CN102846666A - Application of physically-modified Chinese cobra venom in preparation of medicament for treating acute and chronic nephrosis - Google Patents
Application of physically-modified Chinese cobra venom in preparation of medicament for treating acute and chronic nephrosis Download PDFInfo
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Abstract
The invention discloses an application of physically-modified Chinese cobra venom in preparation of medicaments for treating acute and chronic nephrosis. The physically-modified Chinese cobra venom is obtained by dissolving Chinese cobra venom with deionized water, heating for denaturation and then performing renaturation; the heating temperature is controlled to be 50-100 DEG C, and the heating time is controlled to be 1 min-300 min. The invention finds that the heated and denaturated Chinese cobra venom can effectively reduce urine protein in acute and chronic nephrosis, reduce serum creatinine, and urea nitrogen, improve the pathological damage degree of the kidney, and recover kidney functions.
Description
Technical field
The present invention relates to the purposes of Chinese cobra venom in preparation treatment acute and chronic nephropathy medicine behind a kind of physical modification.
Background technology
Snake venom is the complex mixture that is made of the various ingredients that the poison gland of Serpentis is secreted.Snake venom is the complex mixture that is made of the various ingredients that the poison gland of Serpentis is secreted.Fresh venom is Ovum Gallus domesticus album sample thick liquid, has special fishy smell.Different Serpentis kind venom color and lusters are different, and it is faint yellow that Chinese cobra venom is.Being protein more than 90% in the dry of snake venom, is the main component of its toxicity and biologic activity.The Chinese cobra venom composition mainly contains other proteinoid such as cobra venom factor (1%-2%), cardiotoxin (40%-50% has another name called cytotoxin, film toxin), neurotoxin (10%).But motherland's traditional medicine is thought Naja and toxic component the meridian dredging thereof, wind-damp dispelling, and have the effect of building body.As far back as earlier 1900s, people just begin to use snake venom and alleviate malignant, tumor pain, neuralgia and arthralgia, a series of reports that similar morphine sample analgesic activity is arranged about snake venom occur subsequently.Along with deepening continuously of research, present snake venom and goods thereof have been applied to clinical, and except analgesic activity, research is found at rheumatism, antitumor and good curative effect is being arranged aspect the nervous system disease.
The rat acute nephropathy that glycerol is induced can make rat albuminuria, hematuria occur, that kidney becomes is large, edema, color and luster are deepened, glomerule and injury of renal tubular, dysfunction, it is closely similar with the nephropathy that clinically different group blood transfusion, crush syndrome cause, there is no at present effective medicine.
The rat chronic nephropathy that amycin is induced can make rat the performance of typical nephrotic syndrome (nephrotic syndrome) occur, and the pathological change of its animal model is similar with the FSGS nephropathy to human MCN.Nephrotic syndrome is a kind of disease that heals than refractory clinically, and clinically take albuminuria as the Main Diagnosis index, at present, still take glucocorticoids such as prednisones as main, but the prolonged application side effect is large, again easily recurrence for the Drug therapy of nephrotic syndrome.The present invention therefore.
Summary of the invention
Main purpose of the present invention is to provide the purposes of the Chinese cobra venom behind a kind of physical modification in the medicine of the acute and chronic nephropathy of preparation treatment.
Technical scheme of the present invention is:
The purposes of Chinese cobra venom behind a kind of physical modification in the medicine of the acute and chronic nephropathy of preparation treatment.
Preferably, the Chinese cobra venom behind the described physical modification obtains Chinese cobra venom after with the degeneration of deionized water dissolving post-heating and renaturation; Heating and temperature control is controlled at 1min～300min heat time heating time between 50～100 ℃.
Preferably, also comprise Thailand and other cobra-venom behind the physical modification in the described medicine.
Preferably, also comprise a kind of of neurotoxin, cardiotoxin and cobra-venom factor that unmodified Chinese cobra venom, Thailand and other cobra-venom or be selected from exists in the cobra-venom in the described medicine.
Preferably, also comprise cobra-venom or be selected from the compound preparation that a kind of and other medicines of the neurotoxin, cardiotoxin and the cobra-venom factor that exist in the cobra-venom form in the described medicine.
