CN1480142A - compound preparation composed of longspur epimedium and estrogen for treating osteoporosis of women after climacteric - Google Patents
compound preparation composed of longspur epimedium and estrogen for treating osteoporosis of women after climacteric Download PDFInfo
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Abstract
A medicine for preventing and treating the osteoporosis of manopausal woman is prepared from epimedium and estrin. Its advantages are high curative effect and very low untoward effect.
Description
The present invention relates to the compound preparation and the method for making thereof formed by Chinese medicine Herba Epimedii and estrogen of menopausal women treatment osteoporosis.
The data of research shows at present, the women 99% all osteoporosis can occur after menopause, the osteoporosis that this postmenopausal women is taken place is also referred to as primary osteoporosis, this disease be a kind of with the bone amount reduce, the osseous tissue fine structure deteriorates to feature, causes the fragility of bone to increase and the skeletal diseases of the general that is easy to fracture.Along with world population is tending towards aging, the sickness rate of osteoporosis and osteoporotic fracture is the trend of rapid rising.Result according to China's census in 2000, the number that primary osteoporosis is suffered from by prediction China is about 0.88 hundred million, account for 6.97% of country's total population, expect 2010 and will reach 1.14 hundred million, the percent that accounts for total population will rise to 8.2%, and the number that fracture because of osteoporosis every year will be with double-digit growth rate tool height not down.Osteoporotic fracture has become that the old people is disabled, quality of life descends even main causes of death serious harm old people's health.Osteoporosis and osteoporotic fracture have made increasing people deeply hurt, and have become the serious social problem of worldwide concern, also it have been classified as one of Senile disease of three big emphasis tackling key problem researchs in China.Therefore, osteosporosis resistant medicament research just becomes a key areas of contemporary medicine and pharmacology research.
The drug main of treatment osteoporosis will be divided into three types at present, and a class is for suppressing the medicine of bone resorption, as estrogen, calcitonin, progestogen, diphosphate etc.; Another kind of is to promote osteoplastic medicine, as fluoride, anabolic steroid hormone, Yi Pulafen etc.; The 3rd class is for the medicine of effect bone mineralising, as calcium preparation, vitamin D etc.Various kinds of drug has certain curative effect to protect against osteoporosis, but still has brought long-range untoward reaction.Controversies in hormone replacement in the elderly is the main means of present wide clinical application in the control postmenopausal osteoporosis, prevents losing fast of old age or menopausal women bone amount effectively, keeps the bone amount, reduces the fracture incidence rate.But estrogen has serious adverse effects, and its serious adverse reaction is to stimulate endometrial hyperplasia, increases the sickness rate of carcinoma of endometrium, and life-time service also can increase the sickness rate of breast carcinoma and cause metrorrhagia etc.In addition, estrogen belongs to and suppresses bone resorption class medicine, and its effect characteristics are to suppress bone resorption and bone formation simultaneously, and the long term inhibition bone formation can cause the aging of bone, and bone mass descends.Osteoporosis is a kind of chronic senile degenerative disease, requires necessary long-term prescription, how to improve medicine and therapeutic regimen, alleviates estrogenic untoward reaction, is a problem that awaits solving.
