CN1275404A - Anticancer medicine composition - Google Patents

Anticancer medicine composition Download PDF

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Publication number
CN1275404A
CN1275404A CN 00111092 CN00111092A CN1275404A CN 1275404 A CN1275404 A CN 1275404A CN 00111092 CN00111092 CN 00111092 CN 00111092 A CN00111092 A CN 00111092A CN 1275404 A CN1275404 A CN 1275404A
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tetrazolium
pharmaceutical composition
organelle
anticancer pharmaceutical
chlorination
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CN 00111092
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Chinese (zh)
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孔庆忠
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Individual
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Individual
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Priority to CN 00111092 priority Critical patent/CN1275404A/en
Publication of CN1275404A publication Critical patent/CN1275404A/en
Priority to DE60141829T priority patent/DE60141829D1/en
Priority to AT01930891T priority patent/ATE464046T1/en
Priority to AU5738301A priority patent/AU5738301A/en
Priority to IL15248401A priority patent/IL152484A0/en
Priority to CA2407112A priority patent/CA2407112C/en
Priority to AU2001257383A priority patent/AU2001257383B2/en
Priority to PCT/US2001/013730 priority patent/WO2001082780A2/en
Priority to EP01930891A priority patent/EP1294922B1/en
Priority to IL152484A priority patent/IL152484A/en
Pending legal-status Critical Current

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Abstract

The Present invention relates to an anti-cancer medicine composition and its method for curing carcinomatiosis. Said invented anti-cancer medicine composition comtains the cell organ crystallized matter with effective quantity for resisting carcer and medicinal carrier and / or excipient. The contained cell organ crystallized matter can be reduced into crystal by means of succinate dehydrogenase so as to make the cell organ of cancer cell richly containing said enzyme and microtubular system crystallize and make cancer cell go to death. Said invented medicine composition not only can effectively kiee tumor coll, at the same time, but also can raise the sensitivity of tumor cell to other therapeutic methods, such as radiation therapy and chomical therapy.

Description

Anticancer pharmaceutical composition
The present invention relates to anticancer pharmaceutical composition, utilize the method for organelle crystalization and organelle crystal material treatment tumor in addition.
In recent years, tumor treatment has obtained remarkable progress, yet its mortality rate still occupies various common cause of the death firsts, is only second to heart disease.Therefore, inquire into a kind of new effective Therapeutic Method or medicine and just become current important topic.Existing treatment method for cancer is relatively limited to, or acts on certain structure of cancerous cell, or acts on certain molecule of cancerous cell.Yet the adjusting of tanacity and protection structure or mechanism are very fast with impaired structure or function reparation in the cancerous cell.Therefore, the main cause of the failure of treatment of cancer at present is the generation of various tolerances.
The objective of the invention is to remedy the deficiency of prior art, a kind of anticancer pharmaceutical composition is provided.
Another object of the present invention provides a kind of method of using above-mentioned anticancer pharmaceutical composition treatment tumor.
The present invention finds organelle crystal material except that suppressing effectively the tumor growth, can also significantly strengthen the sensitivity of tumor cell to radiotherapy and medicine etc.Therefore, the invention provides a kind of method of utilizing organelle crystal material treatment tumor.The present invention also provides a kind of sharp organelle crystal material to strengthen the method for non-operative treatment action effects such as tumor radiotherapy and chemotherapy.
Because the principal element of decision therapeutic effect is the drug level of tumor by local and the tumor cell sensitivity to medicine.Injection all is difficult to keep long-time active drug concentration at tumor by local in vein, abdominal cavity and artery administration even the tumor body.Simple raising dosage is subjected to the restriction of general reaction again.So seeking effective route of administration and synergist is one of free-revving engine of the present invention.
The present invention finds that the normal cell of the succinate dehydrogenase in the cancerous cell obviously increases.When the complex that contains tetrazolium existed, the amber acidohydrogenase can be converted into it corresponding crystal product, thereby made the cellularity crystalization that is rich in succinate dehydrogenase.Cyto-architectural crystalization not only causes the mechanical injuries of cell, also can cause the function stagnation, and the information transmission is obstructed, cell division arrest.Therefore killing tumor cell effectively can strengthen simultaneously the action effect of other therapies effectively, thereby provides a kind of new effective measures for the treatment tumor.
Organelle crystallization material can suppress growth of tumor in band tumor animal body.If with such matter selective intra-arterial injection, or be injected directly into tumor by local, being that holder is local with the macromolecule polymer particularly discharges, and has not only improved the oncotherapy effect, can avoid general toxic reaction simultaneously.
Especially it should be noted that the organelle crystal material in this anticancer pharmaceutical composition can be reduced into crystal through succinate dehydrogenase, thereby make organelle and the microtubule system crystalization that is rich in this enzyme cancerous cell, and then be directed at cancer cell death.Be different from prior treatment method, the crystalization of organelle and microtubule system, such as nuclear membrane, spindle, centrosome and the interior isostructural crystalization of knitmesh can cause cell division arrest, and protein synthesising disorder, information is transmitted disorderly; The crystalization of microfilament microtubule system not only can cause The above results, also can cause the mechanical injuries and the small-molecule substance running obstacle of membranous structure.
The present invention also find organelle and (or) microtubule system crystalization and the cell death that causes be different from known cell death (comprise downright bad and accent is died).The present invention with organelle and (or) microtubule system crystalization and the cell death that causes be referred to as cruel deadly, claims again " death that the organelle crystalization causes-cellular organelle crystallization induceddeath ", is called for short COCID.
In view of above-mentioned discovery, the present invention with organelle crystal material separately or with packaged in combination such as other chemotherapeutics in the macromolecule polymer, the slow releasing agent of so making helps local the placement.The Main Ingredients and Appearance of anti-cancer composition of the present invention slowly can be released to tumor by local after placing in the tumor body, therefore selectivity strengthens the drug level of tumor by local when reducing contingent whole body complication, and then the action effect of other therapies is further strengthened, thereby provide a kind of more efficient methods for effecting a radical cure former of various human bodies and animal and shifting entity tumor.
Organelle crystal material can be applicable to various cancers, sarcoma, carcinosarcoma and hematopathy, lymphadenomatous treatment among the present invention.Have very high clinical value and remarkable economical and social benefit.
Because anticancer pharmaceutical composition of the present invention can make the action effect of methods such as conventional chemotherapy, immunization therapy, high thermal therapeutical, phototherapy, ultrasound wave, gene therapy, hormone therapy and radiation strengthen, therefore when local slow discharges, can share, thereby its anticancer effect is further strengthened with above-mentioned non-operative treatment.
Anticancer pharmaceutical composition of the present invention contains organelle crystal material and the pharmaceutically suitable carrier and/or the excipient of effective anticancer.
Wherein the shared ratio of organelle crystal material is decided because of concrete condition, can be good with 1%-99% from 0.01%-99.99%, is best with 5%-90%.
Anticancer pharmaceutical composition of the present invention can be made into multiple dosage form.As, but being not limited to, injection, muddy suspension, ointment machin are solid-state as capsule etc.; Be different shape, as, but be not limited to granular, lamellar, sphere, bulk and membranaceous.In various dosage forms slowly to be released to the master.With holder above-mentioned Main Ingredients and Appearance being packed the back topical application then is the main form of this invention.The spendable holder of anticancer pharmaceutical composition of the present invention can be any material, and the compound polymer of forming with macromolecule polymer or different macromolecule polymer is good, and the compound polymer of forming with the different molecular weight high molecular lactic is the best.Holder also can use liquid as, but be not limited to, Oleum sesami, suspension, distilled water, physiology towards liquid and semisolid as, but be not limited to fruit jelly, paste, ointment etc.
This anticancer pharmaceutical composition can with topical, wherein be released to the best with local slow as injection in selective arterial injection and the direct tumor body for good through various administrations.Also can be equipped with local slow during this anticancer pharmaceutical composition selective arterial injection and discharge, the local active ingredient that discharges mainly kills and wounds primary tumo(u)r, and the anticancer composition that tremulous pulse or other approach are taken is used to kill and wound the tumor cell that is dispersed in or has spread.
Available organelle crystal material comprises tetrazolium and complex thereof among the present invention; wherein tetrazolium and complex thereof comprise; but be not limited to; 3-(4; 5-dimethylthiazole-2-yl)-2; (MTT:3-(4 for 5-biphenyl Thiazolyl blue tetrazolium bromide; 5-dimethylthiazole-2-yl)-2; 5-diphenyltetrazolium bromide); Thiazolyl blue (TB:thiazolylblue); the tetrazolium orchid; claim dichloro 3 again; 3 '-[3; 3 '-dimethoxy (1; 1 '-biphenyl)-4; 4 '-two bases]-two [2; 5 biphenyl-2H-tetrazolium] (Tetrazolium Blue:3; 3 '-[3; 3 '-dimethoxy (1,1 '-biphenyl)-4,4 '-diyl]-bis[2; 5-diphenyl-2H-tetrazolium] dichloride); (1H)-tetrazolium (1H-tetrazole); Vitastain (chlorination 2; 3, the 5-Triphenyl Tetrazolium Chloride) (tetrazolium red:2,3; 5-triphenyltetrazolium chloride); 1; 3,5-triphen first (claiming the Triphenyl Tetrazolium Chloride first again) (TPF:1,3; 5-triphenylformazan or1; 3,5-triphenyltetrazoliumformazan); iodonitrotetrazolium first (ITT:iodonitrotetrazoliumformazan); p-iodonitrotetrazolium violet, claim again (2-[4-allusion quotation benzene]-the 3-[4-Nitrobenzol]-5-phenyltetrazole chlorine) (INT:p-iodonitrotetrazolium violet or (2-[4-iodophenyl]-3-[4-nitrophenyl]-5-phenyltetrazolium chloride); tetrazole violet; claim chlorination (2 again; 5-biphenyl-3-[a-naphthyl]-tetrazolium) (tetrazolium violet:2,5-diphenyl-3-[α-naphthyl]-tetrazolium chloride); chlorination 2 (p-iodobenzene)-p-Nitrobenzol-5-benzene tetrazolium (INPT:2-(p-iodophenyl)-p-itrophenyl-5-phenyltetrazolium chloride); neotetrazolium chloride (claim again chlorination 2,2 '; 5; 5 '-four benzene-3,3 '-[p-hexichol] two tetrazoliums) [neotetrazolium chloride:(2,2 '; 5; 5 '-tetraphenyl-3,3 '-[p-diphenylene] ditetrazolium chloride)]; the blue tetrazolium of nitro, the blue tetrazolium of p-nitro; or chlorination 2; 2 '-two-p-Nitrobenzol-5,5 '-diphenyl-3,3 ' [3; 3 '-dimethoxy-4; 4 ' two phenylene]-two tetrazoliums (NBT:itro blue tetrazolium or p-nitrotetrazolium blue or 2,2 ' di-p-nitrophenyl-5,5 '-diphenyl-3; 3 ' [3; 3 '-dimethoxy-4,4 ' diphenylene]-tetrazoliumchloride); 5,5 '-two-p-nitre phenyl-3; 3 '-diphenyl-1; 1 '-[3,3 '-dimethoxy-4,4 '-two phenylene] diformazan (diformazan of NBT:5; 5 ' di-p-nitrophenyl-3; 3 '-dipheneyl-1,1 '-[3,3 '-dimethoxy-4; 4 '-diphenylene] diformazan); TNBT (TNBT:tetronitro bluetetrazolium); chlorination 2; 2 '-two [p-nitre benzene]-5,5 '-two [p-thiocarbamoyl benzene]-3,3 '-[3; 3 '-dimethoxy-4; 4 '-hexichol] two tetrazoliums (TC-NBT:2,2 '-di[p-nitrophenyl]-5,5 ' di[p-thiocarbamylphenyl]-3; 3 '-[3; 3 '-dimethoxy-4,4 '-biphenylene] ditetrazoliumchloride), claim Thiocarbamyl nitro-BT (thiocarbamyl nitro blue tetrazolium) again; tetrazotized o-dianisidine (TTD:tetrazotized 0-dianisidine); 3-(4; 5-dimethylthiazole-2-yl)-5-(3-carboxyl anisyl)-2-(4-sulfophenyl)-(MTS:MTS:3-(4 for the 2H-tetrazolium salts; 5-dimethylthiazol-2-yl)-and 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt) 4-[3-(iodophenyl)-2-(4-Nitrobenzol)-2H-5-tetrazolium]-1, the 3-benzene disulfonate (WST-1:4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5tetrazolio]-1,3-benzenedisulfonate) 2; 2-two (2-methoxyl group-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyl anilid (XTT:2; 2-bis (2-methoxyl-4-notro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide); chlorination 1-[4,5-dimethylthiazole-2-yl]-2,5-hexichol tetrazolium (DDTT:1-[4; 5-dimethylthiazol-2-yl]-2; 5-iphenyltetrazolium bromide); 3 '-[the 1-[(phenyl amino)-phosphinylidyne]-3, the 4-tetrazolium]-two (4-methoxyl group-6-nitro) benzene-sulfo group acid sodium hydroxide (PCTT:PCTT:sodium3 '-[1-[(phenylamino)-carbonyl]-3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene-sulfonic acid hydrate).
Above organelle crystal material can singly select or multiselect.
Organelle among the present invention comprises all subcellular structures, as, but be not limited to interior knitmesh, nucleus, nuclear plate, caryoplasm, nuclear membrane, nuclear pore complex, nuclear cover, chromosome, chromatin, core tube, centromere, telomere, serous coat, Golgi body, centriole, lysosome, centrosome, other centriole material, retraction ring, ribosome, endosome, phagosome, proteasome, peroxisome, and spindle etc.
Organelle among the present invention also comprises all microfilament microtubule systems, as, but be not limited to microvillus, flagellum, cilium, and other microfilament microtubule etc.Organelle among the present invention also comprises the albumen that is positioned on the said structure and small-molecular peptides etc.
Another kind of form of the present invention is to add other medicines in this anticancer pharmaceutical composition.
Available medicine is among the present invention:
One, clinical chemotherapeutics commonly used, as:
1. platinum-like compounds, as: platinum class complex such as cisplatin, carboplatin ex hoc genus anne thing and derivant etc.
2. alkylating agent, as: slide can be rather, chlormethine series pharmaceuticals, Min Erfalan, bird pyrimidine chlormethine, ACNU, GANU, TA-77, MCNU, cyclophosphamide and derivant thereof such as 4-peroxide cyclophosphamide, BCNU, CCNU, Semustine etc.
3. antibiotics, as: amycin, bleomycin A5,4-demethoxy daunorubicin, daunomycin, ametycin, actinomycin D, anthramycin, tetracycline etc.
4. plant class, as: cyclophosphamide and derivant thereof such as 4-peroxide cyclophosphamide, new carzinostatin, daunorubicin, powerful red rhzomorph (doxorubicin), thio-tepa and Cortex Cunninghamiae Lanceolatae extract (Taxanes) etc.
5. antimetabolitas, as: 5-fluorouracil, folic acid, ammonia first talk endlessly sandfly ,-the fast sandfly of sulfydryl ,-the fast sandfly of azepine bird, aminopterin, uracil, cytosine arabinoside, the fast sandfly of sulfur azoles, azaserine, cytarabin etc.
Other, as procarbazine hydrochloride, vincristin, vinblastine and other anthryl complex etc.
Two, quinones complex is as (but being not limited to): general (partly) quinone, emodin and other anthraquinone derivative, benzoquinone and derivant thereof such as anilino-methylamino benzoquinone, vitamin K3 and plumbagin, azophenlyene metilsulfate, benzenetriol and biosynthetic amino-laevulic acid etc.
Three, vanadium compounds, as: vanadate, adjacent vanadate and phenanthroline vanadium complex etc.
Four, free radical and lipid peroxy product, as: aldehyde is closed in acrylic aldehyde, α-insatiable hunger and aldehyde etc. is closed in β-insatiable hunger.
Five, fatty acid is closed in insatiable hunger, as: parinaric acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexenoic acid, alpha-linolenic acid and gamma-Linolenic acid etc.
Six, protein synthesis inhibitor, as: cycloheximide, hippo alkali, anisomycin and fast sandfly mycin etc.
Seven, than pyridine class complex, as N,N'-dimethyl-.gamma..gamma.'-dipyridylium etc.
Also can add other medicinal ingredient in the Main Ingredients and Appearance of the present invention, decide according to concrete condition as the adding of these medicinal components such as antibiotic, antalgica, anticoagulant medicine or hemorrhage, antibiotic medicine, hormone and some Chinese herbal medicine extract.
Main Ingredients and Appearance of the present invention also can with many clinical non-operative treatment commonly used such as use in conjunction such as radiotherapy, immunization therapy, electrotherapy, ultrasound wave, chemotherapy, phototherapy and thermotherapy, thereby strengthen its antitumous effect.
In a word, anticancer pharmaceutical composition of the present invention is guidance with new theory.The present invention finds that succinate dehydrogenase and many other important enzymes are the material bases that tumor is depended on for existence, and its effect is a unlimited hypertrophy of keeping tumor cell and blood vessel thereof; Except that removing the cancer-resisting substance in the oncocyte or reducing tumor cell and thereby the picked-up of cancer-resisting substance is reduced the antitumor action of many chemotherapeutics and cause the generation of cross resistance; and the active and expression of adjustable protective system and function system; therefore, suppressing succinate dehydrogenase is a kind of Comprehensive Treatment approach.And organelle crystal material not only can be exhausted the succinate dehydrogenase of cell, and formed crystal can cause the mechanical damage of cell.Crystalline formation also can make the albumen at position, place and other micromolecule lose function, therefore is different from any known anticarcinogen, and the present invention has anticancer very widely basis.
Anticancer pharmaceutical composition of the present invention is main target of attack with organelle and the microfilament microtubule system that contains succinate dehydrogenase, because the present invention finds many drug effects in cell cycle, particularly anti-mitosis medicine all acts on succinate dehydrogenase.This is found to be treatment of cancer, and particularly the research and development of new drug provide new theoretical direction.
The Main Ingredients and Appearance of anticancer pharmaceutical composition of the present invention is a holder with the bio-capacitivity material, so do not cause foreign body reaction.Support to place in the object back degradable and absorb, so the taking-up of need not performing the operation.Cause discharges contained drug at tumor by local, thereby optionally improves and prolong local drug concentration, can reduce the general toxic reaction that is caused by the conventional route administration simultaneously.The organelle crystal material of being released is except that capable of blocking or tumoricidal protectiveness regulatory mechanism; also can strengthen tumor cell; toleration tumor cell particularly, thus to other therapies such as chemotherapy, gene therapy, and the sensitivity of ultrasonic therapy its action effect strengthened and have more selectivity.
As mentioned above, anticancer pharmaceutical composition of the present invention can be made into various dosage forms, and is solid-state as capsule etc. as injection, muddy suspension, ointment machin; Be released to main application form with local slow, the packing method of its Main Ingredients and Appearance and step are not main contents of the present invention, but anyly can strengthen crystal formation material and method, as, but be not limited to, strengthen the material of succinic dehydrogenase activity and expression, all belong to category of the present invention.
Organic solvent among the present invention can be, but is not limited to, dichloromethane and dimethyl formamide etc.The characteristics of technology of preparing of the present invention are macromolecule polymer, organelle crystal material according to a certain percentage, are dissolved in the organic solvent, fully bleed drying after the mixing.Be shaped immediately after to be dried and sterilize packing.The macromolecule polymer can be made into different shape, and the content of various compositions is decided because of different needs in the macromolecule polymer.Can be good with 1%-99% from 0.01%-99.9%, be best with 5%-90%.This anticancer pharmaceutical composition can be made into various dosage forms, and is solid-state as capsule etc. as injection, muddy suspension, ointment machin; Be different shape, as granular, lamellar, sphere, bulk and membranaceous; Can be good with the tremulous pulse approach through various administrations, directly be placed as the best in the tumor body.End product of the present invention is the solid product that bio-capacitivity, degradable absorb, and can make different shape because of the clinical needs of difference.
Another characteristics of technology of preparing of the present invention are macromolecule polymer, organelle crystal material and other medicines, according to a certain percentage, are dissolved in the organic solvent, fully bleed drying after the mixing.Be shaped immediately after to be dried and sterilize packing.The macromolecule polymer can be made into different shape, and the content of various compositions is decided because of different needs in the macromolecule polymer.Can be good with 1%-99% from 0.01%-99.9%, be best with 5%-90%.This anticancer pharmaceutical composition can be made into various dosage forms, and is solid-state as capsule etc. as injection, muddy suspension, ointment machin; Be different shape, as granular, lamellar, sphere, bulk and membranaceous; Can be good with the tremulous pulse approach through various administrations, directly be placed as the best in the tumor body.Best product of the present invention is the solid product that bio-capacitivity, degradable absorb, and can make different shape because of the clinical needs of difference.Used other medicines include, but not limited to antibiotic, antalgica, anticoagulant medicine or hemorrhage, chemotherapeutic, antibiotic medicine, hormone and some Chinese herbal medicine extract etc.
The flow process that the pastille polymer is processed in the present invention is as follows:
The solid polymer organelle crystal material → dissolving mixing → drying → shaping → packing → sterilization → product of weighing
1. the solid polymer of weighing is put into container, add certain amount of organic solvent dissolving even (weight ratio of the two is not strict, is as the criterion with abundant dissolving).
2. adding the medicine of weighing shakes up again.The ratio of medicine and polymer is not strict, because of specific requirement is decided.
3. pastille polymer vacuum drying is removed organic solvent.Also available cold drying is removed organic solvent.
4. dried solid polymer is shaped immediately.Can make shape everywhere according to different needs.
5. ray sterilizing (roentgendosis is different because of volume) is standby after the packing, also available other method sterilization.The polymer made from this method is a solid, is yellow or silvery white (its color is relevant with the drug level and the medicament categories of packaging).
The invention will be further described below in conjunction with embodiment, but be not limited thereto.
Embodiment 1: molecular weight is 100 milligrams of 50000 lactic acid
100 milliliters of dichloromethane
40 milligrams of crystal materials
It is made the pastille polymer by above-mentioned flow process.
Embodiment 2: molecular weight is 50 milligrams of 20000 lactic acid
Molecular weight is 50 milligrams of 80000 lactic acid
100 milliliters of dichloromethane
50 milligrams of tetrazole violets
It is made the pastille polymer by above-mentioned flow process.
Embodiment 3: molecular weight is 50 milligrams of 20000 lactic acid
Molecular weight is 40 milligrams of 80000 lactic acid
100 milliliters of dichloromethane
100 milligrams of 3-nitropropionic acids
It is made the pastille polymer by above-mentioned flow process.
Embodiment 4: molecular weight is 50 milligrams of 20000 lactic acid
Molecular weight is 40 milligrams of 80000 lactic acid
5 milligrams of Vitastains
40 milligrams of cisplatin
It is made the pastille polymer by above-mentioned flow process.
Embodiment 5: molecular weight is 50 milligrams of 80000 lactic acid
200 milliliters of dimethyl formamides
100 milligrams of 3-nitropropionic acids
40 milligrams of Chlorambucils
It is made the pastille polymer by above-mentioned flow process.
Above-mentioned pastille polymer is placed on tumor by local has improved therapeutic effect to the cerebral tumor greatly, reduced general toxicity simultaneously, in addition, single time spent of the antitumous effect when different components share obviously strengthens.
As mentioned above, the pastille holder is a bio-capacitivity, so do not cause foreign body reaction.Place the back degradable in the body and absorb, so the taking-up of need not performing the operation again, the drug slow with institute's bag in the process of degraded and absorbed discharges, thereby optionally improves and prolong the local drug concentration of tumor.The local placement not only improved therapeutic effect, and reduced the general toxic reaction that is caused by the conventional route administration.Except that placed the part, all right various ways was through the number of ways administration.Except that independent application, also can with many treatment measure use in conjunction, for example:
(1) be used for the treatment of people and the various entity tumors of animal, the operation back is local places and uses anti-cancer composition the radical cure tumor is had unique effect.Some tumor growth can not exenterate at the key position (locating as brain stem etc.) of human body, and the slow release of topical remedy can replace excision.Some malignant tumor, operation technique may promote the tumor diffusion, and the slow release of topical remedy may be the more selection of science.
(2) with high thermal therapeutical use in conjunction.
(3) thank to the treatment use in conjunction with putting.
(4) with the immunization therapy use in conjunction.
(5) with the gene therapy use in conjunction.
During with the gene therapy use in conjunction, its main feature is to use to strengthen the material that succinate dehydrogenase is expressed, the latter comprises plasmid, gene segment and the nucleotide sequence that contains the succinate dehydrogenase of encoding, and the material that can strengthen the succinate dehydrogenase expression also comprises the material that can strengthen succinic dehydrogenase activity.
Anticancer pharmaceutical composition of the present invention is except that share with above-mentioned therapy, and its Main Ingredients and Appearance also can strengthen use in conjunction such as phototherapy, ultrasound wave, electrotherapy, hormone therapy and chemotherapy, therefore has unique action effect and very high clinical value.

Claims (10)

1. an anticancer pharmaceutical composition is characterized in that, contains organelle crystal material and the pharmaceutically suitable carrier and/or the excipient of effective anticancer.
2. the anticancer pharmaceutical composition according to claim 1, it is characterized in that, described organelle comprises all subcellular structures, as, interior knitmesh, nucleus, nuclear membrane, nuclear plate, caryoplasm, nuclear pore complex, nuclear cover, chromosome, chromatin, core tube, centromere, telomere, serous coat, Golgi body, centriole, lysosome, centrosome, other centriole material, retraction ring, ribosome, endosome, phagosome, proteasome, peroxisome, and spindle.
3. the anticancer pharmaceutical composition according to claim 1 is characterized in that described organelle comprises the microfilament microtubule system, as microvillus, flagellum, cilium and other microfilament microtubule.
4. the anticancer pharmaceutical composition according to claim 1 is characterized in that, described organelle crystal material comprises tetrazolium and analog thereof etc.
5. the anticancer pharmaceutical composition according to claim 4; it is characterized in that; tetrazolium and analog thereof comprise 3-(4; 5-dimethylthiazole-2-yl)-2; 5-biphenyl tetrazolium is smelt; Thiazolyl blue; tetrazolium orchid (dichloro 3; 3 '-[3; 3 '-dimethoxy (1; 1 '-biphenyl)-4; 4 '-two bases]-two [2; 5 biphenyl-2H-tetrazolium]; (1H)-tetrazolium; Vitastain (chlorination 2; 3; the 5-Triphenyl Tetrazolium Chloride); 1; 3; 5-triphen first (claiming the Triphenyl Tetrazolium Chloride first again); the iodonitrotetrazolium first; p-iodonitrotetrazolium violet; claim again (2-[4-allusion quotation benzene]-the 3-[4-Nitrobenzol]-5-phenyltetrazole chlorine); tetrazole violet; chlorination (2 again; 5-biphenyl-3-[Alpha-Naphthyl]-tetrazolium); chlorination 2 (p-iodobenzene)-p-Nitrobenzol-5-benzene tetrazolium; (chlorination 2 again for neotetrazolium chloride; 2 '; 5; 5 '-four benzene-3; 3 '-[p-hexichol] two tetrazoliums); the blue tetrazolium of nitro; the blue tetrazolium of p-nitro; chlorination 2; 2 '-two-p-Nitrobenzol-5; 5 '-diphenyl-3; 3 ' [3; 3 '-dimethoxy-4; 4 ' two phenylene]-two tetrazoliums and diformazan (5 thereof; 5 '-two-p-nitre phenyl-3; 3 '-diphenyl-1; 1 '-[3; 3 '-dimethoxy-4; 4 '-two phenylene] diformazan; TNBT; chlorination 2; 2 '-two [p-nitre benzene]-5; 5 '-two [p-thiocarbamoyl benzene]-3; 3 '-[3; 3 '-dimethoxy-4; 4 '-hexichol] two tetrazoliums; Thiocarbamyl nitro-BT; tetrazotized o-dianisidine; 3-(4; 5-dimethylthiazole-2-yl)-5-(3-carboxyl anisyl)-2-(4-sulfophenyl)-2H-tetrazolium salts; 4-[3-(iodophenyl)-2-(4-Nitrobenzol)-2H-5-tetrazolium]-1; 3-benzene disulfonate (WST-1); 2; 2-two (2-methoxyl group-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxyl anilid; chlorination 1-[4; 5-dimethylthiazole-2-yl]-2; 5-carboxyl acyl amine; chlorination 1-[4; 5-dimethylthiazole-2-yl]-2; 5-hexichol tetrazolium; 3 '-[the 1-[(phenyl amino)-phosphinylidyne]-3, the 4-tetrazolium]-two (4-methoxyl group-6-nitro) benzene sulfo group acid sodium hydroxide, above organelle crystal material can singly select or multiselect.