Preferably, the form of administration of described medicine is selected from oral instant medicine film, oral liquid, tablet, capsule, spray, injection and transdermal absorption formulation.
Described medicine can be oral liquid, capsule, tablet, varnish, cataplasma, spray and injection etc., and described medicine can be various folk prescriptions and compound preparation.Described medicine is to form compound preparation or form single preparations of ephedrine by the cobra-venom behind the physical modification and pharmaceutic adjuvant with the other drug active component by the cobra-venom behind the physical modification.
Also comprise unmodified Chinese cobra venom in the described medicine or be selected from neurotoxin, cardiotoxin (film toxin) and the cobra-venom factor that plays a major role in the unmodified Chinese cobra venom.Also comprise other cobra-venoms behind the physical modification in the described medicine.
Cobra-venom is always poison of Naja among the present invention.The present invention finds and will can be used for preparation treatment acute and chronic nephropathy medicine after the modification of the total poisonous substance reason of Naja.The used cobra-venom of the present invention is the total snake venom of Chinese cobra, and according to the homogeny of composition and drug effect, described snake venom also comprises other cobra-venoms.Described medicine can be prepared into and be selected from following dosage form: oral instant medicine film, oral liquid, capsule, tablet, spray, injection and transdermal formulation.Certainly, described medicine also comprises various folk prescriptions and compound preparation.
Although Chinese cobra venom has been used for the treatment of clinically rheumatism and has alleviated malignant, tumor pain, neuralgia and arthralgia etc., also there is not at present the bibliographical information Chinese cobra venom can treat the acute and chronic nephropathy by the spraying of oral, nose (mouth) mucosa, transdermal administration and drug administration by injection.Find first in the present invention research that the laboratory animal chronic nephropathy that laboratory animal acute nephropathy that Chinese cobra venom is induced glycerol and amycin are induced has good therapeutical effect.This discovery will produce great impact to research and the drug development of acute and chronic nephropathy, and value for clinical application will be arranged, for Chinese cobra venom is opened up clinical new purposes.
The present invention relates to the purposes of Chinese cobra venom in preparation treatment acute and chronic nephropathy medicine.The Chinese cobra total poison of the present invention after zoopery confirms physical modification pharmaceutically effective dose (such as rat 1-3000 μ g/kg, people 1～1000 μ g/kg) urine protein of the internal energy effective reduction acute and chronic nephropathy of scope, reduce serum creatinine, blood urea nitrogen, improve the Pathological degree of injury, recover renal function, have consumption little, safe, can be oral, injectable, can be through advantages such as mouth and nose mucosa and percutaneous drug deliveries.
The present invention processes by the total poisons physical method of Chinese cobra and reaches the attenuation synergistic purpose, cobra venom after the physical treatment can effectively reduce the urine protein of acute and chronic nephropathy, reduce serum creatinine, blood urea nitrogen, improve the Pathological degree of injury, recover renal function, its curative effect surpasses undressed cobra venom.Described medicine comprises oral liquid, oral instant medicine film, capsule, tablet, spray, injection and transdermal formulation etc., and described medicine also comprises various folk prescriptions and compound preparation.
Naja among the present invention is artificial breeding's Naja, gathers venom under aseptic condition, becomes pale yellow powder through lyophilization, cryopreservation.The present invention processes by the total poisons physical method of Chinese cobra and reaches the attenuation synergistic purpose.Chinese cobra venom has been used for the treatment of clinically rheumatism and has alleviated malignant, tumor pain, neuralgia and arthralgia etc., but all uses the mix preparation of the neurotoxin of purification, multiple snake venom or the compound preparation of cobra venom and other Chinese medicine.In view of Chinese cobra venom toxicity is larger, the medicinal ingredient in the snake venom mainly is protein, and its structure and biological activity can be changed by chemical factors.Snake venom is after with hydrogen peroxide treatment, and disulfide bond is opened, and its toxicity reduces greatly, but analgesic activity also almost disappears, and the prompting biologic activity is destroyed.And the reversibility degeneration can occur after the protein heating, change has occured in degeneration rear space structure, or the part macro-molecular protein is decomposed into small molecular weight protein because of heating part.Snake venom toxicity after this heat denatured of evidence and the renaturation obviously reduces, and drug effect increases.The present invention finds that the Chinese cobra venom of heat denatured effectively reduces the urine protein of acute and chronic nephropathy, reduces serum creatinine, blood urea nitrogen, improves the Pathological degree of injury, recovers renal function.This discovery will produce great impact to the research of acute and chronic nephropathy and drug development, and value for clinical application will be arranged, for Chinese cobra venom is opened up clinical new purposes.
