CN1081033C - Partial slow-released glutathione inhibitor - Google Patents
Partial slow-released glutathione inhibitor Download PDFInfo
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- CN1081033C CN1081033C CN97105741A CN97105741A CN1081033C CN 1081033 C CN1081033 C CN 1081033C CN 97105741 A CN97105741 A CN 97105741A CN 97105741 A CN97105741 A CN 97105741A CN 1081033 C CN1081033 C CN 1081033C
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- glutathione
- free radical
- mortifier
- slow
- inhibitor
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a partial slow-release glutathione inhibitor which is composed of a biologic-soluble and degradable-absorbing high molecular polymer and a free radical generating product and a glutathione inhibitor which are wrapped into the high molecular polymer. After the slow-release glutathione inhibitor is placed in a body, the partial free radical concentration of a tumor can be increased, and the anti-oxidation protecting mechanism of the glutathione in tumor cells and the whole body toxic reaction caused by systematic medical administration can be selectively decreased. The partial slow-release medicine can enhance the functions of other treating methods, and the selectivity is wide. Thus, the present invention has high clinical applying value and economical and social benefits.
Description
The present invention relates to a kind of prescription and preparation technology who treats the partial slow-released glutathione inhibitor of entity tumor.
The measure of many treatment tumors commonly used at present all generates relevant with free radical as chemotherapy, electrotherapy, photochemical therapy and radiotherapy etc.Use activity and the biosynthesis that a small amount of free radical product could activate or induce glutathione separately.Outside latter's decapacitation promotes tumor growth and shifts, also can strengthen the medicine function of detoxification of tumor cell and to the tolerance of other treatment.
Slow releasing agent purpose of the present invention is glutathione mortifier and free radical product are packaged in the macromolecule polymer of bio-soluble, degradable absorption simultaneously, after placing in the body, agent for slow releasing medicine can slowly discharge free radical product and glutathione mortifier at tumor by local.The glutathione mortifier of local sustained release can reduce the activity of glutathione; capable of blocking or destroy the biosynthesis of glutathione in the tumor cell; then optionally reduce and tumoricidal autoprotection mechanism, therefore can wide and practical be applied to the treatment and the auxiliary treatment of various entity tumors.
Experimental results show that, glutathione mortifier and free radical product are packaged in the macromolecule polymer simultaneously, decapacitation optionally improves and prolongs local drug concentration, outside the fragmentation effect of enhancing to tumor, also can reduce the general toxic reaction that causes through being administered systemically, single better with locally delayed-release free-radical product effect.The glutathione mortifier of local sustained release and free radical product be the kill tumor cell directly, and both act on the tumor body simultaneously and have the obvious synergistic effect, obtain beyond thought effect.
The present invention is made up of glutathione mortifier, free radical product, organic solvent and macromolecule polymer.
Glutathione mortifier among the present invention can be selected following medicine material medicine for use:
1. glutathione reductase mortifier, as: S-nitroso-group glutathione, phenolic compound, ammonium metavanadate, maleic acid diethyl fat, 1 such as ellagic acid, bright essence, 3-two (2 chloroethyl)-1-nitroso ureas (BCNU), chloroethyl-1-nitroso ureas (CCNU), cadmium ion, trivalent organo-arsenic, glutathione disulphide and tetramethylthiuram disulfide etc.
2. glutathione s transferase mortifier, as acidum ethacrynicum glutathione conjugate, acidum ethacrynicum brominated product and other metabolite, caffeic acid and glutathione conjugate thereof, dicoumarol, sulfanilamide salazine, cumene hydroperoxide, anti-(formula)-4-benzene butene-2-ketone, α (or β) beta-unsaturated carbonyl compounds, as (E)-2-octene-2-ketone and (E)-3-nonene-2-ketone etc., acidum ethacrynicum, curcumin, cavatic acid and phenolic compound etc.
3. glutathione peroxidase mortifier, as: DL-Buthionine-(S,R)-sulfoximine BSO, dicoumarol, mercapto succinic acid salt and S-nitrogen-N-N-acetylpenicillamine etc.
4. glutathione competitive inhibitor, as: S-hexyl glutathione, S-octyl group glutathione, acidum ethacrynicum glutathione conjugate, acidum ethacrynicum brominated product and other metabolite, caffeic acid and glutathione conjugate thereof and S-nitroso-group glutathione etc.
