CN1121832A - Anticancer drug - Google Patents
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- CN1121832A CN1121832A CN 94103448 CN94103448A CN1121832A CN 1121832 A CN1121832 A CN 1121832A CN 94103448 CN94103448 CN 94103448 CN 94103448 A CN94103448 A CN 94103448A CN 1121832 A CN1121832 A CN 1121832A
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Abstract
The broad-spectrum anticancer composition contains monoaromatic ring derivatives as antagonist, active peptide, metallic or non-metallic complex and other bioactive matter and serves to have more anticancer mechanisms and improve immunity. It features high curative effect, broad spectrum and no toxic by-effect.
Description
The present invention proposes the compound anticarcinogen of a class, prescription relates to the component of several keys.
Making a general survey of the passing of world's cause of death can find, once accounting for dead first and second tuberculosis, pneumonia, tracheitis has sharply reduced because of the development of antibiotic medicine, once be the cerebrovascular disease of the maximum cause of the death, with the improvement of diet, the exploitation of good medicine has also reduced after the seventies.The cancer but rising always of mortality rate after the war that death two prewar is not high has become first cause of the death in many countries, and the trend of continuous rising has been arranged, and treatment for cancer is very urgent!
Reached an advanced stage by the invasion and attack of cancer cell, the pain that alleviate patient still is difficult to, and carries out surgical operation and radiotherapy method in order to treat cancer, and its injury is bigger.To infect other disease situation that causes death also a lot of because of the immunity degradation that causes patient, therefore will remove the feeling of terror of people to violent misery, need Drug therapy.Chemotherapy and immunotherapy are still that people hope.
Existing at present nearly hundred kinds of anticancer class chemicalses get the nod or enter clinical.Their classes are direct tumoricidal anticarcinogens, and another kind of is that the host is changed to the reaction of cancer, and self the strength treatment cancer that relies on the host i.e. (BBM) method.
Existing anticarcinogen has following a few class by its mechanism of action:
(1) alkylating agent: under normal physiological conditions, cause nucleic acid, the protein alkylation influences cell proliferation, and then kills cell.Comprise β-chloro thioether, tertiary aromatic amine, cyclophosphamide, ethylene amine, sulphonic acid ester, N-nitrosoureas etc.
(2) antagonist: have the normal substrate or the similar structure of coenzyme of enzyme, with competition such as normal substrate, hinder the metabolic response of enzyme in metabolic response, medicine is mounted to and becomes aberrant nucleic acid among DNA or the RNA sometimes, destroys cell.Comprise antifol as (Methotrexute), purine antagonist is as (6-Mercaphopuriue), pyrimidine antagonist (5-fluorouracil and derivant thereof) etc.
(3) cancer-resisting substance of antitumor antibiotic class material and plant extract, existing tens of kinds.They all have extremely complicated chemical constitution.
(4) enzyme, hormone antagonist are as (steroid derivatives etc.).
(5) to have extremely strong anti-tumor activity be one of present widely used cancer therapy drug to antineoplastic platinum compounds (being cisplatin and derivant thereof), but kidney is had infringement and can suppress bone marrow.Produce very violent feeling sick, vomit.Therefore many pairs of few platinum chemical compounds of effect just are being synthesized and are being used for clinical.
(6) immune kind anti-cancer drugs (OK-32 etc.).
Because chemotherapy exists naturality and acquired resistance problem, has the branch problem of cancer, these have caused the multiformity and the inhomogeneity of cancer.Former position and metastasis site are not consistent to the susceptibility of medicine.Halmatogenesis in the cell proliferation process is the major reason (1cm that causes drug resistance and transfer
3The cancer piece just have 10
3Individual cell can make a variation) radical cure cancer basic principle be target to kill whole cancerous cell, even a cancerous cell survives also can take place again in theory.Therefore the difficulty of treatment of cancer is well imagined.Normally several anticarcinogens are used, are about to various independent active ingredients, the composition that mechanism of action is different reduces as far as possible and pays the cooperation of effect composition, and is aided with other complementary therapy and means, to alleviate the strong effect of paying.