Advantage of the present invention is:
1. adopt the Chinese cobra venom through physical modification, toxicity is low and drug effect is high.
2. Chinese cobra venom can reduce the rat 24h urine protein content that the acute and chronic nephropathy causes.
3. Chinese cobra venom can reduce Renal Function in Rats obstacle index-creatinine that the acute and chronic nephropathy causes, the rising of blood urea nitrogen.
4. Chinese cobra venom can alleviate the symptom of the rat chronic nephropathy hyperlipidemia that amycin induces.
5. Chinese cobra venom can improve the rat chronic nephropathy hypoproteinemia that amycin is induced.
6. Chinese cobra venom can improve the rat chronic nephropathy serum electrolyte disorder that amycin is induced.
7. Chinese cobra venom can strengthen the rat chronic nephropathy antioxidant ability of organism that amycin is induced, and alleviates the damage that lipid peroxidation causes.
8. Chinese cobra venom can alleviate the renal tissues of rats pathology damage that the acute and chronic nephropathy causes.
9. the Chinese cobra venom consumption is few, and effective range is large, and the effect of good treatment acute and chronic nephropathy is arranged from 1～3000 μ g/kg.Human dosage is about 1～1000 μ g/kg.
10. the multiple route of administration of Chinese cobra venom comprises that percutaneous drug delivery, oral, mouthful (nose) mucosa spraying and injection etc. are all effective.
Description of drawings
The invention will be further described below in conjunction with drawings and Examples:
Fig. 1 is the comparing result that affects of the Chinese cobra venom of physical modification rat acute nephropathy organ coefficient that glycerol is induced.
Fig. 2 is the comparing result that affects of the Chinese cobra venom of physical modification rat acute nephropathy 24h urine protein content that glycerol is induced.
Fig. 3 is the comparing result that affects of the Chinese cobra venom of physical modification rat acute nephropathy serum creatinine that glycerol is induced, blood urea nitrogen.
Fig. 4 is the comparing result that affects of the Chinese cobra venom of physical modification rat acute nephropathy blood T-CHOL that glycerol is induced.
Fig. 5 is the comparing result that affects of the Chinese cobra venom of physical modification rat acute nephropathy pathology damage that glycerol is induced.
Fig. 6 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy 24h urine protein that amycin is induced.
Fig. 7 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy serum cystatin C that amycin is induced.
Fig. 8 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy serum creatinine that amycin is induced, blood urea nitrogen.
Fig. 9 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy hyperlipidemia that amycin is induced.
Figure 10 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy hypoalbuminemia that amycin is induced.
Figure 11 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy serum electrolyte level that amycin is induced.
Figure 12 is the comparing result that affects of the damage that causes of the Chinese cobra venom of physical modification rat chronic nephropathy antioxidant ability of organism that amycin is induced and lipid peroxidation.
Figure 13 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy Pathological damage that amycin is induced.
Figure 14 is the comparing result that affects of the Chinese cobra venom of physical modification rat chronic nephropathy transmission electron microscope observing kidney injury that amycin is induced.
The specific embodiment
Below in conjunction with specific embodiment such scheme is described further.Should be understood that these embodiment are not limited to limit the scope of the invention for explanation the present invention.The implementation condition that adopts among the embodiment can be done further adjustment according to the condition of concrete experiment, and not marked implementation condition is generally the condition in the normal experiment.