In Chinese medicine research, find that some Chinese medicine compound have certain curative effect to prevention of osteoporosis disease, but many Chinese medicines, no matter compound recipe or folk prescription, the effect of its prevention removal ovary osteoporosis rat all is not so good as estrogen.Therefore, the present invention proposes the design of Chinese medicine and western medicine associating protect against osteoporosis.Herba Epimedii is the traditional kidney-nourishing yang-strengthening medicine of China, and we have proved the effect that the compound recipe of Herba Epimedii and Herba Epimedii composition has significant protect against osteoporosis in recent years, but the preventive effect of removal ovary osteoporosis rat is not so good as estrogen.Lose type fast because removal ovary osteoporosis rat model belongs to the bone of high turnover, because of the coupled action bone formation also obviously increases, the bone resorption increase has surpassed osteoplastic speed, loses fast so bone occurs when bone resorption increases.Herba Epimedii suppresses a little less than the bone conversion, do not suppress because of bone resorption increase due to the coupling bone formation increase.Herba Epimedii can promote medullary cell DNA synthetic, promotes the osseous tissue protein synthesis and promotes function of osteoblast, can promote osteoblastic propagation and differentiation at experiment in vitro.If Herba Epimedii share low dose of estrogen, both can bring into play stronger inhibition bone transduction, can promote bone formation again, have synergism to increasing the bone amount; Simultaneously the Herba Epimedii compound recipe can resist the stimulation of ethinylestradiol to uterus and inner membrance thereof, and Herba Epimedii has androgen-like action, if Herba Epimedii share low dose of estrogen, can alleviate estrogenic untoward reaction.Herba Epimedii total flavones is one of main effective ingredient of Herba Epimedii, can effectively prevent tretinoin and induce and hang down the osteoporosis rat that the calcium feedstuff brings out in conjunction with removal ovary, and can promote external osteoblastic proliferation and differentiation and maturation.
Therefore, task of the present invention is the compound preparation of women prevention and treatment osteoporosis after development a kind of suitable menopause, this compound preparation is formed compound recipe by Herba Epimedii or Herba Epimedii total flavones and estrogen, Herba Epimedii can improve the estrogen function of resisting osteoporosis and reduces its untoward reaction in this compound preparation, therefore, estrogenic consumption can reduce 1/5~1/2, reaches same curative effect and obviously minimizing or disappearance of untoward reaction.Studies show that said preparation can stop further losing of removal ovary rat sclerotin, can promote the formation of new bone again, the uterus is not had tangible stimulation.Therefore, can be used for the osteoporosis due to a variety of causes, be particularly suitable for women's prevention and treatment osteoporosis after menopause.
The approach that solves this task is to realize like this, getting Herba Epimedii or Herba Epimedii total flavones and estrogen combines, form compound recipe, be made into tablet, electuary or capsule by following technology,, studies show that for clinical practice, this preparation is to removal ovary, go the experimental osteoporosis due to the testis, the osteoporosis due to the prolonged application adrenocortical hormone all has good preventive and therapeutic effect to insufficiency of kidney-YANG osteoporosis due to the chemotherapeutic hydroxyurea etc.This preparation can stop further losing of sclerotin, promotes alcium and phosphor metabolization, promotes new bone formation, makes loose osseous tissue become fine and close, and can eliminate the various untoward reaction due to the osteoporosis.There is no report with this compound preparation treatment osteoporosis domestic and foreign literature.
This compound preparation can prepare by following SOME METHODS:
1, Herba Epimedii is ground into powder, adds 75~95% soak with ethanol 24 hours, filters, reclaim ethanol, it is standby to get ethanol extract, and medicinal residues decoct with water 3 times again, merge three times filtrate, filter, filtrate is concentrated in right amount, add aforesaid ethanol extract, cold drying is pulverized, add appropriate amount of auxiliary materials and estrogen, make granule, tabletting, sugar coating or encapsulated, promptly.
2, the Herba Epimedii raw medicinal herbs decocts with several times water logging bubble back, repeats 3 times, and merging filtrate concentrates, and adds 3 times of ethanol precipitations, behind the recovery ethanol, uses ethyl acetate extraction, reclaims ethyl acetate and obtains Herba Epimedii total flavones.(make standard substance, record Herba Epimedii total flavones content is 32% in the extract) with icariine.Herba Epimedii total flavones adds appropriate amount of auxiliary materials and estrogen, makes granule, tabletting, and sugar coating or encapsulated, promptly.
