CN101843876B - Chinese medicinal composition for preventing renal cell apoptosis and anemia caused by cis-platinum (DDP) and preparation method thereof - Google Patents
Chinese medicinal composition for preventing renal cell apoptosis and anemia caused by cis-platinum (DDP) and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a Chinese medicinal composition for preventing renal cell apoptosis and anemia caused by cis-platinum (DDP) and a preparation method thereof. The Chinese medicinal composition comprises the following raw material medicaments in part by weight: 5 to 10 parts of ginseng, 20 to 30 parts of astragalus, 20 to 30 parts of root of rehmannia, 10 to 15 parts of largehead atractylodes rhizome, 10 to 30 parts of Chinese angelica, 10 to 15 parts of medlar, 10 to 30 parts of tuber fleeceflower root, 10 to 15 parts of glossy privet fruit, 10 to 15 parts of Indian buead, 6 to 10 parts of bupleurum, 10 to 15 parts of turmeric root-tuber and 15 to 30 parts of pearl barley. The preparation method comprises the following steps of: 1) washing the raw material medicaments and drying the washed raw material medicaments; and 2) soaking the raw material medicaments in cold water for 4 to 6 hours, decocting the soaked medicaments under normal pressure for 2 to 3 hours, standing obtained decoction for 12 to 28 hours, condensing supernate into extract, granulating the extract and drying the granules to obtain the Chinese medicinal composition. The Chinese medicinal composition of the invention is an effective medicament for relieving renal toxicity and blood toxicity of the DDP, can enhance the anti-tumor activity of the DDP and can be used in the treatment of various malignant tumors together with the DDP.
Description
Technical field
The present invention relates to Chinese medicine composition and preparation method thereof, particularly relate to a kind of Chinese medicine composition that is used to prevent nephrocyte apoptosis and anemia due to the cisplatin and preparation method thereof.
Background technology
Cisplatin (DDP) is a kind of cancer therapy drug of extensive use.Clinical research shows: the DDP antitumaous effect is strong, does not have characteristics such as cross-resistance with other cancer therapy drugs, has obtained significant curative effect in the treatment of multiple malignant tumor, and it is a kind of cancer therapy drug more likely at present.But DDP has tangible toxicity:
One of toxicity: anemia usually appears in clinical practice DDP treatment tumor patient, the Hb level descends, and Hb is bringing into play very important effect in oncotherapy.Discover that Hb has the effect of nitric oxide (NO) synthetase inhibitors and NO scavenger, can alleviate the dilating effect of NO, reduce the blood flow of tumor tissues, make the required source of nutrition of tumor growth limited blood vessel.Other discovers that Hb can obviously improve the anoxia state of tumor cell, improves the sensitivity of tumor cell chemotherapy and radiation.Therefore keep the normal level of Hb in the concurrent chemoradiotherapy of malignant tumor treatment,, improve patient's life quality and have very significant values improving curative effect.
At present, the anemia that causes for chemotherapy clinically mainly contains two kinds of Therapeutic Method: blood transfusion and injection recombinant human erythropoietin (rHuEpo).Blood transfusion is traditional method, also be to alleviate the fastest method of anemia, but blood transfusion has many danger, as acute transfusion reaction, blood transfusion acute lung injury, bacteremia, transmitted virus, cause that alloimmunity and immunity weaken etc., thereby may incur loss through delay patient's treatment or stimulate tumor growth.A large amount of studies show that, rHuEpo can improve the anemia that chemotherapy such as DDP causes effectively, promotes the differentiation and the propagation of CFU-E, has avoided blood transfusion repeatedly simultaneously and because the untoward reaction that blood transfusion brings, for condition has been created in patient's chemotherapy and rehabilitation.In anemiaing correcting, patient's appetite is improved, and nutrient substance is taken in to be increased, and erythropoietin also can partly be corrected the intravital abnormal amino acid metabolism of patient, thereby patient's nutriture is improved.But in the process of using rHuEpo treatment renal anemia, some very important problems have appearred also.As: the several weeks that begin to use rHuEpo in the several months, hypertension can take place about 25% patient or original hypertension increases the weight of, common available antihypertensive drugs or increase the dialysis ultrafiltration and corrected.In addition, the thrombotic danger of arteriovenous fistula may increase in the patient who accepts the rHuEpo treatment.Other has test to point out in some case, need use 3～5 times of rHuEpo standard dose to normal level for regulating haemachrome concentration, not only having increased medical expense also makes the probability that has side effects strengthen, and be not that index such as haemachrome concentration all makes moderate progress in all patients, may worsen sometimes.
Be easy to the proximal tubule epithelial cell at the kidney medulla externa after two of toxicity: DDP enters in the body, particularly the S3 section is accumulated, and 28%～36% patient accepts the cisplatin (50～100mg/m of predose
2) and cause acute renal failure, mainly show as the biochemical and cell function disorder of renal cells, comprise that Profilin is synthesized, the apoptosis of oxidative stress, mitochondrial injury, cytoskeleton reconstruct, the adherent variation of iuntercellular and renal cells.Studies show that, the inductive renal cells apoptosis of DDP is a kind of important mechanisms that DDP produces nephrotoxicity, therefore suppressing the renal cells apoptosis is the important measures of prevention and treatment cisplatin nephrotoxicity, reduces the generation of cisplatin nephrotoxicity, could help tumor treatment more.
Clinical practice shows, the curative effect of heavy dose of DDP treatment kinds of tumors is better than low dose of therapeutic effect, but its nephrotoxicity is also bigger, because finding is arranged when renal failure generation death cases is reported due to the DDP, for this reason, Chinese scholars is devoted to various preventions and is alleviated the DDP nephrotoxicity, improves the research of clinical efficacy, studies show that: amifostine, ligustrazine can suppress cisplatin and cause the nephrocyte apoptosis, have certain effect to alleviating the DDP nephrotoxicity.At present, clinically mainly adopt aquation diuresis method for heavy dose of DDP nephrotoxicity, evident in efficacy, but more because of needs intravenous drip liquid, many patients are difficult to tolerance and end treatment.