The animal pharmacodynamic experiment of the Chinese cobra venom after the embodiment physical treatment
(1) the glycerol rat acute nephropathy experiment of inducing
After this experiment is prohibited water 24h with rat, copy the acute nephropathy model according to rat body weight 8ml/kg minute both sides intragluteal injection 50% glycerol, the Wistar rat is divided into 5 groups at random: normal saline matched group, model group, Chinese cobra venom heating small dose group (20 μ g/kg), middle dosage group (40 μ g/kg), heavy dose of group (80 μ g/kg).Chinese cobra venom behind the physical modification is induced in the test of rat acute nephropathy at treatment glycerol, and embodiment adopts gastric infusion, and dosage is at 1-3000 μ g/kg, once a day.
Behind the duplicating model 72h, adopt 4% chloral hydrate anesthesia rat, abdominal aortic blood, centrifuging and taking serum detects renal function index; Take out kidney and fix section statining with 4% formaldehyde; Collect rat and put to death front 24h urine, detect urine protein and routine urinalysis.Experimental result is as follows:
Fig. 1 is the impact of the Chinese cobra venom of physical modification rat acute nephropathy organ coefficient that glycerol is induced.Wherein * * * represents to compare p＜0.001 with the normal saline matched group; # represents to compare with model group, p＜0.05, and ### represents to compare p＜0.001 with model group.Compare with the normal saline matched group as seen from Figure 1, the rat kidney coefficient of 4 modeling groups all has obvious increase; And with model group relatively, the Kidney coefficients that gives the Chinese cobra venom treatment group of physical modification all has in various degree and reduces.
Fig. 2 is the impact of the Chinese cobra venom of physical modification rat acute nephropathy 24h urine protein that glycerol is induced.Wherein * * * represents to compare p＜0.001 with the normal saline matched group; # represents to compare with model group, p＜0.05, and ### represents to compare p＜0.001 with model group.Compare with the normal saline matched group as seen from Figure 2, the rat 24h urine protein of 4 modeling groups all is increased significantly trend; And compare with model group, the 24h urine protein that gives the Chinese cobra venom treatment group of physical modification all has in various degree reduction.
Fig. 3 is the Chinese cobra venom of physical modification rat acute nephropathy serum creatinine that glycerol is induced, the impact of blood urea nitrogen.Wherein compare with the normal saline matched group, * represents p＜0.05, and * * represents p＜0.01, and * * * represents p＜0.001.Compare with the normal saline matched group as seen from Figure 3, rat serum creatinine, the blood urea nitrogen of 4 modeling groups all are increased significantly trend; And compare with model group, the serum creatinine, the blood urea nitrogen that give the Chinese cobra venom treatment group of physical modification all have in various degree reduction.
Fig. 4 is the impact of the Chinese cobra venom of physical modification rat acute nephropathy blood T-CHOL that glycerol is induced.Wherein compare with the normal saline matched group, * represents p＜0.05, and * * represents p＜0.01.Compare with the normal saline matched group as seen from Figure 4, the rat serum T-CHOL of 4 modeling groups all has rising trend; And compare with model group, the blood T-CHOL that gives the Chinese cobra venom treatment group of physical modification all has in various degree reduction.
Fig. 5 is the impact of the Chinese cobra venom of physical modification rat acute nephropathy pathology damage that glycerol is induced.Can be seen that by Fig. 5 the glomerule sacculus of normal saline control rats is clear, capillary structure is normal in the bead, and the renal tubules profile is clear, and tube chamber is obvious, and epithelial cell has no pathological changes, has no cast, and a matter blood vessel is normal.The renal cells edema of model group rat, generation steatosis, disintegrate necrosis, part proximal convoluted tubule and Distal convoluted tubule coagulation necrosis, most renal tubules have red cell cast and protein cast to form, the tube chamber expansion; Glomerule is subject to the extruding of the renal tubules of edema dilatating and deformable, slightly distortion, and the part glomerule comes off, and overall quantity reduces.The Chinese cobra venom treatment group that gives physical modification obviously alleviates than model group renal tubular necrosis degree, and necrotic extent reduces, and the renal tubules edema changes and alleviates, and the epithelial cell steatosis is recovered to some extent, and red cell cast and protein cast quantity obviously reduce; Numbers of glomeruli increases, bead capillary structure compared with normal.
