CN105012412A - Medicinal composition for treating kidney diseases and pharmaceutical use of medicinal composition - Google Patents
Medicinal composition for treating kidney diseases and pharmaceutical use of medicinal composition Download PDFInfo
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Abstract
The invention relates to a medicinal composition for treating kidney diseases and the pharmaceutical use of the medicinal composition. The composition contains total anthraquinone, astragalus extract, total salvianolic acids and carthamin, wherein the total anthraquinone can be replaced with 1,3,8-trihydroxy-6-methylanthraquinone and/or rhein; the astragalus extract can be replaced with astragalus polysaccharide and/or astragaloside; the total salvianolic acids can be replaced with salvianolic acid B and/or salvianic acid; the carthamin can be replaced with hydroxysafflor yellow A. The composition is a preparation in a solid form, a liquid form, a gas form or a semisolid form, and a great number of experiments show that the composition can be used for treating chronic renal failure, nephrotic syndromes, cardiovascular and cerebrovascular diseases, neoplastic diseases and the like.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of pharmaceutical composition and application thereof for the treatment of kidney disease.
Background technology
Total Radix Et Rhizoma Rhei anthraquinone is brownish black extractum or brown powder crystallization, be the mixture such as dissociated anthraquinone, combined anthraquinone, anthrone, sugar, tannin, wherein free hydroxyanthraquinone compounds is mainly the antimicrobial components such as chrysophanol, emodin, aloe-emodin, physcione and chrysophanic acid; Associativity anthraquinone derivative is glucoside (i.e. chrysophanol monoglucoside, emodin monoglucoside, aloe-emodin monoglucoside, Rhein Glucoside etc.) and the dianthracene ketoside class of dissociated anthraquinone, rushes down lower composition.
Chrysophanic acid (Rhein, 4.5-dihydroxy anthraquinone) belong to single anthracene core class 1,8-dihydroxy-anthracene quinone derivative, coffee-like needle, water insoluble, pyridine, sodium bicarbonate aqueous solution can be dissolved in, be slightly soluble in ethanol, benzene, chloroform, ether and petroleum ether, molecular formula C15H8O6, be mainly distributed in polygonaceae plant, it is one of main component of the multiple Chinese medicines such as Radix Et Rhizoma Rhei, Radix Polygoni Multiflori, Rhizoma Polygoni Cuspidati, pulse family, also containing this composition in goatweed, also obtains by synthetic, its medicine source is enriched, and is easy to get.Recent study finds, chrysophanic acid has pharmacologically active widely, can protect the liver, fibrosis, improve cellular metabolism, antitumor, and protection endotheliocyte, regulates renal function etc., is generally used for treatment nephropathy, tumor, inflammation etc.
Emodin (1,3,8-Trihydroxy-6-methylanthraquinone) belong to single anthracene core class 1,3,8-trihydroxyanthraquinone derivant, orange-yellow long acicular crystal, water-soluble hardly, be dissolved in ethanol and aqueous slkali, molecular formula C15H10O5, mainly being distributed in polygonaceae plant, is one of main component of Radix Et Rhizoma Rhei, also can synthetic.Research finds, emodin has antibacterial, cough-relieving, antitumor, blood pressure lowering, and the effect of protection kidney, can be used for treatment antibacterial or fungal infection, tumor, hepatitis and kidney disease.
Astragaloside is one of main active of the Radix Astragali, has the multiple pharmacological effect such as antiinflammatory, antioxidation, immunomodulating, anti-apoptotic, antiviral, ischemic injuries protection.
Astragalus polysaccharides is water solublity heteropolysaccharide, can be used as immunopotentiating agent or regulator, has the effects such as antiviral, antitumor, defying age, radioprotective, anti-stress, antioxidation simultaneously.
Radix Salviae Miltiorrhizae total phenolic acids is one of main effective site extracted from Radix Salviae Miltiorrhizae, and contained salvianolic acid B is three molecule danshensus and the caffeinic condensation substance of a part, is a kind of depside polyol, faint yellow amorphous powder, molecular formula C36H30O16.Have and improve renal function, prevention and cure of cardiovascular disease, ischemia resisting damages, and have liver injury protection effect, anticoagulation and antithrombotic, antiinflammatory, improves the multiple pharmacological effect such as renal function.Danshensu, white, needle-shaped crystals, molecular formula C9H10O5.There is anticoagulant, antioxidation, also have and improve cardiac function, coronary vasodilation.
Saffloside is one of Flos Carthami principle active component, and bibliographical information saffloside can anticoagulant, has obvious inhibition to rats in vitro thrombosis.S-A Hydroxysafflor yellow A is the compound with single chalcone glycoside structure, it is the most effective water soluble ingredient of Flos Carthami pharmacological effect, the platelet aggregation that platelet activating factor can be suppressed to bring out and release, contestable ground suppresses the combination of platelet activating factor and platelet receptor, is the blood circulation promoting and blood stasis dispelling effective ingredient of Carthamus yellow.
