CN1275377A - Anticancer medicine composition - Google Patents
Anticancer medicine composition Download PDFInfo
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- CN1275377A CN1275377A CN 00111093 CN00111093A CN1275377A CN 1275377 A CN1275377 A CN 1275377A CN 00111093 CN00111093 CN 00111093 CN 00111093 A CN00111093 A CN 00111093A CN 1275377 A CN1275377 A CN 1275377A
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Abstract
The present invention relates to a medicine composition for resisting cancers and its application. Said medicine composition mainly contains effective dose of succinate dehydrogenase inhibitor for resisting cancer, not only can effectively kill tumor cell, but also can raise tumor sensitivity to other therapeutic method, for example the sensitivity for radiation therapy and chemical therapy. Said invented medicine composition can be matched with chemical therapy, immunotherapy, thermal therapy, light therapy, ultrasonic therapy, hormonotherapy, electric therapy, gene therapy and radiation therapy to cure human and animal primary or secondary tumor by means of various routes of medication, such as selective artery injection and direct tumor intra-body injection, in which the local slow-release is optimum.
Description
The present invention relates to a kind of is the anticancer pharmaceutical composition of main component with the succinate dehydrogenase inhibitor, and treats the method for tumor with it.
In recent years, tumor treatment has obtained remarkable progress, yet its mortality rate still occupies first of the various common causes of the death, is only second to heart disease.Therefore, inquire into a kind of new effective Therapeutic Method or medicine and just become current important topic.
The objective of the invention is to remedy the shortcoming of prior art, providing a kind of is the anticancer pharmaceutical composition of main component with the succinate dehydrogenase inhibitor.
The present invention also provides a kind of above-mentioned anticancer pharmaceutical composition treatment method for cancer of utilizing.
The present invention also further provides a kind of method of utilizing the succinate dehydrogenase inhibitor to strengthen mitosis mortifier action effect.
Because the principal element of decision therapeutic effect is the drug level of tumor by local and the tumor cell sensitivity to medicine.The interior injection of vein, abdominal cavity and artery administration even tumor body all is difficult to tumor by local and keeps long-time active drug concentration.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 succinate dehydrogenase inhibitor has the effect of treatment tumor, when share with other medicines, has the obvious synergistic effect.In the multiple medicine that is tried, the most remarkable with the synergistic action effect of mitosis mortifier.The succinate dehydrogenase inhibitor is killing tumor cell effectively, can strengthen the action effect of other therapies simultaneously effectively, thereby provides a kind of new effective measures for treating tumor.
The succinate dehydrogenase inhibitor is injected in the band tumor animal body can suppress growth of tumor, 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, not only improve the oncotherapy effect, can avoid general toxic reaction simultaneously.
In view of above-mentioned discovery, the present invention with the succinate dehydrogenase inhibitor 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 when reducing contingent whole body complication, optionally remove the succinum dehydrogenase of tumor by local, 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, have very high clinical value and remarkable economical and social benefit.
Because anti-cancer composition of the present invention can make the action effect of methods such as conventional chemotherapy, immunization therapy, high thermal therapeutical, phototherapy, superfield ripple, hormone therapy and radiotherapy 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 succinate dehydrogenase inhibitor and the pharmaceutically suitable carrier and/or the excipient of effective anticancer.
Wherein the shared ratio of succinate dehydrogenase inhibitor is decided because of concrete condition; Can be good with 1%-99% from 0.01%-99.99%, be best with 5%-90%.
Anticancer pharmaceutical composition of the present invention can be made into multiple dosage form.As, but it is solid-state as capsule etc. to be not limited to injection, muddy suspension, ointment machin; 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 application 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 is 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 succinic acid dehydrogenation inhibitor comprises that succinic acids is like thing, succinic acid derivative, succinic acid isomers, tetrazolium and complex, 3-nitropropionic acid, Laurel (acyl) sarcosine (Sarkosyl:N-Lauroylsarcosine), succinate dehydrogenase antibody and other antagonist etc. among the present invention.Wherein, the succinate dehydrogenase analog comprises that (-)-Bis(l-menthyl) succinate (dimenthyl Succinate) is as (1R)-(-)-(-)-Bis(l-menthyl) succinate and (1S)-(+)-(-)-Bis(l-menthyl) succinate etc.Tetrazolium and complex succinate dehydrogenase inhibitor thereof also comprise succinate dehydrogenase antibody.Succinate dehydrogenase also can be removed through technique for gene engineering, and then optionally treats tumor from gene level.Above succinate dehydrogenase inhibitor can singly select or multiselect.Multiselect more singly is elected to be with effective.
Another kind of form of the present invention is to be to add chemotherapeutics in this anticancer pharmaceutical composition.
Available chemotherapeutics is among the present invention:
One, clinical commonly used drug, as:
1. platinum-like compounds, as: platinum such as platinum, carboplatin class complex ex hoc genus anne thing and derivant etc. with the wind.