Suitable medicine combines with corresponding therapy, makes that really some incurable diseases are treated, and Burkitt tumor, Wilms tumor, children's's lymph gemmule property leukemia, neural bud swell, Huo Jijin disease etc. can have been cured; Breast carcinoma, lymph tumor, carcinoma of prostate, bone marrow tumor, small cell carcinoma of lung, acute myelogenous leukemia etc. also can prolong life, but regrettably many poor differentiated carcinomas, even nearly all occasion can be thought the effect that has tumor to reduce, but still can not look to prolonging life, chronic lymphocytic leukemia, ovarian cancer, gastric cancer, carcinoma of endometrium still are difficult to treatment, and small cell carcinoma of lung, colorectal cancer, pancreas cancer, cervical cancer, bladder cancer, adrenal gland cancer, renal carcinoma etc. still belong to the cancer that can not cure.
Mostly existing anticarcinogen is cytotoxic substance, and its toxic and side effects is very big, and the scope of application is limited.
Develop that anticancer effectiveness is strong, toxic and side effects is little, can cure the PTS of multiple cancer, just the target painstakingly pursued over several years of present inventors.
It is remarkable that purpose of the present invention is developed a kind of anticancer effect exactly, and toxic and side effects is little, wide spectrum, no addiction and the PTS that can conveniently make, and this obviously needs new thinking and based on the clinical medicine achievement in modern times.Key problem in technology of the present invention is to filter out that 1～2 kind of brand-new anticarcinogen composition is mixed with efficiently, wide spectrum, anticarcinogen that toxic and side effects is little.We notice that the benzopyrene of strong carcinogenecity has the height symmetrical structure, and we think that good anticarcinogen also should have the symmetry and the rigidity of height; Rotten careless toxin is that a kind of toxicity is very little, and the anticarcinogen that clinical result of use is good, there is the structure of insertable dna in it and can produces the active oxygen that the DNA chain is cut off, and can with the coordinate structure of ferrous iron, the structure of this insertable dna and metal chelating agent, the existence of metal ion and the structure of the dissection of DNA just interrelated with its active anticancer, this is the important references that we design PTS.Increasing of interior free yl is a major reason of canceration, and the harm of removing interior free yl is an importance of control cancer.Up-to-date studies show that glutathion (reduced form), Monohydrated selenium dioxide salt show active anticancer really, and they may be to work with the joint matrix immunologic function of withering by catching interior free yl or removing activity in vivo oxygen.Various independent good effects, the poison pair low different component of active ingredient, mechanism of action of effect cooperatively interact and have better effect, should be able to pass cell and enter the canceration position in order to bring into play efficacy of a drug medicine, therefore need some active carriers and some biochemical activity material.In addition, main pharmaceutical compositions should have quite stable, is difficult for degraded in the presence of gastric acid and multiple gastric enzyme.Based on the achievement in research that above-mentioned thought and molecular biosciences study medicine, we have invented a kind of comparatively ideal compound anticarcinogen through screening for many years---the inventor be called ＂ An Tuokejin ＂ (Antuokejin, ATKJ).
Content of the present invention is about a kind of compound PTS, comprises following component:
1.10.1～80% antagonist, general structure is:
R
1, R
2And R
3Carbon number be C
1～C
6Alkyl, C
3～C
6Cycloalkyl or H; R
1With R
2And R
3Can be different, but R
2With R
3Identical; R
1With R
2And R
3Can be all different.