But at present, although existing above-mentioned separate constituent treats the report of some disease, but have no with total Radix Et Rhizoma Rhei anthraquinone, Radix Astragali extract, Radix Salviae Miltiorrhizae total phenolic acids Flos Carthami glycosides is used for the treatment of the report of kidney and other diseases with fixing dosage combination, more has no and is used for the treatment of the report of kidney and other diseases with chrysophanic acid and/or emodin, astragalus polysaccharides and/or astragaloside, salvianolic acid B and S-A Hydroxysafflor yellow A with fixing dosage combination.The invention discloses a kind of composition of medicine for the treatment of kidney disease, for clinical treatment kidney disease and other diseases provide new method.
Summary of the invention
Confirm through lot of experiments research, pharmaceutical composition disclosed by the invention can effectively treat the diseases such as nephropathy, nephrotic syndrome, cardiovascular and cerebrovascular vessel, tumor.
The present composition contains total Radix Et Rhizoma Rhei anthraquinone, Radix Astragali extract, Radix Salviae Miltiorrhizae total phenolic acids Flos Carthami glycosides, wherein in total Radix Et Rhizoma Rhei anthraquinone, the content of chrysophanic acid and/or emodin must not lower than 60%, in Radix Astragali extract, the content of astragalus polysaccharides and/or astragaloside must not lower than 60%, and in Radix Salviae Miltiorrhizae total phenolic acids, the content of salvianolic acid B and/or danshensu must not lower than 50%.
The total Radix Et Rhizoma Rhei anthraquinone that the present composition contains can replace with chrysophanic acid and/or emodin.
The Radix Astragali extract that the present composition contains can replace with astragalus polysaccharides and/or astragaloside.
The Radix Salviae Miltiorrhizae total phenolic acids that the present composition contains can replace with salvianolic acid B and/or danshensu.
The saffloside that the present composition contains can replace with S-A Hydroxysafflor yellow A.
Pharmaceutical composition of the present invention, by weight, containing total Radix Et Rhizoma Rhei anthraquinone 1-80 part, Radix Astragali extract 0.1-50 part, Radix Salviae Miltiorrhizae total phenolic acids 1-30 part Flos Carthami glycosides 1-30 part, wherein total Radix Et Rhizoma Rhei anthraquinone can replace with emodin 1-60 part and/or chrysophanic acid 1-80 part, Radix Astragali extract can replace with astragalus polysaccharides 5-50 part and/or astragaloside 0.1-10 part, Radix Salviae Miltiorrhizae total phenolic acids can replace with salvianolic acid B 1-30 part and/or danshensu 1-30 part, and saffloside can replace with S-A Hydroxysafflor yellow A 1-30 part.
Present composition composition can respectively from Radix Et Rhizoma Rhei, the Radix Astragali, Radix Salviae Miltiorrhizae, extracts and obtains, also can chemosynthesis obtain in the Chinese medicines such as Flos Carthami.
Medicine composition of the present invention is preferred:
1. total Radix Et Rhizoma Rhei anthraquinone 1mg, Radix Astragali extract 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
2. total Radix Et Rhizoma Rhei anthraquinone 80mg, Radix Astragali extract 0.1mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
3. total Radix Et Rhizoma Rhei anthraquinone 40mg, Radix Astragali extract 25mg, Radix Salviae Miltiorrhizae total phenolic acids 15mg, saffloside 15mg;
4. emodin 1mg, astragalus polysaccharides 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
5. emodin 60mg, astragalus polysaccharides 5mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
6. chrysophanic acid 1mg, astragalus polysaccharides 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
7. chrysophanic acid 80mg, astragalus polysaccharides 5mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
8. chrysophanic acid 40mg, astragaloside 25mg, emodin 40mg, Radix Salviae Miltiorrhizae total phenolic acids 40mg, saffloside 1mg;
9. chrysophanic acid 1mg, astragaloside 50mg, emodin 60mg, salvianolic acid B 30mg, saffloside 150mg;
10. chrysophanic acid 80mg, astragaloside 0.1mg, emodin 30mg, danshensu 150mg, saffloside 30mg;
11. chrysophanic acid 1mg, astragalus polysaccharides 25mg, salvianolic acid B 1mg, danshensu 30mg, saffloside 30mg;
12. emodin 60mg, astragalus polysaccharides 50mg, salvianolic acid B 1mg, danshensu 30mg, S-A Hydroxysafflor yellow A 1mg;
13. chrysophanic acid 30mg, astragalus polysaccharides 25mg, salvianolic acid B 15mg, S-A Hydroxysafflor yellow A 30mg;
14. total Radix Et Rhizoma Rhei anthraquinone 1mg, astragalus polysaccharides 5mg, danshensu 30mg, saffloside 30mg;
15. total Radix Et Rhizoma Rhei anthraquinone 80mg, astragalus polysaccharides 50mg, salvianolic acid B 1mg, saffloside 1mg;
16. total Radix Et Rhizoma Rhei anthraquinone 40mg, astragaloside 25mg, salvianolic acid B 15mg, danshensu 1mg, saffloside 15mg;
17. total Radix Et Rhizoma Rhei anthraquinone 1mg, astragaloside 50mg, danshensu 1mg, S-A Hydroxysafflor yellow A 30mg;
18. total Radix Et Rhizoma Rhei anthraquinone 80mg, astragalus polysaccharides 5mg, salvianolic acid B 30mg, danshensu 30mg, S-A Hydroxysafflor yellow A 30mg;
The present composition can make any one dosage form on pharmaceutics, comprises the preparation of solid, liquid, gas and semi-solid form, optimizing injection, tablet, granule, capsule, pill or electuary.