Some Chinese medicines not only have antitumor action, and have extraordinary effect aspect the toxicity that cancer therapy drug causes alleviating, and adopt the Chinese medicine antitumor and alleviate the research of chemotherapeutics side effect very general in China.Be used for Chinese medicine composition of assistant treating cancer and preparation method thereof for 200510002104.7 1 kinds as Chinese patent, disclosing is a kind of Chinese medicine composition that is used for cancer radiation, chemotherapy auxiliary treatment, it mainly is aided with Poria, the Rhizoma Atractylodis Macrocephalae, Fructus Lycii, Colla Corii Asini and eight kinds of raw material of Chinese medicine assembly of Radix Rehmanniae with lentinan, Rhizoma Dioscoreae, Caulis Spatholobi, be used to alleviate feeling sick that radiotherapy, chemotherapy causes, inappetence, toxicities such as hemogram variation, but and enhancing human body immunity function and resistance.The research of Chinese medicine compound control DDP nephrotoxicity is few; Yang Chengxiong etc. adopt the kidney protective agent of school's preparation Cordyceps Capsulae Radix Panacis Quinquefolii as cisplatin chemotherapy; obviously improved renal function (Chinese Hospitals pharmaceutical journal 2007; 27 (8): 1103-1104), a few flavor Chinese herbal medicine such as the Cordyceps that uses in the said preparation, Radix Panacis Quinquefolii, Placenta Hominis.There is tangible preventive and therapeutic effect (Chinese Hospitals pharmaceutical journal 1996,16 (10): 438-440), use Radix Ginseng, the Radix Astragali, Radix Angelicae Sinensis, Radix Salviae Miltiorrhizae, Radix Et Rhizoma Rhei etc. in this decoction application decoction of ten powerful tonics plus-minus sides such as Zhou Shiwen to the injury of kidney due to the cisplatin.Though these Chinese prescriptions have alleviated the toxicity of DDP from some aspect, the anemia and the nephrocyte apoptosis specific aim of bringing out for some obvious toxic and side effects such as DDP are not strong.
Summary of the invention
The invention provides a kind of determined curative effect be used to prevent nephrocyte apoptosis and anemia due to the DDP, and have the Chinese medicine composition of anticancer synergia effect.
For solving the problems of the technologies described above, the present invention takes following technical scheme:
A kind of Chinese medicine composition that prevents nephrocyte apoptosis and anemia due to the cisplatin, this Chinese medicinal composition comprises following bulk drugs: Radix Ginseng 5-10 weight portion, Radix Astragali 20-30 weight portion, Radix Rehmanniae 20-30 weight portion, Rhizoma Atractylodis Macrocephalae 10-15 weight portion, Radix Angelicae Sinensis 10-30 weight portion, Fructus Lycii 10-15 weight portion, Radix Polygoni Multiflori 10-30 weight portion, Fructus Ligustri Lucidi 10-15 weight portion, Poria 10-15 weight portion, Radix Bupleuri 6-10 weight portion, Radix Curcumae 10-15 weight portion, Semen Coicis 15-30 weight portion.
The weight proportion of preferred each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 15 weight portions, Radix Polygoni Multiflori 10 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 10 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
The weight proportion of preferred each crude drug is: Radix Ginseng 10 weight portions, the Radix Astragali 30 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 15 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 10 weight portions, Radix Polygoni Multiflori 10 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 10 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
The weight proportion of preferred each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 30 weight portions, Fructus Lycii 10 weight portions, Radix Polygoni Multiflori 20 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 6 weight portions, Radix Curcumae 15 weight portions, Semen Coicis 15 weight portions.
The weight proportion of preferred each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 30 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 15 weight portions, Radix Polygoni Multiflori 15 weight portions, Fructus Ligustri Lucidi 15 weight portions, Poria 10 weight portions, Radix Bupleuri 6 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
When needing, in said medicine, can also add one or more acceptable accessories, described adjuvant comprises diluent, excipient, filler, binding agent, wetting agent, absorption enhancer, surfactant, lubricant, stabilizing agent of pharmaceutical field routine etc., also can add flavouring agent, sweeting agent and pigment etc. in case of necessity.
Second purpose of the present invention provides a kind of method for preparing the Chinese medicine composition of nephrocyte apoptosis and anemia due to the above-mentioned prevention cisplatin.
Preparation method provided by the present invention can may further comprise the steps:
1) crude drug is cleaned, dried;
2) crude drug was soaked 4-6 hour with cold water, under normal pressure, decocted 2-3 hour again, the gained decocting liquid was left standstill 12-28 hour, get supernatant concentration and become extractum, granulate, drying, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
Chinese medicine composition of the present invention is also contained all suitable dosage forms.This Chinese medicine composition can be made acceptable drug form on any galenic pharmacies such as capsule, the watered pill, tablet, granule, powder, oral liquid, injection, is preferably the capsule or the watered pill.
The recommended dose of pharmaceutical composition of the present invention is equivalent to 2.25g crude drug/day/kg body weight for adult's (pressing the 60kg body weight calculates) 135g every day.
Zoopery is the result prove: medicine of the present invention can prevent the generation of nephrocyte apoptosis due to the cisplatin, the also generation of anemia due to the prevention of the method by the invigorating the spleen and benefiting QI invigorating kidney, promoting blood circulation cisplatin, effect is remarkable, and do not influence the anti-tumor activity of cisplatin, can fundamentally reach the purpose of efficacy enhancing and toxicity reducing with DDP with using, and have no adverse reaction and side effect.Each component of the present invention is common Chinese herbal medicine, and cost is low, when having alleviated patient's slight illness, has also reduced patient's financial burden.In addition, this medical instrument has taking convenience, and the advantage of low production cost is convenient to apply.The present invention will play a great role in the prevention of nephrocyte apoptosis and anemia due to the cisplatin.
Description of drawings
Fig. 1 shows the comparison that the renal cortical cell apoptosis changes (x ± s)
Fig. 2 shows normal control group nephridial tissue section (HE10 * 40)
Fig. 3 shows DDP group nephridial tissue section (HE10 * 10)
Dosage Chinese drug-treated group nephridial tissue section (HE10 * 20) during Fig. 4 shows
Fig. 5 shows normal control group renal cortical cell (TEM * 5000)
Fig. 6 shows DDP group renal cortical cell (TEM * 5000)
Fig. 7 shows DDP group renal cortical cell (TEM * 6000) when injecting 7 days
Fig. 8 shows DDP group renal cortical cell (TEM * 5000) when injecting 7 days
Fig. 9 shows DDP group renal cortical cell (TEM * 6000) when injecting 7 days
Dosage Chinese drug-treated group proximal convoluted tubule (TEM * 4000) during Figure 10 shows when injecting 7 days
The specific embodiment
The patient who uses cisplatin chemotherapy clinically usually shows and has a dizzy spell, and the whole body is weak, the lazy speech of breathing hard, and shallow complexion, soreness of the waist and knees, urine is reduced, lower limbs edema, loss of appetite, nausea and vomiting, pale tongue or light red, how heavy thin arteries and veins is.This is because the chemotherapeutic toxicity medicine is sent an expedition against tumor impairing the spleen and stomach simultaneously from traditional Chinese medical science angle analysis, involves kidney yang, and dysfunction of the spleen in transportation and transformation, medulla renis lose supports, and the blood biochemical source does not fill, lifting imbalance, clear QI being mixed up with turbid QI, clear QI failing to ascend, turbid YIN failing to descend.Invigorating the spleen and benefiting QI is suitable in treatment, and warming the kidney to invigorate YANG is transferred the spleen reinforcing kidney, replenishes medulla renis, transporting and transforming nutrients from foodstuff, biochemical blood, ascending the clear and descending the turbid.
