CN101961309A - Process for preparing pantoprazole sodium for injection - Google Patents

Abstract

The invention relates to a preparation process (preparation method) for pantoprazole sodium for injection, overcomes the defect of the traditional preparation process for the pantoprazole sodium for injection, and provides a preparation process with low cost, high yield and more stable finished product quality. The process comprises the following steps of: (1) feeding materials according to 100 percent of formula quantity, adding mannitol into injection water in an amount which is about 15 percent of preparation quantity, dissolving the materials with stirring, adding medicinal carbon in an amount which is 0.2 percent (weight/volume) of preparation quantity into the solution, boiling the solution for 30 minutes, removing carbon and filtering the solution, cooling the filtered solution to between 10 and 20 DEG C, and introducing nitrogen (the pressure of the nitrogen is 0.3 to 0.5MPa) into the solution for later use; (2) introducing the nitrogen (the pressure of the nitrogen is 0.3 to 0.5MPa) into the 10-20 DEG C injection water in an amount which is about 60 percent of preparation quantity, adding the medicinal carbon in an amount which is 0.1 percent (weight/volume) of preparation quantity into the solution, stirring the solution uniformly, standing the solution for 20 minutes, removing carbon and filtering the solution; and (3) mixing the filtered solution, introducing the nitrogen (the pressure of the nitrogen is 0.3 to 0.5MPa) into the solution for protecting, adjusting the pH value of the solution to between 10.0 and 10.8 by using 10 percent sodium hydroxide solution, adding 10-20 DEG C injection water to the preparation quantity, stirring the solution uniformly, retesting the pH value which should be between 10.0 and 10.8, filtering the solution by using filters with a 0.45mum filter element and a 0.22mum filter element respectively, and filling the product after the submitted semi-finished products are qualified.

Description

Injection Pantoprazole Sodium preparing process

One, technical field

The present invention relates to a kind of preparing process of injection, particularly a kind of new preparing process that is better than traditional handicraft of injection Pantoprazole Sodium.

Two, background technology

Injection Pantoprazole Sodium main component is a Pantoprazole Sodium; chemistry 5--difluoro-methoxy-2{[(3 by name; 4 one dimethoxys, one 2. pyridine radicals) monomethyl]. sulfinyl } .1H one benzimidazole sodium salt monohydrate; it is a kind of novel antiulcerative; it directly acts on the gastric mucosa parietal cell; thereby the gastric acid inhibitory secretion is applicable to treatment gastric ulcer, duodenal ulcer etc.Clinical inaccessible syndrome, thrombophlebitis, the capillary hemorrhage etc. of being mainly used in, because of its good effect, few side effects, the huge market demand.

Domestic have the man enterprise of number to produce, and the compounding and production process of employing all is traditional handicrafts: calculate the raw material use amount by labelled amount 110%; Mannitol, disodium edetate are added successively in the water for injection of about amount of preparation 15%, stirring is dissolved it fully, adds the medicinal charcoal of amount of preparation 0.2% (W/V), boils 30 minutes, and decarbonization filtering cools to 30-40 ℃; Get 30-40 ℃ of water for injection of about amount of preparation 60%, add Pantoprazole Sodium, be stirred to dissolving fully, add the medicinal charcoal of amount of preparation 0.1% (W/V), stir, left standstill decarbonization filtering 20 minutes; Merge above-mentioned filtrate, transfer pH value to 10.0～10.8, add to amount of preparation with 30-40 ℃ of water for injection with 10% sodium hydroxide solution, stir, the repetition measurement pH value should be 10.0～10.8, through 0.45 μ m, 0.22 μ m filter element filtering, after the censorship semi-finished product are qualified, hand over the fill operation.