The experimental study that the present invention carries out 18 groups of pharmaceutical compositions is as follows, and concrete pharmaceutical composition is:
Compositions one: total Radix Et Rhizoma Rhei anthraquinone 1mg, Radix Astragali extract 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
Compositions two: total Radix Et Rhizoma Rhei anthraquinone 80mg, Radix Astragali extract 0.1mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
Compositions three: total Radix Et Rhizoma Rhei anthraquinone 40mg, Radix Astragali extract 25mg, Radix Salviae Miltiorrhizae total phenolic acids 15mg, saffloside 15mg;
Compositions four: emodin 1mg, astragalus polysaccharides 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
Compositions five: emodin 60mg, astragalus polysaccharides 5mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
Compositions six: chrysophanic acid 1mg, astragalus polysaccharides 50mg, Radix Salviae Miltiorrhizae total phenolic acids 1mg, saffloside 30mg;
Compositions seven: chrysophanic acid 80mg, astragalus polysaccharides 5mg, Radix Salviae Miltiorrhizae total phenolic acids 30mg, saffloside 1mg;
Compositions eight: chrysophanic acid 40mg, astragaloside 25mg, emodin 40mg, Radix Salviae Miltiorrhizae total phenolic acids 40mg, saffloside 1mg;
Compositions nine: chrysophanic acid 1mg, astragaloside 50mg, emodin 60mg, salvianolic acid B 30mg, saffloside 150mg;
Compositions ten: chrysophanic acid 80mg, astragaloside 0.1mg, emodin 30mg, danshensu 150mg, saffloside 30mg;
Compositions 11: chrysophanic acid 1mg, astragalus polysaccharides 25mg, salvianolic acid B 1mg, danshensu 30mg, saffloside 30mg;
Compositions 12: emodin 60mg, astragalus polysaccharides 50mg, salvianolic acid B 1mg, danshensu 30mg, S-A Hydroxysafflor yellow A 1mg;
Compositions 13: chrysophanic acid 30mg, astragalus polysaccharides 25mg, salvianolic acid B 15mg, S-A Hydroxysafflor yellow A 30mg;
Compositions 14: total Radix Et Rhizoma Rhei anthraquinone 1mg, astragalus polysaccharides 5mg, danshensu 30mg, saffloside 30mg;
Compositions 15: total Radix Et Rhizoma Rhei anthraquinone 80mg, astragalus polysaccharides 50mg, salvianolic acid B 1mg, saffloside 1mg;
Compositions 16: total Radix Et Rhizoma Rhei anthraquinone 40mg, astragaloside 25mg, salvianolic acid B 15mg, danshensu 1mg, saffloside 15mg;
Compositions 17: total Radix Et Rhizoma Rhei anthraquinone 1mg, astragaloside 50mg, danshensu 1mg, S-A Hydroxysafflor yellow A 30mg;
Compositions 18: total Radix Et Rhizoma Rhei anthraquinone 80mg, astragalus polysaccharides 5mg, salvianolic acid B 30mg, danshensu 30mg, S-A Hydroxysafflor yellow A 30mg.
Experiment one, the present invention are to the therapeutical effect of CRF rats
1. laboratory animal SD rat 300, male and female half and half, body weight 200g ± 20g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center.
2. the ingredient of Experimental agents the present invention 18 groups of compositionss all has is provided by Dalian Mei Lun Bioisystech Co., Ltd, is all made into 3mg/ml solution (chrysophanic acid, emodin, astragalus polysaccharides, astragaloside, danshensu, saffloside group drug level are identical with compositions 16) with 0.5% carboxymethyl cellulose sodium before experiment.
3. experimental technique gets SD rat, and take out 10 immediately as blank group, all the other rat adaptabilities feed 3 days.Except blank group, all the other rats 2.5% adenine suspension presses 250mg/kg/ days gavages, continuous gavage gives 3 weeks, during the renal failure phenomenons such as serum urea nitrogen to appear, creatinine rising, satisfactory rat is divided into immediately model group, compositions one to ten eight group.Compositions one to ten eight group respectively gavage gives relative medicine 10ml/kg, and blank group and model group gavage give isopyknic 0.5% carboxymethyl cellulose sodium solution, daily once, and successive administration 4 weeks.After last administration 24h, abdominal aortic blood, measures serum urea nitrogen, creatinine, sero-abluminous content, dissects kidney and carries out pathological section, basis of microscopic observation pathological change.