The present invention is on the basis of motherland's traditional medicine, in conjunction with the modern pharmacology investigative technique, to the Chinese herb medicine reasonable compatibility of the effect that filters out, obtained a kind of Chinese medicine composition that prevents nephrocyte apoptosis and anemia due to the cisplatin with invigorating the spleen and benefiting QI, invigorating kidney, promoting blood circulation.In compound recipe assembly process, need the special concertedness of considering between each material medicine, the Chinese prescription that has formed determined curative effect and had good stability.
Chinese medicinal composition provided by the invention comprises following bulk drugs: Radix Ginseng 5-10 weight portion, Radix Astragali 20-30 weight portion, Radix Rehmanniae 20-30 weight portion, Rhizoma Atractylodis Macrocephalae 10-15 weight portion, Radix Angelicae Sinensis 10-30 weight portion, Fructus Lycii 10-15 weight portion, Radix Polygoni Multiflori 10-30 weight portion, Fructus Ligustri Lucidi 10-15 weight portion, Poria 10-15 weight portion, Radix Bupleuri 6-10 weight portion, Radix Curcumae 10-15 weight portion, Semen Coicis 15-30 weight portion.
In drug composition of the present invention, use Radix Ginseng, the Radix Astragali, Radix Angelicae Sinensis, Radix Polygoni Multiflori benefiting vital QI and blood, Fructus Lycii, the Radix Rehmanniae, Fructus Ligustri Lucidi kidney tonifying, essence replenishing hemopoietic, the Rhizoma Atractylodis Macrocephalae, Poria, Semen Coicis invigorating spleen to remove dampness, Radix Curcumae, Radix Bupleuri depressed liver-energy dispersing and QI regulating make qi and blood circulation, and regulating the liver and spleen is to promote the source day after tomorrow, pros share, and have obviously alleviated anemia and nephrocyte apoptosis that DDP brings out.Wherein, the property of medicine function of single medicinal material is respectively:
Radix Ginseng: it is earlier in chemotherapy that Radix Ginseng is intended to real whole body vigour, with toleration, the adaptability of enhancing body to chemotherapeutics.Radix Ginseng has immunologic function, antitumor and the hypoglycemic activity of promotion, and Radix Ginseng can also promote hemopoietic function, and effects such as resisting fatigue, stimulating central nervous system are arranged.
The Radix Astragali: the Radix Astragali has the effect of vital energy benefiting and the kidney invigorating, diuretic detoxification, strengthening vital QI to eliminate pathogenic factors.The astragaloside that is rich in the Radix Astragali, astragalus polysaccharides, osajin platform thing and selenium element etc., can remove free radical. remove lipid peroxide, alleviate the infringement of peroxidase cell membrane, thereby can improve the kidney oxidation resistance, improve the progressive kidney injury that dyslipidemias causes, stop glomerular sclerosis and changing function; The Radix Astragali contains 21 seed amino acids, participates in the multiple metabolism of body, and wherein glutamic acid, glycine are the precursor substances of synthesizing glutathion in the body, and glutathion can reduce the nephrotoxicity of cisplatin as heavy metal scavenger and antioxidant, but does not reduce its anti-tumor activity; The Radix Astragali can be by changing the body levels of cyclic nucleotides, suppressing PDE. protection and links such as two-ways regulation T cell and B cell are come the non-specific immunity of enhancing body, regulate humoral immunization and impel cellular immunization to trend towards normally, thereby can reduce the deposition of plasma protein one CDDP complex in kidney by immune modification and immunity identification. reduce the immune complex of kidney mesangial region. alleviate the kidney pathological lesion; Radix Astragali tool diuresis, the energy renal blood flow increasing, the inhibition RAAS of feedback, the inner reaction of raising renal tubular cell increases the urine amount, promotes muriatic metabolism, reaches the purpose of improving renal function.This kind effect may be relevant with contained betanin, the formononetin of the Radix Astragali.
Radix Ginseng is joined Radix Astragali energy human body immunity improving function, promotes hemopoietic function, and resisting fatigue, anti-hypoxia, antitumor, anti-aging effects are all arranged.
The Radix Rehmanniae: the Radix Rehmanniae has the immunologic function of adjusting can obviously improve lymphocyte DNA and proteinic synthetic; generation to the lymphocytic interleukin II of activity (IL-2) has tangible potentiation; low cellular immune function is strengthened; can protect owing to having used cyclophosphamide and dexamethasone to cause immunosuppressant, its effective ingredient is a polysaccharide.The Radix Rehmanniae has bringing high blood pressure down, improves renal function, reduces the effect of renal hypertension to anesthetized dog, and its mechanism of action may cause that blood pressure drops is relevant with the ratio that changes cAMP, cGMP.The Radix Rehmanniae has weak diuresis, and its diuresis mechanism is relevant with the nephrectasia blood vessel with heart tonifying, and its effective ingredient is pure glycosides and derivant thereof.The Radix Rehmanniae has stimulation bone marrow, increases the effect of erythrocyte, hemoglobin, platelet promotion hematopoietic cell function; The Radix Rehmanniae also has antitumor, antiinflammatory, calmness and promotes rats'liver, the synthetic effect of nephridial tissue albumen.In a word, this product has hemostasis, heart tonifying, diuresis, blood sugar lowering, antiinflammatory, effect such as protects the liver.
The Rhizoma Atractylodis Macrocephalae: the Rhizoma Atractylodis Macrocephalae has protecting the liver, promotes immunologic function, antitumor and hypoglycemic activity, and the Rhizoma Atractylodis Macrocephalae can antiulcer and promoted gastrointestinal peristalsis.So partner treatment anemia, diabetes, tumor etc. have better curative effect.The Rhizoma Atractylodis Macrocephalae can suppress renal tubules to the absorption of electrolyte and water and play diuresis
Radix Angelicae Sinensis: Radix Angelicae Sinensis can improve glomerule filtering function and the heavy absorption function of renal tubules behind the rabbit kidney ischemia, alleviates renal damage, promotes the recovery of renal tubules pathological changes.The Radix Angelicae Sinensis effective ingredient is a L MALIC ACID sodium, and L MALIC ACID sodium can generate amino platinum with the DDP reaction, can make DDP lose nephrotoxicity, and not influence its anti-tumor activity.Radix Angelicae Sinensis can improve tissue SOD's activity, removes oxygen-derived free radicals, reduces normal lipofuscin content and the Mitochondrial H in hypoxic-ischemic mouse brain, the hepatic tissue that reach
2O
2Generate, suppress the generation of platelet MDA, improve Aged Mice brain, liver SOD level, reduce Aged Mice brain lipofuscin content, improve the DNA damage repair ability of Aged Mice, prolong silkworm, people's tire nephrocyte and mouse kidney cell life span, improve the rat hypoxia-bearing capability, antagonism vitamin E deficiency chickling encephalopathy prolongs its life-span.Radix Angelicae Sinensis and Radix Astragali compatibility have good synergism, have the effect of the two accent of QI and blood, reinforcing the heart QI invigorating, nourshing blood and promoting blood circulation.
