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Heavy metal toxinicide, its preparation method and application

A technology of medicaments and toxic and side effects, applied in the field of biological medicaments for relieving heavy metal poisoning, can solve problems such as large damage to liver cells

Inactive Publication Date: 2002-09-04
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, when it is applied to patients with acute promyelocytosis (APL), the induction remission rate is 72.3% for the initial cases, and 85.1% for the relapse cases, and the curative effect is significantly higher than that of chemotherapy and retinoic acid drugs used in the past. Efficacy of treatment (usually about 30%), however, As 2 o 3 Great damage to normal cells, especially liver cells, 2 of the 11 first-time patients treated died due to abnormal liver function damage

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Encapsulation of MTL protein with azo aromatic polymer to make oral drug

[0042] The MTL protein is diluted with sucrose powder and packed into capsules or made into pellets, and wrapped (coated) with azo aromatic polymers. The polymer mixes aromatic compounds in a certain ratio, such as copolymerizing styrene and ethyl methacrylic acid at a ratio of 1:6, and then cross-links with azo compounds, such as 1-2% divinyl azobenzene, to form a polymer. Coating can then be accomplished by dissolving the polymer in a chlorinated alkane, such as methylene chloride.

[0043] Since the azoaromatic polymer can protect the protein from acid and enzymatic hydrolysis in the stomach and small intestine, the coating compound will not be completely decomposed immediately in the small intestine; when the coating reaches the large intestine, the coating layer will be affected by internal growth. The action of the flora decomposes, so that the MTL protein enters the colon for local action...

Embodiment 2

[0045] Formulation of MTL protein into microspheres

[0046] Take 500ug-50mg of MTL protein, 60-100mg of gelatin, and 1ml of water, mix and heat to 60°C to form the internal water phase, and the oil phase is polylactic acid (PLA), polylactide-glycolide (PLGA) or polylactic-glycolic acid copolymerization Dissolve in dichloromethane, and then gradually pour the oil phase into the water phase under stirring or ultrasonic treatment to make a microemulsion. This emulsion is cooled to 15 ° C, and added to 0.5 ml of polyvinyl alcohol aqueous solution with a nozzle at 5000 rpm Stir for 1-4 minutes to form an emulsion. Finally, stir at room temperature for 2 hours or remove dichloromethane by rotary evaporation to obtain hardened round microspheres (or capsules).

[0047] The microsphere preparation is administered by intramuscular injection, and according to the different components of the oil phase copolymer, the drug components can be released continuously in the body within differ...

Embodiment 3

[0049] made kit

[0050] Firstly, the MTL protein was dialyzed to desalt, frozen at -70°C for one hour, and then evacuated overnight in a lyophilizer to make a lyophilized powder. Subsequently, it is prepared with phosphate buffer solution, water for injection, glucose saline for infusion and 0.1% arsenic trioxide solution to prepare a kit.

[0051] The kit can be used to treat patients with tumor relapse, such as patients with relapse of acute promyelocytic leukemia. During the treatment, dilute the arsenic trioxide solution to 0.002% with glucose saline and infuse it intravenously for 2-3 hours every day, and detect the changes of its clinical appearance and cell morphology. If symptoms of poisoning appear, stop the intravenous infusion immediately, dissolve the lyophilized powder of MTL protein in phosphate buffer, dilute it with water for injection, and inject it into the patient. For patients with hepatic dysfunction, it should be injected every day, and the dosage depe...

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Abstract

The present invnetion relates to a biological medicine preparation for relieving heavy metal poisoning. It is a heavy metal antidote using human metallothionein-L (MTL) as main component. The MTL contains the polypeptide of amino acid sequence described by SEQ IP NO2, its nucleotide code sequence and the nucleotide sequence described by SEQ ID NO1 have at least 70% of homology. It can relieve heavy metal and semimetals poisoning, in the course of development it can regulate internal balance of zinc and copper, and make metallic metabolism and detoxification, and can eliminate free radical. There, this invention can be used as auxiliary medicine preparation for curing tumor, and also relates to its production method and application.

Description

technical field [0001] The invention relates to a biological agent for alleviating heavy metal poisoning. Specifically, the present invention relates to a heavy metal detoxification agent mainly composed of human metallothionein-L (MTL for short). The invention also relates to the production method and application of the medicament. Background technique [0002] Tumor is a common and frequently-occurring disease that seriously threatens human health, and is characterized by malignant proliferation of cells. At present, the treatment options for most tumors are mainly surgery, radiotherapy, chemotherapy, immunotherapy and Chinese herbal medicine therapy. Prevent its function; (3) embedded in DNA to interfere with its template function; (4) regulate hormone balance in vivo. Heavy metal and semi-metal drugs are one of the commonly used drugs at present, and their main function is to directly destroy the DNA structure and inhibit its function. As 2 o 3 These are the drugs. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P39/02C07K16/18C12N15/12
Inventor 余龙唐丽莎孙璐虹杨玉美万波
Owner FUDAN UNIV
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