(2) the amycin rat chronic nephropathy experiment of inducing
This experiment adopts single dose tail vein injection 6mg/kg amycin to copy the rat chronic nephropathy, and this method will cause that adriamycin-induced nephropathy in Wistar rats syndrome (NS) also is called primary glomerular nephropathy, glomerule nephropathy, nephropathy etc.The main clinical characteristics of nephrotic syndrome (NS) is High-grade Proteinuria, also is the main origin of series of clinical manifestations: can cause hypoproteinemia such as High-grade Proteinuria, and then cause edema, hyperlipemia, infection and malnutrition etc.
This experiment is divided into 5 groups at random with the Wistar rat: normal saline matched group, model group, Chinese cobra venom heating small dose group (20 μ g/kg), middle dosage group (40 μ g/kg), heavy dose of group (80 μ g/kg).Chinese cobra venom behind the physical modification is induced in the test of rat acute nephropathy at treatment glycerol, and embodiment adopts gastric infusion, and dosage is at 1-3000 μ g/kg, once a day.
Respectively at 1 week before the modeling, after the modeling, 2 weeks, 3 weeks, 4 weeks rat being placed the metabolic cage of cleaning, leave and take the 24h urine, measure the 24h urine protein content with the Coomassie brilliant blue method.Duplicating model adopts 4% chloral hydrate anesthesia rat after 4 weeks, abdominal aortic blood, and centrifuging and taking serum detects renal function index, biochemical indicator; Take out kidney and fix section statining with 4% formaldehyde; Detect SOD in serum and kidney homogenate MDA level.Experimental result is as follows:
Fig. 6 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy 24h urine protein that amycin is induced.Wherein, ## represents to compare with model group, p＜0.01, and ### represents to compare p＜0.001 with model group.Can be seen that by Fig. 6 the rat chronic nephropathy that amycin is induced can cause rat urine albumen obviously to raise, and along with the development of the state of an illness constantly raises, but the Chinese cobra venom treatment group that gives physical modification there is in various degree reduction than model group.
Fig. 7 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy serum bladder chalone C that amycin is induced.Wherein compare with the normal saline matched group, * represents p＜0.05.Bladder chalone C is cysteine proteinase inhibitor C, and the serum bladder chalone C reflects the damage that renal function is early stage, slight more delicately than serum creatinine, blood urea nitrogen.Compare with the normal saline matched group as seen from Figure 7, the rat blood serum bladder chalone C of 4 modeling groups all has rising trend; Model group and its difference of normal saline matched group comparison have significant; And with respect to model group, the serum bladder chalone C that gives the Chinese cobra venom treatment group of physical modification all has in various degree reduction.
Fig. 8 is the Chinese cobra venom of physical modification rat chronic nephropathy serum creatinine that amycin is induced, the impact of blood urea nitrogen.Wherein compare with the normal saline matched group, * represents p＜0.05, and * * represents p＜0.01, and * * * represents p＜0.001; Compare with model group, # represents p＜0.05, and ## represents p＜0.01, and ### represents p＜0.001.Compare with the normal saline matched group as seen from Figure 8, rat serum creatinine, the blood urea nitrogen of 4 modeling groups all are increased significantly trend; And compare with model group, the serum creatinine, the blood urea nitrogen that give the Chinese cobra venom treatment group of physical modification all have in various degree reduction.
Fig. 9 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy hyperlipidemia that amycin is induced.Wherein compare with the normal saline matched group, * * * represents p＜0.001; Compare with model group, # represents p＜0.05, and ## represents p＜0.01, and ### represents p＜0.001.Compare with the normal saline matched group as seen from Figure 9, rat blood serum T-CHOL, the triglyceride of 4 modeling groups all are increased significantly trend; And compare with model group, the serum total cholesterol, the triglyceride that give the Chinese cobra venom treatment group of physical modification have in various degree reduction, wherein with Chinese cobra venom 40 μ g/kg treatment group best results.