Fructus Lycii: Fructus Lycii has effects such as good antioxidation, slow down aging, promotion immunity, Antiradiation injury, blood fat reducing, it is generally acknowledged, the lycium barbarum polysaccharide that contains in the Fructus Lycii is its main component that plays a role, antioxidant activity result of study to lycium barbarum polysaccharide shows that it is approaching that lycium barbarum polysaccharide is removed hydroxyl radical free radical, alkyl diradical, DPPH free radical ability and Vc.Lycium barbarum polysaccharide has significant protective effect to the mouse testis cell DNA oxidative damage that hydrogen peroxide causes, and is inhibited to the testicular cell DNA damage due to the oxidative stress.Lycium barbarum polysaccharide can obviously improve the activity of superoxide dismutase, glutathion peroxidase in the mice body and the content that significantly reduces malonaldehyde and lipofuscin.The oxidation resistance of Fructus Lycii heterogeneity is followed successively by dried fruit of lycium barbarum＞lycium barbarum polysaccharide＞Fructus Lycii slag＞betanin.Lycium barbarum polysaccharide has the function of regulating cellular immunization and humoral immunization, it mainly acts on and shows that T, bone-marrow-derived lymphocyte propagation, T cell subsets, CTL, NK and M etc. are had tangible regulating action, and production of cytokines such as IL-2, IL-6 and TNF are had facilitation.Fructus Lycii also has important effect at anti-tumor aspect, lycium barbarum polysaccharide can be simplified the cell induction and the reduction IL-2 consumption of the killer cell (LAK) of lymphokineactivation, can raise immunity, alleviate the chemicotherapy side effect, can promote hemopoietic function, correction hemopoietic disorder, 60 irradiations have antagonism to cobalt, and the radiotherapy primary lung cancer is had enhancement effect
Radix Polygoni Multiflori: Radix Polygoni Multiflori can improve tissue SOD's activity, removes oxygen-derived free radicals, reduces normal lipofuscin content and the Mitochondrial H in hypoxic-ischemic mouse brain, the hepatic tissue that reach
2O
2Generate, suppress the generation of platelet MDA, improve Aged Mice brain, liver SOD level, reduce Aged Mice brain lipofuscin content, improve the DNA damage repair ability of Aged Mice, prolong silkworm, people's tire nephrocyte and mouse kidney cell life span, improve the rat hypoxia-bearing capability, antagonism vitamin E deficiency chickling encephalopathy prolongs its life-span.But the Radix Polygoni Multiflori enhancing human body immunity, the immunosuppressive effect of antagonism cortisone and cyclophosphamide strengthens resisting fatigue, radioprotective and the anti-stress ability of normal and disease model mice.
Fructus Ligustri Lucidi: Fructus Ligustri Lucidi extracting solution has tangible antioxidation, anti-aging effects, and Fructus Ligustri Lucidi polysaccharide can make MDA decline in aging model Mouse Liver, the nephridial tissue, improves the vigor of SOD and glutathion peroxidase, makes lipofuscin decline in the cerebral tissue.Fructus Ligustri Lucidi polysaccharide also can be by removing OH, improves the vigor of SOD and glutathion peroxidase and bring into play anti peroxidation of lipid and anti-aging effects.Iridoid in the Fructus Ligustri Lucidi has stronger antioxidation, can suppress the erythrocyte hemolysis of free yl induction.Fructus Ligustri Lucidi extract has inhibitory action to tumor cells such as A548, and its antitumor action is relevant with the effect that it has inhibition tumour cell reversing record enzyme and multiple archaeal dna polymerase.Fructus Ligustri Lucidi all has regulating action to specificity and nonspecific immunity, and Fructus Ligustri Lucidi water extract can improve the lymphocytic function of T, promotes the lymphopoiesis that PHA, ConA and PWM cause.
Poria: Poria can suppress renal tubules to the absorption of electrolyte and water and play diuresis.But Poria is enhancing human body immunity also, and the immunosuppressive effect of antagonism cortisone and cyclophosphamide strengthens resisting fatigue, radioprotective and the anti-stress ability of normal and disease model mice.Pachyman can increase T-SOD and Cu-SOD activity in old people's serum in various degree, reduces MDA content, has cold-resistant, resisting fatigue and anti-aging effects.
Radix Bupleuri: Radix Bupleuri have evacuate bring down a fever, dispersing the stagnated live-QI to relieve the stagnation of QI makes qi and blood circulation, effects such as regulating the liver and spleen.The main effective ingredient of Radix Bupleuri is saikoside and volatile oil.Modern age, pharmacological research showed, effect such as Radix Bupleuri has protecting the liver, improves immunity, antitumor.
Radix Curcumae: Radix Curcumae has the effect of blood-activating and qi-promoting pain relieving, heart fire-clearing upset-relieving, promoting the function of the gallbladder to alleviate jaundice, cooling blood for hemostasis.Modern age, pharmacological research showed, Radix Curcumae have protect the liver, free radical resisting damage, anticancer, improve immunity.
Semen Coicis: Semen Coicis is the Chinese medicine of China's folk tradition, and the effect of spleen invigorating, tonifying the lung, antiinflammatory, diuresis, eliminating dampness by diuresis, evacuation of pus, town's disease and pain relieving is arranged.In recent years experiment showed, that the Semen Coicis ester in the Semen Coicis is a kind of cancer-resisting substance, cancerous cell is had inhibitory action, contain the very high heart of a lotus seed of medical value eight alcohol and β-γ in the Semen Coicis, 2 kinds of sitosterol, these special composition also are the secret places that Semen Coicis has protective effect on cancer risk.
Preparation method provided by the present invention, with the above-mentioned raw materials medicine by the side take by weighing after, soaked 4-6 hour with cold water, under normal pressure, decocted 2-3 hour again, the gained decocting liquid was left standstill 12-28 hour, get supernatant concentration and become extractum, granulate, drying, promptly obtain preventing the Chinese medicine composition of nephrocyte apoptosis and anemia due to the cisplatin.