3, the used estrogen of this compound preparation can be used estradiol valerate, ethinylestradiol, estriol, nilestriol, premarin, diethylstilbestrol, Chlorotrianisne, tamoxifen.When these estrogen and Herba Epimedii are formed compound recipe, every or every 's content is respectively: estradiol valerate 0.2~0.5mg/ sheet, ethinylestradiol 2.5~5 μ g/ sheets, estriol 0.2~0.5mg/ sheet, nilestriol 5~15 μ g/ sheets, premarin 0.075~0.125mg/ sheet, diethylstilbestrol 0.075~0.125mg/ sheet, Chlorotrianisne 1~2mg/ grain, tamoxifen 2~5mg/ sheet.
The goods that adopt above 1~2 method to make, prove through pharmacology, toxicologic study, this product has tangible prevention and therapeutical effect to the rats with osteoporosis due to the removal ovary, acute toxicity test and long term toxicity test (comprising 3 months to 6 months) confirm that all this product toxicity is low, take for a long time all harmless effects of each vitals such as the heart, liver, kidney, lung, stomach, intestinal, spleen, thymus, lymph nodes.Clinical research shows, this product has good preventive and therapeutic effect to primary osteoporosis such as menopausal women and senile osteoporosis.
Embodiment:
Pharmacodynamic action for the compound preparation of observing the treatment osteoporosis of being made up of Herba Epimedii and estrogen, carried out following experiment:
The extraction Herba Epimedii raw medicinal herbs of 1 materials and methods, 1.1 material 1.1.1 Herba Epimedii total flavones decocts with several times water logging bubble back, repeats 3 times, and merging filtrate concentrates, add 3 times of ethanol precipitations, after reclaiming ethanol, use ethyl acetate extraction, reclaim ethyl acetate and obtain Herba Epimedii total flavones.Make standard substance with icariine, record that Herba Epimedii total flavones content is 32% in the extract.Herba Epimedii total flavones adds appropriate amount of auxiliary materials and estrogen diethylstilbestrol, makes granule, tabletting, and the content of diethylstilbestrol is made into the 0.075mg/ sheet.1.1.2 medicine and reagent diethylstilbestrol be available from Guangdong Bidi Pharmaceutical Co., Ltd, lot number 20010601; Calcein (Calcein), quadracycline, Goldner ' s dye reagent are all available from U.S. Sigma company; Methyl methacrylate is available from the Beijing Chemical Plant; Dibutyl phthalate is available from Tianjin Chemical Reagents Factory No.1; Benzoyl peroxide is available from Guangzhou Chemical Reagent Factory; The estradiol radioimmunological kit is available from Depew, Tianjin company; Serum calcium, phosphorus, alkali phosphatase, T-CHOL test kit are provided by German Beckman company.1.1.3 instrument low speed saw (Buehler LTD.USA); Sclerous tissues's microtome (German Leica 2155); The firm cutter of tungsten carbide (German Leica company product); Automated image digital assay instrument comprises light microscopic and fluorescence microscope (Nikon, Japan); Osseous tissue morphometry Survey Software (KSS ScientificConsultants, UT USA); Automatic clinical chemistry analyzer (German Beckman company); Gamma counter (Finland LKB); AE240 electronic balance (Mettler-Toledo instr.shanghai Ltd); ASD-3D Aiwa electronic weighing scale (Aiwa of Shenzhen weighing apparatus company limited product).1.2 material 1.2.1 animal model and 4 monthly ages of grouping are 60 of female sd inbred rats of copulation (provided by Chinese Academy of Sciences's Shanghai Experimental Animal Center, the quality certification number be No. the 003rd, the moving pipe of middle section) not, cleaning grade, average weight 225 ± 15g; Adaptability was raised 15 days, average weight 240 ± 12g when beginning to test.Sub-cage rearing is raised in 23 ℃ ~ 25 ℃ of room temperatures, in the cleaning ambient of relative humidity 50% ~ 70%, freely ingests and takes the photograph water; Use standard feed, wherein calcium content 1.33%, phosphorus content 0.95%.Be divided into 6 groups at random, every group is 10.Basis matched group (Basal) during the experiment beginning, is drawn materials its execution.Except that the sham operated rats rat, the remaining row bilateral oophorectomy is accepted the different pharmaceutical treatment then.(1) sham operated rats (Sham) and (2) ovariectomized group (OVX) all are 0.056 ethanol (solvent control) with volume fraction; All the other are respectively: (3) diethylstilbestrol DES 22.5 μ gkg
-1D
-1(4) Herba Epimedii total flavones EF300mgkg
-1D
-1(5) Herba Epimedii total flavones EF300mgkg
-1D
-1+ diethylstilbestrol DES22.5 μ gkg
-1D
-1Equal gastric infusion.All animals administer times are 90 days, weigh weekly 1 time, and adjust dosage by body weight change.The the 14th, 13 day and the 4th, 3 day difference subcutaneous injection quadracycline 30mgkg before sacrifice of animal
-1And calcein (Calcein) 5mgkg
-11.2.2 the making rat of bone specimen is put to death with the heart blood drawing of pentobarbital sodium anesthesia back, separation of serum is made the mensuration of biochemical indicator; Take out internal organs, divide another name organ weight in wet base, the organ weight in wet base divided by body weight and multiply by 1000 the organ index; Take out the left side tibia, open pulp cavity with sawing at near-end at a slow speed as sagittal, 1/3 place walks crosswise sawed-off in the tibia epimere, get that the tibia epimere is fixed, dehydration, embedding and section, downcut 5 μ m and 8 μ m section respectively with sclerous tissues's microtome, 5 μ m bone thin slices adopt Masson-Goldner Trichrome colouring method, and the dyeing back is in order to observe bone trabecula surface osteoclast number.The direct mounting of 8 μ m bone sheets adopts semi-automatic image digitization analyser to measure osseous tissue morphometry static parameter and dynamic parameter.1.2.3 proximal tibia cancellous bone tissue morphometry is measured
With KSS Image image analysis system,, measure the static parameter and the dynamic parameter of proximal tibia by the definition and the basis of calculation of international bone morphometry parameter measurement.Static parameter comprises the osseous tissue gross area (T.Ar, mm
2), bone trabecula area (Tb.Ar, mm
2), bone trabecula girth (Tb.Pm, mm) and calculating parameter [the bone trabecula area percent (%Tb.Ar, %), bone trabecula thickness (Tb.Th, μ m) and bone trabecula separating degree (Tb.Sp, μ m)], total osteoclast number (Oc.No) and index thereof (Oc.N/mm, #/mm).Dynamic parameter comprises single labelling girth (sL.Pm, mm), double labelling girth (dL.Pm, mm) and double labelling spacing (Ir.L.Wi, μ m) and calculating parameter [labelling girth percent (%L.Pm, %), bone mineralising deposition (MAR, μ m/d), bone formation rate BER/BS (expression bone surface formation rate, %yr), bone formation rate BER/BV (expression bone degree of conversion, %yr), bone formation rate BER/TV (expression osseous tissue formation rate, %yr)].1.2.4 the mensuration serum calcium (Ca) of serum biochemistry index and estradiol, phosphorus (P), alkali phosphatase (ALP), T-CHOL (Ch), assay adopt German Beckman automatic clinical chemistry analyzer, test kit is provided by German Beckman company, is finished by the land-reclaimable hospital laboratory in Guangdong Province.Estradiol (E
2) assay adopts the radioimmunoassay method of bag quilt-antibody-counting, concrete operations are undertaken by the test kit description, and the teacher of teaching and research room finishes jointly with the court's isotope.After 1.2.5 uterine cancer cell morphologic observation and endometrium thickness are measured and are taken out the uterus, at first weigh and observe the uterus size, get three position strippings and slicings then and carry out paraffin embedding, and make 5 μ m respectively and cut into slices, dye through HE, observe down in 10 * 40 times of mirrors, and measure inner film thickness with automated graphics digital assay instrument.1.2.6 all data of statistical method are represented with x ± s, carry out variance analysis with SPSS 10.0 softwares, relatively with the q check, there is statistical significance P<0.05 in twos.2 results, 2.1 Herba Epimedii total flavones and diethylstilbestrol are to the influence of rat body weight, serum biochemistry index and estradiol
Herba Epimedii total flavones and diethylstilbestrol see Table 1 to the influence of rat body weight, serum biochemistry index and estradiol:
Table 1: Herba Epimedii total flavones and diethylstilbestrol are to the influence of rat body weight, serum biochemistry index and estradiol (m=10, the group dosage body weight of x ± s): begin to finish serum: Ca P ALP CHOL E2/
(mg·kg
-1) g g mmol·L
-1 mmol·L
-1 U·
L-1 mmol·L
-1 pg·mlSham Vehile 240.1±6.6 265.3±6.9 2.49±0.06 2.35±0.43 74.6±24.9 1.27±0.09 34.5±12.6OVX Vehile 236.8±11.1 300.6±15.5
# 2.44±0.10 2.04±0.33 84.3±16.2 1.75±0.45
# 12.3±2.1
##DES 0.0225 241.4±6.1 240.9±25.4
**?2.55±0.06 2.41±0.50 130.1±38.9
*?0.98±0.35
**?15.4±6.3EF 300 23g.6±8.1 294.2±28.5 2.59±0.05
* 2.18±0.15 98.7±38.4 1.88±0.21 27.8±20.1E+D 300+0.0225 244.4±10.6 289.0±18.0
* 2.70±0.06
*△ 2.16±0.33 113.7±26.8 1.59±0.50 26.0±11.9
#:P<0.05;
##:P<0.01?vs?Sham;
*:P<0.05;
**:P<0.05vs?OVX:
△:P<0.05;?
△△:P<0.05vs?DF.S。
From the result of Tab 1 as seen. ovariectomized group (OVX) rat body weight obviously increases, and serum total cholesterol increases and estradiol concentration obviously reduces (P<0.05).Diethylstilbestrol can obviously alleviate removal ovary rat body weight and serum total cholesterol (P<0.05), increases serum alkaline phosphatase (P<0.05); List increases blood calcium concentration with EF, and all the other indexs do not have obvious change; The drug combination group increases (P<0.05) than single with diethylstilbestrol group body weight and blood calcium concentration.2.2 Herba Epimedii total flavones and diethylstilbestrol are to the influence of rat viscera exponential sum endometrium thickness
Barren wort total chromocor and diethylstilbestrol see Table 2 to the impact of rat viscera exponential sum endometrium thickness: table 2 barren wort total chromocor and diethylstilbestrol are on the impact of rat viscera exponential sum endometrium thickness (n=10, rich (g) endometrium thickness (μ m) of group pin gland (g) liver (g) spleen (g) kidney (g) adrenal gland (g) the Sham 0.6 ± 0.2 25.0 ± 1.0 2.2 ± 0.2 7.1 ± 0.4 0.23 ± 0.04 2.2 ± 0.6 23.67 ± 4.20OVX 0.9 ± 0.2 of x ± s)#25.4 ± 2.4
#2.3 ± 0.1 6.4 ± 0.5
#0.19 ± 0.04 0.4 ± 0.2
#9.51 ± 1.06
#DES 0.8 ± 0.3 36.6 ± 5.2
*2.7 ± 0.3
*8.1 ± 1.2
*0.27 ± 0.08
*2.0 ± 0.6
*41.58 ± 8.41
*EF 1.0 ± 0.2 24.5 ± 2.7 2.4 ± 0.2 6.5 ± 0.8 0.22 ± 0.04 0.64 ± 0.3 12.26 ± 2.73EF+DES 0.6 ± 0.2 32.0 ± 2.2
* △2.8 ± 0.3
*7.1 ± 0.4 0.25 ± 0.03 1.6 ± 0.2
* △20.28 ± 2.07
* △ △
#:P<0.05;
##:P<0.01?vs?Sham:
*:P<0.05;
**:P<0.05vs?OVX:
△:P<0.05;
△△:P<0.05?vs?DES。
From the result of Tab 2 as seen, uterus of rat and renal index obviously alleviate behind the removal ovary, and endometrium thickness reduces, and thymus index increases.The uterus of diethylstilbestrol group, liver,spleen,kidney and adrenal gland's index, endometrium thickness obviously increase, and are higher than Sham group (P<0.05); Single do not have influence with EF; The drug combination group increases the uterus regulating liver-QI index of removal ovary rat, endometrium thickness, but is lower than the diethylstilbestrol group, with Sham group indifference.2.3 Herba Epimedii total flavones and diethylstilbestrol influence table 3 Herba Epimedii total flavones and diethylstilbestrol to shadow noon of rat tibia near-end spongy bone static parameter (n=10, Group Tb.Ar (%) Tb.Th (μ m) Tb.N (#mm of x ± s) to rat tibia near-end spongy bone morphometry static parameter
-1) Tb.Sp (μ m) Oc.N (nmm
-2) Basal 23.4 ± 5.2 57.0 ± 5.8 4.1 ± 0.6 194.3 ± 43.8 4.3 ± 1.5Sham, 22.9 ± 6.4 57.3+13.1 4.0 ± 0.2 195.7 ± 25.9 4.1 ± 1.1OVX 4.5 ± 1.6
##46.5 ± 6.6 1.0 ± 0.3
##1111.4 ± 439.7
##18.8 ± 7.4
##DES 11.4+5.4
*44.7 ± 6.6 2.5 ± 0.9
*426.1+208.3
*9.2 ± 5.7
*EF 7.2+4.4 48.2 ± 9.3 1.4 ± 0.8 908.5 ± 669.2 15.7+12.8EF+DES 19.0 ± 3.9
* △ △54.2 ± 7.0
* △3.5 ± 0.4
* △235.4 ± 35.4
* △3.3 ± 1.0
* △ △
*:P<0.05;
##:P<0.01?vs?Sham:
*:P<0.05:
**:P<0.05?vs?OVX:
△:P<0.05:
△△:P<0.05?vs?DES。
From the result of Tab 3 as seen, the removal ovary rat is compared with control rats, and bone loss 80% after 90 days (P<0.01), bone trabecula number reduce by 75% (P<0.01), the bone trabecula separating degree increases by 468% (P<0.01), osteoclast number increase by 358% (P<0.01).Diethylstilbestrol makes the bone amount of removal ovary rat and bone trabecula number increase by 153% and 150% (P<0.01), bone trabecula separating degree and osteoclast number respectively to reduce by 62% and 51% (P<0.05) respectively.List has the bone amount of removal ovary rat with Herba Epimedii total flavones increases by 60%, but not statistically significant (P>0.05).Diethylstilbestrol and Herba Epimedii total flavones share the bone amount that makes the removal ovary rat and bone trabecula number to be increased by 322% and 250% (P<0.01), bone trabecula separating degree and osteoclast number respectively and reduces by 79% and 82% (P<0.01) respectively, the effect that the drug combination group increases the bone amount and suppresses osteoclast is above diethylstilbestrol group (P<0.01), with Sham group indifference.2.4 Herba Epimedii total flavones and diethylstilbestrol are to the influence of rat tibia near-end spongy bone morphometry dynamic parameter
Herba Epimedii total flavones and diethylstilbestrol see Table 4 to the influence of rat tibia near-end spongy bone morphometry dynamic parameter:
Table 4 barren wort total chromocor and diethylstilbestrol are to the impact of rat tibia near-end spongiosa dynamic parameter (n=10, Group L.Pm (%) MAR (μ md) BFR/TV (%/year) BFR/BV (%/year) BFR/BS (%/year) Basal 39.2 ± 9.7 0.82 ± 0.18 79.8 ± 29.4 363.0 ± 170.4 12.2 ± 5.2Sham 31.3 ± 4.9 0.76 ± 0.12 58.5 ± 15.5 264.6 ± 81.3 8.8 ± 2.2OVX 35.5 ± 9.5 1.10 ± 0.21 of x ± s)#21.9 ± 8.3
##548.3 ± 188.9
#14.5 ± 5.7
#DES 27.5 ± 8.4 0.80 ± 0.22 32.9 ± 16.1 312.1 ± 150.3
*8.2 ± 3.7
bEF 28.7 ± 8.5 0.95 ± 0.26 20.8 ± 9.2 370.0 ± 205.8 10.1 ± 4.1E+D 16.8 ± 5.1
*0.58 ± 0.24
*21.0 ± 11.0 123.9 ± 91.5
* △3.8 ± 2.3
* △ △
#:P<0.05;
##:P<0.01?vs?Sham;
*:P<0.05;
**:P<0.05?vs?OVX;
△:P<0.05;
△△:P<0.05?vs?DES。
From the result of Tab 4 as seen, the ovariectomized group rat bone forms index obviously increases: the mineralising deposition increases by 45% (P<0.05), bone formation rate BFR/BV increases by 107% (P<0.05).Diethylstilbestrol can suppress the bone formation rate (BFR/BV reduces by 43%, P<0.05) of removal ovary rat.Single do not have obvious influence with Herba Epimedii total flavones to removal ovary rat bone formation index.Diethylstilbestrol and Herba Epimedii total flavones share the bone formation of obvious inhibition removal ovary rat: mineralising deposition and bone formation rate BFR/BV reduce by 47% and 77% (P<0.01) respectively, and effect is better than single with diethylstilbestrol (P<0.05).
3 discuss
The result shows that Sham group and the equal indifference of every sound attitude parameter that Basal organizes point out rat during 4.5 ~ 7.5 monthly ages, and with the monthly age increase, bone formation and bone resorption are more stable, and bone formation and bone resorption change not obvious, and the bone amount increases not obvious.
The removal ovary rat body weight obviously increases, serum total cholesterol reduces, the bone amount reduces, the uterus index obviously alleviates alleviates and the thymus index increase with inner membrance atrophy, renal index, may be relevant with estrogen deficiency.Point out the ovariectomized rats at 4.5 monthly ages to cause after 90 days that the body inner estrogen reduces rapidly and causes the change of skeleton and other organs, similar to the change of women after menopause, further specifying this experiment, to set up osteoporotic animal model with the removal ovary rat be successful.
Diethylstilbestrol is a synthetic estrogen, the bone formation and the bone resorption that can suppress the removal ovary rat, owing to fail to suppress fully the high conversion of bone behind the removal ovary, so can not make the bone amount of removal ovary rat return to the age group level, diethylstilbestrol is described only partial prophylaxis removal ovary rat is bone trabecular and lose, obviously suppress rat body weight simultaneously and increase, stimulate gland weightening finish and uterus hypertrophy on the liver,spleen,kidney.
Herba Epimedii is the traditional invigorating the kidney and strengthening the bones Chinese medicine of China, discover that in a large number Herba Epimedii has androgen-like action, can promote medullary cell DNA synthetic, promote the osseous tissue protein synthesis and promote osteoblastic proliferation, directly suppress osteoclast, can resist various osteoporosis animal models.But at present less to the research of Herba Epimedii total flavones protect against osteoporosis, this experimental result shows that Herba Epimedii total flavones makes the bone amount of removal ovary rat that the trend of increase be arranged, but does not have statistical significance, may be relevant with the dosage of Herba Epimedii total flavones.In vitro study finds that Herba Epimedii total flavones has significant promotion proliferation function to osteoblast, and relevant with concentration, promotes during low concentration to suppress osteoblastic proliferation when concentration is excessive on the contrary by osteoblastic proliferation.The dose-effect relationship of Herba Epimedii total flavones control removal ovary osteoporosis rat effect how, awaits further research.