Figure 10 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy hypoalbuminemia that amycin is induced.Wherein compare with the normal saline matched group, * * represents p＜0.01; * * represents p＜0.001; Compare with model group, ## represents p＜0.01, and ### represents p＜0.001.Compare with the normal saline matched group as seen from Figure 10, the rat serum albumin of 4 modeling groups reduces, and globulin raises, and the albumins/globulins ratio reduces; And compare with model group, the serum albumin that gives the Chinese cobra venom 40 μ g/kg treatment groups of physical modification obviously raises, and globulin reduces, and the albumins/globulins ratio raises, and difference has significant.
Figure 11 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy serum electrolyte level that amycin is induced.Wherein compare with the normal saline matched group, * represents p＜0.05, and * * * represents p＜0.001; Compare with model group, # represents p＜0.05, and ## represents p＜0.01, and ### represents p＜0.001.Can see that by Figure 11 the rat chronic nephropathy that amycin is induced can cause that serum sodium, chlorine, phosphonium ion content raise; And compare with model group, the serum sodium, chlorine, the phosphonium ion content that give the Chinese cobra venom treatment group of physical modification have in various degree reduction,
Figure 12 is the impact of the damage that causes of the Chinese cobra venom of physical modification rat chronic nephropathy antioxidant ability of organism that amycin is induced and lipid peroxidation.Wherein compare with the normal saline matched group, * represents p＜0.05; Compare with model group, # represents p＜0.05.SOD in serum has been widely used in estimating antioxidant ability of organism, and nephridial tissue MDA is used for estimating level of lipid.Can be seen by Figure 12, compare with the normal saline matched group that the rat blood serum SOD of 4 modeling groups reduces, nephridial tissue MDA raises; And compare with model group, the SOD in serum that gives the Chinese cobra venom treatment group of physical modification has in various degree rising, nephridial tissue MDA that in various degree reduction is arranged.
Figure 13 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy Pathological damage that amycin is induced.
Can be seen by Figure 13, the HE(hematoxylin-eosin) dyeing: normal saline control rats renal glomerulus mesangial region is without hypertrophy, deposit, the blood capillary clump has no hypertrophy, capillary wall has no and thickens, it is narrow that lumen of vessels has no, basement membrane has no pathological changes, and renal capsule is without the adhesion pathological changes, and the glomerule layer of structure is obvious; Model group and normal saline matched group are relatively, the crimp of model group rat kidney glomerule, glomerular capillary clump and cyst wall have the part adhesion, the renal tubules dilatancy, a large amount of protein casts occur, the gathering of having a liking for Yihong thing is arranged in the tube chamber, vacuolar degeneration appears in renal cells, the epithelial cell even the necrosis that have are withered and fallen, and have inflammatory cell to invade profit around matter and the kidney blood vessel between kidney; And the rat kidney Glomerular lesions that gives the Chinese cobra venom treatment group of physical modification makes moderate progress, and the tamm-Horsfall protein cast is more rare, and a matter inflammatory cell is invaded profit and reduced, and its pathological change obviously alleviates than model group.
PAS (periodic acid snow husband) dyeing: model group and normal saline matched group compare, and model group rat kidney glomerular basement membrane obviously thickens, and the blood capillary ball destroys atrophy, and renal tubules is seen protein cast; And the Chinese cobra venom treatment group and the model group that give physical modification compare, and rat kidney glomerular basement membrane thickening situation makes moderate progress, and the tamm-Horsfall protein cast reduces, and its pathological change obviously alleviates than model group.
The Masson trichrome stain: model group and normal saline matched group are relatively, model group rat kidney glomerular capillary plex structure is destroyed to some extent, the glomerular capsule wall thickening, and glomerular capillary clump and cyst wall have the part adhesion, between matter have the phenomenon of Collagen Proliferation, inflammatory cell to invade profit obviously; And the Chinese cobra venom treatment group and the model group that give physical modification compare, and Glomerular lesions makes moderate progress, and cyst wall has no and thickens, and the tamm-Horsfall protein cast is more rare, and a matter inflammatory cell is invaded profit and reduced, and its pathological change obviously alleviates than model group.