Because of having the chemical constitution of sulfinyl benzimidazole, its stability, Pantoprazole Sodium is subject to light, heavy metal ion, oxidisability and the reproducibility influence of various factors that becomes to grade.The production technology of domestic general employing is dissolved metal chelating agent with adjuvant, preparation is higher with the temperature control of water for injection and medicinal liquid, process for preparation and medicinal liquid course of conveying be nitrogen filled protection not, thereby the process for preparation material content descends and generally to reach 8%-10%, must feed intake by 110% of recipe quantity; And because of a small amount of aerial oxidation Decomposition of medicine in the process for preparation causes that 2%-5% lamp inspection stain waste product is arranged in every batch of lamp inspection dried frozen aquatic products; More than two directly cause the production cost height, and have certain potential risk, directly influence the production in enormous quantities of this product.The injection Pantoprazole Sodium that domestic other enterprises produce has several visible foreign matters (clarity) to check underproof report.

Analyzing above-mentioned reason is that traditional preparing process is unreasonable to the processing method of medicinal liquid; through experimentation and checking repeatedly; measures such as reduction water temperature and nitrogen filled protection have been adopted; formulated new preparing process: it is characterized in that on former technology basis; to in adjuvant, add the metal complex ion originally; change first dissolution process adjuvant into, in material solution, directly add the metal complex ion, again adjuvant solution is added in the material solution.Preparation is strict controlled in 10 ℃-20 ℃ with the temperature of water for injection and medicinal liquid, and process for preparation fills nitrogen, by the explained hereafter after the improvement, and the intermediate products content 1-2% that only descends.Compare with former technology, improved 8-10 percentage point, product yield improves, and has solved the lamp inspection stain problem that medicinal liquid causes because of the partial oxidation variable color simultaneously, and the visible foreign matters passed examination has guaranteed product quality stability.

Three, summary of the invention:

Purpose of the present invention: overcome the defective of the tradition of injection Pantoprazole Sodium in the past preparing process, provide that a kind of cost is low, yield is high, the preparing process that end product quality is more stable:

(1) feed intake by recipe quantity 100%, mannitol is added in the water for injection of about amount of preparation 15%, stirring is dissolved it fully, add the medicinal charcoal of amount of preparation 0.2% (W/V), boiled decarbonization filtering 30 minutes, cool to 10～20 ℃, it is standby that solution fills nitrogen (nitrogen pressure 0.3-0.5Mpa);

(2) get 10 ℃～20 ℃ waters for injection of about amount of preparation 60%, fill nitrogen (nitrogen pressure 0.3-0.5Mpa), add disodium edetate, fully after the dissolving, add Pantoprazole Sodium again, be stirred to dissolving fully, the medicinal charcoal that adds amount of preparation 0.1% (W/V), stir, left standstill decarbonization filtering 20 minutes;

(3) after above-mentioned filtrate is mixed; nitrogen filled protection (nitrogen pressure 0.3-0.5Mpa); transfer pH value to 10.0～10.8 with 10% sodium hydroxide solution; add to amount of preparation with 10～20 ℃ of waters for injection; stir, the repetition measurement pH value should be 10.0～10.8, and the filter through 0.45 μ m, 0.22 μ m filter element filters respectively; after the censorship semi-finished product are qualified, hand over the fill operation.

Positive beneficial effect of the present invention

The product that makes by this preparing process has following characteristic:

(1) improves raw material availability, reduced production cost;

(2) product quality stability improves, and efficiently solves lamp inspection waste product many (stain) problem of long-term this product of puzzlement, helps producing in enormous quantities, is convenient to store and market sale;

Research report:

Test basis: new drug the 34 WS of standard that become a full member ₁-(X-076)-2003Z

Medicine source: with the sample of three batches of each pilot scales of injection Pantoprazole Sodium preparing process of the present invention.Every crowd of 60000ml, all strictness feeds intake by formulation and technology requirement 100%;

(1) assay: it is all up to specification that the new technology sample is examined the result entirely.100% feeds intake, and the content of new preparing process is (standard is 90%-110%) between the 98%-99% of labelled amount;

In the middle of the new technology pilot scale, dried frozen aquatic products content statistics