Other, as cobaltous chloride, quinone, hydroquinone, alkylating agent (as Min Erfalan etc.), cyclophosphamide and derivant (as 4 hydrogen peroxide cyclophosphamide) and platinum class complex (as cisplatin, carboplatin) etc.
Free radical product among the present invention can be selected following medicine material medicine for use:
1. some chemotherapeutics, as: amycin, daunorubicin, daunomycin, bleomycin A5, new carzinostatin, ametycin, D actinomycin D, anthramycin, hydrochloride methyl benzyl callosity, vincristine, vincaleucoblastine, ammonia first dish purine, cyclophosphamide and derivant, Chlorambucil, platinum class complex, Min Erfalan and other anthryl chemical compound etc.
2. quinones, as: 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.
3. some biooxidation reactions material, as: xanthine (or hypoxanthine)/xanthine oxidase, xanthine dehydrogenase, glucose-glucoseoxidase, vitamin C/ferrum redox couple, hypochlorous acid/myeloperoxidase, flavin oxidoreductase, nadide (II) oxidoreductase and quinone oxidoreductase etc.
4. vanadium compounds, as: vanadate, adjacent vanadate and phenanthroline vanadium complex etc.
5. some free radical and lipid peroxidation product, as: acrylic aldehyde, α-unsaturated aldehyde and beta-unsaturated aldehyde etc.
6. unsaturated fatty acid, as: parinaric acid, eicosatetraenoic acid, eicosapentaenoic acid, docosahexenoic acid, alpha-linolenic acid and gamma-Linolenic acid etc.
7. some enzyme and protein synthesis inhibitor, as: guanylate cyclase inhibitor (phenylamino quinolyl dione) etc.; Protein synthesis inhibitor is as cycloheximide, ipecine, anisomycin and puromycin etc.
8. free radical generates reinforcing agent, as: N-acetylcystein, cytochrome C, Cytochrome P450, hydrochloric acid different name morpholino and nitroso-group N-acetylpenicillamine etc.
9. pyridine compounds and their, as: N,N'-dimethyl-.gamma..gamma.'-dipyridylium etc.
Organic solvent among the present invention can be selected dichloromethane or dimethyl formamide etc. for use,
Macromolecule polymer among the present invention can be high molecular lactic, Oleum sesami and fruit peptone etc.
The characteristics of partial slow-released glutathione inhibitor technology of preparing of the present invention are macromolecule polymer (according to a certain percentage) is dissolved in the organic solvent, add a certain amount of free radical product and glutathione mortifier behind while or the mixing.Fully bleed after the mixing, thing to be mixed adds small amounts of emulsifiers when being semi-fluid state, changes the vacuum desiccator inner drying behind the mixing over to.Be shaped immediately after the drying and sterilize packing.The macromolecule polymer that contains medicine can be made into different shape.Free radical product and glutathione inhibitor contents in the macromolecule polymer are advisable with 5%～50%, and the ratio of free radical product and glutathione mortifier is decided because of different pharmaceutical.Can be from 1: 2～2: 1.
End product of the present invention is the solid product that bio-soluble, degradable absorb, and the technological process of its technology of preparing is as follows: the free radical product-→ organic glutathione mortifier of weighing → weigh-→ dissolving mixing → dry forming → sterilization packing → product macromolecule polymer-→ solvent of weighing
The present invention further is illustrated by following examples.
Embodiment 1: molecular weight is 100 milligrams of 50000 lactic acid
30 milliliters of dimethyl formamides
20 milligrams of DL-Buthionine-(S,R)-sulfoximine BSO
20 milligrams of N,N'-dimethyl-.gamma..gamma.'-dipyridyliums
It is made the partial slow-released glutathione mortifier by above-mentioned flow process.
Embodiment 2: molecular weight is 80 milligrams of 80000 lactic acid
30 milliliters of dimethyl formamides
20 milligrams of DL-Buthionine-(S,R)-sulfoximine BSO
20 milligrams of N,N'-dimethyl-.gamma..gamma.'-dipyridyliums
It is made the partial slow-released glutathione mortifier by above-mentioned flow process.
