CN103768158B - Pharmaceutical composition of a kind of protect against osteoporosis and preparation method thereof - Google Patents
Pharmaceutical composition of a kind of protect against osteoporosis and preparation method thereof Download PDFInfo
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- CN103768158B CN103768158B CN201410037992.5A CN201410037992A CN103768158B CN 103768158 B CN103768158 B CN 103768158B CN 201410037992 A CN201410037992 A CN 201410037992A CN 103768158 B CN103768158 B CN 103768158B
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- extract
- herba epimedii
- ligustri lucidi
- fructus ligustri
- ethanol
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Landscapes
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses pharmaceutical composition of a kind of protect against osteoporosis and preparation method thereof.A kind of pharmaceutical composition disclosed by the invention is made up of the extract of Herba Epimedii and the extract of Fructus Ligustri Lucidi.Tool of the present invention has the following advantages: (1) traditional Chinese medicine extract composition of the present invention is for the feature of OP pathogenesis it " deficiency of kidney-essence, deficiency of both YIN and YANG ", selecting the medicine of negative and positive in flat the kidney invigorating to be object of study to Herba Epimedii, Fructus Ligustri Lucidi, providing basis for developing the new drug of flat nourishing YIN sun medicine to Herba Epimedii, Fructus Ligustri Lucidi effective ingredient osteoporosis.(2) the crude drug resource distribution of Chinese medicinal composition preparation of the present invention is wide, and toxic and side effects is low, can long-term taking.(3) Chinese medicinal composition preparation prescription of the present invention is simplified, and effective ingredient is clear and definite, and determined curative effect is quality controllable, and need not the decoction process of Chinese medicine, taking convenience.
Description
Technical field
The present invention relates to pharmaceutical composition of a kind of protect against osteoporosis and preparation method thereof.
Background technology
Osteoporosis (osteoporosis, OP) reduces with bone amount and the degeneration of osseous tissue fibre structure, then causes skeletal fragility and fracture risk to increase to the systemic skeletal disease of feature, leapt to the 7th into world's commonly encountered diseases sickness rate at present.Along with China's life-time dilatation per capita, social senilization, the sickness rate of OP also significantly increases, and has become the important public health problem affecting Chinese society.According to China drug in some provinces statistics, the sickness rate of the old people OP of more than 60 years old is about 59.89%.The sickness rate of the annual concurrent fracture because of OP is about 9.6%, and has the trend increased year by year, brings serious burden to society, family.Therefore, to screen and to develop anti-OP medicine significant.
At present, Western medicine adopts the medicine such as calcium preparation and vitamin D, bis phosphoric acid salt, calcitonin, selective estrogen receptor modulators for the treatment of OP more, although achieve certain curative effect, needs conbined usage more, simple medication is for this complex lesions of OP, and difficulty plays long-term effect; The drawbacks such as the carcinogenecity that medical expense is high in addition, the course for the treatment of is long, untoward reaction is many and potential, its clinical practice is restricted, therefore current treatment status are unsatisfactory.
In view of modern medicine does not have the medicine of good control OP, many doctors turn to TCM Therapy sight.Compared with western medicine, Chinese medicine is prevented and treated in process integrally-regulated emphatically at OP, determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs, transfer endogenous cause of ill, act on multiple link, finally reach the effect of correcting body hormone imbalances and negative calcium balance, and there is the unique advantage that toxic and side effects is little, late result is good, in control OP, achieve larger progress.OP belongs to Chinese medicine " atrophic debility of bones ", " rheumatism involving the bone " category.Chinese medicine is thought, the pathogenesis of OP with suffer from a deficiency of the kidney, insufficiency of the spleen, blood stasis, stagnation of liver-QI have close relationship, wherein suffering from a deficiency of the kidney is that the pathogenesis of primary disease is crucial.Kidney storing essence, raw marrow of refining, marrow is supplemented nutrition in bone, the growth of skeleton, growth, withered and flourishing closely related with the vital essence prosperity and decline of kidney.Then bone marrow biochemistry is active for kidney essense abundance, and bone is nourished and strong; Deficiency of kidney-essence is the biochemical weary source of bone marrow then, and skeleton loses foster and paralysis is weak unable.Modern medicine by bone density, bone mineral content and sex hormone level and kidney deficiency correlation analysis, confirm the science that the traditional Chinese medical science " kidney governing bones " is theoretical equally.As can be seen here, deficiency of kidney essence is the pathogenesis that OP is the most basic, and the method for tonifying both YIN and YANG, kidney tonifying, essence replenishing bone strengthening is the fundamental law for the treatment of OP.
