CN110117379A - One kind is for blood perfusion removal LDL adsorbent material and preparation method thereof - Google Patents

One kind is for blood perfusion removal LDL adsorbent material and preparation method thereof Download PDF

Info

Publication number
CN110117379A
CN110117379A CN201810111001.1A CN201810111001A CN110117379A CN 110117379 A CN110117379 A CN 110117379A CN 201810111001 A CN201810111001 A CN 201810111001A CN 110117379 A CN110117379 A CN 110117379A
Authority
CN
China
Prior art keywords
ldl
resin
removal
blood perfusion
pore
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201810111001.1A
Other languages
Chinese (zh)
Other versions
CN110117379B (en
Inventor
张婷
罗章凯
张文
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH AND DEVELOPMENT Co Ltd
Original Assignee
CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH AND DEVELOPMENT Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH AND DEVELOPMENT Co Ltd filed Critical CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH AND DEVELOPMENT Co Ltd
Priority to CN201810111001.1A priority Critical patent/CN110117379B/en
Publication of CN110117379A publication Critical patent/CN110117379A/en
Application granted granted Critical
Publication of CN110117379B publication Critical patent/CN110117379B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3687Chemical treatment
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08FMACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2/00Processes of polymerisation
    • C08F2/44Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08FMACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/04Acids; Metal salts or ammonium salts thereof
    • C08F220/06Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G81/00Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
    • C08G81/02Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J9/00Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof
    • C08J9/28Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum
    • C08J9/286Working-up of macromolecular substances to porous or cellular articles or materials; After-treatment thereof by elimination of a liquid phase from a macromolecular composition or article, e.g. drying of coagulum the liquid phase being a solvent for the monomers but not for the resulting macromolecular composition, i.e. macroporous or macroreticular polymers
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08JWORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
    • C08J2387/00Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds

Abstract

It is a kind of highly-safe the present invention relates to synthesizing, validity is ideal, structural behaviour is stablized, the specific good macroporous absorbent resin adsorbent of adsorptive selectivity, it will be filled in blood perfusion device tank body after the adsorbent coating, low-density lipoprotein in blood is removed by blood perfusion (HP) therapy, it is mainly used for treating coronary cardiopathy, lipoprotein is higher, adsorb patient's nephrotic syndrome, chronic renal failure, hepatopathy, diabetes, hyperlipidemia, excessive total cholesterol in low-density caused by obesity or strenuous exercise, triglycerides, low-density lipoprotein etc..The resin adsorption material synthesizes according to the following steps: using acrylic acid and divinylbenzene as monomer, using glycerine as crosslinking agent, using benzoyl peroxide as initiator, using atoleine as pore-foaming agent, using gelatin as dispersing agent, using aluminum trichloride (anhydrous) as catalyst, cross linked polyacrylate divinylbenzene sphere before gel-type is prepared;Then polyacrylic acid divinylbenzene sphere is modified with heparin, to improve the anticoagulant, hydrophily and biocompatibility of resin.