Lot number	Middle product content %	With rate of charge content decline %	Dried frozen aquatic products content %
				0903121	98.9	1.1	98.5
0903122	98.5	1.5	98.9
				0903131	99.0	1.0	98.6

New technology pilot scale dried frozen aquatic products lamp inspection stain, total lamp inspection percent defective statistics:

Lot number	Lamp inspection stain rate	Total lamp inspection percent defective
			0903121	0	0.5％
0903122	0	0.2％
			0903131	0	0.3％

(2) safety testing: " Chinese pharmacopoeia injection security inspection guideline is checked, and new technology three batch samples are all up to specification to press 2005 editions;

(3) study on the stability result: " Chinese pharmacopoeia injection study on the stability method check new technology three batch samples are all up to specification in effect duration to press 2005 editions;

(4) the clinical application reaction is collected: since producing in October, 2009, produced 50 batches by registered new technology, market enjoys a good reputation, and does not collect the untoward reaction of this medicine.

Four, the specific embodiment

A kind of injection Pantoprazole Sodium preparing process that is different from traditional handicraft adopts the water temperature nitrogen filled protection of keeping under strict control, and its concrete grammar is:

(1) feed intake by recipe quantity 100%, mannitol is added in the water for injection of about amount of preparation 15%, stirring is dissolved it fully, adds the medicinal charcoal of amount of preparation 0.2% (W/V), boils decarbonization filtering 30 minutes; Cool to 10～20 ℃, it is standby that solution fills nitrogen (nitrogen pressure 0.3-0.5Mpa);

(2) get 10～20 ℃ of waters for injection of about amount of preparation 60%, fill nitrogen (nitrogen pressure 0.3-0.5Mpa), add disodium edetate, fully after the dissolving, add Pantoprazole Sodium again, be stirred to dissolving fully, the medicinal charcoal that adds amount of preparation 0.1% (W/V), stir, left standstill decarbonization filtering 20 minutes;

(3) after above-mentioned filtrate is mixed, fill nitrogen (nitrogen pressure 0.3-0.5Mpa), transfer pH value to 10.0～10.8 with 10% sodium hydroxide solution, add to amount of preparation with 10～20 ℃ of waters for injection, stir, the repetition measurement pH value should be 10.0～10.8, and the filter through 0.45 μ m, 0.22 μ m filter element filters respectively, after the censorship semi-finished product are qualified, hand over the fill operation.

Claims (1)

1. the preparing process of an injection Pantoprazole Sodium, its concrete grammar is:

Prescription (per 1000 consumptions)

The supplementary material recipe quantity

Pantoprazole Sodium (by anhydride) 40.0g

Mannitol 70.0g

Disodium edetate 4.0g

Medicinal charcoal 6.0g

Fresh water for injection adds to 2000ml

(1) feed intake by recipe quantity 100%, mannitol is added in the water for injection of about amount of preparation 15%, stirring is dissolved it fully, adds the medicinal charcoal of amount of preparation 0.2% (W/V), boils decarbonization filtering 30 minutes; Cool to 10～20 ℃, it is standby that solution fills nitrogen (nitrogen pressure 0.3-0.5Mpa);

(2) get 10～20 ℃ of waters for injection of about amount of preparation 60%, fill nitrogen (nitrogen pressure 0.3-0.5Mpa), add disodium edetate, fully after the dissolving, add Pantoprazole Sodium again, be stirred to dissolving fully, the medicinal charcoal that adds amount of preparation 0.1% (W/V), stir, fill nitrogen and left standstill decarbonization filtering 20 minutes;

(3) after above-mentioned filtrate is mixed, fill nitrogen (nitrogen pressure 0.3-0.5Mpa), transfer pH value to 10.0～10.8 with 10% sodium hydroxide solution, add to amount of preparation with 10～20 ℃ of waters for injection, stir, the repetition measurement pH value should be 10.0～10.8, and the filter through 0.45 μ m, 0.22 μ m filter element filters respectively, after the censorship semi-finished product are qualified, hand over the fill operation.