CN105412410A - Traditional Chinese medicine preparation for preventing and treating radiographic contrast nephropathy - Google Patents

Traditional Chinese medicine preparation for preventing and treating radiographic contrast nephropathy Download PDF

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CN105412410A
CN105412410A CN201510955057.1A CN201510955057A CN105412410A CN 105412410 A CN105412410 A CN 105412410A CN 201510955057 A CN201510955057 A CN 201510955057A CN 105412410 A CN105412410 A CN 105412410A
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radix
chinese medicine
rhizoma
medicine preparation
blood
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杨桂望
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Qingdao Huaren Technology Incubator Co Ltd
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Abstract

The invention provides a traditional Chinese medicine preparation for preventing and treating radiographic contrast nephropathy. The Traditional Chinese medicine preparation is prepared from crude drugs of poria cocos, grifola, semen plantaginis, rhizoma alismatis, herba lycopi, cassia twig, platycodon grandiflorum, raw atractylodes, the rhizome of chuanxiong, the root of red-rooted salvia, caulis spatholobi, pseudo-ginseng powder, radix paeoniae alba, moutan bark, raw rhubarb, raw radix astragalis, codonopsis pilosula, radix sophorae flavescentis, oldenlandia diffusa, licorice roots northwest origin and medicinal cyathula root. The preparation provided by the invention adopts an effective and safe therapy of traditional Chinese medicine, has excellent effect in the aspect of preventing radiographic contrast nephropathy, and has the advantages of low price, convenience in use and small toxic and side effects.

Description

A kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy
Technical field
The present invention relates to technical field of Chinese medicine, particularly relate to a kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy.
Background technology
Radiographic contrast nephropathy (RCIN) is the 3rd cause of disease causing acute renal failure at present.After it is defined as injection of contrast medium, in 48 hours, the absolute value of serum creatinine raises 0.5mg/dL or relative value and raises 25%.In population, the incidence rate of radiographic contrast nephropathy is not high, lower than 1%; But high-risk group, as patients such as renal insufficiency, diabetes, dehydration, hypertension, liver cirrhosis, congestive heart failure, nephrotic syndrome, multiple myelomas, the sickness rate of RCIN then obviously raises.In addition, take the medicine that can damage renal function, as angiotensin-convertion enzyme inhibitor, NSAID (non-steroidal anti-inflammatory drug), heavy dose of contrast agent and ionizing hypertonic contrast media etc., also can increase the incidence rate of RCIN.Update shows, and RCIN exists obvious dependency with the rising of relative number of patients and relative death toll in recent years.RCIN, once occur, can cause severe complication (as septicemia, hemorrhage, respiratory failure etc.), even directly threaten patient vitals.Therefore, the generation of RCIN is prevented to become the focus of concern.Summarize RCIN pathogenesis herein, and inquire into emphatically the effect of related drugs in day CIN prevents.
Modern medicine study, its pathogenesis has following 2 main causes:
1) hemodynamic responses causes kidney hypoxic damage:
It is the first of short duration expansion of renal blood vessels about 20 minutes that the Pathophysiology of contrast agent on renal hemodynamic affects main manifestations, then occurs Renal vascular spasmodic contraction, the time reach 4 hours even longer.This renal blood vessels changes and bulb reflect lack of proper care and vasodilation-vasoconstriction hormone proportional imbalance relevant.Its result causes renal blood flow to show on the one hand and steals blood effect, and namely blood flow is from the renal medulla field flow orientation renal cortex of relatively hypoxia, thus increases the weight of renal medulla ischemia, reduces oxygen and supplies; Contrast agent is drained from tubular secretion on the other hand, and renal medulla metabolism amount is increased relatively, and oxygen demand increases, and increases the weight of the degree of oxygen deficiency of renal medulla.Finally because renal ischemic hypoxic damage causes apoptosis or necrosis, there is infringement in renal function.
2) cytotoxic effect
Contrast agent itself can cause the increase of oxygen-derived free radicals (OFR) and then produce direct toxic action to kidney.The increase of contrast agent induction oxygen-derived free radicals is to ischemia injury and cause Ink vessel transfusing hyperosmosis relevant.In addition, research finds that contrast agent also reduces the activity of renal cortex anticatalase and superoxide dismutase, and the generation of OFR also can be caused to increase.Hypertonic contrast media also can cause the destruction of epithelial cell integrity, the obstruction of renal tubules and immunological response net thereof simultaneously, and above-mentioned factor all directly can produce the toxic action of kidney cell.
How could prevent and treat the infringement of contrast agent to kidney, modern medicine study proposes, and uses the medicine increasing contrast agent excretion, the medicine using blood vessel dilating, uses antioxidative medicine etc., have preventive effect to RCIN.
One, general adopt be aquation medicine and use diuretic to promote its metabolism.
1) aquation medicine
Saline chemical medicine thing (mainly referring to the aqueous solution of sodium salt) has been applied to prevention RCIN since producing appreciable results, as the goldstandard preventing RCIN from the eighties in 20th century.Its mechanism is the concentration diluting contrast agent in blood on the one hand, and diuresis also promotes the excretion of contrast agent on the other hand.Nearest research mainly concentrates in the improvement of hydrating fluid.The larger randomized clinical research that Mueller etc. carry out, compare the effect of isotonic saline solution and half isotonic saline solutionization prevention RCIN, found that, the incidence rate of isotonic saline solution group RCIN obviously lower (0.7%), and the incidence rate of half isotonic saline solution group RCIN is 2%, RCIN is more effective for the prevention of prompting isotonic saline solutionization.119 routine patients are then divided into two groups by Merten etc. at random, and one group of patient accepts isotonic NaHCO 3aquation (3ml/ (kgh), 59 examples), another group, patient accepts isotonic NaCl aquation (3ml (kgh, 60 examples), aquation in first 1 hour of injection of contrast medium, and after continuing to contrast agent application 6 hours, result NaCl aquation group RCIN incidence rate is 13.6%, and NaHCO 3aquation group RCIN incidence rate is, 1.7%, show NaHCO.The potential applicability in clinical practice of aquation, on the other hand, NaHCO 3the patient that aquation controls for capacity required is more useful, but its definite curative effect is still needed, the Randomized multicentre trial of certain sample size confirms further.
2) diuretic
Diuretic can promote (comprising furosemide, mannitol) excretion of contrast agent in theory, reduces storage in its body and stays the time, thus reduce the generation of RCIN.The action effect to diuretic prevention RCIN such as Riehard is studied, accept saline solution (28 example), saline solution and mannitol (25 example), saline solution before 78 routine chronic renal insufficiency patient injection of contrast medium respectively at random and reflect plug rice (25 example) process, the incidence rate of three groups of patient RCIN is followed successively by 11%, 28% and 40% as a result, diuretic effectively can not reduce the generation of RCIN, even has the danger increasing the weight of RCIN.Thus, at present clinically not using the routine administration of diuretic as prevention RCIN.
Two, at present in the drug use of the blood vessel dilating of prevention RCIN, using is calcium antagonist, Endothelin receptor antagonist, atrial natriuretic peptide, prostaglandin E, adenosine receptor antagonists etc. comparatively widely.
1) calcium antagonist
Calcium antagonist can reverse the change of Acute Hemodynamic that contrast agent causes, and can prevent the vasoconstriction that gland former times causes, in suppression Mouse Kidney tubule cells calcium increase and reduce the generation of apoptosis, also can suppress the minimizing that NO synthesizes simultaneously.Seyss etc. have studied the effect of calcium antagonist prevention RCIN, 3rd day glomerular filtration rate (GFR) the obviously decline (27%) of result display matched group patient after contrast agent application, and the GFR of calcium antagonist group patient keeps previous level, and the excretion of urine protein also obviously improves.This is that display calcium antagonist prevention RCIN unique at present effectively studies.Regrettably, the research only has 35 routine patients to participate in, and studies evidence fully and considers the toxic and side effects (as myocardiac inhibition, dizzy headache etc.) of calcium antagonist, not yet recommend calcium antagonist to use as the prevention of RCIN at present owing to lacking.
2) Endothelin receptor antagonist (ET a)
ET aseveral is vasoconstrictive factors, in the generating process of radiographic contrast nephropathy, has played certain effect.Block ET aeffect can prevent the generation of RCIN? a clinical studies show including 58 cases in, ET, the incidence rate of receptor blocking agent group RCIN reaches 56%, and the incidence rate of placebo group RCIN is only 29%, has negated ET athe prevention of receptor blocking agent in RCIN occurs is done.
3) atrial natriuretic peptide (ANP)
ANP is a kind of polypeptide with the effect of sharp sodium diuresis expander of myocardial cell secretion.Prospective multicenter randomized controlled evaluation in clinical ANP prevents the effect of RCIN, 247 first 30 minutes of routine patient's contrast agent application accept placebo or each dosage (0.01,0.05 or 0.1mg/ (kgmin) ANP) at random, and after continuing to contrast agent application 30 minutes.All patients accept normal hydration simultaneously.Found that, the incidence rate of placebo group RCIN is 19%, ANP001mg/ (kgmin) group be 23%, ANP0.05mg/ (kgmin) group be 23%, ANP0.1mg/ (kgmin) group is 25%.Weisberg etc. also find that ANP promotes the generation of RCIN.As can be seen here, ANP can not prevent the generation of RCIN.
4) prostaglandin E 1(PGE 1)
PGE 1renal blood flow and blood distribution can be kept, the electrolytical excretion in equilibrium water, there is the effect that potential prevention RCIN occurs.A clinical research is to PGE 1the effect of prevention radiographic contrast nephropathy is assessed, and 30 routine patients accept placebo or each dosage [10,20 or 40ng/ (kgmin)] PGE at random 1.Within after injection of contrast medium 48 hours, 08 routine patient carries out the measurement that serum flesh joins value to wherein, and four groups of patients serum's fleshes are joined value and are respectively 0.72,0.30,0 as a result, and 12 and 0.29mg/dl; Each PGE 1group serum flesh is liquor-saturated is starkly lower than placebo group (P < 0.05).In diabetics, the liquor-saturated value of serum flesh of latter three groups is respectively 0.53,0.07 and 0.66mg/dl (P < 0.05).Prompting, PGE 1the serum flesh that obviously can reduce patient's (comprising diabetics) joins value, and best with 20ng/ (kgmjn) dosage.But to study each group of case load relatively less due to this, its result of study needs to be confirmed further.