Figure 14 is the impact of the Chinese cobra venom of physical modification rat chronic nephropathy transmission electron microscope observing kidney injury that amycin is induced.Can be seen by Figure 14, normal saline control rats glomerular basement membrane (GBM) pucker-free, podocytic process is clear; Model group rat GBM shrinkage is obvious, and podocytic process extensively merges; And the Chinese cobra venom 20 μ g/kg treatment group rat podocytic processes that give physical modification extensively disappear, the collagen fiber showed increased, give Chinese cobra venom 40 μ g/kg, the 80 μ g/kg treatment group rat GBM pucker-frees of physical modification, podocytic process fusion situation alleviates.
Can find out from above-mentioned test:
Chinese cobra venom can reduce the rat 24h urine protein content rising that the acute and chronic nephropathy causes.Chinese cobra venom can reduce Renal Function in Rats obstacle index-creatinine that the acute and chronic nephropathy causes, the rising of blood urea nitrogen.Chinese cobra venom can alleviate the symptom of the rat chronic nephropathy hyperlipidemia that amycin induces.Chinese cobra venom can improve the rat chronic nephropathy hypoproteinemia that amycin is induced.Chinese cobra venom can improve the rat chronic nephropathy serum electrolyte disorder that amycin is induced.Chinese cobra venom can strengthen the rat chronic nephropathy antioxidant ability of organism that amycin is induced, and alleviates the damage that lipid peroxidation causes.Chinese cobra venom can alleviate the renal tissues of rats pathology damage that the acute and chronic nephropathy causes.
Above-mentioned example only is explanation technical conceive of the present invention and characteristics, and its purpose is to allow the people who is familiar with technique can understand content of the present invention and according to this enforcement, can not limit protection scope of the present invention with this.All equivalent transformations that spirit is done according to the present invention or modification all should be encompassed within protection scope of the present invention.
Claims (6)
1. the purposes of the Chinese cobra venom behind the physical modification in the medicine of the acute and chronic nephropathy of preparation treatment.
2. according to claim 1 purposes is characterized in that the Chinese cobra venom behind the described physical modification obtains Chinese cobra venom after with the degeneration of deionized water dissolving post-heating and renaturation; Heating and temperature control is controlled at 1min～300min heat time heating time between 50～100 ℃.
3. according to claim 1 purposes is characterized in that also comprising in the described medicine Thailand's Naja and other cobra-venom behind the physical modification.
4. according to claim 1 purposes is characterized in that also comprising unmodified Chinese cobra venom in the described medicine or is selected from a kind of of the neurotoxin, cardiotoxin and the cobra-venom factor that exist in the Chinese cobra venom.
5. according to claim 1 purposes is characterized in that also comprising in the described medicine compound preparation that a kind of and other medicines of the neurotoxin, cardiotoxin and the cobra-venom factor that exist in modification and unmodified Chinese cobra venom or the cobra-venom form.
6. according to claim 1 purposes is characterized in that the form of administration of described medicine is selected from oral instant medicine film, oral liquid, tablet, capsule, spray, injection and transdermal absorption formulation.
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| WO2016145256A1 (en) * | 2015-03-10 | 2016-09-15 | Reid Paul F | Use of components of cobra venom for treatment of chronic kidney disease |
| WO2021042645A1 (en) * | 2019-09-03 | 2021-03-11 | 祁展楷 | Application of cobra neurotoxin peptide molecule in treating nephritis proteinuria |
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| CN103070887A (en) * | 2013-01-30 | 2013-05-01 | 苏州人本药业有限公司 | Modified snake venom gelling agent and preparation method thereof |
| CN103751766A (en) * | 2013-12-06 | 2014-04-30 | 苏州人本药业有限公司 | Use of cobra venom cardiotoxins in preparation of drug for diminishing inflammation, easing pain and resisting arthritis |
| WO2016145256A1 (en) * | 2015-03-10 | 2016-09-15 | Reid Paul F | Use of components of cobra venom for treatment of chronic kidney disease |
| WO2021042645A1 (en) * | 2019-09-03 | 2021-03-11 | 祁展楷 | Application of cobra neurotoxin peptide molecule in treating nephritis proteinuria |
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