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Extraction of tetraodontoxin, and preparation thereof used in drug dependence of dolantin

A technology of tetrodotoxin and pethidine, which is applied to medical preparations with non-active ingredients, medical preparations containing active ingredients, and devices for making medicines into special physical or ingestible forms, which can solve the problem of poor stability of preparations and treatment problems. Poor effect, epimerization and other problems, to achieve the effect of fast onset, easy acceptance, and good separation effect

Inactive Publication Date: 2009-07-08
王维国
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the stability of the preparation of the above formula is very poor. After a long period of storage, it is easy to produce epimerization, which makes tetrodotoxin gradually reduce its content with the increase of time, affects the performance of the drug, and has poor therapeutic effect.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Tetrodotoxin extraction, including stock solution extraction, resin exchange and elution steps,

[0037] The first step of stock solution extraction: take 100kg of chrysanthemum yellow oriental porpoise ovary, cut into 1-2cm flakes, soak and stir with 100L of 0.1%-0.5% HAC solution, and dry it with a dryer for 48 hours to obtain the stock solution. Heat to boiling, stop heating immediately, remove coagulated protein, and use 50-80 mesh nylon net to filter the stock solution after cooling, and then filter through kaolin-pulp to obtain a light yellow transparent stock solution, and continue soaking egg dregs for 24 hours. Repeat the above steps to collect the filtrate, obtain a total of 20L of the original solution, adjust the pH to 5-7 with ammonia water, add 1-5% n-butanol or 1-2% formaldehyde for corrosion protection, and store it at room temperature for later use;

[0038] The second step of resin exchange: the resin is D152 positive macroporous acrylic acid weak acid...

Embodiment 2

[0046] The tetrodotoxin prepared in Example 1 is used for the preparation of peperidine drug dependence, and 1000 injection preparations are prepared from the following raw materials in parts by weight, each 1ml:

[0047] Tetrodotoxin 480μg

[0048] 0.5% citric acid 2ml

[0049] Chondroitin Sulfate 960μg

[0050] The balance of water for injection.

[0051] The specific preparation method is as follows: dissolving tetrodotoxin in 0.5% citric acid solution, chondroitin sulfate in water for injection, mixing the two solutions, adding water for injection, adjusting the pH value to 4-6, fully stirring, and sterilizing and filtering, Ultrafiltration, metered filling into ampoule under aseptic conditions, half-opened and sent to freeze dryer for pre-cooling at -40 degrees, open the cold well for refrigeration, start the vacuum pump when the temperature reaches -55 degrees, and the vacuum pump is at a vacuum degree of 5 Pa Below, maintain for 24 hours, then raise the temperature a...

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PUM

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Abstract

The invention relates to the extraction of tetraodontoxin and a preparation of the same. The extraction of the tetraodontoxin comprises: a fist step of extracting a stock solution, in which ovaries of Takifugu flavidus are soaked in an HAC solution to form the stock solution; a second step of resin exchange, in which resin which is D152 positive macroporous weakly acidic acrylic resin is converted to NH4 type by a conventional method, two columns carry out resin exchange for two times, a lower layer of the inside of the A column which is a glass column contains resin, an upper layer of the the inside of the A column contains diatomaceous earth, a lower layer of the inside of the B which is a glass column contains neutral alumina, an upper layer of the inside of the B column contains resin; and a third step of elution carried out after exchange of the two columns, in which strong toxins collected after exchanged and elution are mixed after the elution of the two columns and a coarse product of tetraodontoxin is obtained by crystallization. The method for extracting the tetraodontoxin improves the product yield and purity. The preparation has the characteristics of longer storage period, and quick effect, complete control over symptoms, smooth transition, easy reception and the like in use for de-addiction treatment.

Description

1. Technical field: [0001] The invention relates to a preparation method of tetrodotoxin, and also relates to a raw material preparation of tetrodotoxin used in narcotic drugs such as peperidine. 2. Background technology: [0002] Tetrodotoxin (TTX for short) is a non-protein small molecular compound extracted and isolated from puffer fish ovary or liver, its molecular formula: C 11 h 17 N 3 o 8 , with a molecular weight of 319.27. Tetrodotoxin is a highly specific cell membrane sodium ion channel blocker, which can block nerve conduction and thus play an analgesic and detoxification role. Clinically used in internal medicine, surgery, dermatology and other fields. [0003] The extraction and separation of tetrodotoxin was first obtained in 1909 by Japan Tahara from puffer fish ovary to obtain crude tetrodotoxin crystallization, and established its chemical structure. In 1972, Japanese scholar Kishi Yoshito's group chemically synthesized tetrodotoxin. my country's Bei...

Claims

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Application Information

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IPC IPC(8): C07D491/22A61K31/529A61K47/36A61P25/30A61J3/00
Inventor 王维国
Owner 王维国
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