5) adenosine receptor antagonists
Contrast agent causes the dynamic (dynamical) change of renal blood flow by adenosine mediation.Adenosine is via two kinds of receptor (A 1-R and A 2-R) play a role, A 1-R suppresses the activity of adenyl cyclase and causes renal cortex vasoconstriction, A 2-R then the activity of activated adenyl cyclase and nephrectasia blood vessel.Theophylline is non-specific adenosine receptor antagonists, and optionally A 1-R antagonist DPCPX (8-cyclopenta-1,3-dipropyl xanthine), the effect of all relax by change renal blood vessels contracting and performance prevention RCIN.In a RCIN experiment mice animal model, before injection of contrast medium, after theophylline or DPCPX pretreatment, the minimizing of renal blood flow (RBF) and the minimizing of GFR all obviously improve.A meta analyzes and has carried out comprehensive assessment to the effect of theophylline prevention RCIN, (wherein 4 show that theophylline can prevent the generation of RGIN to analyze 7 clinical study results altogether, 3 display theophylline can not reduce the generation of RCIN), finally reach a conclusion: the renal function that prophylactic use theophylline can prevent contrast agent from causing reduces.In view of this, adenosine receptor antagonists can be tried out in clinical.
Three, the anti-oxidation medicine of Clinical practice is generally N-acetylcystein (NAC), ascorbic acid (Vc)
1) N-acetylcystein (NAC)
NAC is the derivant of cysteine, namely on the nitrogen-atoms of cysteine, is loaded with a phthalidyl group.Once enter in body, the very fast deacidification base of NAC, metabolism is cysteine, skin propylhomoserin, inorganic sulphide etc., and main metabolites cysteine wherein can in order to synthesizing glutathion in liver, glutathion is a very strong antioxidant, and namely NAC plays antioxidation by glutathion.NAC also can chemical bond NO to stablize its structure, the expression of NO synzyme can be increased thus promote the synthesis of NO, can Angiotensin-converting enzyme inhibition activity and reduce the generation of angiotensin.By above-mentioned mechanism, NAC can play nephrectasia blood vessel, maintain the effect of renal hemodynamic.The first time such as Tebel confirms that NAC prevents the effectiveness of RCIN.In the research of this double blind control, the patient of 83 customary Enhanced CT accepts oral NAC or placebo at random, and all patients carry out salt aquation simultaneously.As a result, the incidence rate of NAC group RCIN is 2%, and placebo group be 21%, NAC group significantly lower than placebo group (P < 0.05), the confirmation such as Huber in addition, intravenous injection NAC also can reduce the incidence rate of RCIN.A rear route of administration is mainly used in Emergency Patients.But, the research of Gomes etc. then obtains different conclusions, random oral NAC (each 600mg of 156 routine patient, day/2 times) or placebo, result, the incidence rate of NAC group RCIN is 10.4%, matched group be then 10.1%, two groups without significant difference (P > 0.05).Above-mentioned inconsistent the possibility of result is inconsistent relevant with the objective metric including research in, the standard that Gomes etc. include study subject in is serum creatinine level >=106 μm ol/L or creatinine clearance rate stamen 50mUmin or diabetics, and Tebel etc. do not make particular/special requirement to the study subject included in.Although, still can not determine that NAC prevents RCIN whether effective at present, because NAC is cheap, easy to use, toxic and side effects is little, recommend the routine administration that it can be used as prevention RCIN, with the coupling of salt aquation.
2) ascorbic acid (Vc)
Ascorbic acid is potent water-soluble antioxidant, can effectively remove a large amount of oxygen-derived free radicals.A nearest randomized controlled research to its can effectively prevent RCIN done assess four; 231 routine patients take ascorbic acid (13 example) or placebo (118 example) at random; the incidence rate of result ascorbic acid group RCIN is 9% and placebo group is 20%; tentatively show the effectiveness of ascorbic acid prevention RCIN; but the apoptotic impact also needing larger scale clinical taurine Hizou etc. to have studied taurine (taurine) to cause high osmosis ionizing contrast agent, using ONA degraded as apoptotic mark.Found that; high osmosis ionizing contrast agent can cause the nephrocyte ONA of 49.5% to degrade, and after taurine process, the degraded of nephrocyte ONA is kept to 39.4%; show that it may have the effect of prevention RCIN generation, its value for clinical application waits further confirmation.
Although RCIN is clinical FAQs, its prevention Intervention Strategy should be paid much attention to.The medicine of prevention RCIN is a lot, but majority is proved and there is no positive effect.Chinese medicine treats the generation of primary disease at present, has done certain research in theory, and has carried out the clinical research of certain limit, proves that its clinical efficacy is fine.Chinese medicine primary disease, has cheap, easy to use, the advantage that toxic and side effects is little, therefore at the routine administration of part one line city quilt as prevention RCIN.The invention provides the Chinese medicine preparation of a kind of novel control contrast agent god soldier, by developing the clinical application made new advances, preventing the generation of RCIN timely and effectively.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy, confirmed by clinical research and experimentation, invention formulation adopts effective, safe TCM Therapy, excellent results is had in prevention radiographic contrast nephropathy, have cheap, easy to use, the advantage that toxic and side effects is little.
The invention provides a kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy, its crude drug comprises Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan, Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Glycyrrhizae and Radix Cyathulae.
Wherein, in described Chinese medicine preparation, the weight of each crude drug is respectively Poria 20g ~ 30g, Polyporus 10g ~ 20g, Semen Plantaginis 15g ~ 25g, Rhizoma Alismatis 25g ~ 35g, Herba Lycopi 10g ~ 20g, Ramulus Cinnamomi 5g ~ 15g, Radix Platycodonis 10g ~ 20g, Rhizoma Atractylodis Macrocephalae 20g ~ 30g, Rhizoma Chuanxiong 15g ~ 25g, Radix Salviae Miltiorrhizae 20g ~ 30g, Caulis Spatholobi 20g ~ 30g, Radix Notoginseng powder 15g ~ 25g, Radix Paeoniae Alba 20g ~ 30g, Cortex Moutan 15g ~ 25g, Radix Et Rhizoma Rhei 20g ~ 30g, Radix Astragali 35g ~ 45g, Radix Codonopsis 25g ~ 35g, Radix Sophorae Flavescentis 10g ~ 20g, Herba Hedyotidis Diffusae 15g ~ 25g, Radix Glycyrrhizae 10g ~ 20g and Radix Cyathulae 20g ~ 30g.
Wherein, in described Chinese medicine preparation, the weight of each crude drug is respectively Poria 23g ~ 27g, Polyporus 13g ~ 17g, Semen Plantaginis 18g ~ 22g, Rhizoma Alismatis 28g ~ 32g, Herba Lycopi 13g ~ 17g, Ramulus Cinnamomi 8g ~ 12g, Radix Platycodonis 13g ~ 17g, Rhizoma Atractylodis Macrocephalae 23g ~ 27g, Rhizoma Chuanxiong 18g ~ 22g, Radix Salviae Miltiorrhizae 23g ~ 27g, Caulis Spatholobi 23g ~ 27g, Radix Notoginseng powder 18g ~ 22g, Radix Paeoniae Alba 23g ~ 27g, Cortex Moutan 18g ~ 22g, Radix Et Rhizoma Rhei 23g ~ 27g, Radix Astragali 38g ~ 42g, Radix Codonopsis 28g ~ 32g, Radix Sophorae Flavescentis 13g ~ 17g, Herba Hedyotidis Diffusae 18g ~ 22g, Radix Glycyrrhizae 13g ~ 17g and Radix Cyathulae 23g ~ 27g.
Wherein, in described Chinese medicine preparation, the weight of each crude drug is respectively Poria 25g, Polyporus 15g, Semen Plantaginis 20g, Rhizoma Alismatis 30g, Herba Lycopi 15g, Ramulus Cinnamomi 10g, Radix Platycodonis 15g, Rhizoma Atractylodis Macrocephalae 25g, Rhizoma Chuanxiong 20g, Radix Salviae Miltiorrhizae 25g, Caulis Spatholobi 25g, Radix Notoginseng powder 20g, Radix Paeoniae Alba 25g, Cortex Moutan 20g, Radix Et Rhizoma Rhei 25g, Radix Astragali 40g, Radix Codonopsis 30g, Radix Sophorae Flavescentis 15g, Herba Hedyotidis Diffusae 20g, Radix Glycyrrhizae 15g and Radix Cyathulae 25g.
Wherein, described Chinese medicine preparation routinely technique add adjuvant and make tablet, capsule, granule, drop pill, micropill, dispersible tablet, oral cavity disintegration tablet, pill or oral liquid.
Wherein, the dosage form of described Chinese medicine is oral liquid.
Present invention also offers the preparation method that above-mentioned Chinese medicine preparation is prepared into oral liquid, it comprises:
The first step, each crude drug is taken by above-mentioned weight, first rinse twice with clear water, residual to remove dust, pesticide etc., all put into decocting container, add the water of 2 ~ 4 times of crude drug quality sum, after boiled with big fire, be transferred to 1 hour ~ 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70 ~ 80% to alcohol volume, dark place leaves standstill 20 ~ 36h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders;
Second step, get sucrose join relative to sucrose weight 30% ~ 50% distilled water in, heating sucrose is dissolved completely, make simple syrup, filter, for subsequent use;
3rd step, the micropowders that the first step of getting 30% according to mass percent obtains, 20% second step obtain simple syrup and 50% water add successively in Agitation Tank, stir 20 ~ 40min, filter, filtrate is placed in high pressure homogenizer, 65 ~ 75 DEG C, carry out twice homogenization under 20 ~ 40MPa condition, obtain homogenizing fluid;
4th step, the homogenizing fluid filling and sealing the 3rd step obtained, in the vial of cleaning, then uses flowing steam sterilizing 30min under 100 DEG C of conditions, and namely hot water injection, pouring obtain this oral liquid after doing.
