Tiopronin sterile powder and preparation and preparation method thereof

Abstract

The invention relates to the field of pharmaceutical engineering, in particular to a tiopronin sterile powder and a preparation and a preparation method thereof. The preparation method disclosed by the invention comprises the following steps of: adding an ethyl formate-dissolvable tiopronin raw material into an active carbon heat removing source for injection; adding ether or methyl tert-butyl ether for recrystallizing; and drying at a low temperature to obtain tiopronin sterile powder which is free from pyrogen and has high purity. The preparation method disclosed by the invention is easy and convenient to operate, and has high yield; and the obtained tiopronin sterile powder has high purity and safe and reliability quality, is suitable for preparing a tiopronin sterile powder injection, and can be widely applied to mass production of tiopronin sterile powder injections.

Description

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a tiopronin aseptic powder and its formulation and preparation method. Background technique

[0002] Tiopronin, English name Tiopronin, chemical name N-(2-mercaptopropionyl)-glycine, is a new type of glycine derivative containing free sulfhydryl, molecular formula is C 5 h 9 NO 3 S, the molecular weight is 163.20, the structural formula is as follows:

[0003]

[0004] Tiopronin is a thiol-containing drug similar in nature to penicillamine, and has the effect of protecting liver tissue and cells. Animal experiments have shown that tiopronin can prevent liver damage caused by carbon tetrachloride, ethionine, acetaminophen, etc. by providing sulfhydryl groups, and can inhibit the accumulation of triglycerides in chronic liver damage. The activity of ATPase in the mitochondria of liver cells is reduced, thereby protecting the structure of liver mitochondria and impr...

Examples

preparation example Construction

[0031] A preparation method of tiopronin aseptic powder, comprising:

[0032] Step 1: Take tiopronin raw material, add 4 to 10 times ethyl formate in g / mL to dissolve, heat to reflux, add 0.1% to 0.5% injection in weight / volume percentage in g / mL Adsorb with activated carbon and filter;

[0033] Step 2: Take the filtrate obtained in Step 1, add 5v / v% to 30v / v% of ethyl formate ether or methyl tert-butyl ether, heat and stir to dissolve, and filter it with a 0.22μm microporous membrane below 0.1Mpa;

[0034] Step 3: Freeze the filtrate obtained in step 2 to -5-5°C for crystallization, collect the obtained crystals, filter, dry under reduced pressure at 15-30°C, and pulverize.

Embodiment 1

[0035] In order to further understand the present invention, the present invention will be described in detail below in conjunction with examples. Embodiment 1: the preparation of tiopronin sterile powder injection

[0036] (1) Take by weighing 500g tiopronin raw material, purity is 95.3%, add in the reactor, add 6 times of amount, i.e. ethyl formate of 3L, heat reflux;

[0037] (2) After tiopronin is dissolved, add 9g of activated carbon for injection, and filter under reflux for 30 minutes;

[0038] (3) After filtering, add 300mL methyl tert-butyl ether to the filtrate, heat and stir to dissolve;

[0039] (4) After dissolving, below 0.1Mpa, use a 0.22μm microporous membrane to filter under positive pressure;

[0040] (5) After filtering, freeze the filtrate to 0°C, and crystallize at low temperature for 2 hours;

[0041] (6) After the crystallization is completed, filter, and vacuum-dry the obtained crystals at 15° C. for 4 hours;

[0042](7) After drying, the crystals w...

Embodiment 2

[0044] Embodiment 2: the preparation of tiopronin sterile powder injection

[0045] (1) Take by weighing 500g tiopronin raw material, purity is 95.3%, add in the reactor, add 10 times of amount, i.e. ethyl formate of 5L, heat to reflux;

[0046] (2) After tiopronin is dissolved, add 25g of active carbon for injection, and filter under reflux for 30 minutes;

[0047] (3) After filtering, add 1000mL methyl tert-butyl ether to the filtrate, heat and stir to dissolve;

[0048] (4) After dissolving, below 0.1Mpa, use a 0.22μm microporous membrane to filter under positive pressure;

[0049] (5) After filtering, freeze the filtrate to 5°C, and crystallize at low temperature for 2 hours;