6. the anticancer pharmaceutical composition according to claim 1 is characterized in that, also contains other medicines, comprises antibiotic, antalgica, chemotherapeutics, anticoagulant medicine or hemorrhage, antibiotic medicine, hormone and/or Chinese herbal medicine extract.
7. the anticancer pharmaceutical composition according to claim 1 is characterized in that, the organelle crystal substance weight percentage ratio of anticancer pharmaceutical composition is 0.01-99.99%, is good with 1-99% part, is best with 5-90%.
8. the anticancer pharmaceutical composition according to claim 1 is characterized in that, makes various dosage forms, and be solid-state as capsule etc. as injection, muddy suspension, ointment machin; Be different shape, as granular, lamellar, sphere, bulk and membranaceous.
9. a treatment method for cancer comprises the anticancer pharmaceutical composition and chemotherapy, immunization therapy, thermotherapy, phototherapy, hormone therapy, ultrasound wave, electrotherapy, gene therapy and radiotheraping method use in conjunction treatment people and former of animal or the secondary tumor that use claim 1.
10. the treatment method for cancer according to claim 9 is characterized in that the cancer of being treated comprises cancer, sarcoma, carcinosarcoma, blood and the lymph tumor that originates from various histoorgans; Through various administrations,, directly place in the tumor body as the tremulous pulse approach.
CN 00111092 2000-04-29 2000-04-29 Anticancer medicine composition Pending CN1275404A (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
CN 00111092 CN1275404A (en) 2000-04-29 2000-04-29 Anticancer medicine composition
EP01930891A EP1294922B1 (en) 2000-04-29 2001-04-27 Treating cancer using organelle crystallizing agents
IL15248401A IL152484A0 (en) 2000-04-29 2001-04-27 Method for treating cancer, visualizing cell structures, and isolating organelles using organelle crystallizing agents
AT01930891T ATE464046T1 (en) 2000-04-29 2001-04-27 TREATMENT OF CANCER USING ORGANELLIC CRYSTALLIZING COMPOUNDS
AU5738301A AU5738301A (en) 2000-04-29 2001-04-27 Method for treating cancer, visualizing cell structures, and isolating organelles using organelle crystallizing agents
DE60141829T DE60141829D1 (en) 2000-04-29 2001-04-27 TREATMENT OF CANCER USING ORGANIC CRYSTALLIZING COMPOUNDS
CA2407112A CA2407112C (en) 2000-04-29 2001-04-27 Method for treating cancer, visualizing cell structures, and isolating organelles using organelle crystallizing agents
AU2001257383A AU2001257383B2 (en) 2000-04-29 2001-04-27 Method for treating cancer, visualizing cell structures, and isolating organelles using organelle crystallizing agents
PCT/US2001/013730 WO2001082780A2 (en) 2000-04-29 2001-04-27 Method for treating cancer, visualizing cell structures, and isolating organelles using organelle crystallizing agents
IL152484A IL152484A (en) 2000-04-29 2002-10-24 Salts of tetrazolium derivatives as organelle and cytoskeleton crystallizing agents and compositions containing them for killing tumor cells

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