The present invention also provides a kind of oral liquid preventing and treating radiographic contrast nephropathy, and its crude drug comprises Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan, Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Glycyrrhizae and Radix Cyathulae;
In described oral liquid, the weight of each crude drug is respectively Poria 20g ~ 30g, Polyporus 10g ~ 20g, Semen Plantaginis 15g ~ 25g, Rhizoma Alismatis 25g ~ 35g, Herba Lycopi 10g ~ 20g, Ramulus Cinnamomi 5g ~ 15g, Radix Platycodonis 10g ~ 20g, Rhizoma Atractylodis Macrocephalae 20g ~ 30g, Rhizoma Chuanxiong 15g ~ 25g, Radix Salviae Miltiorrhizae 20g ~ 30g, Caulis Spatholobi 20g ~ 30g, Radix Notoginseng powder 15g ~ 25g, Radix Paeoniae Alba 20g ~ 30g, Cortex Moutan 15g ~ 25g, Radix Et Rhizoma Rhei 20g ~ 30g, Radix Astragali 35g ~ 45g, Radix Codonopsis 25g ~ 35g, Radix Sophorae Flavescentis 10g ~ 20g, Herba Hedyotidis Diffusae 15g ~ 25g, Radix Glycyrrhizae 10g ~ 20g and Radix Cyathulae 20g ~ 30g.
Useful technique effect
The invention provides a kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy, confirmed by clinical research and experimentation, invention formulation adopts effective, safe TCM Therapy, in prevention radiographic contrast nephropathy, have excellent results, have cheap, easy to use, the advantage that toxic and side effects is little.
Detailed description of the invention
The invention provides a kind of Chinese medicine preparation preventing and treating radiographic contrast nephropathy, its crude drug comprises Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan, Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Glycyrrhizae and Radix Cyathulae.
Further preferably, described Chinese medicine preparation is only prepared from by above-mentioned raw materials medicine.
The treatment of radiographic contrast nephropathy is divided into diuresis, blood vessel dilating, antioxidation three main thought at doctor trained in Western medicine modern study, Chinese medicine is without the record of this disease, but along with the development of medical science, therapy of combining Chinese and Western medicine primary disease or the simple treatment by Chinese herbs primary disease that uses achieve certain curative effect.For pathogenesis and the Therapeutic Principle of primary disease, invention formulation is on the basis of clinical efficacy, and by selected medicine, the theory analysis of prescription compatibility and relevant experimentation, finally determine invention formulation, and its prescription thinking is as follows:
One, diuresis
Radiographic contrast nephropathy, one of the main reasons is exactly that contrast agent accumulates at kidney, cannot drain, Chinese medicine effect has identical effect with Western medicine diuretic, selected by prescription, select following medicine Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, these medicines wherein Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis promoting diuresis with drugs of tasteless flavour is with diuresis, Ramulus Cinnamomi activates yang diuresis, lung qi dispersing gas opened by Radix Platycodonis, rise and put forward the meaning that lid taken off by kettle, play diuresis, Rhizoma Atractylodis Macrocephalae, Poria compatibility plays invigorating spleen for diuresis effect, Herba Lycopi can activating blood and promoting diuresis, because contrast-medium injection enters blood, therefore from learning diuretic, particularly important.
Two, blood vessel dilating
By the research of doctor trained in Western medicine for radiographic contrast nephropathy, blood vessel dilating is also Conventional treatment regimens, invention formulation select experimentation clear and definite can blood vessel dilating, the particularly medicine of renal blood vessels, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan are to play vasodilative effect, wherein Rhizoma Chuanxiong is walked to alter, sensible whole body, Caulis Spatholobi can dampness removing, coordinates diuretic, plays wet effect of better sharp blood vessels, because contrast agent accumulates at kidney, easily cause local blood stasis, therefore Radix Notoginseng powder, Radix Paeoniae Alba blood circulation promoting and blood stasis dispelling, play good effect.
Three, antioxidation
Modern pharmacology is studied, and Chinese medicine Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis have good scavenging free radicals, antioxidation.In conjunction with theory of Chinese medical science analysis, this drug regimen is except antioxidation, also Rhizoma Atractylodis Macrocephalae, Poria invigorating spleen to remove dampness can be coordinated, because free radical or oxidation mechanism, the traditional Chinese medical science thinks pyretic toxicity, with Radix Et Rhizoma Rhei, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Salviae Miltiorrhizae, Cortex Moutan, Radix Glycyrrhizae, there is clearing away heat and cooling blood pathogenic fire purging effect, therefore there is the effect of well verification treatment.
In addition, add the effect that Radix Cyathulae a herb can play invigorating the liver and kidney, improve renal function, the traditional Chinese medical science thinks that Radix Cyathulae can also be drawn hot descending, diuretic.
Comprehensive analysis invention formulation, its prescription compatibility is simplified, and for primary disease Etiological pathogenesis prescription medicine, therefore can play good therapeutical effect.
In described Chinese medicine preparation, the weight of each crude drug is respectively Poria 20g ~ 30g, Polyporus 10g ~ 20g, Semen Plantaginis 15g ~ 25g, Rhizoma Alismatis 25g ~ 35g, Herba Lycopi 10g ~ 20g, Ramulus Cinnamomi 5g ~ 15g, Radix Platycodonis 10g ~ 20g, Rhizoma Atractylodis Macrocephalae 20g ~ 30g, Rhizoma Chuanxiong 15g ~ 25g, Radix Salviae Miltiorrhizae 20g ~ 30g, Caulis Spatholobi 20g ~ 30g, Radix Notoginseng powder 15g ~ 25g, Radix Paeoniae Alba 20g ~ 30g, Cortex Moutan 15g ~ 25g, Radix Et Rhizoma Rhei 20g ~ 30g, Radix Astragali 35g ~ 45g, Radix Codonopsis 25g ~ 35g, Radix Sophorae Flavescentis 10g ~ 20g, Herba Hedyotidis Diffusae 15g ~ 25g, Radix Glycyrrhizae 10g ~ 20g and Radix Cyathulae 20g ~ 30g.
Further preferably, in described Chinese medicine preparation, the weight of each crude drug is respectively Poria 23g ~ 27g, Polyporus 13g ~ 17g, Semen Plantaginis 18g ~ 22g, Rhizoma Alismatis 28g ~ 32g, Herba Lycopi 13g ~ 17g, Ramulus Cinnamomi 8g ~ 12g, Radix Platycodonis 13g ~ 17g, Rhizoma Atractylodis Macrocephalae 23g ~ 27g, Rhizoma Chuanxiong 18g ~ 22g, Radix Salviae Miltiorrhizae 23g ~ 27g, Caulis Spatholobi 23g ~ 27g, Radix Notoginseng powder 18g ~ 22g, Radix Paeoniae Alba 23g ~ 27g, Cortex Moutan 18g ~ 22g, Radix Et Rhizoma Rhei 23g ~ 27g, Radix Astragali 38g ~ 42g, Radix Codonopsis 28g ~ 32g, Radix Sophorae Flavescentis 13g ~ 17g, Herba Hedyotidis Diffusae 18g ~ 22g, Radix Glycyrrhizae 13g ~ 17g and Radix Cyathulae 23g ~ 27g.
Most preferably, in described Chinese medicine preparation, the weight of each crude drug is respectively Poria 25g, Polyporus 15g, Semen Plantaginis 20g, Rhizoma Alismatis 30g, Herba Lycopi 15g, Ramulus Cinnamomi 10g, Radix Platycodonis 15g, Rhizoma Atractylodis Macrocephalae 25g, Rhizoma Chuanxiong 20g, Radix Salviae Miltiorrhizae 25g, Caulis Spatholobi 25g, Radix Notoginseng powder 20g, Radix Paeoniae Alba 25g, Cortex Moutan 20g, Radix Et Rhizoma Rhei 25g, Radix Astragali 40g, Radix Codonopsis 30g, Radix Sophorae Flavescentis 15g, Herba Hedyotidis Diffusae 20g, Radix Glycyrrhizae 15g and Radix Cyathulae 25g.
Described Chinese medicine preparation routinely technique adds adjuvant and makes tablet, capsule, granule, drop pill, micropill, dispersible tablet, oral cavity disintegration tablet, pill or oral liquid, and described adjuvant comprises one or more in solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent, lubricant and substrate.
Further preferably, the dosage form of described Chinese medicine is oral liquid.
Present invention also offers the preparation method that above-mentioned Chinese medicine preparation is prepared into oral liquid, it comprises:
The first step, each crude drug is taken by above-mentioned weight, first rinse twice with clear water, residual to remove dust, pesticide etc., all put into decocting container, add the water of 2 ~ 4 times of crude drug quality sum, after boiled with big fire, be transferred to 1 hour ~ 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70 ~ 80% to alcohol volume, dark place leaves standstill 20 ~ 36h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders;
Second step, get sucrose join relative to sucrose weight 30% ~ 50% distilled water in, heating sucrose is dissolved completely, make simple syrup, filter, for subsequent use;
3rd step, the micropowders that the first step of getting 30% according to mass percent obtains, 20% second step obtain simple syrup and 50% water add successively in Agitation Tank, stir 20 ~ 40min, filter, filtrate is placed in high pressure homogenizer, 65 ~ 75 DEG C, carry out twice homogenization under 20 ~ 40MPa condition, obtain homogenizing fluid;
4th step, the homogenizing fluid filling and sealing the 3rd step obtained, in the vial of cleaning, then uses flowing steam sterilizing 30min under 100 DEG C of conditions, and namely hot water injection, pouring obtain this oral liquid after doing.
Each crude drug pharmacology is as follows:
Poria: sweet in the mouth, light, property is put down, and enters spleen, lung, bladder, heart channel, has the effect of eliminating dampness and diuresis, spleen invigorating mind calming, be mainly used in the edema of retention of water-damp, dysuria; The pyretic stranguria of damp-heat accumulation, the card such as anorexia and loose stool, phlegm retention stagnation, epilepsy of stagnation of dampness due to deficiency of the spleen.
Polyporus: sweet in the mouth, light, property is put down, and enters kidney, urinary bladder channel, has the effect of promoting diuresis to eliminate damp pathogen, be mainly used in the edema of retention of water-damp, dysuria, and the having loose bowels of stagnation of dampness due to deficiency of the spleen, vomits; The card such as leucorrhea, nebulousurine of damp invasion of lower energizer.
Semen Plantaginis: sweet in the mouth, cold in nature, enter liver, kidney, small intestinal, lung, urinary bladder channel, have clearing away heat and promoting diuresis, expelling phlegm for arresting cough, the effect of improving eyesight, the cough being mainly used in wind-heat invading the lung is spat; The conjunctival congestion and swelling pain of liver-fire rising; The damp and hot dysuria accumulate in the part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels, accumulation of heat in the urinary bladder, the cards such as jaundice due to damp-heat.