[0050] (6) After the crystallization is completed, filter, and vacuum-dry the obtained crystals at 30° C. for 3 hours;

[0051] (7) After drying, the crystals were pulverized to obtain 456.5 g of white tiopronin sterile powder, with a yield of 91.3%. 99.5% purity;

[0052] (8) The sterile powde...

technical field

[0001] The invention relates to the field of pharmaceutical preparations, in particular to a tiopronin aseptic powder and its formulation and preparation method. Background technique

[0002] Tiopronin, English name Tiopronin, chemical name N-(2-mercaptopropionyl)-glycine, is a new type of glycine derivative containing free sulfhydryl, molecular formula is C 5 h 9 NO 3 S, the molecular weight is 163.20, the structural formula is as follows:

[0003]

[0004] Tiopronin is a thiol-containing drug similar in nature to penicillamine, and has the effect of protecting liver tissue and cells. Animal experiments have shown that tiopronin can prevent liver damage caused by carbon tetrachloride, ethionine, acetaminophen, etc. by providing sulfhydryl groups, and can inhibit the accumulation of triglycerides in chronic liver damage. The activity of ATPase in the mitochondria of liver cells is reduced, thereby protecting the structure of liver mitochondria and impr...

Examples

preparation example Construction

[0031] A preparation method of tiopronin aseptic powder, comprising:

[0032] Step 1: Take tiopronin raw material, add 4 to 10 times ethyl formate in g / mL to dissolve, heat to reflux, add 0.1% to 0.5% injection in weight / volume percentage in g / mL Adsorb with activated carbon and filter;

[0033] Step 2: Take the filtrate obtained in Step 1, add 5v / v% to 30v / v% of ethyl formate ether or methyl tert-butyl ether, heat and stir to dissolve, and filter it with a 0.22μm microporous membrane below 0.1Mpa;

[0034] Step 3: Freeze the filtrate obtained in step 2 to -5-5°C for crystallization, collect the obtained crystals, filter, dry under reduced pressure at 15-30°C, and pulverize.

Embodiment 1

[0035] In order to further understand the present invention, the present invention will be described in detail below in conjunction with examples. Embodiment 1: the preparation of tiopronin sterile powder injection

[0036] (1) Take by weighing 500g tiopronin raw material, purity is 95.3%, add in the reactor, add 6 times of amount, i.e. ethyl formate of 3L, heat reflux;

[0037] (2) After tiopronin is dissolved, add 9g of activated carbon for injection, and filter under reflux for 30 minutes;

[0038] (3) After filtering, add 300mL methyl tert-butyl ether to the filtrate, heat and stir to dissolve;

[0039] (4) After dissolving, below 0.1Mpa, use a 0.22μm microporous membrane to filter under positive pressure;

[0040] (5) After filtering, freeze the filtrate to 0°C, and crystallize at low temperature for 2 hours;

[0041] (6) After the crystallization is completed, filter, and vacuum-dry the obtained crystals at 15° C. for 4 hours;

[0042](7) After drying, the crystals w...

Embodiment 2

[0044] Embodiment 2: the preparation of tiopronin sterile powder injection

[0045] (1) Take by weighing 500g tiopronin raw material, purity is 95.3%, add in the reactor, add 10 times of amount, i.e. ethyl formate of 5L, heat to reflux;

[0046] (2) After tiopronin is dissolved, add 25g of active carbon for injection, and filter under reflux for 30 minutes;

[0047] (3) After filtering, add 1000mL methyl tert-butyl ether to the filtrate, heat and stir to dissolve;

[0048] (4) After dissolving, below 0.1Mpa, use a 0.22μm microporous membrane to filter under positive pressure;

[0049] (5) After filtering, freeze the filtrate to 5°C, and crystallize at low temperature for 2 hours;

[0050] (6) After the crystallization is completed, filter, and vacuum-dry the obtained crystals at 30° C. for 3 hours;

[0051] (7) After drying, the crystals were pulverized to obtain 456.5 g of white tiopronin sterile powder, with a yield of 91.3%. 99.5% purity;

[0052] (8) The sterile powde...

Images