X is NO
2, NH
2, NO, SO
3H, NH
2OH.1.20.1～10% aminoacid and two, tripeptides, two, the general structure of tripeptides is:
R
1, R
2Can for H, SH, OH ,-S-S-or other amino acid side chain base, can be the same or different.R can be that H, carbon number are 1～6 alkyl or aminoacid.Described aminoacid comprises 20 kinds of natural amino acids or synthesizing amino acid and composition thereof.1.30.01～10% metal or nonmetal salt or its complex
Slaine can be hydrochloric acid, nitric acid, sulphuric acid, carbonic acid and acylate; Metal ion can be Na
+, K
+, Ca
++, Mg
++, Mn
++, Fe
++, Co
++, Cu
++, Al
+++, Zn
++, Pt
++, Pd
++, Rh
++, chelating agent can be power 1.2 described chemical compounds.
Nonmetallic hydrochlorate comprises, hydrochlorate, bicarbonate, carbonate, sulfate, nitrate, selenite, germanate.
1.4 V
COr V
E, pollen
1.5 pharmaceutical adjuvant commonly used
With they rational proportions, the porphyrize mixing, fill becomes capsule to be oral medicine---＂ An Tuokejin ＂
The present composition can adopt habitual pharmaceutical formulation form and habitual diluent or carrier to prepare these preparations, and the example of described diluent or carrier has: surfactant, lubricant, add and fill agent, thickening agent, binding agent, wetting agent, disintegrating agent.Representational dosage form has tablet, pilule, powder, Emulsion, granule, capsule, suppository, injection (solution, suspension etc.), as required, in pharmaceutical preparation, can at random mix coloring agent, antiseptic, spice, flavoring agent, sweetener and other medicines.
Experiment shows, R
1Be the bigger alkyl of spatial volume (tert-butyl group) R
3, R
2Be the less methyl of spatial volume, X shows significant anti-cancer activity when being nitro, does not have significantly poison pair effect.This chemical compound has good spatial symmetry and rigidity, and have a strong polar group, suitable molecular size can insert in RNA and the DNA chain after it enters cancerous cell, simultaneously the nitro of being with can form two hydrogen bonds and destroy RNA and dna structure with base, influence it and duplicate.The formation of simultaneously two hydrogen bonds also makes this associated complex comparatively stable, is difficult for dissociating, thereby reaches the purpose of control and final kill cancer cell.Chemical compound can act on the metabolic process of enzyme simultaneously, participates in striving unexpectedly of substrate, combines with the active site of some enzyme, thereby enzyme is lost activity, and final control cancer cell increases.So simple in structure, the discovery of the chemical compound that the poison effect of paying is little, active anticancer is good provides PTS synthetic new thought, may impel capturing and treat and new favourable turn occurring of cancer.
Described active small peptide can be reduced glutathion.Glutathion is one of most important bioactive substance of generally acknowledging at present, and it is regulating the human homergy, removes intravital active free radical, active oxygen, the aspect effect of enhancing body immunity and can not underestimate.Therefore it is another crucial composition of this cancer medicine, and its γ-amido link has quite stable to enzymolysis, is that it can enter appointed part and not deactivated major reason smoothly.It not only can bring into play the biological function of self, also is metal ion killer's most important chelating agent and carrier simultaneously, and the synergism of it and metal ion can make the DNA of cancerous cell and RNA destructurized or be cut.
Slaine can be mineral acid or acylate; Metal ion can be Na
+, K
+, Ca
++, Mg
++, Mn
++, Fe
++, Co
++, Cu
++, Al
+++, Zn
++, Pt
++, Pd
++, Rh
++, chelating agent can be active small peptide, aminoacid.Fact proved that more and more metal ion can change the synergism of the activity of enzyme and aminoacid and peptide can destruction and cutting DNA and RNA, directly destroys basic substance---the nucleic acid and the albumen of cell, thereby can effect a radical cure cancer.
Vitamin, pollen and bioactive peptide etc. have been to remove interior free yl, adjusting physical function, the effect of enhancing human body immunity function.
Cooperatively interacting of above-mentioned multiple components, with different machining functions in cancerous cell, can be so that drug effect greatly improves and different cancer is produced curative effect.