Rhizoma Alismatis: sweet in the mouth, light, cold in nature, enters kidney, urinary bladder channel, has promoting diuresis to eliminate damp pathogen, purging heat and treating stranguria, the lung that clears away heart-fire, rushes down the effect of kidney fire, is mainly used in insufficiency of the spleen retention of water-damp, the wet hydrosarca of spreading unchecked of water; The tired resistance of the heresy of diseases caused by retention of fluid phlegm-damp, what cause that clear YANG failing to ascend voiced sound do not fall is dizzy; The dysuria of damp invasion of lower energizer, red short puckery pain, and the card such as jaundice due to damp-heat.
Herba Lycopi: bitter in the mouth, pungent, slightly warm in nature, enters liver, spleen channel, has blood circulation promoting and blood stasis dispelling, the effect of line water detumescence, for amenorrhea due to stagnation of blood, disease purplish or white patches on the skin, puerperal stasis of blood pain, edema, the cards such as traumatic injury.
Ramulus Cinnamomi: latin name cinnamomiramulus is the dry twig of canella Cortex Cinnamomi, acrid in the mouth, sweet, warm in nature, GUIXIN, lung, urinary bladder channel, have diaphoresis expelling pathogenic factors from muscles, warming the meridian and promoting blood circulation, supporing yang activating QI, the effect of dispersing cold for relieving pain, Ramulus Cinnamomi warming the meridian and promoting blood circulation, horizontal logical podomere, for affection of exogenous wind-cold exterior syndrome, no matter have antiperspirant, losslessly all can to apply, also for rheumatic arthralgia, cold syndrome of the stomach stomachache, amenorrhea, dysmenorrhea, rheumatic arthralgia, the cards such as shoulder arm podomere cold type of pain, phlegm retention syndrome and bladder water-retention, heart deficiency of spleen-YANG, retention of water-damp in the body, fullness and distention in the chest and hypochondrium, cough with dyspnea dizziness waits phlegm retention syndrome.
Radix Platycodonis: bitter in the mouth, pungent, slightly warm in nature, enters lung meridian, has expelling phlegm for arresting cough, and has lung qi dispersing, evacuation of pus effect, cures mainly: cough with copious phlegm, laryngopharynx swelling and pain, lung abscess vomiting pus, fullness in the chest and hypochondriac pain, dysentery stomachache, aphtha of the mouth and tongue, conjunctival congestion and swelling pain, uroschesis.
Rhizoma Atractylodis Macrocephalae: latin name atractylodismacrocephalaerhizoma, bitter in the mouth, sweet, warm in nature, enter spleen, stomach warp, there is invigorating the spleen and benefiting QI, dampness diuretic, hidroschesis, antiabortive effect.For deficiency of spleen-QI and stomach-QI, transporting is unable, anorexia and loose stool, the soft Mental fatigue of limb, spleen insufficiency, dysuria caused by retention of water-damp in the body, edema, distention and fullness in the chest and hypochondrium, deficiency of spleen-QI and stomach-QI, the cards such as frequent fetal movement.
Rhizoma Chuanxiong: acrid in the mouth, warm in nature, return liver, gallbladder, pericardium channel, have blood-activating and qi-promoting, the effect of wind-expelling pain-stopping, for menoxenia; Amenorrhea dysmenorrhea; The stagnant raw meat pain of the stasis of blood in puerperal; Lump in the abdomen lump; Pain in chest and hypochondrium; Have a headache dizzy; Anemofrigid-damp arthralgia; Traumatic injury; The cards such as ulcer sores.
Radix Salviae Miltiorrhizae: bitter in the mouth, cold in nature, enters the heart, Liver Channel, has the effect of blood circulation promoting and blood stasis dispelling, promoting tissue regeneration by removing blood stasis, removing heat from blood mind calming, be mainly used in the ambition of stagnation of QI and blood, the twinge of the breast side of body, sensation of oppression over the chest with shortness of breath, abdominal distention; The menoxenia of women's disharmony between QI and blood, dysmenorrhoea amenorrhea; Stagnation of QI-blood, the cards such as trusted subordinate's pain.
Caulis Spatholobi: latin name spatholobicaulis, bitter in the mouth, sweet, warm in nature, enter liver, kidney channel, there is blood vessel dilating, enrich blood and invigorate blood circulation, regulating menstruation, the effect of relaxing muscles and tendons and activating QI and blood in the collateral, there is obvious inhibitory action to platelet aggregation, promote animal kidney and the total phosphorus metabolism in uterus, be mainly used in treating the menoxenia that blood deficiency has silt, limbs pain is meciless, the card such as soreness of the waist and knees, pain.
Radix Notoginseng powder: latin name notoginsengradixetrhizoma, for the dry root welding technology of panax araliaceae plant: sweet in the mouth, micro-hardship, warm in nature, enter liver, stomach warp, have hemostasia and dissipation blood stasis, the effect of reducing swelling and alleviating pain, be mainly used in hemoptysis, metrorrhagia etc. various go out blood disorder, blood vessel dilating, to reduce blood pressure, improve microcirculation, increase blood flow, prevention and therapy heart and brain tissues ischemia, anoxia; Promote the synthesis of protein, ribonucleic acid (RNA), DNA (deoxyribonucleic acid) (DNA), building body; Promote blood cell metabolism, balance adjustment blood cell; Two-ways regulation nervus centralis, improves mental, strengthens learning and memory ability; Hemostasis, blood circulation promoting and blood stasis dispelling; Protect the liver, antiinflammatory.
The Radix Paeoniae Alba: bitter in the mouth, cold nature.Return Liver Channel.Have the function of clearing away heat and cooling blood, eliminating stasis to stop pain, for maculae caused by violent heat pathogen, hematemesis and epistaxis, conjunctival congestion and swelling pain, hypochondriac pain due to stagnation of liverQI, amenorrhea dysmenorrhea, lump in the abdomen is suffered from abdominal pain, injury from falling down, the cards such as carbuncle skin infection.
Cortex Moutan: latin name MoutanCortex, bitter in the mouth, pungent, cold nature, enters the heart, liver, kidney channel, has the effect of clearing away heat and cooling blood, blood circulation promoting and blood stasis dispelling, for the card such as fever due to yin deficiency, the acute appendicitis of damp and hot knot poison, depressed blood stasis, xerostomia, deep red tongue of excessive noxious heat; And liver-fire conjunctival congestion and swelling pain, stomach-fire gingiva pain.
Radix Et Rhizoma Rhei: latin name RheiRadixetRhizoma, bitter in the mouth, cold in nature, return stomach warp; Large intestine channel; Liver Channel; Spleen channel, have attack stagnant; Clearing away damp-heat; Pathogenic fire purging; Removing heat from blood; Blood stasis dispelling; Effect of removing toxic substances, cures mainly excess-heat constipation; The accumulation of heat feeling of stuffiness in chest; Damp-heat dysentery; Jaundice; Gonorrhea; Edema abdominal distention; Dysuria; Conjunctival congestion; Laryngopharynx swelling and pain; Aphtha of the mouth and tongue; Gastropyretic vomiting; Spit blood; Spitting of blood; Epistaxis; Have blood in stool; Hematuria; Blood-retention; Amenorrhea; The stagnant stomachache of the stasis of blood in puerperal; Lump in the abdomen; Traumatic injury; Pyretic toxicity carbuncle and ulcer; Erysipelas; The cards such as scald.
Radix Astragali: latin name astragaliradix, sweet in the mouth, warm in nature, return spleen, lung meridian, there is tonification spleen soil, elevate a turnable ladder yang-energy, strengthening superficial resistance to stop perspiration, the effects such as holder skin ulcer granulation promoting, cure mainly the weak anorexia and loose stool that deficiency of both the splenic and pulmonary QI is caused, shortness of breath and palpitation, the visceroptosis of sinking of QI of middle-JIAO, the metrorrhagia of QI failing to control blood is had blood in stool, chronic diarrhea proctoptosis; The spontaneous sweating of exterior deficiency, the cards such as insufficiency of vital energy and blood.
Radix Codonopsis: sweet in the mouth, property is put down, and enters lung, spleen channel, has QI invigorating strengthening the spleen, the symptoms such as the effect of nourishing blood to promote the production of body fluid, is mainly used in the fatigue and weakness of deficiency of both the splenic and pulmonary QI or QI and blood deficiency, breathes hard, cough spontaneous perspiration, spleen reinforcing nourishing the stomach is longer than by Radix Codonopsis, adjust regulating the function of middle-JIAO, have the effect of nourishing blood concurrently, its property put down, spleen invigorating fortune and not dry; Flavour is cloudy and do not wet, and can improve the immune state of body, improves resistance against diseases, and facilitating digestion absorbs, and improves metabolism, promotes that intestinal is to the absorption of nutrient substance.
Radix Sophorae Flavescentis: latin name SophoraeFlavescentisRadix, bitter in the mouth; Cold in nature, enter liver; Kidney; Large intestine; Small intestinal; Bladder; Heart channel, has heat clearing and damp drying, parasite killing, and effect of diuresis, cures mainly hematodiarrhoea, has blood in stool, jaundice urine retention, leucorrhea with red and white discharge, swelling of the vulva pudendal pruritus, eczema, eczema, skin pruritus, the cards such as scabies leprosy.
Herba Hedyotidis Diffusae: bitter in the mouth, sweet, cold in nature, enters the heart, liver, spleen, large intestine channel, has heat-clearing and toxic substances removing, the effect of promoting diuresis to eliminate damp pathogen, for dyspnea and cough due to lung-heat, laryngopharynx swelling and pain, acute appendicitis, furuncle and phyma skin infection, venom, the puckery pain of pyretic stranguria, edema, dysentery, enteritis, jaundice due to damp-heat, the cards such as cancerous protuberance.
Radix Glycyrrhizae: sweet in the mouth, property put down, return 12 warps, have heat-clearing and toxic substances removing, be in harmonious proportion the property of medicine, the effect of expelling phlegm for arresting cough, and can spleen invigorating and in, relieving spasm to stop pain, is mainly used in the abdominal distension and anorexia of weakness of the spleen and stomach, weak; Can alleviate contracture pain in abdomen, relax the strong and toxicity of some drugs, alleviating medicine stimulates to the toxic and side effects of body or to gastrointestinal, can play QI invigorating neutralization by adding Radix Glycyrrhizae, is in harmonious proportion the effect of each component.
