application of icariin and epimedium flavone containing icariin |
| CN101843629B (en) * | 2010-06-11 | 2012-03-14 | 首都医科大学宣武医院 | New application of icariin and epimedium flavone containing icariin |
| CN105384786A (en) * | 2015-11-13 | 2016-03-09 | 江苏康缘药业股份有限公司 | Compound as well as preparation method and application thereof |
| CN105384786B (en) * | 2015-11-13 | 2018-09-14 | 江苏康缘药业股份有限公司 | A kind of compound and its preparation method and application |
| CN112891366A (en) * | 2019-12-03 | 2021-06-04 | 暨南大学 | Traditional Chinese medicine active ingredient formula for treating postmenopausal osteoporosis and application thereof |
| CN112891366B (en) * | 2019-12-03 | 2022-08-09 | 暨南大学 | Traditional Chinese medicine active ingredient formula for treating postmenopausal osteoporosis and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1245202C (en) | Medicine for preventing and treating bone fracture and osteoporosis | |
| CN1698713A (en) | Compound composition for treating arthralgia caused by wind-dampness and preparation thereof | |
| CN1539427A (en) | Icariin in application of preparing medication for treating and preventing osteoporosis | |
| CN1990006A (en) | Chenopodium ambrosioides extract, preparation thereof, preparation method and use thereof | |
| CN1283291C (en) | Compound preparation for bone fracture and its preparation method | |
| CN1872278A (en) | A composition of medication | |
| CN1245189C (en) | Composition for strengthening body resistance and restoring and function, strengthening spleen and kidney, relieving metal stress and promoting blood circulation to remove blood stasis | |
| CN100344315C (en) | Medicinal composition for promoting bone fracture healing and its preparing method | |
| CN1742778A (en) | Cervus and cucumis polypeptide injection composition and preparing method | |
| CN101041024A (en) | Medicinal composition for treating tuberculosis and its preparing process | |
| CN1565473A (en) | Water soluble nightshade extract, its preparation method and pharmaceutical compositions | |
| CN1634025A (en) | Use of erberry and its lignanoids compound in drug for osteoporosis | |
| CN1289105C (en) | Bone pain dispersing granular composition and its preparation method | |
| CN1973872A (en) | Medicine for nourishing Yin, invigorating kidney, strengthening physique and nourishing brain and its prepn | |
| CN100349595C (en) | Medicinal composition for catharsis | |
| CN1316997C (en) | Preparation for free flowing ginew and bone and its preparation method | |
| CN1296069C (en) | Preparing technics of composition of Guizhi and Fuling and its use | |
| CN1166402C (en) | Composite Chinese medicine with health care function | |
| CN1742749A (en) | Gugua polypeptide medicinal composition for injetion and preparing method therefor | |
| CN1336233A (en) | Hepatitis B treating medicine | |
| CN1626103A (en) | Combination of medication of containing general saponin of notoginseng and icariin as well as usage | |
| CN1772122A (en) | Indian stringbush prepn with antiphlogistic and detoxicating functions | |
| CN1502357A (en) | Use of crataegus pit extract in preparation of medicine for treating mycosis | |
| CN101057954A (en) | Traditional Chinese medicine compound for treating transient ischemic attack and its preparation method | |
| CN1623554A (en) | Anticancer auxiliary medicine using C-K as effective component and its application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |