CN100394990C - Method for specific adsorption of low density fat-cholesterine in hyperlipemia - Google Patents

Method for specific adsorption of low density fat-cholesterine in hyperlipemia Download PDF

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Publication number
CN100394990C
CN100394990C CNB021384193A CN02138419A CN100394990C CN 100394990 C CN100394990 C CN 100394990C CN B021384193 A CNB021384193 A CN B021384193A CN 02138419 A CN02138419 A CN 02138419A CN 100394990 C CN100394990 C CN 100394990C
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China
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blood plasma
lipid
adsorbent
adsorption
supernatant
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CN1488410A (en
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邹元国
孙启俊
李爱华
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Nanjing Red-Cross Blood Center
Nanjing Shuangwei Biotechnology Co., Ltd.
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NANJING RED CROSS BLOOD CENTER
Sinoma Science and Technology Co Ltd
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Abstract

The present invention provides a method for the specific adsorption of fat-cholesterol with low density in hyperlipemia, which is an improved external heparin precipitation method (HELP). An adsorption reaction is completed by a water-insoluble carrier coupled with heparin and another water-insoluble carrier grafted to bivalent positive ions, wherein the water-insoluble carriers are respectively used as an adsorbing agent I and an adsorbing agent II. The method comprises the following reaction steps: 1) in a lipid blood plasma collector, the total blood plasma volume of lipid is used as a base number, 5 to 10g of adsorbing agent I and 3 to 5g of adsorbing agent II are added to each 100 ml of blood plasma, and the blood plasma is softly shaken for 10 to 15 minutes at a room temperature; the blood plasma is put on a centrifugal machine with large capacity, and the rotary speed is from 2000 to 3500 rpm; the blood plasma is centrifuged for 10 to 20 minutes, is separated and deposited, and supernatant degreasing blood plasma is collected; 3) floating lipid suspended substances in the supernatant degreasing blood plasma are removed by a lipid filter; 4) excessive bivalent positive ions in the degreasing blood plasma are adsorbed by filtrated supernatant degreasing blood plasma, and blood calcium concentration in the blood plasma is adjusted to reach normal physiological concentration. Thereby, the whole degreasing process is simplified, and the reaction time is saved. The method has good economical and social benefits.