Radix Cyathulae: bitter in the mouth acid, property is put down, and enters the heart, liver, large intestine three warp, has promoting blood circulation to remove blood stasis, damp eliminating diuresis, effect of heat-clearing and toxic substances removing.Cure mainly gonorrhea, hematuria, women's amenorrhea, lump in the abdomen, rheumatic arthritis, beriberi, edema, dysentery, malaria, diphtheria, carbuncle, the cards such as traumatic injury.
Below adopt embodiment to describe embodiments of the present invention in detail, to the present invention, how application technology means solve technical problem whereby, and the implementation procedure reaching technique effect can fully understand and implement according to this.
Embodiment 1 oral liquid 1
Take Poria 25g, Polyporus 15g, Semen Plantaginis 20g, Rhizoma Alismatis 30g, Herba Lycopi 15g, Ramulus Cinnamomi 10g, Radix Platycodonis 15g, Rhizoma Atractylodis Macrocephalae 25g, Rhizoma Chuanxiong 20g, Radix Salviae Miltiorrhizae 25g, Caulis Spatholobi 25g, Radix Notoginseng powder 20g, Radix Paeoniae Alba 25g, Cortex Moutan 20g, Radix Et Rhizoma Rhei 25g, Radix Astragali 40g, Radix Codonopsis 30g, Radix Sophorae Flavescentis 15g, Herba Hedyotidis Diffusae 20g, Radix Glycyrrhizae 15g and Radix Cyathulae 25g, first rinses twice, to remove dust with clear water respectively, pesticide etc. remain, all put into decocting container, add the water of 1.3kg, after boiled with big fire, be transferred to 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70% to alcohol volume, dark place leaves standstill 6h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders, get sucrose join relative to sucrose weight 40% distilled water in, heating makes sucrose dissolve completely, makes simple syrup, filters, for subsequent use, the micropowders of 300g is taken according to quality, the simple syrup of 200g and the water of 500g add in Agitation Tank successively, stir 40min, filter, filtrate are placed in high pressure homogenizer, at 70 DEG C, carry out twice homogenization under 30MPa condition, obtain homogenizing fluid, by the homogenizing fluid filling and sealing that obtains in the vial of cleaning, then use flowing steam sterilizing 30min under 100 DEG C of conditions, hot water injection, drench after doing and namely obtain this oral liquid.
Embodiment 2 oral liquid 2
Take Poria 23g, Polyporus 13g, Semen Plantaginis 18g, Rhizoma Alismatis 28g, Herba Lycopi 13g, Ramulus Cinnamomi 8g, Radix Platycodonis 13g, Rhizoma Atractylodis Macrocephalae 23g, Rhizoma Chuanxiong 18g, Radix Salviae Miltiorrhizae 23g, Caulis Spatholobi 23g, Radix Notoginseng powder 18g, Radix Paeoniae Alba 23g, Cortex Moutan 18g, Radix Et Rhizoma Rhei 23g, Radix Astragali 38g, Radix Codonopsis 28g, Radix Sophorae Flavescentis 13g, Herba Hedyotidis Diffusae 18g, Radix Glycyrrhizae 13g and Radix Cyathulae 23g, first rinses twice, to remove dust with clear water respectively, pesticide etc. remain, all put into decocting container, add the water of 1.3kg, after boiled with big fire, be transferred to 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70% to alcohol volume, dark place leaves standstill 6h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders, get sucrose join relative to sucrose weight 40% distilled water in, heating makes sucrose dissolve completely, makes simple syrup, filters, for subsequent use, the micropowders of 300g is taken according to quality, the simple syrup of 200g and the water of 500g add in Agitation Tank successively, stir 40min, filter, filtrate are placed in high pressure homogenizer, at 70 DEG C, carry out twice homogenization under 30MPa condition, obtain homogenizing fluid, by the homogenizing fluid filling and sealing that obtains in the vial of cleaning, then use flowing steam sterilizing 30min under 100 DEG C of conditions, hot water injection, drench after doing and namely obtain this oral liquid.
Embodiment 3 oral liquid 3
Take Poria 27g, Polyporus 17g, Semen Plantaginis 22g, Rhizoma Alismatis 32g, Herba Lycopi 17g, Ramulus Cinnamomi 12g, Radix Platycodonis 17g, Rhizoma Atractylodis Macrocephalae 27g, Rhizoma Chuanxiong 22g, Radix Salviae Miltiorrhizae 27g, Caulis Spatholobi 27g, Radix Notoginseng powder 22g, Radix Paeoniae Alba 27g, Cortex Moutan 22g, Radix Et Rhizoma Rhei 27g, Radix Astragali 42g, Radix Codonopsis 32g, Radix Sophorae Flavescentis 17g, Herba Hedyotidis Diffusae 22g, Radix Glycyrrhizae 17g and Radix Cyathulae 27g, first rinses twice, to remove dust with clear water respectively, pesticide etc. remain, all put into decocting container, add the water of 1.5kg, after boiled with big fire, be transferred to 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70% to alcohol volume, dark place leaves standstill 6h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders, get sucrose join relative to sucrose weight 40% distilled water in, heating makes sucrose dissolve completely, makes simple syrup, filters, for subsequent use, the micropowders of 300g is taken according to quality, the simple syrup of 200g and the water of 500g add in Agitation Tank successively, stir 40min, filter, filtrate are placed in high pressure homogenizer, at 70 DEG C, carry out twice homogenization under 30MPa condition, obtain homogenizing fluid, by the homogenizing fluid filling and sealing that obtains in the vial of cleaning, then use flowing steam sterilizing 30min under 100 DEG C of conditions, hot water injection, drench after doing and namely obtain this oral liquid.
Embodiment 4 pharmacology acute toxicity test
Experiment material and method
This acute toxicity test selects SPF level, kunming mice, 40 (22 ~ 24g, male and female half and half), thered is provided by Qingdao Agricultural University's animal experimental center, animal quality certification SCXK (Shandong) 2013-0014, is divided into two groups at random, experimental group (oral liquid 1 prepared by the gavage embodiment of the present invention 1, aqueous solution is made into the solution of crude drug content 1.85g/ml, 4 DEG C save backup), matched group (gavage normal saline, all the other conditions are with medicine group of the present invention).
Medication
Before experiment, the fasting of each group mice can't help water 12h, matched group gavage distilled water 0.2ml/20g body weight, 3 times/day, experimental group, oral liquid 1,0.2ml/20g body weight prepared by the gavage embodiment of the present invention 1,3 times/day, dosing interval 4h.Successive administration 7 days, drug withdrawal observes 3 days.
Observation index and result
By observing during administration and drug withdrawal viewing duration respectively organizes the ordinary circumstance of mice, as developmental state (body temperature, body weight, heart rate), coat condition, the mental status, each natural hole situation, autonomic activities situation, the change no difference of science of statistics P > 0.05 before and after two groups of mice administrations, statistical analysis is carried out, no difference of science of statistics P > 0.05 after two groups of mice administrations.
, there is animal dead during administration in experimentally requirement, dissects immediately, observes each internal organs situation, peel off each internal organs, weigh, and calculate organ index, heart extracting blood Physico-chemical tests; As nothing is dead, then experimentally requirement, after the observation period, gives 10% chloral hydrate anesthesia, opens abdominal cavity, observes each internal organs situation, and abdominal aortic blood is put to death, and does Physico-chemical tests, peels off each internal organs, weigh, and calculate organ index.During administration, mice, without death, experimentally arranges, after the observation period, give 10% chloral hydrate anesthesia, abdominal aortic blood is put to death, and opens abdominal cavity, observes each internal organs situation, each group of mice organs arrangement is normal, and without adhesion, without hemorrhage, blood of getting does Physico-chemical tests, each group of Mouse Blood routine is without exception, and liver function, kidney merit check without exception, peel off each internal organs, weigh, calculate organ index, through statistical analysis, no difference of science of statistics, two groups of same periods compare, statistics zero difference.
Carry out HE dyeing to renal tissue to observe, at stripping each internal organs after calculating organ index, rapidly according to requirement of experiment, carry out HE dyeing to kidney to observe, by observing, renal tissue structural integrity, HE dyeing is normal, and each cellularity is normal, without pathological manifestations such as necrosis.
Conclusion
Invention formulation is 55.5g/kg/d to the dosage of mice, the dosage being converted into health adult is 555g/kg/d, for 158.57 times (normal 60kg adult Chinese medicine intake is 3.5g/kg/d) that adult normal daily measures, it is generally acknowledged, in zoopery, administration behaves more than 100 times, and without obvious toxic-side effects, can think that medicine is safe.Can be confirmed by this experiment, Chinese medicine of the present invention is in acute toxicity test, and without acute toxic reaction, without delayed toxicity, carrying out HE dyeing to kidney proves, it has no side effect to kidney, substantially can think safe, therefore Clinical practice is safe.
Embodiment 5 mice long term toxicity test of the present invention
Experiment material and method
This long term toxicity test selects SPF level, kunming mice, 40 (22 ~ 24g, male and female half and half), thered is provided by Qingdao Agricultural University's animal experimental center, animal quality certification SCXK (Shandong) 2013-0014, be divided into 4 groups at random, matched group 10 respectively, high dose group 10, middle dosage group 10, low dose group 10, senior middle school's low dose group (Chinese medicine oral liquid 1 of the gavage embodiment of the present invention 1 preparation respectively, aqueous solution is made into crude drug content 1.0g/ml, 0.75g/ml, the solution of 0.5g/ml, 4 DEG C save backup), matched group (gavage normal saline, all the other conditions are with medicine group of the present invention).
Medication
Before experiment, the fasting of each group mice can't help water 12h, matched group gavage distilled water 0.2ml/20g body weight, 2 times/day, high, medium and low dosage group, oral liquid 1.0g/ml, 0.75g/ml, 0.5g/ml of the gavage embodiment of the present invention 1 preparation respectively, 0.2ml/20g body weight, 2 times/day, dosing interval 6h.Successive administration 14 days, drug withdrawal observes 7 days.