4. Testing index
(1) serum urea nitrogen, creatinine and sero-abluminous content is measured
(2) pathological examination
5. experimental result
(1) the present invention is on chronic kidney hypofunction rat model serum urea nitrogen, creatinine and sero-abluminous impact.In table 1.
Table 1 the present invention is on CRF rats serum urea nitrogen, creatinine and sero-abluminous impact
Note: each group compares with model group
*p<0.05,
*p<0.01
Result shows: blank group compares blood urea nitrogen with model group and creatinine is obviously lower, serum albumin is obviously higher, and have significant difference (p<0.01), after showing modeling, major injury is caused to rat, significantly reduce through the treatments of 4 weeks each administration group rat blood urea nitrogen and creatinine, serum albumin obviously raises, and has significant difference (p<0.05 or p<0.01).
(2) HE dyeing basis of microscopic observation result
Blank group: glomerule and renal tubules clear, structure is normal, has no pathological change; Model group: glomerule atrophy, renal tubules is obviously expanded, and proximal convoluted tubule and Distal convoluted tubule epithelial cell all have obvious cloudy swelling and degeneration to occur, renal interstitial proliferation of fibrous tissue, and have chronic inflammation cellular infiltration; Each administration group: glomerule is slightly congested, structure no abnormality seen, renal tubules has mild dilation, without obvious cell infiltration.
6. conclusion The results confirms, each administration group all has therapeutical effect preferably to CRF rats, is in particular in the improvement result to serum creatinine, blood urea nitrogen, serum albumin and pathological characteristics.
Experiment two, the present composition are to brightic therapeutical effect
1. laboratory animal SD rat 270, male and female half and half, body weight 180-220g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center.New Zealand white rabbit 8, purchased from Xi'an Di Lepu bio-resource exploitation company limited.
2. the ingredient of Experimental agents the present invention 18 groups of compositionss all has is provided by Dalian Mei Lun Bioisystech Co., Ltd, is all made into 3mg/ml solution (chrysophanic acid, emodin, astragalus polysaccharides, astragaloside, danshensu, saffloside group drug level are identical with compositions 16) with 0.5% carboxymethyl cellulose sodium before experiment.
3. experimental technique
(1) prepare rabbit anti-rat chest cell serum and get aseptic SD rat 12, put to death, carefully win rat chest gland and liver.Hepar siccatum is made stand-by after liver PBS wash buffer is clean; Separately thymus is placed in PBS buffer, rinse 2-3 time, careful separation, the lymph node removing its surface and blood vessel, put on 200 order rustless steel mesh screens, scratch thymus gently with dissecting needle to dissociate thymocyte cell, use PBS wash buffer, collect thymus cell suspension, centrifugal 10min, with PBS buffer recasting 2 × 10
7the thymus cell suspension of/ml, the thymus cell suspension of 1:2 mixing by volume and Freund's complete adjuvant, fully mix, using mixed suspension as rat chest cell immunizing antigen liquid.By rat chest cell immunizing antigen liquid multi-point injection in 8 New Zealand white rabbit dorsal sc, every rabbit injection 3ml.Routine is raised after 2 weeks, rabbit ear edge intravenous injection 2 × 10
7the thymus cell suspension of/ml, often only injects 1.5ml.After 7d, heart extracts rabbit blood, collects rabbit anteserum.Surveying the anti-rat chest cell serum titer of anti-rabbit by immunodiffusion method is 1:160-1:320.The anti-rat chest cell serum of rabbit in 56 DEG C, after 30min deactivation, respectively with individual rat hepar siccatum absorption to remove non-specific antibody, the centrifugal 30min of room temperature, discards hepar siccatum, and the anti-rat chest cell serum of collection rabbit ,-20 DEG C save backup.
(2) healthy SD rat is got in the preparation of chronic glomerulonephritis rat model, and after adaptability feeds 3 days, collect urine, detect urine protein, result is feminine gender.Be divided into Normal group, model group, compositions one to ten eight group immediately, often organize 10.Except rats in normal control group tail vein injection 2ml normal saline, all the other group rat disposable tail vein injection rabbits anti-rat chest cell serum 2ml.
(3) medication and the anti-rat chest cell serum of testing index injection rabbit are after 6 days, compositions one to ten eight group respectively gavage gives relative medicine 10ml/kg, blank group and model group gavage give isopyknic 0.5% carboxymethyl cellulose sodium solution, daily once, successive administration 4 weeks.Last administration is after 24 hours, and abdominal aortic blood, measures IL-6, IL-8 and TNF-alpha levels respectively, dissects kidney, carries out pathology investigation.