Below further specify the present invention with specific embodiment.Following embodiment 1-4 adopts best experimental program of the present invention, and those of ordinary skill in the art can expect some identical, replacement schemes apparently according to content disclosed by the invention, all should belong to disclosure of the present invention.Method therefor is conventional method if no special instructions among the embodiment.
The Chinese medicine composition of anemia due to embodiment 1, the preparation prevention cisplatin
With the Chinese medicine composition of anemia due to the method preparation prevention cisplatin of the present invention, concrete grammar may further comprise the steps:
1) weighting raw materials: Radix Ginseng 50g, Radix Astragali 200g, Radix Rehmanniae 200g, Rhizoma Atractylodis Macrocephalae 100g, Radix Angelicae Sinensis 100g, Fructus Lycii 150g, Radix Polygoni Multiflori 100g, Fructus Ligustri Lucidi 100g, Poria 100g, Radix Bupleuri 100g, Radix Curcumae 100g, Semen Coicis 150g.
2) crude drug is cleaned, dried.
3) crude drug is soaked 5 hours (4-6 hour all can) with cold water, under normal pressure, decoct 2.5 hours (2-3 hour all can) again, the gained decocting liquid is left standstill 20 hours (12-28 hour all can), get supernatant concentration and become extractum, granulation, drying, incapsulate or make the watered pill, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
The Chinese medicine composition of anemia due to embodiment 2, the preparation prevention cisplatin
With the Chinese medicine composition of anemia due to the method preparation prevention cisplatin of the present invention, concrete grammar may further comprise the steps:
1) weighting raw materials: Radix Ginseng 100g, Radix Astragali 300g, Radix Rehmanniae 200g, Rhizoma Atractylodis Macrocephalae 150g, Radix Angelicae Sinensis 100g, Fructus Lycii 100g, Radix Polygoni Multiflori 100g, Fructus Ligustri Lucidi 100g, Poria 100g, Radix Bupleuri 100g, Radix Curcumae 100g, Semen Coicis 150g.
2) crude drug is cleaned, dried.
3) crude drug was soaked 4 hours with cold water, under normal pressure, decocted 3 hours again, the gained decocting liquid was left standstill 28 hours, get supernatant concentration and become extractum, granulate, drying, make the watered pill, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
The Chinese medicine composition of anemia due to embodiment 3, the preparation prevention cisplatin
With the Chinese medicine composition of anemia due to the method preparation prevention cisplatin of the present invention, concrete grammar may further comprise the steps:
1) weighting raw materials: Radix Ginseng 50g, Radix Astragali 200g, Radix Rehmanniae 200g, Rhizoma Atractylodis Macrocephalae 100g, Radix Angelicae Sinensis 300g, Fructus Lycii 100g, Radix Polygoni Multiflori 200g, Fructus Ligustri Lucidi 100g, Poria 100g, Radix Bupleuri 60g, Radix Curcumae 150g, Semen Coicis 150g.
2) crude drug is cleaned, dried.
3) crude drug was soaked 6 hours with cold water, under normal pressure, decocted 2 hours again, the gained decocting liquid was left standstill 12 hours, get supernatant concentration and become extractum, granulate, drying, incapsulate, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
The Chinese medicine composition of anemia due to embodiment 4, the preparation prevention cisplatin
With the Chinese medicine composition of anemia due to the method preparation prevention cisplatin of the present invention, concrete grammar may further comprise the steps:
1) weighting raw materials: Radix Ginseng 50g, Radix Astragali 200g, Radix Rehmanniae 300g, Rhizoma Atractylodis Macrocephalae 100g, Radix Angelicae Sinensis 100g, Fructus Lycii 150g, Radix Polygoni Multiflori 150g, Fructus Ligustri Lucidi 150g, Poria 100g, Radix Bupleuri 60g, Radix Curcumae 100g, Semen Coicis 150g.
2) crude drug is cleaned, dried.
3) crude drug was soaked 5.5 hours with cold water, under normal pressure, decocted 2.8 hours again, the gained decocting liquid was left standstill 24 hours, get supernatant concentration and become extractum, granulate, drying, make the watered pill, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
Experiment one, pharmaceutical composition of the present invention are to the influence of DDP anti-tumor activity
Pharmaceutical composition recommended dose of the present invention is equivalent to 2.25g crude drug/day/kg body weight for adult's (pressing the 60kg body weight calculates) 135g every day.Three dosage groups are established in experiment, are equivalent to 5 times, 10 times, 15 times of human body recommended amounts, and promptly every day, 11.25g crude drug/kg, 22.5g crude drug/kg, 33.75g crude drug/kg were respectively low dosage Chinese drug-treated group, middle dosage Chinese drug-treated group, high dose Chinese drug-treated group.
(1) laboratory animal and reagent
Laboratory animal: Kunming mouse, ♀ ♂ half and half, body weight 18-22g is available from Hebei province's Experimental Animal Center.
Reagent: DDP: injection, Dezhou, Shandong pharmaceutical factory produces.
The tumor strain: the S180 type, available from Experimental Animal Center Animal Experimental Study chamber, Hebei province.
(2) pharmaceutical composition of the present invention is to the test of DDP antitumor action
Kunming mouse abdominal cavity inoculation S180 recovery was got ascites on the 6th day, and transferring cell concentration is 1 * 10
8Individual/mL, according to a conventional method, inoculate this tumor liquid 0.2mL for respectively 50 kunming mices, subcutaneous in the right fore armpit, behind the 24h 50 mices are divided into 5 groups at random, normal saline group, DDP group, low dosage Chinese drug-treated group, middle dosage Chinese drug-treated group, high dose Chinese drug-treated group.The disposable injection isometric(al) of normal saline group normal saline, DDP and three the disposable injection DDP of dosage Chinese drug-treated group 8mg/kg, three dosage Chinese drug-treated group are irritated stomach with Chinese herbs decoction simultaneously, 7 days execution mices behind the inoculation tumor liquid, win tumor tissue and weigh the heavy suppression ratio of calculating tumor.
(3), result and analysis
Referring to table 1.
Table 1 pharmaceutical composition of the present invention is to the influence of DDP anti-tumor activity (X ± S)
| Group | Tumor heavy (g) | The heavy suppression ratio (%) of tumor |
| The normal saline group | 1.923±0.68 | 0 |
| The DDP group | 0.465±0.23 ** | 75.8％ |
| The low dosage Chinese drug-treated group | 0.421±0.16 ** | 76.5％ |
| Middle dosage Chinese drug-treated group | 0.382±0.19 ** | 78.16％ |
| The high dose Chinese drug-treated group | 0.375±0.26 ** | 78.42％ |
As can be seen from Table 1, give lotus tumor S180 mice shot DDP 8mg/kg, the heavy suppression ratio of tumor is 75.8%, very significantly less than normal saline group tumor heavy (P＜0.01). and each Chinese drug-treated group of DDP+ is single heavily slightly light with DDP group tumor, but difference does not have significance (P＞0.05).