Observation index and result
By observing during administration and drug withdrawal viewing duration respectively organizes the ordinary circumstance of mice, as developmental state (body temperature, body weight, heart rate), coat condition, the mental status, each natural hole situation, autonomic activities situation, the change no difference of science of statistics P > 0.05 before and after two groups of mice administrations, statistical analysis is carried out, no difference of science of statistics P > 0.05 after two groups of mice administrations.
, there is animal dead during administration in experimentally requirement, dissects immediately, observes each internal organs situation, peel off each internal organs, weigh, and calculate organ index, heart extracting blood Physico-chemical tests; As nothing is dead, then experimentally requirement, after the observation period, gives 10% chloral hydrate anesthesia, opens abdominal cavity, observes each internal organs situation, and abdominal aortic blood is put to death, and does Physico-chemical tests, peels off each internal organs, weigh, and calculate organ index.During administration, mice, without death, experimentally arranges, after the observation period, give 10% chloral hydrate anesthesia, abdominal aortic blood is put to death, and opens abdominal cavity, observes each internal organs situation, each group of mice organs arrangement is normal, and without adhesion, without hemorrhage, blood of getting does Physico-chemical tests, each group of Mouse Blood routine is without exception, and liver function, kidney merit check without exception, peel off each internal organs, weigh, calculate organ index, through statistical analysis, no difference of science of statistics, two groups of same periods compare, statistics zero difference.
Carry out HE dyeing to renal tissue to observe, at stripping each internal organs after calculating organ index, rapidly according to requirement of experiment, carry out HE dyeing to kidney to observe, by observing, renal tissue structural integrity, HE dyeing is normal, and each cellularity is normal, without pathological manifestations such as necrosis.
Conclusion
Invention formulation is 20g/kg/d, 15g/kg/d, 10g/kg/d to the dosage of mice, the dosage being converted into health adult is 200g/kg/d, 150g/kg/d, 100g/kg/d, 57.14 times, 42.86 times, 28.57 times that daily measure for adult normal, can be confirmed by this experiment, Chinese medicine of the present invention in long term toxicity test, without cumulative toxicity, without delayed toxicity, substantially can think safe, therefore Clinical practice is safe.
Embodiment 6 clinical research
Data and method
Case selection
Be chosen at heart internal medicine in hospital to be in hospital and the patient accepting percutaneous coronary radiography (PCI), before getting rid of radiography, 1 week interior renal function is unstable, fluctuation range exceedes 20% of baseline, serious hepatic and renal function damage, Left Ventricular Ejection Fraction < 30%, peri-operation period uses nephrotoxic drugs, contrast medium sensitivity person.Two groups all use hypotonic non-ionic contrast agent (Yangtze River pharmaceutcal corporation, Ltd, the accurate word H10970327 of traditional Chinese medicines), and dosage is different because of individual patients.After CIN refers to and uses contrast agent, in 48h, serum creatinine (Cr) absolute value rising > 44.2 μm of ol/L or Cr risings are greater than 25% of basic value, and without the soluble person of other reasons.
Physical data
156 routine coronary heart disease undergoing percutaneous coronary patients are divided into two groups at random.Treatment group 78 example, man 43 example, female 35 example; 42 ~ 69 years old age, average (56.7 ± 14.5) year; Complication with diabetes 19 example, essential hypertension 23 example; Contrast agent dosage (120 ± 45) ml; T-CHOL (4.6 ± 1.4) mmol/L.Matched group 78 example, man 42 example, female 36 example; 46 ~ 71 years old age average (56.8 ± 13.1) year; Complication with diabetes 18 example, essential hypertension 22 example; Contrast agent dosage (116 ± 47) ml; T-CHOL (4.4 ± 1.2) mmol/L.Two groups of physical data comparing difference not statistically significants (P > 0.05), have comparability.
Therapeutic Method
Matched group 12h before and after radiography gives 0.9% sodium chloride injection and carries out hydration treatment with the speed of 1mL/ (kgh).
The same matched group for the treatment of group hydration treatment, gives oral liquid 1 prepared by the embodiment of the present invention 1, each 20ml before radiography after 12h and radiography, every day 2 times, oral.
Observation index
2 groups all before radiography, after radiography, 48h detects Cr, blood urea nitrogen (BUN) and creatinine clearance rate (Ccr), and Ccr is by Cockcroft-Gault formula: Ccr (ml/min)=(140-age) × weight × (0.85 women)]/(72 × Cr).Stay urine examination to survey guanoside drugs (N-acetyl-β-D-glucosaminidase, NAG), and add up the incidence rate of CIN.
Statistical method
SPSS13.0 software kit is adopted to carry out statistical procedures, measurement data mean ± standard deviation represent, adopt t inspection; The comparison of enumeration data rate adopts χ 2inspection.
Result
Two groups of CIN incidence rates compare
A table 1 liang group CIN incidence rate compares
Group N There is number of cases in CIN CIN incidence rate
Treatment group 78 3 3.8%
Matched group 78 11 14.1%
Treatment group CIN incidence rate lower than matched group, P < 0.05.
Cr, BUN, Ccr and urinary NAG level before and after two groups of radiographies
Cr, BUN, Ccr and urinary NAG level before and after table 2 liang group radiography
*p > 0.05 is compared with before this group radiography; >compare with after matched group radiography, P > 0.05.
Treatment group before and after radiography, index no difference of science of statistics before indices and radiography, P > 0.05, matched group has significant difference before BUN and urinary NAG and radiography; Treatment group and matched group after radiography in the comparing of indices, BUN relatively in no difference of science of statistics, P > 0.05, all the other indexs all have significant difference, P < 0.05.Comprehensive analysis indexes, illustrates that treatment group general curative effect is better than matched group.
Discuss and conclusion
Along with iconography with get involved the developing rapidly of Diagnosis Technique, the application of contrast agent is more and more extensive, and CIN has become the third-largest reason of hospital acquired acute injury of kidney.Its definite pathogenesis is not yet clear, think at present to decline with contrast agent influences renal blood flow, glomerular filtration rate, directly injury of renal tubular, renal tubules block relevant with immunologic mechanism etc., there is developing effect at Contrast Media-induced Nephrotoxicity and now cause extensive concern in oxidative stress.Current research is thought, contrast agent can destroy kidney oxygen-derived free radicals and produce and the dynamic equilibrium of removing, and changes renal blood flow kinetics and causes Renal lesion.Contrast agent significantly can reduce the biological activity of renal tubular cell, increases the generation of oxygen-derived free radicals, and reduction antioxidase and peroxide intensify enzymatic activity, and its lipid peroxidation also can increase simultaneously, thus causes injury of renal tubular.According to statistics, in the CIN institute occurred after percutaneous coronary intervention (pci), case fatality rate reaches 40%, 2 years survival rates 19%, and especially for the patient of concurrent CIN high risk factor, its incidence rate is higher, therefore takes effectively preventing measure to prevent the generation of CIN of crucial importance.Existing preventive measure have use the hypotonic and isotonic contrast agent of nonionic, hydration therapy, antioxidant, minimizing contrast agent consumption, hemofiltration or hemodialysis, diuretic, preoperative inactive nonsteroidal antiinflammatory drug, cerebrocrast and vasodilator etc.NAG enzyme is the acid hydrolase being positioned at lysosome, relative molecular weight is about 14000, be present in a organized way in, wherein in the nearly bent renal tubules of kidney, content is the highest, when nearly bent renal tubules is impaired, in urine, the activity of NAG enzyme significantly increases, and comparatively other urine enzymes increase more early, and therefore renal transplants is the index of sensitivity rapidly of reaction injury of renal tubular.
This research finds, two groups of 48hCr after radiography, BUN, urinary NAG increase than before radiography, and Ccr reduces than before radiography, illustrate that contrast agent not only has damage to glomerule, also has damage to renal tubules simultaneously.By the acute renal injury that clinical administration invention formulation decoction liquor energy available protecting contrast agent causes; remarkable reduction Cr level; improve renal function; alleviate renal pathology to change; reduce renal tissue malonaldehyde (MDA) content, improve superoxide dismutase (SOD) activity, protect glutathion (GSH) level; point out its renal protection and alleviate oxygen-derived free radicals and produce and accelerate free radical scavenging, thus it is relevant with the dynamic equilibrium of removing to maintain oxygen-derived free radicals generation.Therefore, after multicenter, random, double-blind clinical perspective study, illustrate that invention formulation is applicable to the control of clinical prevention radiographic contrast nephropathy.
Animal experiment study
Experiment material
Laboratory animal
144 adult male SD rats, body weight is 200 ~ 300g about, purchased from Qingdao Agricultural University's animal experimental center.Experimental animal feeding is in the special animal feeding room of hospital, and indoor temperature controls at 20 ~ 25 DEG C, and relative humidity controls 40 ± 10%, naturally optical illumination round the clock, normal rats forage feed, normal diet, drinking-water.
Major experimental instrument and equipment
No. 16, No. 20 rat oral gavage pin Beijing-Han great mansion wound exhibition science and technology
Automatic clinical chemistry analyzer Japan-Hitachi 7170A
Electronic balance China-Sai Duolisi
Ultramicroscope Japan-Nikon instrument
Microsurgery and general surgery apparatus Ningbo-medical apparatus and instruments
76% Injectio Meglumni Diatrizoatis Composita Shanghai-general Pharmaceutical in the rising sun East Sea
Affiliated Hospital of Chinese medicine preparation granule Fudan University of the present invention Drug Manufacturing Room
The great biotechnology in Hematoxylin-eosin staining kit Beijing-hundred
Trichloroethane (analytical pure) Shenzhen-authority's glass apparatus company
Experimental technique
Prepared by CIN rat model
Adopt tail vein injection diodone legal system for CIN rat model: to be fixed by rat rat fixator, reservation Mus tail is inserted in 50 ~ 60 DEG C of warm water outside and by Mus tail and is soaked about 1min.To use again in 75% cotton ball soaked in alcohol wiping Mus tail and upper 1/3, tail vein enlargement of pipe is filled.Left hand, makes a full tail vein (side) and, forefinger and middle finger are clamped and fixed root of the tail portion, and thumb, fourth finger and little finger of toe fix tail point upward left by afterbody or right rotation 70 ~ 90 °.No. 24 trocars of right hand held tape 5ml syringe, 1/3 skin is entered along tail vein pipe trend with tail vein < 15 ° from Mus tail, down, parallelly thrust tail intravenous about 1cm, and pumpback syringe observes whether see blood back, adjustment tip position ensures that pumpback is shown in that blood back is unobstructed, can think needle point completely at tail intravenous.Change ready cardiografin contrast agent 5ml syringe, slowly at the uniform velocity push cardiografin contrast agent to tail intravenous, observe the ordinary circumstances such as rats breathing frequency, lip and bronchia mucosal color in bolus infusion processes simultaneously, prevent Rats Exposed To Hypoxia death by suffocation.With band cotton ball soaked in alcohol sterilization also pressing haemostatic after injection, Gentian Violet labelling rat also records the modeling time.