4. result
(1) the present invention is on the impact of chronic glomerulonephritis rat blood serum IL-6, IL-8 and TNF-α
Table 3 the present invention is on the impact of chronic glomerulonephritis rat blood serum IL-6, IL-8 and TNF-α
Note: each group compares with model group
*p<0.05,
*p<0.01
Result shows: model group rats blood serum IL-6, IL-8 and TNF-alpha levels compared with normal matched group significantly raise (P<0.01), shows modeling success.Medicine group rat blood serum IL-6, IL-8 and TNF-alpha levels of the present invention is lower than model group (P<0.05 or P<0.01), show that each administration group all can improve serum cytokines to a certain extent, thus improve glomerulonephritis symptom.
(3) pathological examination rats in normal control group glomerule profile, clear in structure, form is normal; Model group rats renal tubules obvious tumefaction, have hyperemia, tube chamber narrows, and the visible albumen of part is tubular, and glomerular volume increases, and visible inflammatory cell infiltrates; Each administration group Renal Glomeruli In Rats structure shows no obvious abnormalities, and glomerule capillary tube has slight swelling, and basement membrane slightly thickens, and cell infiltration is not obvious.
5. conclusion experimental result confirms, each administration group all has therapeutical effect preferably to chronic glomerulonephritis rat, is in particular in and reduces blood inflammatory cytokines levels in non-diabetic and improve pathological characteristics aspect.
Experiment three, investigation medicine of the present invention are to the therapeutical effect of hypertensive nephropathy
1. laboratory animal spontaneous hypertensive rat 270, male and female half and half, body weight 180-220g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center; SD rat 10, male and female half and half, body weight 180-220g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center.
2. the ingredient of Experimental agents the present invention 18 groups of compositionss all has is provided by Dalian Mei Lun Bioisystech Co., Ltd, is all made into 3mg/ml solution (chrysophanic acid, emodin, astragalus polysaccharides, astragaloside, danshensu, saffloside group drug level are identical with compositions 16) with 0.5% carboxymethyl cellulose sodium before experiment.
3. experimental technique
Spontaneously hypertensive rat urine microalbumin to be measured is that spontaneously hypertensive nephropathy model copies successfully when being 20-200mg/L, rejects defective rat, is divided into model group and compositions one to ten eight group at random.Separately get 10 SD rats as matched group.Each administration group gavage gives relative medicine 0.5ml/10g, and model group and matched group give isopyknic 0.5% carboxymethyl cellulose sodium, and every day is administered once, successive administration 4 weeks.
4. Testing index
4.1 measure blood pressure.Before administration, measure the tail vein systolic pressure under rat waking state, at the end of experiment, again measure the systolic pressure of rat tail vein, and each survey is averaged for three times.
4.2 measure microdose urine protein in each group of rat urine, urine β
2microglobulin.Collect 12h urine before experiment terminates, fasting during collecting urine, can't help water.
The content of serum creatinine and blood urea nitrogen in 4.3 mensuration blood.Heart extracting blood at the end of experiment, the automatic clinical chemistry analyzer produced with Jinan Chinese prescription Medical Devices Co., Ltd. measures serum creatinine and blood urea nitrogen.
5 experimental results
5.1 compositionss on the impact of spontaneously hypertensive nephrotic rats blood pressure, in table 4.
Table 4 present composition is on the impact of spontaneously hypertensive nephrotic rats blood pressure before and after experiment
Note: compare with matched group
*p ﹤ 0.05
*p ﹤ 0.01
Experimental result shows: at the end of experiment, and blank group compares with model group, and blood pressure is obviously lower.Each administration group rat blood pressure obviously reduces after administration compared with model group, and has significant difference (p<0.01).Show that the blood pressure of pharmaceutical composition of the present invention to essential hypertension nephrotic rats has certain reducing effect.
5.2 the present invention are to microdose urine protein, urine β in essential hypertension nephrotic rats urine
2the impact of microglobulin content, in table 5.
Table 5 pair hypertensive nephropathy rat urine microdose urine protein, urine β
2the impact of microglobulin content
Note: compare * P ﹤ 0.05**P ﹤ 0.01 with matched group
Experimental result shows: pharmaceutical composition of the present invention obviously can lower the content of hypertensive nephropathy rat urine microalbumin and urinal beta2 microglobulin, compares have significant difference (p<0.01) with model group.Show that the kidney of pharmaceutical composition of the present invention to essential hypertension nephrotic rats has certain protective role.
5.3 the present invention on the impact of serum creatinine and blood urea nitrogen in essential hypertension nephrotic rats blood, in table 6.
Table 6 the present invention is on the impact of essential hypertension nephrotic rats serum creatinine and blood urea nitrogen
Note: compare * P ﹤ 0.05**P ﹤ 0.01 with model group
Result shows: pharmaceutical composition of the present invention obviously can lower the content of hypertensive nephropathy rat serum creatinine and blood urea nitrogen, compares have significant difference (p<0.01) with model group.Show that the kidney of pharmaceutical composition of the present invention to essential hypertension nephrotic rats has certain protective role.