The prevention of toxic and side should be a prerequisite not weaken its antitumor usefulness.The tumor body average weight of each Chinese drug-treated group is all used the cisplatin group less than single, but both there was no significant differences (P＞0.05).Each Chinese drug-treated group and single tumor body average weight with the cisplatin group all obviously are lighter than the normal saline group (P＜0.01) without cisplatin.Above-mentioned experimental result shows that the utilization of Chinese medicine does not have to reduce even may strengthen the anti-tumor activity of cisplatin.The heavy a little higher than middle dosage Chinese drug-treated group of the tumor of high dose Chinese drug-treated group, but both do not have significant difference (P＞0.05).Illustrate that pharmaceutical composition of the present invention does not influence the anti-tumor activity of DDP.
The effect experiment of experiment two, pharmaceutical composition of the present invention anemia due to the prevention cisplatin
The recommended dose of pharmaceutical composition of the present invention is equivalent to 2.25g crude drug/day/kg body weight for adult's (pressing the 60kg body weight calculates) 135g every day.Three dosage groups are established in experiment, are equivalent to 5 times, 10 times, 15 times of human body recommended amounts, and promptly every day, 11.25g crude drug/kg, 22.5g crude drug/kg, 33.75g crude drug/kg were respectively low dosage Chinese drug-treated group, middle dosage Chinese drug-treated group, high dose Chinese drug-treated group.
(1) laboratory animal and reagent
Laboratory animal: male SD rat, body weight 180-220g, available from Beijing Medical University's Experimental Animal Center, quality certification Scxk 11-00-0004.
Reagent: the DDP injection, Dezhou, Shandong pharmaceutical factory produces.
(2) laboratory animal grouping and processing
The laboratory animal routine feeding is divided into 5 groups after one week at random, normal control group (n=12), DDP group (n=12), low dosage Chinese drug-treated group (n=12), middle dosage Chinese drug-treated group (n=12), high dose Chinese drug-treated group (n=12).Cisplatin group and three the disposable tail vein injection DDP of Chinese drug-treated group 8mg/kg, normal control group injection isometric(al) normal saline, injection DDP rose the same day, three Chinese drug-treated group are irritated stomach with Chinese herbs decoction, irritating body of stomach long-pending is the 1mL/100g body weight, once a day, continuous irrigation stomach 21 days, respectively at the 7th day, the 21st day each treated animal heart extracting blood 1.5-2 milliliter under waking state, detect the content of rat whole blood hemoglobin (Hb), erythrocyte (RBC) and serum erythropoietin (Epo), blood urea nitrogen (BUN).In whole experiment, remember the animal amount of drinking water every day, regularly survey body weight.
(3) statistical analysis: adopt SPSS to carry out statistical analysis, test data is all with mean ± standard deviation (x ± s) expression.
(4), result and analysis
1, general situation
Cisplatin group rat is injected and beginning to occur ingesting obviously minimizing on the cisplatin same day or second day, few moving closing one's eyes, lethargy, curling hogback, emaciated physique, hair color tarnishing.Normal control group well-grown does not have above-mentioned phenomenon.Middle dosage Chinese drug-treated group does not have above-mentioned phenomenon substantially.Low dosage Chinese drug-treated group and high dose Chinese drug-treated group symptom are lighter.
2, pharmaceutical composition of the present invention causes the influence of rat whole blood Hb (g/L), RBC number of variations to DDP
Referring to table 2 data.By table 2 as seen, the 21st day, Hb, the RBC of DDP group rat are starkly lower than normal control group (p＜0.01), Hb, the RBC of middle dosage Chinese drug-treated group is apparently higher than DDP group (p＜0.05), though the Hb of low dosage Chinese drug-treated group and high dose Chinese drug-treated group, RBC are higher than the DDP group, with DDP group no significant difference (p＞0.05).
This zoopery shows, of the present invention in the dose drug compositions can obviously alleviate rat Hb, the RBC that DDP causes and reduce, so can alleviate the anemia of the rat that cisplatin causes.
Table 2 is respectively organized the comparison (X ± S) of rat whole blood Hb changes of contents
*Compare with normal group
*P＜0.01
*P＜0.05
# compares ##P＜0.01 #P＜0.05 with the DDP group
3, pharmaceutical composition of the present invention causes the influence that rat blood serum Epo changes to DDP
Referring to table 3 data.By table 3 as seen, the 7th day, DDP group rat blood serum Epo is starkly lower than normal control group (P＜0.05), middle dosage Chinese drug-treated group rat blood serum Epo is apparently higher than DDP group (P＜0.05), the 21st day, DDP group rat blood serum Epo was apparently higher than normal control group (P＜0.05), and middle dosage Chinese drug-treated group rat blood serum Epo is starkly lower than DDP group (P＜0.05), though low dosage Chinese drug-treated group and high dose Chinese drug-treated group rat blood serum Epo are different with the DDP group, difference does not have significance (P＞0.05).
This zoopery shows, of the present invention in can obviously the raise reduction of rat blood serum Epo due to the DDP of dose drug compositions, alleviate the inhibitory action that DDP produces Epo, thereby suppress the anemia that DDP brings out.
Table 3 is respectively organized the comparison (X ± S) of rat BUN changes of contents
*Compare with the normal control group
*P＜0.01
*P＜0.05
# compares ##P＜0.01 #P＜0.05 with the DDP group
Test two results and show, the pharmaceutical composition of the present invention that per os gives the rat various dose can obviously alleviate the anemia of rat due to the DDP.In dosage Chinese drug-treated group Hb, RBC apparently higher than low dosage Chinese drug-treated group and high dose Chinese drug-treated group, confirmed that dosage and drug effect within the specific limits are the basic law of this pharmacodynamics of parallel relation.Point out the pharmaceutical composition of the present invention of suitable dosage could more effectively alleviate rat anemia due to the DDP.In the time of the 7th day, middle dosage Chinese drug-treated group rat blood serum Epo organizes apparently higher than DDP, illustrate that Chinese medicine can obviously alleviate the inhibitory action that DDP produces Epo, the serum Epo level of dosage Chinese drug-treated group rat is organized obvious decline Hb, RBC than the obviously rising of DDP group than DDP in after the 21st day, prompting Chinese medicine is by alleviating the inhibitory action that DDP produces Epo, and alleviated the anemia that DDP brings out, stimulated the erythrocytic growth of bone marrow.