This medicine has showed stem-winding therapeutic effect, its outstanding feature is wide spectrum, has no side effect, produce effects, cure rate height, several years experiment and hundreds of volunteers are taken, have better curative effect mostly, take this product after, feel that generally appetite increase, pain relief, sleep increase, the cancer of early, middle and late phase cancer and different parts (the depancreatize cancer is outer) all there are the case of healing, the several Nian Weijian recurrences that have.Its feature also is instant effect, and development and transfer that can very fast control cancer reduce its cancer piece even disappear, and become recessive, and end-stage patients' ascites of existing ascites also can be by reducing or disappearing.May become generation wide spectrum, efficient, the poison pair little PTS of effect.
Feature according to the present invention and relevant explanation constitute the protection domain and the claim of inventing.Below be the embodiment and the clinical effectiveness of this anticarcinogen.Embodiment 1. (1) 2,6-dimethyl-4-tert-butyl group Nitrobenzol (840 gram) (2) glutathion (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) compound vitamin (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram) embodiment 2. (1) 2,6-dimethyl-4-tert-butyl group Nitrobenzol (400 gram) the sweet Guang peptide of (2) paddy (20 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) glycerol fatty acid monoester (20 gram), sucrose ester (20 gram), sorbitol anhydride ester (20 gram) (5) pollen (200 gram) (6) compound vitamin (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram) embodiment 3. (1) 2,6-dimethyl-4-tert-butyl group Nitrobenzol (1000 gram) the sweet Guang peptide of (2) paddy (10 gram), the sweet Guang peptide of paddy (10 gram) the various natural amino acid mixture of (3) platinum complex (1 gram), the various natural amino acid mixture of ferrum complex (1 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) vitamin C (10 gram) (7) sodium selenite (20 gram) (8) potassium bicarbonate (50 gram) embodiment 4. (1) 2,6-dimethyl-4-the tert-butyl group 1,3-dinitro benzene (500 gram) the sweet Guang peptide of (2) paddy (20 gram), the sweet Guang peptide of paddy (15 gram) (3) platinum glycine complexes (3 gram), ferrum glycine complexes (5 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) vitamin E (10 gram) (7) potassium selenite (20 gram) (8) sodium bicarbonate (50 gram) embodiment 5. (1) 2,6-dimethyl-4-tert-butyl group aniline (840 gram) the sweet Guang peptide of (2) paddy (10 gram), the sweet Guang peptide of paddy (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) compound enzyme powder (400 gram) (5) glycerol fatty acid monoester (50 gram) (6) pollen (200 gram) (7) compound vitamin (10 gram) (8) sodium selenite (20 gram) (9) sodium bicarbonate (50 gram) embodiment 6. (1) 2,6-dimethyl-4-tertiary pentyl Nitrobenzol (800 gram) the sweet Guang peptide of (2) paddy (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) compound vitamin (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram) embodiment 7. (1) 2,6-dimethyl-4-tert-butyl group nitrosobenzene (840 gram) the sweet Guang peptide of (2) paddy (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) compound enzyme powder (400 gram) (5) glycerol fatty acid monoester (50 gram) (6) pollen (200 gram) (7) compound vitamin (10 gram) (8) sodium selenite (20 gram) (9) sodium bicarbonate (50 gram) embodiment 8. (1) 2,6-dimethyl-4-tert-butyl benzene sodium sulfonate (700 gram) (2) glutathion (10 gram) (3) platinum glycine complexes (2 gram), ferrum glycine complexes (1 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) compound vitamin (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram)
Embodiment 9. (1) 2, the 6-methyl-6-ethyl-4-tert-butyl group-Nitrobenzol (600 gram) (2) glutathion (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4) glycerol fatty acid monoester (50 gram) (5) pollen (200 gram) (6) compound vitamin (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram)
Embodiment 10. (1) 2,6-dimethyl-4-cyclohexyl Nitrobenzol (800 gram) the sweet Guang peptides of (2) paddy (10 gram) (3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram) (4 glycerol fatty acid monoesters (50 gram) (5) pollen (200 gram) (6) compound vitamines (10 gram) (7) sodium selenite (20 gram) (8) sodium bicarbonate (50 gram)
Embodiment 11.
(1) 2,6-dimethyl-3-acetyl 4-tert-butyl group Nitrobenzol (800 gram)
(2) the sweet Guang peptide of paddy (10 gram)
(3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram)
(4) glycerol fatty acid monoester (50 gram)
(5) pollen (200 gram)
(6) compound vitamin (10 gram)
(7) sodium selenite (20 gram)
(8) sodium bicarbonate (50 gram)
Embodiment 12.
(1) 2,6-dimethyl-4-tert-butyl-phenyl azanol (500 gram)
(2) the sweet Guang peptide of paddy (10 gram)
(3) platinum glycine complexes (1 gram), ferrum glycine complexes (1 gram)
(4) glycerol fatty acid monoester (50 gram)
(5) pollen (200 gram)
(6) compound vitamin (10 gram)
(7) sodium selenite (20 gram)
(8) sodium bicarbonate (50 gram)
According to a conventional method the mixture of above-mentioned composition is packed into hard capsule and soft capsule can make capsule.Experimental example 1. is pressed the PTS of the described component preparation of embodiment 1, the inventor be called ＂ An Tuokejin ＂ (Antuokejin, ATKJ) acute, long term toxicity, three genicity tests result are as follows:
The oral acute toxicity of An Tuokejin (ATKJ) mice is limited the quantity of to test and is shown that toxicity is extremely low, is difficult to look for fatal dose.The medicinal 2% soluble starch paste of powder stock is made into 40% (g/v) Cmax suspension, measures oral maximum administration volume peace Tuo Kejin (ATKJ) the chmice acute toxic reaction.With two groups of male and female, every group each 10, maximum is limited the quantity of respectively, and (dosage is movable diet situation and the death condition that 20g/kg (administration at twice) observes animal to volume filling stomach for i, g) administration.Continuous seven days observed result shows that the part Mus is taken medicine had jitter in back 20 minutes, and remission about two hours promptly recovers normal thereafter, and death is seen at the end.Therefore, An Tuo can gold to the oral LD50 value of mice greater than 20g/kg.
The oral peace holder of rat can golden trimestral long term toxicity test: be the safety of estimating peace Tuo Kejin, observe successive administration and after three months the body master is given birth to the reversibility that reaction and the order of severity thereof provide anti-target organ of toxicity and infringement thereof, determine nontoxic amounts of reactants, providing reference for drafting the human safe dose, is that the oral peace holder of rat can golden trimestral long term toxicity test result below.With acute toxicity test LD50＞20g/kg is reference, gives the rat can golden continuous oral 90 days in the 6g/kg that limits the quantity of (take 12 of the complete approximately capsules of 3.6g every day with 60kg people, be equivalent to 100 times of human dosage) An Tuo.The medicine preparation, administering mode is with anxious poison experiment, the dosage 6.0g/kg An Tuokejin that limits the quantity of is roughly equal to 40% (g/v) suspension 15ml that 2% soluble starch liquid and medicated powder are made into, be administered once every day, inferior on every Saturdays, surveys body weight weekly once, and carry out dose titration according to body weight, 12 weeks of continuous oral, observed again for 2 weeks after the drug withdrawal, the result shows:
1. clinical observation shows that rat continuously sees death in 90 days ends of clothes, and Non Apparent Abnormality administration groups such as hair, activity, stool in most cases appetite increase, and weight increase is very fast, but with blank group comparing difference little (P＞0.05).Illustrate that peace Tuo Kejin has no adverse effects to the general situation of rat.
2. hematological examination and blood biochemical check: respectively administration 90 days and drug withdrawal 14 days, the eyeball blood sampling is carried out above-mentioned check and is shown, red white corpuscle number, content of hemoglobin and classification, platelet be all in range of normal value, no significant difference between group (P＞0.05); All there is not significant difference (P＞0.05) between blood urea nitrogen (BUN), glutamate pyruvate transaminase (GPT), each group of three indexs of glutamic oxaloacetic transaminase, GOT (GOT).
3. pathologic finding: animal after 90 days, is put to death the part animal in administration, measure the main organs coefficient results and find that the increase of administration treated animal liver weight is higher than the blank group, but its organ coefficient value is in range of normal value, and other equal end of organ coefficient value is seen unusually.
4. tissue slice: all animal hearts, liver, spleen, lung, kidney, stomach, duodenum, ovary, testis, prostate, adrenal gland, thyroid etc. are carried out histological examination, administration group liver, spleen have hyperemia in various degree, edema, jenny obvious than buck, and other internal organs end is seen drug-induced organic disease.
An Tuokejin teratogenesis toxicity test: test peace Tuo Kejin more helps illustrating the teratogenesis toxicity of peace Tuo Kejin to the teratogenesis that the is subjected to pregnant rat toxic action its sensitive period (becoming pregnant 7～17 days).With rat from day of looking into sperm for becoming pregnant the 0th day, the Mus of will becoming pregnant is taken out, sub-cage rearing is divided into five groups at random, divides to be in addition, An Tuo can gold (ATKJ) 2g/kg group; The 1g/kg group; 0.5g/kg blank group aspirin (ASP) the 0.2g/kg positive controls of group and 2% starch, in 7～17 days successive administrations of becoming pregnant, once a day, increase the timely dosage of adjusting to becoming pregnant 20 days in the filling of 1ml/100g ratio and with body weight, put to death with the cervical vertebra method that fractures, laparotomy inspection corpus luteum number immediately, the implantation number, absorb tire number (early absorb tire and absorb tire late period), the stillborn fetus number, the body weight of the tire number alive and the tire of living, height, tail is long, sex, Placenta Hominis is heavy, and observation has or not outward appearance unusual, then, 1/2 tire Mus alive is fixed in BouinShi liquid, to do the internal organs inspection, in addition 1/2 is fixed in and spills in the essence, dyes through alizarin red, after glycerol is transparent, do the skeleton inspection, the gained data are checked with t, and statistical procedures is carried out in u-test and f check.
The result shows the average weight growth pattern of pregnant Mus, there is not significant difference between five groups, illustrate that (0.5～2g/kg) no maternal toxicity occurs peace Tuo Kejin at this dosage range, fetal development also there is not influence, and the absorption tire rate of ASP group, apparently higher than reference group (P＜0.001), its fetal toxicity is apparent.Therefore in An Tuo can gold 0.5～2.0g/kg dosage range, be subjected to pregnant rat not have fetal toxicity and teratogenesis toxic action.
An Tuokejin mutagenesis (micronucleus) experiment: the purebred male mice of NIH is divided into five groups at random, (6/group) first group are the blank group, every mouse stomach 0.5ml2% starch solution: second group of positive matched group gives 60mg/kg cyclophosphamide (CP) intraperitoneal injection; The 3rd group is high dose group, gives 5g/kg ATKJ; The 4th group is middle dosage group, gives 2.5g/kg ATKJ; The 5th group is low dose group, gives 1.25g/kg ATKJ; 3rd, 4,5 groups of ATKJ use 2% starch solution to suspend, and irritate the stomach single administration.Put to death mice in 24 hours after the administration, clip one side femur, extracting marrow cell is made bone marrow smear by preceding method, fixing, dyeing, microscopy, 6 mices of each combined lens, every mice is observed 1000 PCE, calculates micronuclear rates, does statistical procedures with the t check.
The result shows that peace Tuo Kejin group (5g/kg, 25g/kg and 125g/kg) micronuclei in mice generation permillage of three dosage (is respectively 1.50 ± 1.38,2.00 ± 1.79,1.83 ± 1.33) compare difference that there are no significant (P＞0.05) with blank group (2.33 ± 1.03); And compare with positive controls (53.33 ± 6.92), micronuclear rates is obviously much lower, and significant differences (P＜0.01) is all arranged.So An Tuo can not have the effect that the PCEMNR micronuclear rates increases of bringing out by gold.The experiment of experimental example 2. isolated cells:
Normal cell is 100% survival when but the An Tuo gold concentration is 0.5mg/ml.But the existing nearly half of the lung carcinoma cell (LD that is killed under this concentration
50～0.5mg/ml) the LD of melanoma cell
50＜0.01mg/ml.But illustrate the selective kill cancer cell of peace holder gold utensil function and to little (the anxious malicious LD of Normocellular destruction
50＞20g/kg) (Nanjing University's school of life and health sciences experimental result).
The isolated experiment result in December in 1992 U.S. Columbia University's clinic study institute on the 8th cancer card research center is as follows:
The F1 cancerous cell when An Tuo can kill off during golden 320ug/ml substantially, is suppressed during for 40ug/ml to increase.
Major part was killed when the C8161 cancerous cell can goldenly be 160ug/ml as An Tuo, all killed during for 320ug/ml.To the E cancerous cell, but when the An Tuo gold concentration is 40ug/ml, suppress to increase, almost kill full during for 160ug/ml, all kill during for 320ug/ml.The experimental example 3. embodiment 1 clinical typical case of described PTS oral capsule entirely more case name sex age unit or address diagnosis Time of Administration cumulative volume observation of curative effect open * * the low differentiation of male 50 Beijing aviations boat lungs squama 91,10. 1500 tumors of clothes are by 4cm φ
The senior engineer of it cancer lymph metastasis was with three months Australia simultaneously that disappears
Anti-turn out cloudy the week * * the outer spermatogonium in Zunhua, male 35 Hebei slips 92,3. obeys 2000 recurrence tumor 5cm φ
The section chief of trade company postoperative recurrence with disappeared in five months working recklessly * * Daxing County, male 61 Beijing hepatocarcinoma (B ultrasonic 91,1. 1500 rights lobe of liver of clothes
Medical material company and CT diagnosis) with four months 4.6 * 3.16
Manager 7.2 * 3.4cm
Tumor is obvious
Absorption improvement king * * 1500 liver left and right sides tumors of later period of hepatocarcinoma 92,8 clothes are moved back by women 65 Mudanjiang Cities
Stop workman's (being critically ill fever) with three months 4.7 * 3.1cm
92,9 quiet notes medications 45 days
Behind the plain 30mg of AT, narrow down to
2.3×1.7cm
92,11.
Smudgy
(to share effect obvious with interferon) Qi * * Mentougou, women 42 Beijing rectal cancer 92,5. 2000 tumors of clothes are by 4 * 4cm
Annotate with three months disappearance *: every capsules nearly weighs this case of 0.3g. and assert through the expert.
No matter the above fact proves all that from isolated cells experiment, clinical effectiveness, toxicity, three genicity tests and to Normocellular failure test conclusion ＂ An Tuokejin ＂ is the effective PTS of a generation, and its theory and practice has science.Its prescription is that reasonably clinical effectiveness is significant.The release of An Tuokejin and further improving will be brought hope to curing cancer!
Claims (7)
1. the prescription of a compound anticarcinogen comprises the antagonist of following component 1.10.1～80%, and general structure is:
R
1, R
2And R
3Carbon number be C
1～C
6Alkyl, C
3～C
6Cycloalkyl or H;
R
1With R
2And R
3Can be different, but R
2With R
3Identical; R
1With R
2And R
3Can be all different;
X is NO
2, NH
2, NO, SO
3H, NH
2OH; 1.20.1～10% aminoacid and two, tripeptides, two, the general structure of tripeptides is:
R
1, R
2Can for H, SH, OH ,-S-S-or other amino acid side chain base, can be the same or different.R can be that H, carbon number are 1～6 alkyl or aminoacid.Described ammonia
Base acid comprises various natural amino acids and composition thereof;
1.30.01～10% metal or nonmetal salt or its complex
Slaine is hydrochloric acid, nitric acid, sulphuric acid, carbonic acid and acylate;
Metal ion is Na
+, K
+, Ca
++, Mg
++, Mn
++, Fe
++, Co
++, Cu
++,
Al
+++, Zn
++, Pt
++, Pd
++, Rh
++, chelating agent can be right 1.2 described chemical combination
Thing;
Nonmetallic hydrochlorate comprises selenite, germanate.
1.4V
COr V
E, pollen
1.5 pharmaceutical adjuvant commonly used
2. as right 1 said anticarcinogen, wherein antagonist is the 4-tert-butyl group-2,6-dimethyl-Nitrobenzol.
3. as the said anticarcinogen of claim 1, peptide wherein is a reduced glutathion, R in the general formula 1.2
1Be SH, R
2With R be the structure of H.
4. as the said anticarcinogen of claim 1, metal wherein or nonmetal salt or its complex are aminoacid, the peptide complex of platinum, ferrum, sodium selenite.
5. PTS as claimed in claim 1 is characterized in that comprising following preferable amount (weight %):
(a) 20～60%4-tert-butyl group-2,6-dimethyl-Nitrobenzol
(b) 1～5% glutathion (reduced form)
(c) 2～10% sodium selenite
(d) aminoacid of 1～5 ‰ platinum, peptide complex
(e) V
COr V
E, pollen and commonly used pharmaceutical adjuvant be an amount of
6. anticarcinogen as claimed in claim 1, the consumption that it is characterized in that 1.1,1.2,1.3,1.4 described active constituents are 1 ‰～80% (weight %).
7. as the described compositions of claim 1., said composition contains drug excipient commonly used in addition
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94103448A CN1056082C (en) | 1994-04-08 | 1994-04-08 | Anticancer drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94103448A CN1056082C (en) | 1994-04-08 | 1994-04-08 | Anticancer drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1121832A true CN1121832A (en) | 1996-05-08 |
| CN1056082C CN1056082C (en) | 2000-09-06 |
Family
ID=5031075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94103448A Expired - Fee Related CN1056082C (en) | 1994-04-08 | 1994-04-08 | Anticancer drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1056082C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001037823A1 (en) * | 1999-11-05 | 2001-05-31 | Tewa Men | Substituted nitrobenzene derivatives as medicines and other useful uses thereof |
| CN1101804C (en) * | 2000-04-29 | 2003-02-19 | 刘全志 | Pharmaceutical compound for killing cancer cells and pathogenic bacteria and prepn. method therefor |
| WO2006045238A1 (en) * | 2004-10-25 | 2006-05-04 | Hanxiang Sun | Carbonized pollen and the use thereof for the preparation of anticancer drugs |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0087865B1 (en) * | 1982-03-01 | 1986-10-01 | Efamol Limited | Pharmaceutical composition |
| GB9026114D0 (en) * | 1990-11-30 | 1991-01-16 | Norsk Hydro As | New compounds |
-
1994
- 1994-04-08 CN CN94103448A patent/CN1056082C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001037823A1 (en) * | 1999-11-05 | 2001-05-31 | Tewa Men | Substituted nitrobenzene derivatives as medicines and other useful uses thereof |
| CN1101804C (en) * | 2000-04-29 | 2003-02-19 | 刘全志 | Pharmaceutical compound for killing cancer cells and pathogenic bacteria and prepn. method therefor |
| WO2006045238A1 (en) * | 2004-10-25 | 2006-05-04 | Hanxiang Sun | Carbonized pollen and the use thereof for the preparation of anticancer drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1056082C (en) | 2000-09-06 |
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