The antitumor action of experiment four, investigation medicine of the present invention
1. laboratory animal BALB/C white mice 270, male and female half and half, body weight 18-22g, purchased from Chinese Academy of Sciences's Shanghai Experimental Animal Center.
2. the ingredient of Experimental agents the present invention 18 groups of compositionss all has is provided by Dalian Mei Lun Bioisystech Co., Ltd, is all made into 3mg/ml solution (chrysophanic acid, emodin, astragalus polysaccharides, astragaloside, danshensu, saffloside group drug level are identical with compositions 16) with 0.5% carboxymethyl cellulose sodium before experiment.Hepatoma cells strain H22 is so kind as to give by ShanXi Chinese Medicine Academy pharmaceutical research room.
3. experimental technique
Set up tumor model and carefully extract from planting Mus intraperitoneal the ascites inoculating H22 cell strain out, transfer is inoculated into another mouse peritoneal, goes down to posterity three times.Get inoculation H22 cell strain and the mice of three times of going down to posterity, 1-2ml milk shape, ascites compared with thickness is gone out with 5ml syringe pump under aseptic condition, first with 0.4% trypan blu e dyeing, cell counting count board meter living cell rate >90%, then adjusts tumor cell concentration for 1.0 × 10 with the dilution of sterilizing D-Hanks liquid
7individual/ml.Mix up the tumor cell of concentration at all the other mice right fore axillary fossas and subcutaneous vaccination, injection volume is 0.15ml/.
Solid tumor mice, after 72 hours, is divided into 26 groups by medication Modling model at random, i.e. carboxymethyl cellulose sodium matched group, compositions one to ten eight group, often organizes 10.Each administration group gavage awards relative medicine 0.5ml/10g, and carboxymethyl cellulose sodium matched group gives isopyknic carboxymethyl cellulose sodium, once a day, and successive administration 2 weeks.Record dead mouse number every day, and weigh different dosing group Mouse Weight.
During antitumor activity evaluation administration, every day weighs the weight of animals, puts to death animal after last administration 48h, peels off tumor, weighs, be placed in 10% formalin solution fixing after, carry out pathological section.
Calculate the suppression ratio of drug on tumor growth as follows.The average tumor of inhibition rate of tumor growth=(matched group average tumor weight-administration group average tumor weight)/matched group heavy × 100%.
4. experimental result
Medicine anti-tumor in vivo Activity Results of the present invention is as following table.
Table 7 anti-tumor in vivo activity experiment result
Note: each group compares with matched group
*p<0.05,
*p<0.01
Experimental result shows: different dosing group can obviously Tumor suppression be active compared with matched group, all has significant difference (P<0.05), shows that medicine of the present invention has antineoplastic action.
5. conclusion drug on tumor of the present invention has inhibitory action, can be used for the treatment of tumor disease.
Experiment five, medicine of the present invention are to the protective effect of vascular endothelial cell
1. experiment material human umbilical vein endothelial cell strain (heart injuries) is purchased from Bai Li bio tech ltd, Shanghai; DMEM high glucose medium, hyclone are all purchased from Gibco company.MDA, SOD test kit builds up biological company limited purchased from Nanjing; H
2o
2be purchased from Tianjin Ke Miou chemical reagent company limited; Pancreatin, tetrazole orchid (MTT) purchased from American SIGMA company.
2. the ingredient of Experimental agents the present invention 18 groups of compositionss all has is provided by Dalian Mei Lun Bioisystech Co., Ltd, test front dimethyl sulfoxide and be mixed with 3mg/ml solution (chrysophanic acid, emodin, astragalus polysaccharides, astragaloside, danshensu, saffloside group drug level are identical with compositions 16), for subsequent use.
3. experimental technique
Human umbilical vein endothelial cell is placed in the RPMI-1640 being mixed with 2mmol/L L-glutaminate, 100 μ g/ml heparin, 100U/ml penicillin, 30 μ g/ml endothelial cell growth factor (ECGF) and 10% hyclone by cell culture, in 37 DEG C, 5%CO
2cultivate in the cell culture incubator of saturated humidity.When Growth of Cells merge to 80% time, pour out old culture medium, with PBS liquid fine laundering cell 2 ~ 3 times, then add about 1ml 0.125% pancreatin, to 37 DEG C, 5%CO
2incubator hatches 2min, when seeing under mirror that cell shrinkage becomes circle, intercellular substance increases, inhales and abandons pancreatin, adds complete culture solution containing 10% hyclone to stop the effect of pancreatin, repeatedly blows and beats cell gently, make it to come off into cell suspension from bottle wall with suction pipe.Cell counting, adjustment cell density is 1 × 10
5individual/ml, is inoculated in 96 orifice plate every hole 100 μ l, is placed in 37 DEG C, 5%CO
2cultivate under condition.After about 24h, for experiment.