Experiment three, the pharmaceutical composition of the present invention effect that the nephrocyte apoptosis takes place due to the prevention cisplatin
(1) laboratory animal and reagent
Laboratory animal: male SD rat, body weight 180-220g is provided by Beijing Medical University's Experimental Animal Center, quality certification Scxk 11-00-0004.
Reagent: the DDP injection, Dezhou, Shandong pharmaceutical factory produces
(2) laboratory animal grouping and processing
The laboratory animal routine feeding is divided into 5 groups after one week at random, normal control group (n=8), DDP group (n=8), low dosage Chinese drug-treated group (n=8), middle dosage Chinese drug-treated group (n=8), high dose Chinese drug-treated group (n=8).Cisplatin group and three the disposable tail vein injection DDP of Chinese drug-treated group 8mg/kg, normal control group injection isometric(al) normal saline, injection DDP rose the same day, and three Chinese drug-treated group are irritated stomach with Chinese herbs decoction, and irritating body of stomach long-pending is the 1ml/100g body weight, once a day, continuous irrigation stomach 7 days breaks end under waking state in the 7th day each treated animal and to get blood, and it is collected in the tubule that does not contain anticoagulant, after treating blood coagulation, centrifugal 10 minutes (3000 rev/mins).Get the content that serum is used to detect rat blood serum blood urea nitrogen (BUN), creatinine (Cr).Cut open the belly rapidly simultaneously and take out the bilateral kidney, remove peplos, it is fixing in (1) 10% formaldehyde to leave and take nephridial tissue, specimens paraffin embedding slices, and HE dyeing, the light border is observed.Be fixed for transmissioning electric mirror checking in (2) 2.5% glutaraldehydes.Being fixed for fluidic cell in (3) the 70% cold ethanol detects.(4) the rapid cold preservation of all the other specimen detects other indexs fully in-80 ℃ of refrigerators.Write down the animal diet followed amount every day in whole experiment, regularly surveys body weight.
(3) statistical analysis: adopt SPSS to carry out statistical analysis, test data is all with mean ± standard deviation (x ± s) expression.
(4) experimental result and analysis
1, general situation:
Cisplatin group rat is injected and beginning to occur ingesting obviously minimizing on the cisplatin same day or second day, few moving closing one's eyes, lethargy, curling hogback, emaciated physique, hair color tarnishing.Normal control group well-grown does not have above-mentioned phenomenon.Middle dosage Chinese drug-treated group does not have above-mentioned phenomenon substantially.Low dosage Chinese drug-treated group and high dose Chinese drug-treated group symptom are lighter.
2, pharmaceutical composition of the present invention causes the influence of rat blood serum BUN, Cr changes of contents to DDP
Experimental data is referring to table 4.As seen from Table 4, DDP group rat blood serum BUN, Cr content are all apparently higher than normal control group (P＜0.01), and middle dosage Chinese drug-treated group rat blood serum BUN, Cr content are starkly lower than DDP group (P＜0.05).Though low, high dose Chinese drug-treated group rat blood serum BUN, Cr content are lower than DDP group, there was no significant difference (P＞0.05).
This zoopery shows, of the present invention in the dose drug compositions can obviously alleviate rat BUN, the Cr that DDP causes and reduce, so can alleviate the nephrotoxicity of the rat that cisplatin causes.
Table 4 is respectively organized the variation (X ± S) of rat blood serum BUN, Cr content
| Group | BUN(mmol/L) | Cr(umol/L) |
| The normal control group | 5.47±0.51 | 45.64±13.86 |
| The DDP group | 14.83±3.39 ** | 96.71±17.91 ** |
| The low dosage Chinese drug-treated group | 13.21±3.24 | 88.43±21.11 |
| Middle dosage Chinese drug-treated group | 9.28±3.26## | 72.24±15.32# |
| The high dose Chinese drug-treated group | 11.19±3.51 | 81.97±14.06 |
Compare with the normal control group
*P＜0.01,
*##p＜0.01, #p＜0.05 are compared with the DDP group in p＜0.05
3, pharmaceutical composition of the present invention causes the influence of kidney of rats cortex MDA, SOD changes of contents to DDP
Referring to table 5 data.As can be seen from Table 5, DDP group kidney of rats cortex MDA content is apparently higher than normal control group (P＜0.01), middle dosage Chinese drug-treated group rat MDA content is starkly lower than DDP group (P＜0.05), though high and low dose Chinese drug-treated group rat MDA content is lower than DDP group, there was no significant difference (P＞0.05).
DDP group kidney of rats cortex SOD activity is starkly lower than the normal control group, and middle dosage Chinese drug-treated group SOD activity is apparently higher than DDP group (P＜0.05); Though active DDP group, the there was no significant difference (P＞0.05) of being higher than of low, high dose Chinese drug-treated group kidney of rats cortex SOD.
This zoopery shows that pharmaceutical composition of the present invention can reduce the nephrotoxicity that oxygen-derived free radicals content alleviates DDP by rising nephridial tissue SOD activity, shows that qi-supplementing, spleen-invigorating, kidney-tonifying side's medical instrument has the defencive function of pair kidney, anti-oxidation function.
Table 5 is respectively organized kidney of rats cortex MDA content, the active variation of SOD (X ± S)
| Group | SOD(Nu/mgprot) | MDA(nmol/mgprot) |
| The normal control group | 441.02±35.7 | 2.36±0.19 |
| The DDP group | 372.7±37.5 ** | 3.18±0.28 ** |
| The low dosage Chinese drug-treated group | 390.5±36.8 | 3.09±0.23 |
| Middle dosage Chinese drug-treated group | 418.64±38.5# | 2.86±0.25# |
| The high dose Chinese drug-treated group | 403.21±35.9 | 2.98±0.29 |
Compare with the normal control group
*P＜0.01,
*##p＜0.01, #p＜0.05 are compared with the DDP group in p＜0.05
4, pharmaceutical composition of the present invention causes the influence of rat kidney cell apoptosis to DDP
The fluidic cell testing result is seen shown in Figure 1, show: the injection DDP after the 7th day, DDP group kidney of rats cortex cell apoptosis rate content is apparently higher than normal control group (P＜0.01), middle dosage Chinese drug-treated group kidney of rats cortex cell apoptosis rate is starkly lower than DDP group (P＜0.05), though high and low dose Chinese drug-treated group kidney of rats cortex cell apoptosis rate is lower than DDP group, there was no significant difference (P＞0.05).
Nephridial tissue om observation: extremely shown in Figure 4 referring to Fig. 2.Rats in normal control group cell (referring to Fig. 2) structure is normal; In the DDP group rat cell (referring to Fig. 3), proximal tubular epithelial cells comes off, multiple, Distal convoluted tubule epithelial cell shedding, and the tube chamber cavitation expands into bulla, in the matter lymphocytic infiltration is arranged, the visible hyaline cast of urinary cast intracavity.The low dosage Chinese drug-treated group, the above-mentioned pathological change of high dose Chinese drug-treated group all alleviates to some extent, obviously diminishes as tubular ectasia, and middle dosage Chinese drug-treated group (referring to Fig. 4) be cannot see above-mentioned pathological changes basically, near normal group.