It should be noted that Chinese medicine decoction decocting bothers, decocting liquid volume be comparatively large, bitter in the mouth, take, carry inconvenience; And easy mouldy fermentation, should not store for a long time and prepare in a large number.Traditional Chinese patent medicine is as loose in kidney bone, the loose health-care composition of bone, Gu Yu Ling Capsules, Six-element bone-strengthening grain etc., these some dosage forms wherein not Portable belt or take, then flavour of a drug are more for some, and active constituent content is few, quality control standard is low, is difficult to obtain satisfied curative effect in clinical treatment.Modern Chinese medicine effective ingredient, as on-off total saponin as well as, Process of Total Flavonoids in Drynaria Fortunei, Herba Epimedii total flavones etc., although determined curative effect, quality controllable, acts on single, fails to embody the integrally-regulated idea of the traditional Chinese medical science.Therefore, based on traditional Chinese medicine theory, in conjunction with modern medicine theory and technology, develop a kind of effective ingredient clear and definite, determined curative effect, quality controllable anti-OP medicine is significant.
Herba Epimedii is kidney-nourishing yang-strengthening medicine, is the Chinese herbal medicine that treatment OP frequency of utilization is the highest.Large quantity research confirms, and Herba Epimedii and effective ingredient thereof effectively can improve biochemical markers of bone metabolism, corrects abnormal bone metabolism, reduce bone turnover rate, increase bone density, improve bone pathology state, promote experimental osteoporosis fracture repair, thus play anti-OP effect.Modern study shows that the mechanism of Herba Epimedii control OP is mainly summarised as following approach: 1. gonadotropic Effect.2. directly bone resorption and promoting bone growing is suppressed.3. contained anti-inflammatory component may affect bone metabolism.4. the various trace elements be rich in is formed with special role to osteoblast and ossein.5. act on bone matrix cell, promote the mineralising of collage synthesis and substrate.Herba Epimedii anti-OP effect is relevant with the Flavonoid substances contained by it, and it has mainly played class sex hormone function.
Fructus Ligustri Lucidi belongs to the medicine of the cloudy essence of conventional nourishing the liver and kidney, and have report, be that the tonifying kidney-yin class medicine of representative has good action equally to the treatment of OP with Fructus Ligustri Lucidi, its action intensity is not only close with Herba Epimedii, even may be better; Vitamin D sample active substance contained by it and estrogen-like product, can directly by maintaining calcium homeostasis in body to the expression of intestinal VDR and the regulation and control of calcium absorption; Be that the nourishing kidney yin recipe ERZHI WAN of principal agent can effectively alleviate the diseases such as postmenopausal osteoporotic patients Tidal fever with perspiration, insomnia and dreamful sleep and soreness of the waist and knees with Fructus Ligustri Lucidi, increase bone mineral density, bone mineral content, raise estradiol level, thus improve osteoporosis symptoms.The main component of its anti-OP is based on flavonoid, terpenoid.
Large quantity research confirmed single Herba Epimedii and Herba Epimedii and/or Fructus Ligustri Lucidi be correlated with compound recipe control OP in remarkable result, we are deficiency of kidney essence based on the basic pathogenesis of OP, select suitable dose ratio application Herba Epimedii, Fructus Ligustri Lucidi compatibility to prevent and treat OP in the clinical middle degree according to patient's kidney yang and deficiency of kidney-YIN, curative effect certainly.OP belongs to chronic complexity disease, palpus Long-term taking medicine, the unsuitable long-term clinical application of alone yang-tonifying drug Herba Epimedii character warm-dryness syndrome, if the Fructus Ligustri Lucidi of energy compatibility benefiting kidney-essence is with treating YANG within YIN, then can reach in " the new side eight of Jing Yue's complete work slightly " and say: " magical effect of this coordination of YIN and YANG also.”
Summary of the invention
The object of this invention is to provide pharmaceutical composition of a kind of protect against osteoporosis and preparation method thereof.
A kind of pharmaceutical composition provided by the invention, said composition is made up of the extract of Herba Epimedii and the extract of Fructus Ligustri Lucidi;
The extract of described Herba Epimedii is prepared as follows: the aqueous solution being the ethanol of 85%-95% by crude drug Herba Epimedii volumn concentration extracts, and obtains extracting solution; By the ethanol removing in extracting solution, and carry out petroleum ether extraction, removing chlorophyll, obtains aqueous phase extract; Aqueous phase extract is carried out the separation of D-101 absorption with macroporous adsorbent resin, wash with water colourless to eluent after, carry out eluting with the ethanol water that volumn concentration is 85%-95%, obtain object eluent; By object eluent evaporate to dryness, obtain the extract of Herba Epimedii;
The extract of described Fructus Ligustri Lucidi is prepared as follows: the ethanol water being 70%-80% by crude drug Fructus Ligustri Lucidi volumn concentration extracts, and obtains extracting solution; By the ethanol removing in extracting solution, obtain the extracting solution without ethanol; Extracting solution without ethanol is carried out the separation of AB-8 absorption with macroporous adsorbent resin, and washing except sugar, then carries out eluting with the ethanol water that volumn concentration is 70%-80%, obtains object eluent; By object eluent evaporate to dryness, obtain the extract of Fructus Ligustri Lucidi.
In above-mentioned composition, described crude drug Herba Epimedii volumn concentration is that the condition that the aqueous solution of the ethanol of 85%-95% carries out extracting is as follows: be that the ethanol water of 85%-95% extracts 3 times as the coarse powder of Extraction solvent to described crude drug Herba Epimedii with volumn concentration, 1st time according to 1g Herba Epimedii: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extract 3h; 2nd, 3 times all before the medicinal residues that once obtained and Extraction solvent according to 1g: 10mL ratio mix and extract, 70 DEG C, extraction 2h, merges 3 extracting solution and is described extracting solution;
In the aqueous solution of described ethanol, the volumn concentration of ethanol is specially 90%.
In above-mentioned arbitrary described compositions, described crude drug Fructus Ligustri Lucidi volumn concentration is that the condition that the ethanol water of 70%-80% carries out extracting is as follows: be that the ethanol water of 70%-80% extracts 3 times as the coarse powder of Extraction solvent to described crude drug Fructus Ligustri Lucidi with volumn concentration, 1st time according to 1g Fructus Ligustri Lucidi: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extract 3h; 2nd, 3 times all before the medicinal residues that once obtained and Extraction solvent according to 1g: 10mL ratio mix and extract, 70 DEG C, extraction 2h, merges 3 extracting solution and is described extracting solution;
In the aqueous solution of described ethanol, the volumn concentration of ethanol is specially 75%.
The mass percentage of the epimedium flavone compounds in the extract of described Herba Epimedii is not less than 50%;
Fructus Ligustri Lucidi triterpenoid compound in the extract of described Fructus Ligustri Lucidi and the gross mass percentage composition of Fructus Ligustri Lucidi flavone compound are not less than 50%.
In above-mentioned arbitrary described compositions, the mass ratio of the extract of described Herba Epimedii and the extract of described Fructus Ligustri Lucidi is 2-5:3-10, is specially 2:3.
Above-mentioned arbitrary described pharmaceutical composition also belongs to protection scope of the present invention in the preparation application prevented and/or treated in the product of osteoporosis;
Described osteoporosis is specially glucocorticoid-induced osteoporosis.
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the weight levels of animal decline also to belong to protection scope of the present invention in preparation.
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of animal bone conversion ratio level rising also to belong to protection scope of the present invention in preparation;
The application that above-mentioned arbitrary described pharmaceutical composition suppresses the alkali phosphatase of animal, Tartrate resistant acid phosphatase and/or Bone Gla protein to depart from the product of the alkali phosphatase of the correspondence of the animal do not suffered from the disease, Tartrate resistant acid phosphatase and/or osteocalcin level in preparation also belongs to protection scope of the present invention;
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of serum I procollagen type amino-terminal propeptide, I procollagen type carboxypropeptide, the rising of NTx crosslinked carboxy terminal peptide level also to belong to protection scope of the present invention in preparation;
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the synthesis of the bone NTx of animal and degradation rate rising also to belong to protection scope of the present invention in preparation;
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the bone maximum load of animal and/or the maximum radial degree decline of bone also to belong to protection scope of the present invention in preparation;
And/or,
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the BMD of animal decline also to belong to protection scope of the present invention in preparation;
And/or,
Application in above-mentioned arbitrary described pharmaceutical composition suppresses the impact capacity level of the bearing capacity of the osseous tissue of animal and/or opposing external force to reduce product in preparation also belongs to protection scope of the present invention;
And/or,
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the level of the bone trabecula area percentage of animal, bone trabecula thickness and/or trabecular bone density decline also to belong to protection scope of the present invention in preparation;
And/or,
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the bone trabecula separating degree of animal rising also to belong to protection scope of the present invention in preparation;
Described bone is specially femur.
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of the serum cortisol of animal, estradiol and/or testosterone levels decline also to belong to protection scope of the present invention in preparation;
Above-mentioned arbitrary described pharmaceutical composition suppresses the application in the product of animal serum Levels of Sexual Hormone decline also to belong to protection scope of the present invention in preparation;
Described gonadal hormone is specially estrogen and/or androgen.
In above-mentioned arbitrary described application, described animal is the animal suffering from osteoporosis.
Prescription of the present invention is according to clinical experience and selected initiative of national distinguished veteran doctors of TCM professor Li Shizeng long-pending more than 40 years, and the medicine of flat nourishing YIN sun has protective effect to Herba Epimedii, Fructus Ligustri Lucidi clinical compatibility to applying the abnormal bone metabolism that hormone causes.Pharmaceutical composition of the present invention causes model rat with osteoporosis to glucocorticoid-induced osteoporosis rat model and retinoic acid all has preventive and therapeutic effect, proves that this pharmaceutical composition can be used for preventing and/or treating osteoporosis.
Tool of the present invention has the following advantages:
(1) traditional Chinese medicine extract composition of the present invention is for the feature of OP pathogenesis it " deficiency of kidney-essence, deficiency of both YIN and YANG ", selecting the medicine of negative and positive in flat the kidney invigorating to be object of study to Herba Epimedii, Fructus Ligustri Lucidi, providing basis for developing the new drug of flat nourishing YIN sun medicine to Herba Epimedii, Fructus Ligustri Lucidi effective ingredient osteoporosis.
(2) the crude drug resource distribution of Chinese medicinal composition preparation of the present invention is wide, and toxic and side effects is low, can long-term taking.
(3) Chinese medicinal composition preparation prescription of the present invention is simplified, and effective ingredient is clear and definite, and determined curative effect is quality controllable, and need not the decoction process of Chinese medicine, taking convenience.
Accompanying drawing explanation
Fig. 1 is each group of rat decalcification bone tissue pathological slice (HE, × 100).
Detailed description of the invention
The experimental technique used in following embodiment if no special instructions, is conventional method.
Material used in following embodiment, reagent etc., if no special instructions, all can obtain from commercial channels.
In following embodiment except specified otherwise, % all represents g/100mL.
Male 3 months aged Wistar rats tie up laboratory animal technical concern company limited of tonneau China purchased from Beijing, the quality certification number: SCXK(capital) 2012-0001.
Cleaning grade healthy SD rat ties up laboratory animal technical concern company limited of tonneau China purchased from Beijing, the quality certification number: SCXK(capital) 2007-0001.
The preparation of embodiment 1, Herba Epimedii and Fructus Ligustri Lucidi extract and the preparation of pharmaceutical composition
One, decoction is divided to prepare Herba Epimedii and Fructus Ligustri Lucidi extract:
(1) preparation of Herba Epimedii extract: get Herba Epimedii 8000g, chopping, be that the ethanol water of 90% extracts 3 times as Extraction solvent with volumn concentration, the 1st time according to 1g Herba Epimedii: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extracts 3h; 2nd, the medicinal residues once obtained all in the past for 3 times mix (ratio is 1g medicinal residues: 10mL Extraction solvent) and extract, 70 DEG C with Extraction solvent, extract 2h.Merge extractive liquid, the ethanol in removing extracting solution, then use petroleum ether extraction extracting solution 3 times (removing chlorophyll), discard petroleum ether phase, collect aqueous phase; D-101 macroporous adsorbent resin on aqueous portion, with water carry out being eluted to eluent colourless after, carry out eluting with the ethanol water that volumn concentration is 90%, obtain eluent, by eluent evaporate to dryness, obtain brown color Herba Epimedii total flavones extract finished product, weight is about 200g, and extraction ratio is 2.5%.Wherein containing total flavones (in icariin) is 80% (mass percentage), mainly comprises icariin, icariside I, icariside II, precious icariin, Epimedin A, B, C etc.
(2) preparation of Fructus Ligustri Lucidi extract: get Fructus Ligustri Lucidi 8000g, shatter into coarse powder, with volumn concentration be the ethanol water of 75% as Extraction solvent heating extraction 3 times, the 1st time according to 1g Fructus Ligustri Lucidi: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extract 3h; 2nd, the medicinal residues once obtained all in the past for 3 times mix (ratio is 1g medicinal residues: 10mL Extraction solvent) and extract, 70 DEG C with Extraction solvent, extract 2h.Merge extractive liquid, the ethanol in removing extracting solution, upper AB-8 macroporous adsorbent resin, washing (except sugar), discard water liquid, then be the ethanol water eluting of 75% with volumn concentration, collect eluent, evaporate to dryness, obtains sepia Fructus Ligustri Lucidi extract.Weight is about 400g, and extraction ratio is 5%.Effective ingredient is total iridoid and total flavonoid, and content in oleanolic acid and rutin total content > 80%, mainly comprises specnuezhenside respectively, nuezhenoside, oleuropein, wooden slippers olive glycosides dimethyl ester, Fructus Ligustri Lucidi acid, new nuezhenoside, Fructus Ligustri Lucidi fruit glycosides A, B, C, D, apigenin-7-O-glucoside etc.
Two, the preparation of medicament composition capsule: the Herba Epimedii extract 200g and the Fructus Ligustri Lucidi extract 300g that get step one preparation, mix homogeneously, granulates, encapsulated, makes 1000, every 0.5g.
Three, the preparation of medicinal composition tablets: the Herba Epimedii extract 200g and the Fructus Ligustri Lucidi extract 300g that get step one preparation, the mixture of two kinds of extracts mixes with 500g dextrin, make soft material, cross sieve series granule, 70 DEG C of constant pressure and dries 3 hours, add 0.5% magnesium stearate mixing, with tabletting after 14 mesh sieve granulate, every sheet 0.4g.
Embodiment 2, Herba Epimedii Fructus Ligustri Lucidi effective component extracts cause the impact of rats with osteoporosis on retinoic acid
One, by male 3 months aged Wistar rats 60, be divided into 6 groups at random, namely Normal group, model control group, Herba Epimedii Fructus Ligustri Lucidi water decoction matched group (being called for short: water decoction group), Herba Epimedii Fructus Ligustri Lucidi extract basic, normal, high dosage group (being called for short respectively: basic, normal, high dosage group), often organize 10.
Except Normal group, all the other respectively organize rat retinoic acid suspension (compound method: first with distilled water preparation 0.5%(0.5g/100mL) sodium carboxymethyl cellulose (CMC-Na) solution, with this solution preparation 7mgmL
-1retinoic acid suspension) by 10mLkg
-1gavage, Normal group with isopyknic 0.5%CMC-Na gavage, continuous modeling 2 weeks.While modeling, each treated animal gavage gives following corresponding medicine or normal saline, amounts to 3 weeks.
1. water decoction group: the water decoction of Herba Epimedii Fructus Ligustri Lucidi is according to 10mLkg
-1body weight gavage, every day 1 time.
Herba Epimedii Fructus Ligustri Lucidi water decoction preparation method: take Herba Epimedii, Fructus Ligustri Lucidi (mass ratio 4:3) mixing in right amount, head decocts the water soaking 1h post-heating adding 8 times of volumes and boils, and slow fire keeps boiling 30min, stirring, while hot leaching medicinal liquid; Medicinal residues add the water heated and boiled of former dose 6 times again, filter, merge twice medicinal liquid, be concentrated into containing crude drug 0.95g/mL, place refrigerator cold-storage (4 DEG C) for subsequent use after changing that slow fire is continuous and decocting 30min.
2. basic, normal, high dosage group: mixture (mass ratio 2:3 dissolves with the distilled water) 5mgmL giving Herba Epimedii extract and Fructus Ligustri Lucidi extract respectively
-1, 10mgmL
-1, 20mgmL
-1, all with 10mLkg
-1body weight gavage, every day 1 time.
3. Normal group, model control group: with 10mLkg
-1body weight gavages normal saline, every day 1 time.
Two, fasting 16h after each group rat last gavage, intraperitoneal anesthesia, abdominal aortic blood; It is that the aqueous solution of the neutral formalin of 10% is fixed that each rats with left femur of each group is placed in volumn concentration, carries out pathological examination; The wet gauze parcel that right side femur normal saline soaks is frozen, detects for bone density and bone biomechanical.Experimental data adopts mean ± standard deviation
represent, compare between group and adopt homogeneity test of variance and one factor analysis of variance.Result is as follows:
(1) comparison of each group rat general status and experiment front and back body weight:
The comparison of body weight before and after rat experiment respectively organized by table 1
Note: compare with Normal group
*p ﹤ 0.01; Compare with model control group
△ △p ﹤ 0.01; Compare with middle dosage group
##p ﹤ 0.01; Compare with high dose group
▲p ﹤ 0.05,
▲ ▲p ﹤ 0.01.
Result shows, after the modeling of application retinoic acid, model control group rat engenders that body weight increasess slowly, lazy dynamic few food, and hair color is withered, the back of the body that collapses of bending over, cyllopodia, and the phenomenons such as poly-heap are rolled up in happiness; Each administration group (i.e. water decoction group, basic, normal, high dosage group) above-mentioned symptom all comparatively model group is improved.Table 1 shows, when experiment starts, and no significant difference between each treated animal body weight.At the end of experiment, compare with Normal group, model control group body weight obviously reduces (P ﹤ 0.01); Middle and high dosage group rat body weight comparatively model control group significantly raises (P ﹤ 0.01).
Herba Epimedii Fructus Ligustri Lucidi extract obviously can improve retinoic acid and cause osteoporosis model rat general status, and rat weight is increased.
(2) each group rat biochemical markers of bone metabolism, the comparison of alkali phosphatase (AKP), Tartrate resistant acid phosphatase (StrACP) and Bone Gla protein (BGP):
The comparison of rat blood serum AKP, StrACP, BGP content respectively organized by table 2
Note: compare with Normal group
*p ﹤ 0.05,
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01; Compare with high dose group
▲p ﹤ 0.05.
Result shows, model control group serum AKP level, the active all compared with normal matched groups of StrACP, BGP significantly raise (P ﹤ 0.05 or 0.01).Compare with model control group, middle and high dosage group serum AKP level, StrACP content significantly reduce (P ﹤ 0.05 or 0.01); Basic, normal, high dosage group serum BGP content all significantly reduces (P ﹤ 0.05 or 0.01).
Research shows, retinoic acid can activate osteoclast, strengthens bone resorption, makes body be in high conversion type bone metabolism state.Herba Epimedii Fructus Ligustri Lucidi extract raises AKP, StrACP, BGP level of Induced by Retinoic Acid antagonism, obviously suppresses too fast bone turnover rate, makes the coupling between bone resorption and bone formation be in poised state.
(3) comparison of each group rat bone density:
The comparison of rat bone density respectively organized by table 3
Note: compare with Normal group
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01; Compare with high dose group
▲p ﹤ 0.05,
▲ ▲p ﹤ 0.01.
Result shows, the full femur of model control group, upper 1/3rd femurs and femoral head bone density equal compared with normal matched group significantly reduce (equal P ﹤ 0.01).Compared with model control group, Herba Epimedii Fructus Ligustri Lucidi extract basic, normal, high dosage group all significantly can raise full femur and upper 1/3rd thighbone density (P ﹤ 0.05 or 0.01); Middle and high dosage group femoral head bone density comparatively model control group significantly raises (equal P ﹤ 0.01).
Model control group thighbone density declines and shows that osteoporosis model successfully constructs, and Herba Epimedii Fructus Ligustri Lucidi extract can improve the bone amount of unit osseous tissue volume, and effectively antagonism retinoic acid causes the bone amount reduction of osteoporosis model.
(4) comparison of each group rat bone biomechanics:
The comparison of rat bone biomechanics respectively organized by table 4
Note: compare with Normal group
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01; Compare with middle dosage group
#p ﹤ 0.05; Compare with high dose group
▲p ﹤ 0.05,
▲ ▲p ﹤ 0.01.
Result shows, model control group femur maximum load and maximum radial degree equal compared with normal matched group significantly decline (equal P ﹤ 0.01).Compare with model control group, Herba Epimedii Fructus Ligustri Lucidi extract each dosage group femur maximum load and maximum radial degree all significantly raise (P ﹤ 0.05 or 0.01).
Herba Epimedii Fructus Ligustri Lucidi extract can prevent and treat the reduction that retinoic acid causes Osteoporosis in Rats bone structure mechanical property, increases the bearing capacity of osseous tissue, improves the impact capacity of skeleton opposing external force.
(5) each group rat bone tissue form and metrological comparison:
The comparison of rat bone tissue morphometry respectively organized by table 5
Note: compare with Normal group
*p ﹤ 0.05,
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01; Compare with middle dosage group
#p ﹤ 0.05,
##p ﹤ 0.01; Compare with high dose group
▲ ▲p ﹤ 0.01.
Each group of rat decalcification bone tissue pathological slice as shown in Figure 1.
Fig. 1 shows, Normal group bone trabecula size even thickness, proper alignment also connects into net.Model control group bone trabecula number obviously reduces, and narrow and attenuate and sparse, fracture, major part can not connect into netted, changes in typical osteoporosis sample.Herba Epimedii Fructus Ligustri Lucidi extract each dosage group bone pathology form all has improvement in various degree, and bone trabecula quantity increases, and broaden, trabecular space diminishes, and arranges still neatly and be interconnected to reticulate.
Table 5 shows, the equal compared with normal matched group of model control group bone trabecula area percentage, bone trabecula thickness, density significantly reduces (P ﹤ 0.05 or 0.01), and bone trabecula separating degree compared with normal matched group enlarges markedly (P ﹤ 0.01).Compared with model control group, Herba Epimedii Fructus Ligustri Lucidi extract each dosage group bone trabecula area percentage and bone trabecula thickness significantly increase (P ﹤ 0.05 or 0.01), and middle and high dosage group trabecular bone density significantly increases (equal P ﹤ 0.05) and separating degree significantly subtracts reduction (equal P ﹤ 0.01).
Research shows, after modeling, trabecular bone structure is destroyed, and Bones morphology presents typical osteoporosis sample and changes, and Herba Epimedii Fructus Ligustri Lucidi extract effectively can reverse bone pathology sample and change, and suppresses bone loss, makes the sclerotin loosened be returned to normal level.
(6) each group rat affects the comparison of NTx metabolism:
The comparison of rat blood serum I procollagen type amino-terminal propeptide (PINP), I procollagen type carboxypropeptide (PICP), NTx crosslinked carboxy terminal peptide (ICTP) content respectively organized by table 6
Note: compare with Normal group
*p ﹤ 0.05; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01; Compare with high dose group
▲p ﹤ 0.05.
Table 6 shows, model control group blood-serum P INP, PICP, ICTP level are significantly higher than Normal group (P ﹤ 0.05 or 0.01).Compared with model control group, the basic, normal, high dosage group of Herba Epimedii Fructus Ligustri Lucidi extract all significantly can lower blood-serum P ICP level (P ﹤ 0.05 or 0.01), and high dose group blood-serum P INP, ICTP level all significantly reduce (equal P ﹤ 0.05).
Result shows, after modeling, the speed that associating blood-serum P INP, PICP and ICTP horizontal reverse mirror the synthesis of bone NTx and degraded is all accelerated, and bone conversion is active.The synthesis that Herba Epimedii Fructus Ligustri Lucidi extract can suppress NTx too fast and degraded, effectively improve the high transition status of osteoporosis model bone metabolism, and the coupling between bone formation and bone resorption is tended to balance.
(7) comparison of each group sex hormone level in rats:
Table 7 is group rat blood serum E respectively
2(estradiol), T(testosterone) comparison of content
Note: compare with Normal group
*p ﹤ 0.05,
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01.
Table 7 shows, model control group serum E
2, the horizontal compared with normal matched group of T significantly reduces (P ﹤ 0.05 or 0.01).Herba Epimedii Fructus Ligustri Lucidi extract basic, normal, high dosage group serum T content significantly raises (P ﹤ 0.05 or 0.01), middle and high dosage group E
2content significantly raises (P ﹤ 0.01).
Result shows, Induced by Retinoic Acid osteoporosis can cause blood Levels of Sexual Hormone to reduce.Herba Epimedii Fructus Ligustri Lucidi extract has class gonadotropic Effect, and by raising the level of estrogen and androgen thus playing function of resisting osteoporosis, two medicine compatibilities may be one of mechanism of its control OP to the protective effect of gonadal hormone.
Experimental example 3, Herba Epimedii Fructus Ligustri Lucidi effective component extracts are on the impact of glucocorticoid-induced osteoporosis rat model
Cleaning grade healthy SD rat, male and female half and half, body weight (200 ± 20) g, is divided into 6 groups by random digits table, with experimental example 2.Except Normal group, all the other are respectively organized rat and give two femoribus internus respectively and replace intramuscular injection of dexamethasone 1mgkg
-1body weight, 2 times weekly, amount to 8 weeks, rats in normal control group gives isopyknic normal saline.While modeling, each treated animal gavage gives corresponding medicine or normal saline, every day 1 time, amounts to 8 weeks.Dosage, puts to death, draws materials, and experimental result statistical method is all with experimental example 2.
One, the comparison of each group rat bone density:
The comparison of rat bone density respectively organized by table 8
Note: compare with Normal group
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01.
Table 8 shows, the full femur of model control group, upper 1/3rd femurs and the equal compared with normal matched group of femoral head bone density significantly reduce (P ﹤ 0.01).Compared with model control group, the middle and high dosage group of Herba Epimedii Fructus Ligustri Lucidi extract all significantly can raise the bone density (P ﹤ 0.05 or 0.01) of femur different parts, and the bone density of low dose group 1/3rd femur comparatively model control group significantly raises (P ﹤ 0.01).
Research shows, model control group thighbone density declines and shows that osteoporosis model successfully constructs, and Herba Epimedii Fructus Ligustri Lucidi extract can improve the bone amount of unit osseous tissue volume, effectively Antiglucocorticoid is caused to the bone amount reduction of osteoporosis model.
Two, each group rat is on the impact of biochemical markers of bone metabolism:
The comparison of rat blood serum AKP, StrACP, BGP respectively organized by table 9
Note: compare with Normal group
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01.
Table 9 shows, the active all compared with normal matched groups of model control group serum AKP level, StrACP significantly raise (P ﹤ 0.01), BGP is active significantly reduces (P ﹤ 0.01).Compare with model control group, Herba Epimedii Fructus Ligustri Lucidi extract basic, normal, high dosage group serum AKP level, there were significant differences for BGP content (P ﹤ 0.01), wherein AKP content significantly reduces, and BGP content significantly raises, and high dose group serum StrACP content significantly reduces (P ﹤ 0.05).
Research shows, glucocorticoid can be suppressed to osteocyte, activates osteoclast, makes bone resorption hyperfunction, and bone formation suppresses.Herba Epimedii Fructus Ligustri Lucidi extract can make the coupling between bone resorption and bone formation be in poised state.
Three, the comparison of each group Rat Hormone level:
Table 10 is group rat blood serum COR, T, E respectively
2comparison
Note: compare with Normal group
*p ﹤ 0.05,
*p ﹤ 0.01; Compare with model control group
△p ﹤ 0.05,
△ △p ﹤ 0.01.