Medication
Being extracted by rat is placed on smooth platform, after clutching rat ears with glove left hand thumb and forefinger and neck skin of back, its excess-three assigns the heart of putting the palms together before one and catches skin of back, make it swing back, ensure that mouth, pharynx, esophagus are on same straight line as far as possible, the 5ml syringe of right hand held tape No. 16 rat oral gavage pins also containing grain dissolution liquid of the present invention, slowly inserts gastric perfusion needle in esophagus along its swallowing act from pharynx rear wall along side bicker, notes rat General reactions situation in insertion process.When insertion is smooth and easy, rat, as without strong pinprick and obviously anoxia performance, can continue insertion and enter gastric, inject the invention formulation grain dissolution liquid calculated to gastric.Slowly stomach tube is exited in the other direction along inserting after injection.
Grouping
144 male SD rats, body weight is about 200 ~ 300g.Adapt to raising after 1 week, be divided into 3 groups at random: matched group (n=48), CIN group (n=48) and treatment group (oral liquid 1 prepared by the embodiment of the present invention 1) group (n=48).CIN group and experimental group all set up CIN rat model from tail vein injection 76% Injectio Meglumni Diatrizoatis Composita contrast agent (10ml/kg body weight), and matched group normal saline substitutes.Experimental group gives oral liquid (being adjusted to containing crude drug amount is 0.5g/ml, 2ml/200g/ time, 2 times/d) gavage every day of the embodiment of the present invention 1 preparation for 1 week before modeling to execution animal, and CIN group normal saline substitutes.After modeling in 48 ~ 72h CIN group blood serum Bun raise > 0.5mg/dL (44.2 μm of ol/L) or > basic value 25% for modeling success.
The mensuration of collection of specimens and Scr, BUN
Each group respectively after modeling 6h, 12h, 24h, 48h, 72h, 5d, 10d and 15d time point put to death each 6 of rat in batches, and leave and take ventral aorta blood and bilateral renal specimen.Method is as follows: chloral hydrate (3ml/kg) the lumbar injection 5-10 minute anesthetized rat of 10%, lie on the back and be fixed on experiment operating-table, after conventional preserved skin and sterilization, aseptically successively cut skin, subcutaneous tissue, rectus abdominis m. and peritoneum along abdomen median line, open abdominal cavity.First, push intestinal tube aside with aseptic cotton carrier and isolate ventral aorta, leaving and taking ventral aorta blood 5ml with 5ml biochemical tube, be ready to use in biochemistry detection.Then, the free opposite side kidney base of a fruit this kidney is taken off in ligation, laterally and longitudinally cuts along kidney respectively with sharp cutter, is placed in 10% neutral formalin fixative, is ready to use in routine histopathologic and SABC detects.Leave standstill 2 ~ 3h to the blood preparation room temperature left and taken, after serum layering, the centrifugal 5min of 2000r/min, leaves and takes supernatant, detects blood serum Bun, BUN situation with Japan-Hitachi 7170A automatic clinical chemistry analyzer,
Statistical method
SPSS13.0 software kit is adopted to carry out statistical procedures, measurement data mean ± standard deviation represent, adopt t inspection; The comparison of enumeration data rate adopts chi-square criterion, with P < 0.05 for difference has statistical significance.
Experimental result
Blood Scr, BUN detect control rats blood serum Bun, BUN level
In each time point change all little (P > 0.05); CIN group blood serum Bun, BUN are in raising trend gradually after modeling, and peak value all appears at 48h, declines gradually afterwards, and 15d roughly recovers normal; Experimental group blood serum Bun, BUN and CIN group have identical variation tendency.Two groups in 12h, 24h, 48h, 72h and 5d time point blood serum Bun, BUN level all apparently higher than matched group (P < 0.05), but except 10d and 15d, experimental group blood serum Bun, BUN level are all starkly lower than CIN group (P < 0.05).
Table 3 three groups of rat blood serum Scr (μm ol/L) are in the comparison (μm ol/L) of different time sections
Group Matched group CIN group Treatment group 14-->
6h 47.56±11.21 62.82±6.97 * 61.15±7.87 *
12h 50.54±8.96 78.91±12.24 * 60.71±7.43
24h 47.85±12.09 113.01±14.97 * 75.87±12.33
48h 56.78±13.19 125.91±18.00 * 91.19±8.98
72h 52.14±15.49 116.08±10.73 * 81.92±12.12
5d 48.75±12.02 94.12±12.08 * 69.17±7.25
10d 53.80±9.32 62.16±12.02 * 52.44±8.47 Δ
15d 52.14±15.12 54.48±8.27 48.64±9.13 Δ
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Table 4 three groups of rat blood serum BUN (mmol/L) are in the comparison of different time sections
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Tubulointerstitial injury pathological score
Control rats each time point glomerular capillary loop after modeling is clear, volume and form no abnormality seen; Renal cells clear in structure, complete, marshalling, basement membrane is complete, and tube chamber is clog-free; Renal interstitial has no inflammatory cell infiltration and fibrosis phenomenon, pathological score no significant difference (P > 0.05).It is visible renal cells edema after CIN group modeling 6h, tube chamber blocks, after 24h, visible a small amount of renal cells brush border comes off, part renal tubules structural damage, epithelial cell degeneration necrosis, part renal interstitial region is also shown in a small amount of inflammatory cell infiltration and fibrosis is formed, and in 24h time point medullary substance, district is impaired the most serious; The experimental group rat giving Chinese medicine preparation granule of the present invention and intervene, renal cells edema, tube chamber degree of congestion, medullary substance district renal tubules structural damage degree and interstitial inflammation cellular infiltration,
Fibrosis forms degree, except 15d, is all lighter than the CIN group (P < 0.05) of same time point.
Table 5 three groups of tubulointerstitial fibrosis in rats Injury scores are in the comparison of different time sections
Group Matched group CIN group Treatment group
6h 0.13±0.18 1.15±0.30 * 0.98±0.28
12h 0.06±0.08 2.15±0.37 * 1.61±0.34 15 -->
24h 0.08±0.10 3.81±0.68 * 2.48±0.45
48h 0.10±0.15 4.34±0.74 * 3.02±0.48
72h 0.07±0.16 3.96±0.91 * 2.15±0.44
5d 0.07±0.17 2.84±0.82 * 1.41±0.24
10d 0.06±0.10 1.02±0.68 * 0.68±0.19
15d 0.10±0.11 0.41±0.35 0.24±0.14
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Immunohistochemical staining
Control rats each time point KIM-1, NF-κ B and TNF-α protein expression level all lower, no significant difference (P > 0.05); CIN group KIM-1, NF-κ B and TNF-α protein expression are in strengthening trend gradually after modeling, and wherein KIM-1 protein expression reaches peak at 24h, and NF-κ B and TNF-α protein expression reach peak at 48h.Experimental group KIM-1, NF-κ B and TNF-α protein expression level and CIN group have Similar trend, but KIM-1 protein level significantly lower than CIN group, has significant difference (P < 0.05) at 6h, 12h, 24h, 48h, 72h, 5d, 10d time point; NF-kB protein level significantly lower than CIN group, has significant difference (P < 0.05) at 12h, 24h, 48h, 72h and 5d time point; TNF-α protein level significantly lower than CIN group, has significant difference (P < 0.05) at 12h, 24h, 48h, 72h, 5d and 10d time point.
Table 6 three groups of rat kidney KIM-1 average optical density values are in the comparison of different time sections
Group Matched group CIN group Treatment group
6h 0.24±0.03 0.45±0.30 * 0.38±0.28
12h 0.26±0.08 0.47±0.37 * 0.39±0.32
24h 0.24±0.06 0.52±0.68 * 0.41±0.33
48h 0.24±0.05 0.59±0.74 * 0.38±0.30
72h 0.25±0.06 0.63±0.91 * 0.37±0.29
5d 0.27±0.07 0.54±0.82 * 0.32±0.24 Δ
10d 0.26±0.06 0.42±0.02 * 0.31±0.19 Δ
15d 0.28±0.07 0.31±0.03 0.29±0.14
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Table 7 three groups of rat kidney NF-κ B average optical density values are in the comparison of different time sections
Group Matched group CIN group Treatment group
6h 0.28±0.02 0.33±0.03 * 0.31±0.02 *
12h 0.30±0.01 0.37±0.03 * 0.35±0.02 *
24h 0.29±0.01 0.42±0.03 * 0.36±0.03
48h 0.31±0.01 0.53±0.04 * 0.43±0.04
72h 0.30±0.02 0.44±0.03 * 0.39±0.03
5d 0.29±0.01 0.39±0.03 * 0.31±0.02
10d 0.30±0.01 0.34±0.02 * 0.29±0.01
15d 0.27±0.01 0.30±0.02 0.28±0.01
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Table 8 three groups of rat kidney TNF-α average optical density values are in the comparison of different time sections
Group Matched group CIN group Treatment group
6h 0.29±0.02 0.31±0.02 0.31±0.01
12h 0.28±0.01 0.39±0.02 * 0.36±0.02 *
24h 0.29±0.03 0.45±0.03 * 0.39±0.02
48h 0.28±0.02 0.52±0.03 * 0.41±0.02
72h 0.27±0.01 0.42±0.02 * 0.35±0.01
5d 0.29±0.02 0.40±0.03 * 0.33±0.02
10d 0.28±0.02 0.35±0.02 * 0.31±0.01
15d 0.29±0.01 0.32±0.03 0.30±0.01
Compared with matched group, *p < 0.05; Compared with CIN, Δp < 0.05
Conclusion
CIN is after the oral liquid 1 prepared through the embodiment of the present invention 1 is intervened, and impaired renal function situation and histopathology aspect all obviously alleviate.In our zoopery, in CIN generation, evolution, the expression of nephridial tissue KIM-1, NF-κ B, TNF-α albumen and mRNA is all raised, and Chinese medicine preparation granule of the present invention can lower the expression of the above-mentioned factor, inhibit contrast agent to the damaging action of kidney, thus have certain preventive and therapeutic effect to CIN.Therefore, invention formulation, after completing Related Experimental Study, can use invention formulation to provide experiment support for clinical safety.