2. alkylating agent, as: Chlorambucil, chlormethine series pharmaceuticals, Min Erfalan, bird pyrimidine chlormethine, ACNU, GANU, TA-77, MCNU, GANU, 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 psychopsid, the fast sandfly of 6-sulfydryl, the fast sandfly of 8-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, as, but be 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, pyridines complex is as N,N'-dimethyl-.gamma..gamma.'-dipyridylium etc.
In various chemotherapeutics, be first-selected with the anti-mitosis medicine.Anti-mitosis medicine in this anti-cancer composition can be, but is not limited to, and vinblastine is as vincristine, vincaleucoblastine; Colchicine etc.; Arsenicum class medicine; Cytochalasin; The macrolide medicine is as amycin etc.; Carbaril and metabolite thereof comprise naphthols or naphthyl complex, as 1-naphthyl phosphate etc.; Malonate; Methyl-(5-[2-thiophene phenyl-phosphinylidyne]-1H-benzimidazolyl-2 radicals base) carbamate; Pyridines is as monocrotaline (pyrroles); The propionic acid amide. complex; The Opium alkaloid; Other is as estramustine, podophyllinic acid lactone, 3-bromine acyl phenalgin formoxyl urea and benzene sulfanilamide complex and taxine kind (taxanes) etc.
The taxine kind medicine comprises nature, synthetic, semisynthetic.The taxine kind medicine can extract from animal, plant and microorganism, also available technique for gene engineering preparation.Adaptable taxine kind medicine comprises taxine kind medicine congener, precursor substance, isomers among the present invention.Commonly used as, but be not limited to, taxotere, paclitaxel, docetaxel, yew (Taxus baccata), PiceameyeriRehd. Et Wils., Semen Caesalpiniae Ramulus et folium taxi cuspidatae (Taxus brevifolia), Tetraol (baccatins) (remove acetyl Tetraol (DAB) III, 7-epi-DAB, Tetraol V, Baccatine III, 9-dihydro-13-acetyl Baccatine III (DHB) etc. as 10-.Above anti-mitosis medicine can singly select or multiselect.Multiselect more singly is elected to be with effective.
Also can add other medicinal component in the Main Ingredients and Appearance of the present invention, as antibiotic, antalgica, anticoagulant medicine or hemorrhage, antibiotic medicine, hormone and/or Chinese herbal medicine extract.
In the pharmaceutical composition 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, chemotherapy, superfield ripple, 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 is the material base that tumor is depended on for existence, and its effect is a unlimited hypertrophy of keeping tumor cell and blood vessel thereof; The cancer-resisting substance in can scavenger cell or reduce 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, has anticancer widely basis.
Anticancer pharmaceutical composition of the present invention is main target of attack with succinate dehydrogenase, all acts on succinate dehydrogenase because the present invention finds many medicines, particularly anti-mitosis medicine.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 no longer operation is taken out.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 succinate dehydrogenase inhibitor of being released is except that capable of blocking or tumoricidal protectiveness regulatory mechanism; also can strengthen chemotherapeutics; the particularly cell-cytotoxic reaction of anti-mitosis medicine and tumor cell; toleration tumor cell particularly; to the sensitivity of other therapies, thereby its action effect is 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, can reduction but any, the material of deactivation, inhibition succinate dehydrogenase, comprise and select for use acid holder and surfactant all to 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, succinate dehydrogenase inhibitor and chemotherapeutics (according to a certain percentage) are dissolved in the organic solvent, and abundant mixing is bled afterwards, drying.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%-99.99%, be best with 5%-90%.This anti-cancer 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.
The preparation method of anticancer pharmaceutical composition of the present invention is as follows:
The solid polymer of weighing
The succinate dehydrogenase inhibitor
→ dissolving mixing → drying → shaping → packing → sterilization → product
1. the solid polymer of weighing is put into container, add the certain amount of organic solvent dissolving evenly, be 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 different shape according to different needs.
5. ray sterilizing after the packing, roentgendosis is different because of volume.Also available other method sterilization.
The polymer made from this method is a solid, is yellow or silvery white, and 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
0 milligram of succinate dehydrogenase inhibitors 4
It is made the pastille polymer by above-mentioned flow process.
Embodiment 2: molecular weight is 50 milligrams of 20000 lactic acid
Dividing quantum is 50 milligrams of 80000 lactic acid
100 milliliters of dichloromethane
5 milliliters of Vitastains
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
100 milliliters of (-)-Bis(l-menthyl) succinates
40 milligrams of vincristine
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 taxine kinds (paclitaxel)
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.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) with the radiotherapy use in conjunction.
(4) with the immunization therapy use in conjunction.
(5) with the other therapies use in conjunction.
(6) with the gene therapy use in conjunction.