Nephridial tissue electron microscopic observation: referring to Fig. 5-shown in Figure 10.Rats in normal control group kidney cell (referring to Fig. 5) structure is normal, and endochylema does not have concentrated, and nuclear chromatin is evenly distributed, and does not see that cell has the apoptosis characteristic to change, rich in mitochondria, and ridge is flat, and stratification is arranged, the substrate uniform distribution, lysosome is more.DDP group kidney of rats proximal tubule epithelial cell morphosis mainly contains following two aspects to be changed: the first, and apoptotic cell increases; Apoptosis can be divided into for three phases: the initial stage: in the nuclear chromatin from the trend cohesion of disperse shape and the limitization that becomes, around nuclear membrane, have simultaneously many in the cavity structure (referring to Fig. 6) of sky.Mid-term: nuclear diminishes, in the nuclear chromatin concentrate, increase in density and gather the nuclear membrane periphery, the chromatin limit is poly-in the form of a ring, mitochondrial swelling in the first quarter moon shape, kytoplasm, the dissolving of part ridge, film breakage (referring to Fig. 7).Late period: karyopycnosis, diminish, chromatin is the block or spherical of densification, or is broken into a plurality of fritters, mitochondrial swelling in the kytoplasm, be the cavity sample, reticulum dilatation encystation blister forms apoptotic body at last, and the apoptotic body form is irregular, and what have is outer by plasma membrane, exposing of having is electron-dense agglomerate, or includes the damaged nuclear chromatin and the organelle of some degeneration disintegrates.Some apoptotic body is engulfed (referring to Fig. 8) by contiguous cell.The second, the degeneration of proximal tubule epithelial cell, necrosis, cell surface microvilli is impaired, mitochondrial swelling in the kytoplasm, ridge is damaged, dissolving vacuolation, dilatation of rough endoplasmic reticula (referring to Fig. 9).The middle above-mentioned change of dosage Chinese drug-treated group rat proximal convoluted tubule obviously alleviates the lysosome of accidental increase (referring to Figure 10).
Testing three results shows: the pharmaceutical composition of the present invention that per os gives the rat various dose can obviously alleviate injury of kidney, the nephrocyte apoptosis of rat due to the DDP.In dosage Chinese drug-treated group rat blood serum BUN, Cr be starkly lower than low dosage Chinese drug-treated group and high dose Chinese drug-treated group, confirmed that dosage and drug effect within the specific limits are the basic law of this pharmacodynamics of parallel relation.Point out the pharmaceutical composition of the present invention of suitable dosage could more effectively alleviate kidney of rats toxicity due to the DDP.Middle dosage Chinese drug-treated group rat MDA content is starkly lower than DDP group (P＜0.05), the SOD activity is apparently higher than DDP group (P＜0.05), the renal cortical cell apoptosis rate is starkly lower than the DDP group, dosage Chinese drug-treated group kidney of rats cortex cell apoptosis feature obviously reduced during Electronic Speculum, om observation also showed, injury of kidney obviously alleviates, show that pharmaceutical composition of the present invention can reduce oxygen-derived free radicals content by rising nephridial tissue SOD activity, the nephrocyte apoptosis alleviates the nephrotoxicity of DDP.
The Comprehensive Experiment result, illustrate that pharmaceutical composition of the present invention is not a certain the index of regulating body, but many target spot set correlation effects, suitably the pharmaceutical composition of the present invention of dosage (middle dosage) is to alleviate the nephrotoxicity of DDP and the active drug of hematotoxicity, and can strengthen the anti-tumor activity of cisplatin, can cooperate cisplatin in multiple treating malignant tumor, to use.
Claims (7)
1. a Chinese medicine composition that prevents nephrocyte apoptosis and anemia due to the cisplatin is made up of following bulk drugs: Radix Ginseng 5-10 weight portion, Radix Astragali 20-30 weight portion, Radix Rehmanniae 20-30 weight portion, Rhizoma Atractylodis Macrocephalae 10-15 weight portion, Radix Angelicae Sinensis 10-30 weight portion, Fructus Lycii 10-15 weight portion, Radix Polygoni Multiflori 10-30 weight portion, Fructus Ligustri Lucidi 10-15 weight portion, Poria 10-15 weight portion, Radix Bupleuri 6-10 weight portion, Radix Curcumae 10-15 weight portion, Semen Coicis 15-30 weight portion.
2. Chinese medicine composition according to claim 1 is characterized in that: the weight proportion of each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 15 weight portions, Radix Polygoni Multiflori 10 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 10 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
3. Chinese medicine composition according to claim 1 is characterized in that: the weight proportion of each crude drug is: Radix Ginseng 10 weight portions, the Radix Astragali 30 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 15 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 10 weight portions, Radix Polygoni Multiflori 10 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 10 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
4. Chinese medicine composition according to claim 1 is characterized in that: the weight proportion of each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 20 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 30 weight portions, Fructus Lycii 10 weight portions, Radix Polygoni Multiflori 20 weight portions, Fructus Ligustri Lucidi 10 weight portions, Poria 10 weight portions, Radix Bupleuri 6 weight portions, Radix Curcumae 15 weight portions, Semen Coicis 15 weight portions.
5. Chinese medicine composition according to claim 1 is characterized in that: the weight proportion of each crude drug is: Radix Ginseng 5 weight portions, the Radix Astragali 20 weight portions, the Radix Rehmanniae 30 weight portions, the Rhizoma Atractylodis Macrocephalae 10 weight portions, Radix Angelicae Sinensis 10 weight portions, Fructus Lycii 15 weight portions, Radix Polygoni Multiflori 15 weight portions, Fructus Ligustri Lucidi 15 weight portions, Poria 10 weight portions, Radix Bupleuri 6 weight portions, Radix Curcumae 10 weight portions, Semen Coicis 15 weight portions.
6. method for preparing the Chinese medicine composition of anemia due to each described prevention cisplatin of claim 1-5 may further comprise the steps:
1) crude drug is cleaned, dried;
2) crude drug was soaked 4-6 hour with cold water, under normal pressure, decocted 2-3 hour again, the gained decocting liquid was left standstill 12-28 hour, get supernatant concentration and become extractum, granulate, drying, obtain preventing the Chinese medicine composition of anemia due to the cisplatin.
7. preparation method according to claim 6 is characterized in that: step 2) in this medicine is made the capsule or the watered pill.
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