Set up H
2o
2induction human umbilical vein endothelial cell damage model vascular endothelial cell is with 10
4individual/hole is inoculated in 96 well culture plates.With serum-free medium by H
2o
2be made into 0,75,150,300,600 μm of ol/L dosage group, add in 96 orifice plates respectively, every hole 100 μ l, act on 12 respectively, 24, after 48h, discarded by supernatant, every hole adds 100 μ l culture medium and 20 μ lMTT (5g/L) act on 4h, supernatant is discarded, every hole adds 150 μ l dimethyl sulfoxide, measures cell absorbance (A) under 15min, 570nm microplate reader that microtiter shaker vibrates.Cell inhibitory rate %=(blank group absorbance-respectively organize absorbance) (A)/blank group absorbance (A) × 100%.
Medication by cell with 2 × 10
5individual/hole is inoculated in 6 orifice plates, and experiment is divided into 27 groups, Normal group: every hole gives 2ml serum-free medium; Model group: it is 300 μm of ol/LH that every hole gives 2ml final concentration
2o
2, effect 24h; Prescription of the present invention one to ten eight group: giving 2ml final concentration is 50mg/ml relative medicine, after hatching 4h, giving 2ml final concentration is 300 μm of ol/L H
2o
2effect 24h.Detect the content of SOD, MDA in cell: each group of cell is collected in digestion, often group adds 1ml PBS, take the method (-80 ° of refrigerator 15min, room temperature 20min so repeat 5 times) of multigelation, to cell breakage, content flows out, the centrifugal 15min of 3000r/min, draws supernatant, carry out BCA protein quantification, then carry out the assay of MDA, SOD by test kit description.
4. experimental result
The protective effect that medicine of the present invention damages people's vein blood vessel, in table 8
Table 8 medicine of the present invention is on the impact of people's vein blood vessel SOD, MDA
Note: each group compares with model group
*p<0.05,
*p<0.01
Experimental result shows: each administration group comparatively model group SOD activity raises, and MDA content declines, and has statistical significance (P<0.05 or P<0.01).
5. conclusion experiment proves that prescription of the present invention can improve impaired vein endothelial cell, and prompting may be used for treating cardiovascular and cerebrovascular disease.
Specific embodiment
Embodiment 1
Get total Radix Et Rhizoma Rhei anthraquinone 2.5g, Radix Astragali extract 4g, Radix Salviae Miltiorrhizae total phenolic acids 2.6g, saffloside 2.5g, adds PEG-20050ml, then injects and be diluted with water to 500ml, filter, add water for injection to 800ml, adjust ph, to 6.5-7.0, injects and is diluted with water to 1000ml, filter with 0.22 μm of microporous filter membrane, subpackage, sterilizing, obtains injection.
Embodiment 2
Get total Radix Et Rhizoma Rhei anthraquinone 250g, Radix Astragali extract 230g, Radix Salviae Miltiorrhizae total phenolic acids 260g, saffloside 250g, Portugal's first ammonia and arginine in right amount, add water for injection and are diluted to 5L, stir until dissolve, filter, filtrate adjust pH, to 5.0-7.0, carries out fine straining with 0.22 μm of microporous filter membrane; Get mannitol to inject in right amount and be mixed with solution with water, mix with above-mentioned filtrate, filter with 0.22 μm of microporous filter membrane, inject and be diluted with water to 10L, by the dosage subpackage of unit formulation 10ml, lyophilization, obtains lyophilized powder.
Embodiment 4
Get total Radix Et Rhizoma Rhei anthraquinone 250g, Radix Astragali extract 230g, Radix Salviae Miltiorrhizae total phenolic acids 260g, saffloside 250g, Portugal's first ammonia and arginine in right amount, add water for injection and are diluted to 5L, stir until dissolve, filter, filtrate adjust pH, to 5.0-7.0, carries out fine straining with 0.22 μm of microporous filter membrane; Get mannitol to inject in right amount and be mixed with solution with water, mix with above-mentioned filtrate, filter with 0.22 μm of microporous filter membrane, inject and be diluted with water to 10L, by the dosage subpackage of unit formulation 10ml, lyophilization, obtains lyophilized powder.
Embodiment 5
Get total Radix Et Rhizoma Rhei anthraquinone 78g, Radix Astragali extract 93.75g, Radix Salviae Miltiorrhizae total phenolic acids 80g, saffloside 83g, pre-paying starch, micropowder silica gel, magnesium stearate, Pulvis Talci is appropriate, after crossing 80 mesh sieves respectively, mix homogeneously with medicated powder, add appropriate adhesive and make soft material, granulate, granule is in 60 DEG C of dryings.Add mix homogeneously after micropowder silica gel, magnesium stearate and Pulvis Talci, be pressed into 1000.
