Method for producing heparin sodium by using membrane and resin column

A resin column and heparin sodium technology are applied in the preparation methods of peptides, chemical instruments and methods, organic chemistry and other directions, which can solve the problems of difficult wastewater treatment, product quality, low product yield, and high odor, and achieve less impurities, The effect of shortened precipitation time and fast adsorption

Inactive Publication Date: 2020-11-10
丰润生物科技股份有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The purpose of the present invention is to provide a method for producing heparin sodium using a membrane and a resin column to solve the problems of the existing heparin sodium enzymatic hydrolysis process such as long time consumption, high odor, low product yield, difficult wastewater treatment and poor product quality.

Method used

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specific Embodiment approach 1

[0014] Embodiment 1: This embodiment describes a method for producing heparin sodium by utilizing a membrane and a resin column, which can improve the product quality and yield of heparin sodium. The method steps are as follows:

[0015] Step 1: The porcine small intestinal mucosa is hydrolyzed with protease. The hydrolyzed solution after enzymolysis is firstly filtered, and then filtered with a microfiltration membrane. The microfiltration membrane can be used to concentrate 9-10 times. After filtration, the intestinal residue, retentate and dialysis are obtained At this time, heparin sodium basically exists in the dialysate; because the intestinal residue is an insoluble impurity, it is discarded.

[0016] Step 2: Filter the dialysate in step 1 with a nanofiltration membrane, which can be concentrated by 5 to 6 times, and obtain retentate and dialysate after filtration. At this time, heparin sodium mainly exists in the retentate; It is water and salt, as well as a small amou...

specific Embodiment approach 2

[0020] Embodiment 2: A method for producing heparin sodium using a membrane and a resin column according to Embodiment 1, in step 1, the coarse filtration refers to the use of tubular filters, bag filters, plate and frame filters , a plug-in filter or a centrifuge, the filter material mesh is 100-200 mesh, and the filter material material is one of PP, PE, nylon or stainless steel. The purpose of coarse filtration is to filter intestinal residue, reduce insoluble impurities in the enzymatic hydrolyzate, and prepare for further membrane filtration.

specific Embodiment approach 3

[0021] Embodiment 3: In the method for producing heparin sodium using a membrane and a resin column according to Embodiment 1, in step 1, the microfiltration membrane is a tubular ceramic membrane, and the pore size of the membrane is 200-500 nm. The purpose of membrane filtration is to completely permeate heparin sodium, while retaining impurities such as proteins, amino acids, and peptides with large molecular weights, and reducing soluble and insoluble impurities in the enzymatic hydrolyzate.

[0022] Embodiment 4: The method for producing heparin sodium using a membrane and a resin column according to Embodiment 1, in steps 2 and 4, the nanofiltration membranes are organic membrane roll-up membranes, and the membrane molecular weight cut-off range is 200 ~500Da. In step 2, the purpose of membrane filtration is to retain all the heparin sodium, concentrate the enzymatic hydrolysis solution, increase the concentration of heparin sodium in the enzymatic hydrolysis solution, a...

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Abstract

The invention discloses a method for producing heparin sodium by using a membrane and a resin column, and belongs to the technical field of heparin sodium production. In order to solve the problems oflong consumed time, low product yield, difficult treatment of enzymatic hydrolysate and the like in the existing heparin sodium enzymolysis process, the method comprises the following steps: carryingout enzymolysis on small intestinal mucosa of pigs, coarsely filtering the enzymatic hydrolysate, and then filtering by using a microfiltration membrane to obtain intestinal residues, trapped fluid and dialysate; filtering the dialysate by using a nanofiltration membrane to obtain trapped fluid and dialysate; adsorbing the trapped fluid by using resin, and washing and desorbing the resin by usingsaline water after adsorption to obtain adsorbed residual liquid, washing liquid and desorbed liquid; filtering the desorbed solution by using a nanofiltration membrane to obtain trapped fluid and dialysate; and precipitating the trapped fluid with ethanol, collecting the precipitate, dehydrating, and drying to obtain heparin sodium. According to the method, heparin is adsorbed faster and more, adsorption adopts a resin column for adsorption, and compared with adsorption of an adsorption tank, the method has the advantages of less resin consumption, short adsorption time and high adsorption rate.

Description

technical field [0001] The invention belongs to the technical field of heparin sodium production, and in particular relates to a method for producing heparin sodium by utilizing a membrane and a resin column. Background technique [0002] At present, there are two processes used in the production of heparin sodium: enzymatic hydrolysis process and salt hydrolysis process. At present, the common enzymatic hydrolysis process steps are: enzymatic hydrolysis (filtration), resin adsorption (filtration), resin washing / elution (filtration), precipitation , dehydration, drying. After enzymolysis, 80-100 mesh filter cloth is generally used for filtration, mainly to remove insoluble intestinal residue and reduce the pollution to the resin; resin adsorption is generally to put the enzymolyzed liquid into the adsorption tank, and then according to 25-30g / root Add resin column, stir and adsorb for 7-10 hours, and then filter with 80-100 mesh filter cloth to collect resin. The resin is w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/10C07K1/34C12P21/06
CPCC07K1/34C08B37/0003C08B37/0075C12P21/06
Inventor 赵邵宇马保社李英刚马希旺王承亮
Owner 丰润生物科技股份有限公司
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