Description

The method of low density fat in the specific adsorption hyperlipoidemia---cholesterol
Technical field:
The present invention relates to remove the method for low density fat-cholesterol in the hyperlipoidemia (LDL-C), is the improvement to the external sedimentation method of LDL-C method-heparin (HELP) in the former removal hyperlipoidemia.
Background technology:
LDL-C is the main paathogenic factor in the hyperlipemia, and existing great mass of data proves that increasing in a large number of LDL-C can cause body cardiovascular disease and blood circulatory disorder in the blood.Block, have a dizzy spell and dyskinesia disease etc. as atherosclerosis, cerebrovascular.At present, many scholars have worked out the way of LDL-C in the multiple removal hyperlipoidemia, and wherein the external sedimentation method technology of heparin with the development of German B.Braun company is the most ripe, and clinical practice is the widest, and the patient who receives treatment is maximum.
Though the external sedimentation method of heparin are mature technique, because the heparin itself that uses as adsorbent has high anticoagulating active, can make patient produce bleeding tendency, exist hidden danger.For this reason, after adsorption reaction is finished, must remove excessive heparin.In addition, heparin combines need and carries out under the condition of PH=5.12 with LDL-C.So before the reaction, must regulate blood plasma PH to 5.12, after adsorption reaction is finished, must PH be transferred to physiological range with alkali again with certain density acid.Can produce a large amount of Yan Heshui in the process of acid adjustment, accent alkali.Before feedback defat blood plasma is in body, also individual desalting and dewatering process must be arranged, therefore, this adsorption reaction course is long, the step complexity.
Summary of the invention:
The objective of the invention is to: active high at the employed heparin anti-coagulating of the external sedimentation method of heparin, the hidden danger that exists, propose the external sedimentation method of a kind of heparinoid, it substitutes the active heparin of highly blood coagulation resistant as adsorbent with the heparinoid of low anticoagulant active, has eradicated unsafe factor.In addition, as catalyst, in skimming processes, need not to regulate the blood plasma pH value, omitted desalination in (HELP) method, dehydration, simplify the defat course of reaction greatly, saved the response time with bivalent cation.
Technical solution of the present invention is as follows: it comprises adsorption reaction and centrifugal, isolation technics, it is characterized in that: be adsorbent I with water insoluble carrier coupling heparinoid in the adsorption reaction and be that adsorbent II finishes jointly with water insoluble carrier grafting bivalent cation, the every gram coupling of adsorbent I heparinoid 10~50mg wherein, the every gram grafting of adsorbent II 300~600mg bivalent cation, its reactions steps is as follows:
1) in lipid plasma collection device, be radix with the lipid total plasma volume, add in the ratio that adds 5~10g adsorbent I and 3~5g adsorbent II in every 100ml blood plasma, at room temperature jolting 10~15 minutes gently;
2) above-mentioned blood plasma is placed on the high capacity centrifuge, with the 2000-3500rpm rotating speed, centrifugal 10-20 minute, precipitation separation was collected supernatant defat blood plasma;
3) with the floating lipid suspension thing in the lipid filter removal supernatant defat blood plasma.
4) the supernatant defat blood plasma after will filtering by excessive bivalent cation in the Subacidity cation adsorption column absorption defat blood plasma, is collected supernatant defat blood plasma after treatment, regulates that blood calcium concentration reaches normal physiological concentration in this blood plasma.
Because the part heparinoid on the water insoluble carrier can carry out specific adsorption to low density lipoprotein, LDL, and itself be exactly a kind of fat-reducing medicament, be fool proof reliable as adsorbent therefore with it.After reaction is finished, also economized the operating procedure of removing excess reactant, saved the reaction mechanism mechanism of reaction.After adding adsorbent II, adsorbent II goes up the bivalent cation of grafting, by the effect of ionic bridge performance catalyst, makes the adsorbent I that contains the part heparinoid to finish and the combining of LDL-C in moment, form macroscopic granule, shortened the response time greatly.
In the above-mentioned reaction, water insoluble carrier can be for one of following two types: 1) glass microballoon: 2) cellulose grain, the granularity of carrier is between 200 orders-2mm.
Subacidity cation adsorption column used in the above-mentioned reactions steps 4 can be one of following several types: 1) sulfonic acid type cation adsorption column; 2) CM group high flow rate cation-adsorption post.
Adopt the inventive method to remove hyperlipoidemia, the LDL-C clearance is greater than 95%, the HDL-C response rate is greater than 95%, and the cholesterol clearance is 40-50%, and the clearance of triglyceride is greater than 50%, compare with the external sedimentation method of former heparin, have identical degreasing effect, biggest advantage is not need to adsorb excessive heparin, does not need acid adjustment, transfers sequence of operations steps such as alkali, desalination, dehydration, whole skimming processes is oversimplified, greatly reduced the cost of skimming processes.The response time has been saved in the use of catalyst, has good economic benefits and social benefit.
The specific embodiment:
The used water insoluble carrier coupling heparinoid carrier of adsorbent I is 200 purpose glass microballoons in the present embodiment, with VTES [CH 2=CHSi (OC 2H 5) 3] be coupling agent, generate adsorbent I (, being coupling agent then), coupling heparinoid on every gram glass microballoon (sulfonation glucosan) 50mg through heating, dehydration with epoxychloropropane as being carrier with the cellulose grain.With macroporous resin D002 (Jiangyin, Jiangsu Organic Chemical Plant) is carrier, injects the divalent calcium ion and generates adsorbent II, and grafting 300mg divalent calcium ion is stand-by on every gram microsphere.
Its reactions steps is as follows:
1) gathers hyperlipoidemia 500ml and place lipid plasma collection device, put into 50g adsorbent I and 15g adsorbent II, at room temperature jolting 10 minutes gently;
2) above-mentioned blood plasma is placed on the high capacity centrifuge, with the 3000rpm rotating speed, centrifugal 15 minutes, precipitation separation was collected supernatant defat blood plasma;
3) with the floating lipid suspension thing in the lipid filter removal supernatant defat blood plasma.Glass-film aperture 10 μ m in the filter;
4) the supernatant defat blood plasma after will filtering, by sulfonic acid cation resin 732 adsorption columns, the divalent calcium ion in the absorption defat blood plasma is collected supernatant defat blood plasma after treatment, regulates that blood calcium concentration reaches normal physiological concentration in this blood plasma.
After handling with this method, the LDL-C clearance is greater than 95% in the hyperlipoidemia, and the HDL-C response rate is 95% (lipoprotein electrophoresis method).T-CHOL decline 40% ± 10 (enzyme process).The triglyceride clearance is 50% (oxidation enzyme process).Obtained ideal effect.