Herba Epimedii total flavones and diethylstilbestrol drug combination can obviously increase bone amount and the bone trabecula number of removal ovary rat, reduce the bone trabecula separating degree, and its effect is better than independent application diethylstilbestrol; Drug combination also obviously suppresses the activity of osteoclast, reduces bone formation rate and bone turnover rate, and effect also is better than independent application diethylstilbestrol.In addition, drug combination does not suppress rat body weight and increases, and is less to the stimulation in liver and uterus.This experiment prompting, Herba Epimedii total flavones and diethylstilbestrol drug combination can improve the diethylstilbestrol function of resisting osteoporosis and reduce its toxic and side effects.
Claims (5)
1, a kind of compound preparation for the treatment of osteoporosis is characterized in that this compound preparation is made up of Chinese medicine Herba Epimedii extract and estrogen.
2, a kind of compound preparation for the treatment of osteoporosis as claimed in claim 1, the Chinese medicine Herba Epimedii Herba Epimedii extract in this compound preparation is meant Herba Epimedii total flavones.
3, a kind of compound preparation for the treatment of osteoporosis as claimed in claim 1, the estrogen in this compound preparation is meant estradiol valerate, ethinylestradiol, estriol, nilestriol, premarin, diethylstilbestrol, Chlorotrianisne, tamoxifen.
4, a kind of compound preparation for the treatment of osteoporosis as claimed in claim 1, the Chinese medicine Herba Epimedii Herba Epimedii extract in this compound preparation is meant the extract by following prepared:
A, Herba Epimedii are ground into powder, add 75~95% soak with ethanol 24 hours, filter, reclaim ethanol, it is standby to get ethanol extract, and medicinal residues decoct with water 3 times again, merge three times filtrate, filter, filtrate is concentrated in right amount, add aforesaid ethanol extract, cold drying is pulverized, add appropriate amount of auxiliary materials and estrogen, make granule, tabletting, sugar coating or encapsulated, promptly.
B, Herba Epimedii raw medicinal herbs decoct with several times water logging bubble back, repeat 3 times, and merging filtrate concentrates, and adds 3 times of ethanol precipitations, behind the recovery ethanol, uses ethyl acetate extraction, reclaims ethyl acetate and obtains Herba Epimedii total flavones.Herba Epimedii total flavones adds appropriate amount of auxiliary materials and estrogen, makes granule, tabletting, and sugar coating or encapsulated, promptly.
5, a kind of compound preparation that contains estrogenic treatment osteoporosis as claimed in claim 3, when these estrogen and Herba Epimedii are formed compound recipe, every or every 's content is respectively: estradiol valerate 0.2~0.5mg/ sheet, ethinylestradiol 2.5~5 μ g/ sheets, estriol 0.2~0.5mg/ sheet, nilestriol 5~15 μ g/ sheets, premarin 0.075~0.125mg/ sheet, diethylstilbestrol 0.075~0.125mg/ sheet, Chlorotrianisne 1~2mg/ grain, tamoxifen 2~5mg/ sheet.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNA031451675A CN1480142A (en) | 2003-06-30 | 2003-06-30 | compound preparation composed of longspur epimedium and estrogen for treating osteoporosis of women after climacteric |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102397550A (en) * | 2011-08-30 | 2012-04-04 | 广东医学院 | Medicinal composition composed of aspirin and estrogen and used for preventing and treating osteoporosis |
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 |
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2003
- 2003-06-30 CN CNA031451675A patent/CN1480142A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102397550A (en) * | 2011-08-30 | 2012-04-04 | 广东医学院 | Medicinal composition composed of aspirin and estrogen and used for preventing and treating osteoporosis |
CN102397550B (en) * | 2011-08-30 | 2013-05-08 | 广东医学院 | Medicinal composition composed of aspirin and estrogen and used for preventing and treating osteoporosis |
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 |
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