As synergist, anti-cancer composition of the present invention is except that share with above-mentioned therapy, and its Main Ingredients and Appearance also can strengthen the effect of phototherapy, electrotherapy, hormone therapy and chemotherapy etc., therefore has unique action effect and very high clinical value.
Claims (10)
1. an anticancer pharmaceutical composition is characterized in that, contain in this anticancer pharmaceutical composition effective anticancer by the succinate dehydrogenase inhibitor, and pharmaceutically suitable carrier and/or excipient.
2. the anticancer pharmaceutical composition according to claim 1, it is characterized in that, the succinate dehydrogenase inhibitor comprises succinic acids like thing, succinic acid derivative, succinic acid isomers, tetrazolium and complex, 3-nitropropionic acid, Laurel sarcosine, succinate dehydrogenase antibody and other antagonist, and the succinate dehydrogenase inhibitor can singly select or multiselect.
3. the anticancer pharmaceutical composition according to claim 2 is characterized in that the succinate dehydrogenase analog comprises (-)-Bis(l-menthyl) succinate, reaches (1S)-(+)-(-)-Bis(l-menthyl) succinate as (1R)-(-)-(-)-Bis(l-menthyl) succinate.
4. the anticancer pharmaceutical composition according to claim 1 is characterized in that, also contains chemotherapeutics.
5. the anticancer pharmaceutical composition according to claim 4 is characterized in that the chemotherapeutics in this anti-cancer composition comprises anti-mitosis medicine.
6. the anticancer pharmaceutical composition according to claim 5 is characterized in that the anti-mitosis medicine in this anti-cancer composition is a vinblastine, as vincristine, vincaleucoblastine; Colchicine; Arsenicum class medicine, taxine kind, as (taxotere, paclitaxel, docetaxel); Cytochalasin; The macrolide medicine is as amycin etc.; Carbaril and metabolite thereof comprise naphthols or naphthyl complex, as 1-naphthyl phosphoric acid fat, salt etc.; Malonate; Methyl-(5-[2-thiophene phenyl-phosphinylidyne]-1H-benzimidazolyl-2 radicals base) carbamate, pyridines are as monocrotaline (pyrroles); The propionic acid amide. complex; The Opium alkaloid; Other is as estramustine, podophyllinic acid lactone, 3-bromine acyl phenalgin formoxyl urea and benzene sulfanilamide complex etc.
7. the anticancer pharmaceutical composition according to claim 6 is characterized in that the taxine kind in this anti-cancer composition can be nature, synthetic, semisynthetic, as (taxotere, paclitaxel, docetaxel).
8. the anticancer pharmaceutical composition according to claim 1 is characterized in that, adds other medicines in this anti-cancer composition, comprises antibiotic, antalgica, anticoagulant medicine or hemorrhage, antibiotic medicine, hormone and/or Chinese herbal medicine extract.
9. the anticancer pharmaceutical composition according to claim 1 is characterized in that, can be made into multiple dosage form, as, but be not limited to injection, muddy suspension, ointment or solid-state as capsule; Be different shape, as, but be not limited to, granular, lamellar, sphere, bulk or membranaceous, in various dosage forms slowly to be released to the master.
10. treat method for cancer for one kind, comprise and use claim 1 anti-cancer composition and chemotherapy, immunization therapy, thermotherapy, phototherapy, ultrasound wave, hormone therapy, electrotherapy, gene therapy and radiotheraping method use in conjunction treatment people and former of animal or secondary tumor, through various administrations, with topical, wherein be released to the best as injection in selective arterial injection and the direct tumor body for good with local slow.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00111093 CN1127952C (en) | 2000-04-29 | 2000-04-29 | Anticancer medicine composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 00111093 CN1127952C (en) | 2000-04-29 | 2000-04-29 | Anticancer medicine composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1275377A true CN1275377A (en) | 2000-12-06 |
| CN1127952C CN1127952C (en) | 2003-11-19 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 00111093 Expired - Fee Related CN1127952C (en) | 2000-04-29 | 2000-04-29 | Anticancer medicine composition |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1299674C (en) * | 2004-12-29 | 2007-02-14 | 山东蓝金生物工程有限公司 | Slow released combination of anticancer drugs embedded in vivo |
| CN1311872C (en) * | 2004-12-29 | 2007-04-25 | 山东蓝金生物工程有限公司 | Anticancer combination of medication |
-
2000
- 2000-04-29 CN CN 00111093 patent/CN1127952C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1299674C (en) * | 2004-12-29 | 2007-02-14 | 山东蓝金生物工程有限公司 | Slow released combination of anticancer drugs embedded in vivo |
| CN1311872C (en) * | 2004-12-29 | 2007-04-25 | 山东蓝金生物工程有限公司 | Anticancer combination of medication |
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| Publication number | Publication date |
|---|---|
| CN1127952C (en) | 2003-11-19 |
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