All above-mentioned this intellectual properties of primary enforcement, not setting restriction this new product of other forms of enforcement and/or new method.Those skilled in the art will utilize this important information, and foregoing is revised, to realize similar implementation status.But all modifications or transformation belong to the right of reservation based on new product of the present invention.
The above is only preferred embodiment of the present invention, and be not restriction the present invention being made to other form, any those skilled in the art may utilize the technology contents of above-mentioned announcement to be changed or be modified as the Equivalent embodiments of equivalent variations.But everyly do not depart from technical solution of the present invention content, any simple modification, equivalent variations and the remodeling done above embodiment according to technical spirit of the present invention, still belong to the protection domain of technical solution of the present invention.

Claims (9)

1. prevent and treat a Chinese medicine preparation for radiographic contrast nephropathy, it is characterized in that: crude drug comprises Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan, Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Glycyrrhizae and Radix Cyathulae.
2. the Chinese medicine preparation of control radiographic contrast nephropathy as claimed in claim 1, it is characterized in that: the weight of each crude drug is respectively Poria 20g ~ 30g, Polyporus 10g ~ 20g, Semen Plantaginis 15g ~ 25g, Rhizoma Alismatis 25g ~ 35g, Herba Lycopi 10g ~ 20g, Ramulus Cinnamomi 5g ~ 15g, Radix Platycodonis 10g ~ 20g, Rhizoma Atractylodis Macrocephalae 20g ~ 30g, Rhizoma Chuanxiong 15g ~ 25g, Radix Salviae Miltiorrhizae 20g ~ 30g, Caulis Spatholobi 20g ~ 30g, Radix Notoginseng powder 15g ~ 25g, Radix Paeoniae Alba 20g ~ 30g, Cortex Moutan 15g ~ 25g, Radix Et Rhizoma Rhei 20g ~ 30g, Radix Astragali 35g ~ 45g, Radix Codonopsis 25g ~ 35g, Radix Sophorae Flavescentis 10g ~ 20g, Herba Hedyotidis Diffusae 15g ~ 25g, Radix Glycyrrhizae 10g ~ 20g and Radix Cyathulae 20g ~ 30g.
3. the Chinese medicine preparation of control radiographic contrast nephropathy as claimed in claim 1 or 2, it is characterized in that: the weight of each crude drug is respectively Poria 23g ~ 27g, Polyporus 13g ~ 17g, Semen Plantaginis 18g ~ 22g, Rhizoma Alismatis 28g ~ 32g, Herba Lycopi 13g ~ 17g, Ramulus Cinnamomi 8g ~ 12g, Radix Platycodonis 13g ~ 17g, Rhizoma Atractylodis Macrocephalae 23g ~ 27g, Rhizoma Chuanxiong 18g ~ 22g, Radix Salviae Miltiorrhizae 23g ~ 27g, Caulis Spatholobi 23g ~ 27g, Radix Notoginseng powder 18g ~ 22g, Radix Paeoniae Alba 23g ~ 27g, Cortex Moutan 18g ~ 22g, Radix Et Rhizoma Rhei 23g ~ 27g, Radix Astragali 38g ~ 42g, Radix Codonopsis 28g ~ 32g, Radix Sophorae Flavescentis 13g ~ 17g, Herba Hedyotidis Diffusae 18g ~ 22g, Radix Glycyrrhizae 13g ~ 17g and Radix Cyathulae 23g ~ 27g.
4. the Chinese medicine preparation of the control radiographic contrast nephropathy as described in claims 1 to 3, is characterized in that: the weight of each crude drug is respectively Poria 25g, Polyporus 15g, Semen Plantaginis 20g, Rhizoma Alismatis 30g, Herba Lycopi 15g, Ramulus Cinnamomi 10g, Radix Platycodonis 15g, Rhizoma Atractylodis Macrocephalae 25g, Rhizoma Chuanxiong 20g, Radix Salviae Miltiorrhizae 25g, Caulis Spatholobi 25g, Radix Notoginseng powder 20g, Radix Paeoniae Alba 25g, Cortex Moutan 20g, Radix Et Rhizoma Rhei 25g, Radix Astragali 40g, Radix Codonopsis 30g, Radix Sophorae Flavescentis 15g, Herba Hedyotidis Diffusae 20g, Radix Glycyrrhizae 15g and Radix Cyathulae 25g.
5. the Chinese medicine preparation of the control radiographic contrast nephropathy as described in Claims 1-4, is characterized in that: described Chinese medicine preparation routinely technique adds adjuvant and makes tablet, capsule, granule, drop pill, micropill, dispersible tablet, oral cavity disintegration tablet, pill or oral liquid.
6. the Chinese medicine preparation of the control radiographic contrast nephropathy as described in claim 1 to 5, is characterized in that: the dosage form of described Chinese medicine is oral liquid.
7. Chinese medicine preparation described in claim 1 to 6 is prepared into the preparation method of oral liquid, it is characterized in that, comprising:
The first step, each crude drug is taken by above-mentioned weight, first rinse twice with clear water, residual to remove dust, pesticide etc., all put into decocting container, add the water of 2 ~ 4 times of crude drug quality sum, after boiled with big fire, be transferred to 1 hour ~ 2 hours at a simmer, collecting decoction after decocting twice, filter, during concentrated 60 DEG C of decoction liquor, relative density is 1.30, and add dehydrated alcohol and reach 70 ~ 80% to alcohol volume, dark place leaves standstill 20 ~ 36h, filter, reclaim ethanol, obtain and get dry extract, superfine powder is broken into 300 order micropowders;
Second step, get sucrose join relative to sucrose weight 30% ~ 50% distilled water in, heating sucrose is dissolved completely, make simple syrup, filter, for subsequent use;
3rd step, the micropowders that the first step of getting 30% according to mass percent obtains, 20% second step obtain simple syrup and 50% water add successively in Agitation Tank, stir 20 ~ 40min, filter, filtrate is placed in high pressure homogenizer, 65 ~ 75 DEG C, carry out twice homogenization under 20 ~ 40MPa condition, obtain homogenizing fluid;
4th step, the homogenizing fluid filling and sealing the 3rd step obtained, in the vial of cleaning, then uses flowing steam sterilizing 30min under 100 DEG C of conditions, and namely hot water injection, pouring obtain this oral liquid after doing.
8. prevent and treat an oral liquid for radiographic contrast nephropathy, it is characterized in that: crude drug comprises Poria, Polyporus, Semen Plantaginis, Rhizoma Alismatis, Herba Lycopi, Ramulus Cinnamomi, Radix Platycodonis, Rhizoma Atractylodis Macrocephalae, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Caulis Spatholobi, Radix Notoginseng powder, the Radix Paeoniae Alba, Cortex Moutan, Radix Et Rhizoma Rhei, Radix Astragali, Radix Codonopsis, Radix Sophorae Flavescentis, Herba Hedyotidis Diffusae, Radix Glycyrrhizae and Radix Cyathulae;
In described oral liquid, the weight of each crude drug is respectively Poria 20g ~ 30g, Polyporus 10g ~ 20g, Semen Plantaginis 15g ~ 25g, Rhizoma Alismatis 25g ~ 35g, Herba Lycopi 10g ~ 20g, Ramulus Cinnamomi 5g ~ 15g, Radix Platycodonis 10g ~ 20g, Rhizoma Atractylodis Macrocephalae 20g ~ 30g, Rhizoma Chuanxiong 15g ~ 25g, Radix Salviae Miltiorrhizae 20g ~ 30g, Caulis Spatholobi 20g ~ 30g, Radix Notoginseng powder 15g ~ 25g, Radix Paeoniae Alba 20g ~ 30g, Cortex Moutan 15g ~ 25g, Radix Et Rhizoma Rhei 20g ~ 30g, Radix Astragali 35g ~ 45g, Radix Codonopsis 25g ~ 35g, Radix Sophorae Flavescentis 10g ~ 20g, Herba Hedyotidis Diffusae 15g ~ 25g, Radix Glycyrrhizae 10g ~ 20g and Radix Cyathulae 20g ~ 30g.
9. the application of Chinese medicine preparation described in claim 1 to 6 in the medicine of preparation control radiographic contrast nephropathy.
CN201510955057.1A 2015-12-17 2015-12-17 Traditional Chinese medicine preparation for preventing and treating radiographic contrast nephropathy Pending CN105412410A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105963569A (en) * 2016-06-25 2016-09-28 许风英 Traditional Chinese medicine preparation for preventing and alleviating side effect of iodic contrast agent
CN105963570A (en) * 2016-06-25 2016-09-28 张元春 Traditional Chinese medicine preparation for preventing and alleviating side effect of iodic contrast agent
CN106074991A (en) * 2016-06-30 2016-11-09 姜拥军 A kind of combination of Chinese and Western medicine mode treats Chinese medicine and the preparation method of radiographic contrast nephropathy
CN112316069A (en) * 2020-11-27 2021-02-05 温州市人民医院 Pill for treating adverse reaction after CT enhanced scanning and preparation method

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105125803A (en) * 2015-08-28 2015-12-09 龙威 Traditional Chinese medicine used in radiology department and for preventing ographic contrast nephropathy, and preparation method

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105125803A (en) * 2015-08-28 2015-12-09 龙威 Traditional Chinese medicine used in radiology department and for preventing ographic contrast nephropathy, and preparation method

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105963569A (en) * 2016-06-25 2016-09-28 许风英 Traditional Chinese medicine preparation for preventing and alleviating side effect of iodic contrast agent
CN105963570A (en) * 2016-06-25 2016-09-28 张元春 Traditional Chinese medicine preparation for preventing and alleviating side effect of iodic contrast agent
CN106074991A (en) * 2016-06-30 2016-11-09 姜拥军 A kind of combination of Chinese and Western medicine mode treats Chinese medicine and the preparation method of radiographic contrast nephropathy
CN112316069A (en) * 2020-11-27 2021-02-05 温州市人民医院 Pill for treating adverse reaction after CT enhanced scanning and preparation method

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Application publication date: 20160323