Embodiment 3: molecular weight is 40 milligrams of 20000 lactic acid
Molecular weight is 40 milligrams of 50000 lactic acid
30 milliliters of dimethyl formamides
20 milligrams of DL-Buthionine-(S,R)-sulfoximine BSO
20 milligrams of Chlorambucils
It is made the partial slow-released glutathione mortifier by above-mentioned flow process.
Above-mentioned pastille polymer is placed on tumor by local improves greatly, reduced general toxic reaction simultaneously the tumor treatment effect.The polymer that the present invention will contain 1 milligram of DL-Buthionine-(S,R)-sulfoximine BSO and 1 milligram of N,N'-dimethyl-.gamma..gamma.'-dipyridylium is placed on the brain tissue of rat tumor by local, found that its effective percentage is 100%, and cure rate is 60%.And the polymer that only contains 1 milligram of DL-Buthionine-(S,R)-sulfoximine BSO or 1 milligram of N,N'-dimethyl-.gamma..gamma.'-dipyridylium is when using separately, and its cure rate is respectively 41% and 29%.In therapeutic process, do not see the obvious adverse reaction that causes because of medication combined.Contain the polymer treatment rat liver tumor of 1 milligram of DL-Buthionine-(S,R)-sulfoximine BSO and 1 milligram of N,N'-dimethyl-.gamma..gamma.'-dipyridylium, found that height when its effective percentage and cure rate are all used more separately, and obvious enhancing is not seen in untoward reaction.
Claims (1)
1. a new drug partial slow-released glutathione inhibitor for the treatment of entity tumor is characterized in that said preparation is by an amount of glutathione mortifier and free radical product, packs with macromolecule polymer etc. and makes granular, sphere, block apperance; The content of glutathione mortifier and free product is 5%～50% of total amount, and the weight ratio of glutathione mortifier and free radical product is 2: 1～1: 2; Wherein the glutathione mortifier is a DL-Buthionine-(S,R)-sulfoximine BSO, and the free radical product is selected Chlorambucil or N,N'-dimethyl-.gamma..gamma.'-dipyridylium for use.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97105741A CN1081033C (en) | 1997-03-28 | 1997-03-28 | Partial slow-released glutathione inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN97105741A CN1081033C (en) | 1997-03-28 | 1997-03-28 | Partial slow-released glutathione inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1194829A CN1194829A (en) | 1998-10-07 |
| CN1081033C true CN1081033C (en) | 2002-03-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN97105741A Expired - Fee Related CN1081033C (en) | 1997-03-28 | 1997-03-28 | Partial slow-released glutathione inhibitor |
Country Status (1)
| Country | Link |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5168066A (en) * | 1990-03-07 | 1992-12-01 | Cytyc Corporation | Thionin staining and imaging technique |
| US5460819A (en) * | 1991-12-13 | 1995-10-24 | Children's Medical Center Corporation | Method for treating PQQ-responsive heavy metal toxicity |
-
1997
- 1997-03-28 CN CN97105741A patent/CN1081033C/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5168066A (en) * | 1990-03-07 | 1992-12-01 | Cytyc Corporation | Thionin staining and imaging technique |
| US5460819A (en) * | 1991-12-13 | 1995-10-24 | Children's Medical Center Corporation | Method for treating PQQ-responsive heavy metal toxicity |
Non-Patent Citations (3)
| Title |
|---|
| 《中国新药与临床杂志》17(4) 1998.4.30 马胜林等谷胱甘肽治疗肿瘤病人伴肝，肾损害和药物性肝，肾损害和药物性肝，损害 * |
| 《中国新药与临床杂志》17(4) 1998.4.30 马胜林等谷胱甘肽治疗肿瘤病人伴肝，肾损害和药物性肝，肾损害和药物性肝，损害;《中国肿瘤生物治疗杂志》6(4) 1999.4.30 高小平等cjun反义核酸消除人体卵巢癌细胞的搞药性研究 * |
| 《中国肿瘤生物治疗杂志》6(4) 1999.4.30 高小平等cjun反义核酸消除人体卵巢癌细胞的搞药性研究 * |
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| Publication number | Publication date |
|---|---|
| CN1194829A (en) | 1998-10-07 |
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