Table 10 shows, model control group change of serum C OR(hydrocortisone), E
2, the horizontal compared with normal matched group of T significantly reduces (P ﹤ 0.05 or 0.01).Compared with model control group, Herba Epimedii Fructus Ligustri Lucidi extract basic, normal, high dosage group change of serum C OR content significantly raises (P ﹤ 0.05 or 0.01), and high dose group T content significantly raises (P ﹤ 0.05).
Research shows, glucocorticoid causes endogenous CO R level to reduce, and Herba Epimedii Fructus Ligustri Lucidi extract has protective effect to endogenous glucocorticoid levels; Glucocorticoid can cause blood hormone level to reduce, and Herba Epimedii, Fructus Ligustri Lucidi all have class gonadotropic Effect, and extract is mainly through raising androgenic level thus playing function of resisting osteoporosis.
Claims (5)
1. prevent and/or treat an osteoporosis agents compositions, said composition is made up of the extract of Herba Epimedii and the extract of Fructus Ligustri Lucidi;
The extract of described Herba Epimedii is prepared as follows: the aqueous solution being the ethanol of 85%-95% by crude drug Herba Epimedii volumn concentration extracts, and obtains extracting solution; By the ethanol removing in extracting solution, and carry out petroleum ether extraction, removing chlorophyll, obtains aqueous phase extract; Aqueous phase extract is carried out the separation of D-101 absorption with macroporous adsorbent resin, wash with water colourless to eluent after, carry out eluting with the ethanol water that volumn concentration is 85%-95%, obtain object eluent; By object eluent evaporate to dryness, obtain the extract of Herba Epimedii;
The extract of described Fructus Ligustri Lucidi is prepared as follows: the ethanol water being 70%-80% by crude drug Fructus Ligustri Lucidi volumn concentration extracts, and obtains extracting solution; By the ethanol removing in extracting solution, obtain the extracting solution without ethanol; Extracting solution without ethanol is carried out the separation of AB-8 absorption with macroporous adsorbent resin, and washing except sugar, then carries out eluting with the ethanol water that volumn concentration is 70%-80%, obtains object eluent; By object eluent evaporate to dryness, obtain the extract of Fructus Ligustri Lucidi;
Described crude drug Herba Epimedii volumn concentration is that the condition that the aqueous solution of the ethanol of 85%-95% carries out extracting is as follows: be that the ethanol water of 85%-95% extracts 3 times as the coarse powder of Extraction solvent to described crude drug Herba Epimedii with volumn concentration, 1st time according to 1g Herba Epimedii: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extract 3h; 2nd, 3 times all before the medicinal residues that once obtained and Extraction solvent according to 1g: 10mL ratio mix and extract, 70 DEG C, extraction 2h, merges 3 extracting solution and is described extracting solution; In the aqueous solution of described ethanol, the volumn concentration of ethanol is 90%;
Described crude drug Fructus Ligustri Lucidi volumn concentration is that the condition that the ethanol water of 70%-80% carries out extracting is as follows: be that the ethanol water of 70%-80% extracts 3 times as the coarse powder of Extraction solvent to described crude drug Fructus Ligustri Lucidi with volumn concentration, 1st time according to 1g Fructus Ligustri Lucidi: the ratio of 15mL Extraction solvent is extracted, 70 DEG C, extract 3h; 2nd, 3 times all before the medicinal residues that once obtained and Extraction solvent according to 1g: 10mL ratio mix and extract, 70 DEG C, extraction 2h, merges 3 extracting solution and is described extracting solution; In the aqueous solution of described ethanol, the volumn concentration of ethanol is 75%;
The mass ratio of the extract of described Herba Epimedii and the extract of described Fructus Ligustri Lucidi is 2-5:3-10.
2. compositions according to claim 1, is characterized in that: the mass ratio of the extract of described Herba Epimedii and the extract of described Fructus Ligustri Lucidi is 2:3.
3. the pharmaceutical composition described in claim 1 or 2 is preparing the application prevented and/or treated in the product of osteoporosis;
Described osteoporosis is embodied at least one in following aspect:
(1) weight levels declines;
(2) bone turnover rate level rises or reduces;
(3) BMD declines;
(4) bearing capacity of osseous tissue and/or the impact capacity level of opposing external force reduce;
(5) level of bone trabecula area percentage, bone trabecula thickness and/or trabecular bone density declines;
(6) bone trabecula separating degree rises;
(7) serum cortisol, estradiol and/or testosterone levels decline;
(8) Serum Sex Hormones declines.
4. want the application described in 3 according to right, it is characterized in that: described bone is femur.
5. want the application described in 3 according to right, it is characterized in that: described gonadal hormone is estrogen and/or androgen.
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