Claims (3)

1. the method for low density fat and cholesterol in the specific adsorption hyperlipoidemia, comprise adsorption reaction with centrifugal, separate etc., it is characterized in that: be adsorbent I with water insoluble carrier coupling heparinoid in the adsorption reaction and be that adsorbent II finishes jointly with water insoluble carrier grafting bivalent cation, the every gram coupling of adsorbent I heparinoid 10~50mg wherein, the every gram of adsorbent II injects 300~600mg bivalent cation, and its reactions steps is as follows:
1) in lipid plasma collection device, be radix with the lipid total plasma volume, add in the ratio that adds 5~10g adsorbent I and 3-5g adsorbent II in every 100ml blood plasma, at room temperature jolting 10~15 minutes gently;
2) above-mentioned blood plasma is placed on the high capacity centrifuge, with the 2000-3500rpm rotating speed, centrifugal 10-20 minute, precipitation separation was collected supernatant defat blood plasma;
3) with the floating lipid suspension thing in the lipid filter removal supernatant defat blood plasma.
4) the supernatant defat blood plasma after will filtering by excessive bivalent cation in the Subacidity cation adsorption column absorption defat blood plasma, is collected supernatant defat blood plasma after treatment, regulates that blood calcium concentration reaches normal physiological concentration in this blood plasma.
2. according to the method for low density fat and cholesterol in the specific adsorption hyperlipoidemia described in the claim 1, it is characterized in that: water insoluble carrier is one of following two types: 1) glass microballoon; 2) cellulose grain, the granularity of water insoluble carrier is between 200 orders-2mm.
3. the method for low density fat and cholesterol in the specific adsorption hyperlipoidemia according to claim 1 is characterized in that: the Subacidity cation adsorption column is one of following several types: 1) sulfonic acid type cation adsorption column; 2) CM group high flow rate cation-adsorption post.
CNB021384193A 2002-10-11 2002-10-11 Method for specific adsorption of low density fat-cholesterine in hyperlipemia Expired - Fee Related CN100394990C (en)

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Publication number Priority date Publication date Assignee Title
CN109045379A (en) * 2018-07-12 2018-12-21 安陆恩彼饲料有限公司 A kind of plasma purification method
CN109092262B (en) * 2018-08-28 2019-07-05 广州达济医学科技有限公司 Low-density lipoprotein adsorption microspheres and preparation method and adsorbent material
CN109580303A (en) * 2018-12-06 2019-04-05 潍坊泽成生物技术有限公司 The preparation method of low-density lipoprotein

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH06269500A (en) * 1992-05-14 1994-09-27 Wr Grace & Co Connecticut Microporous polysulfone carrier suitable for eliminating low-density lipoprotein-choresterol
US5418061A (en) * 1990-11-27 1995-05-23 W. R. Grace & Co.-Conn. Microporous polysulfone supports suitable for removal of low density lipoprotein-cholesterol
CN2505092Y (en) * 2001-09-20 2002-08-14 上海江夏血液技术有限公司 Filtering device for lowering blood-lipid

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5418061A (en) * 1990-11-27 1995-05-23 W. R. Grace & Co.-Conn. Microporous polysulfone supports suitable for removal of low density lipoprotein-cholesterol
JPH06269500A (en) * 1992-05-14 1994-09-27 Wr Grace & Co Connecticut Microporous polysulfone carrier suitable for eliminating low-density lipoprotein-choresterol
CN2505092Y (en) * 2001-09-20 2002-08-14 上海江夏血液技术有限公司 Filtering device for lowering blood-lipid

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