Embodiment 6
Get total Radix Et Rhizoma Rhei anthraquinone 78g, Radix Astragali extract 93.75g, Radix Salviae Miltiorrhizae total phenolic acids 80g, saffloside 83g, pre-paying starch, micropowder silica gel, magnesium stearate, Pulvis Talci is appropriate, and after crossing 80 mesh sieves respectively, Homogeneous phase mixing, adds appropriate adhesive and make soft material, granulates; Granule is 60 DEG C of dryings.Add carboxymethylstach sodium, micropowder silica gel, magnesium stearate and Pulvis Talci mix homogeneously, encapsulated, make 1000.
Embodiment 7
Get Radix Et Rhizoma Rhei extract 1320g, Radix Astragali extract 1584g, Radix Salviae Miltiorrhizae total phenolic acids 1584g, saffloside 1411g, pre-paying starch, micropowder silica gel, magnesium stearate, Pulvis Talci is appropriate, then it is appropriate to add aspartame, make soft material, granulate, after 60 DEG C of dryings, detect qualified after, be sub-packed in medicinal polyethylene plastic bag, every bag of 5g, make 1000 bags altogether.
Claims (10)
1. treat a pharmaceutical composition for kidney disease, it is characterized in that: by weight, containing total Radix Et Rhizoma Rhei anthraquinone 1-80 part, Radix Astragali extract 0.1-50 part, Radix Salviae Miltiorrhizae total phenolic acids 1-30 part Flos Carthami glycosides 1-30 part.
2. a kind of pharmaceutical composition for the treatment of kidney disease according to claim 1, is characterized in that: total Radix Et Rhizoma Rhei anthraquinone can replace with emodin 1-60 part and/or chrysophanic acid 1-80 part.
3. a kind of pharmaceutical composition for the treatment of kidney disease according to claim 1 or 2, is characterized in that: Radix Astragali extract can replace with astragalus polysaccharides 5-50 part and/or astragaloside 0.1-10 part.
4. according to the arbitrary described a kind of pharmaceutical composition for the treatment of kidney disease of claim 1-3, it is characterized in that: Radix Salviae Miltiorrhizae total phenolic acids can replace with salvianolic acid B 1-30 part and/or danshensu 1-30 part.
5. according to the arbitrary described a kind of pharmaceutical composition for the treatment of kidney disease of claim 1-4, it is characterized in that: saffloside can replace with S-A Hydroxysafflor yellow A 1-30 part.
6. the application of the arbitrary described pharmaceutical composition of claim 1-5 in the medicine for the preparation for the treatment of kidney disease.
7. the application of pharmaceutical composition according to claim 6 in the medicine for the preparation for the treatment of nephrotic syndrome.
8. the application of pharmaceutical composition according to claim 6 in the medicine for the preparation for the treatment of hypertensive nephropathy.
9. the arbitrary described pharmaceutical composition of claim 1-5 is for the preparation of the application in treatment tumor, cardiovascular and cerebrovascular disease or hepatopathy.
10., according to the arbitrary described a kind of pharmaceutical composition for the treatment of kidney disease of claim 1-5, it is characterized in that: said composition is the preparation of solid form, liquid form, gas form or semi-solid form.
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| CN201410172436.9A CN105012412A (en) | 2014-04-25 | 2014-04-25 | Medicinal composition for treating kidney diseases and pharmaceutical use of medicinal composition |
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| CN201410172436.9A CN105012412A (en) | 2014-04-25 | 2014-04-25 | Medicinal composition for treating kidney diseases and pharmaceutical use of medicinal composition |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1977889A (en) * | 2005-12-05 | 2007-06-13 | 黄振华 | Medicinal composition of astragalus, salvia miltrorrhiza and oxymatrine, and its preparing method |
| CN1977888A (en) * | 2005-12-05 | 2007-06-13 | 黄振华 | Medicinal composition of baicalin, ganoderma lucidum and salvia miltrorrhiza |
| CN101507760A (en) * | 2009-03-13 | 2009-08-19 | 四川省中医药科学院 | Medicine composite for treating kidney disease |
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2014
- 2014-04-25 CN CN201410172436.9A patent/CN105012412A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1977889A (en) * | 2005-12-05 | 2007-06-13 | 黄振华 | Medicinal composition of astragalus, salvia miltrorrhiza and oxymatrine, and its preparing method |
| CN1977888A (en) * | 2005-12-05 | 2007-06-13 | 黄振华 | Medicinal composition of baicalin, ganoderma lucidum and salvia miltrorrhiza |
| CN101507760A (en) * | 2009-03-13 | 2009-08-19 | 四川省中医药科学院 | Medicine composite for treating kidney disease |
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| 张小鸿: "黄芪保护血管内皮细胞作用机制研究进展", 《中国医学杂志》 * |
| 徐守竹: "RP-HPLC法同时测定肾康注射液中5种蒽醌类成分", 《中成药》 * |
| 旭: "丹参水溶性成分在慢性肾脏病中的研究进展"", 《环球中医药》 * |
| 白雪梅: "红花黄色素对早期糖尿病肾病患者hs-CRP、IL-8的影响", 《中国中西医结合肾病杂志》 * |
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