Description

One kind is for blood perfusion removal LDL adsorbent material and preparation method thereof
Technical field
The invention belongs to biomedical engineering fields, attached more particularly to a kind of resin for blood perfusion removal LDL Material and preparation method thereof.
Background technique
According to conservative statistics in 2012, existing more than 200,000,000 hypertensive patients in China, more than 9,000 ten thousand diabetics had 200 every year Ten thousand people die of cardiovascular and cerebrovascular disease.By the end of the year 2015, China's Patients with Chronic Renal Disease is even more up to 1.3 hundred million person-times.Domestic blood The product of field of purification is less, especially the higher blood perfusion product of low-density lipoprotein to the ill, even more fewer and fewer;At present Mainly there are a companies of four, five production blood perfusion devices in the country, year gross sales amount at 1,000,000,000 yuan or so, and as people are to life The requirement of quality is higher and higher, and this demand can be increasing, therefore the good market prospect of product, once it puts goods on the market, in advance Meter can bring biggish economic benefit.
With the development of blood perfusion device industry, the purification style of blood perfusion has obtained recognizing for domestic and international medical expert Together, and with the development of science and technology, some new technologies, new material, new therapy constantly occur, blood perfusion device Application field, indication also constantly expands.With the development of China's national economy, the raising of medical equipment level, society Constantly building for medical security system is complete, and hospital more than ground level, which is substantially all, is equipped with dialysis machine, possesses Laminar Airflow Room, has Province hospital artificial kidney machine equipment rate above county level reaches 70% or more, and in some areas in China, some blood perfusion devices are produced Product have incorporated the range of medical insurance, these are all that substance important foundation has been established in the development of blood perfusion.
Summary of the invention
This patent is intended to develop the adsorbent in a kind of new type resin adsorption column, is mainly used for treating coronary artery Property heart disease, nephrotic syndrome, chronic renal failure, hepatopathy, diabetes, hyperlipidemia, obesity or strenuous exercise cause Low-density lipoprotein it is higher, excessive total cholesterol, triglycerides, the low-density lipoprotein etc. of absorption patient's body.
Technical solution is as follows:
Step 1: acrylic acid, divinylbenzene monomers to be mixed to join to the water of dispersing agent containing gelatin and atoleine pore-foaming agent In solution, while glycerine crosslinking agent is added, reaction is crosslinked white polypropylene acid phenylethylene micro ball before obtaining;
Step 2: carrying out test tube of hepari to preceding cross linked polyacrylate phenylethylene micro ball using heparin, test tube of hepari acrylic acid benzene second is obtained Alkene microballoon;
Step 3: polyacrylic acid phenylethylene micro ball is purified and removed pore-foaming agent using petroleum ether, obtain cleaner and not Final resin containing chloromethyl ether etc..
Summary of the invention of the invention is described in further detail With reference to embodiment.It should be understood that this hair It is bright that the embodiments are used only to illustrate the invention is not intended to limit the present invention, in the case where not departing from technical thought of the invention, according to Ordinary skill knowledge and customary means, the various replacements and change made, should all be included within the scope of the invention.
Step 1: the synthesis (lab scale) of polyacrylic acid phenylethylene micro ball:
Reagent list needed for table 1. synthesizes poly- polyacrylic acid phenylethylene micro ball
Concrete operations:
500ml purified water is added in 1000mL three-necked flask (dress blender, return pipe and thermometer), adds the gelatin point of 30g Powder, is warming up to 45-50 DEG C, and stirring and dissolving forms and stablizes moisture dephasing;By acrylic acid, divinylbenzene, glycerine, peroxidating Benzoyl, pore cause, atoleine and anhydrous aluminum chloride are thoroughly mixed, and form miscella phase, miscella is added to It in moisture dephasing, persistently stirs and is warming up to 80 DEG C, carry out polymerization crosslinking and react 4 hours, it is further heated up to 90 DEG C, polymerization is anti- It answers 4 hours;
After reaction, the Archon of synthesis is filtered, and is cleaned twice with 100 DEG C of boiling water, removal resin surface residual Gelatin, glycerine etc..
Step 2: the synthesis of test tube of hepari polyacrylic acid phenylethylene micro ball;
Reagent list needed for table 2. synthesizes test tube of hepari polyacrylic acid phenylethylene micro ball
Concrete operations: the acetate buffer solution 500mL that PH is 3.5-4.0 is first prepared, uses anhydrous zinc chloride for catalyst, is gathered The feed ratio mass ratio of styrene microballoon and heparin sodium is 1:1.5, and the temperature of solution reaction is 60 DEG C, to polyacrylic acid Phenylethylene micro ball carries out test tube of hepari, the test tube of hepari time about 4 hours, obtains test tube of hepari polyacrylic acid phenylethylene micro ball.
Step 3: the removal of pore-foaming agent and the purifying of resin
Reagent list needed for table 3. closes the removal of pore-foaming agent and the purifying of resin
Concrete operations:
1. drying: by the test tube of hepari polyacrylic acid phenylethylene micro ball of synthesis in forced air drying 2-3 hours at 60 DEG C;
2. the removal of pore-foaming agent: being extracted in the ratio of resin and petroleum ether volume ratio 1:2, renew petroleum ether and carry out continuing to mention It takes 2-4 times, as far as possible the atoleine in removal microballoon.
3. boiling: adding suitable quantity of water to be heated to boiling in three-necked flask in adsorbent, boiling the retention time is 30 minutes, such as This repeatedly boiling to pH value to 5.0-7.0 extract: control the residual quantity of liquid wax less than 1%;
4. alcohol extracting: water cooking liquid being replaced into alcohol, electric jacket is heated to alcohol boiling, insulated and stirred about 30 minutes, filters, renew Alcohol, repeatedly, until adsorbent alcohol washing lotion is in value≤0.03 OD of ultraviolet 200-400nm;
5. redrying: test tube of hepari polyacrylic acid phenylethylene micro ball after boiling, the alcohol extracting vacuum drying 6-8 at 60 DEG C Hour.
Specific embodiment
Embodiment 1
The Pore Characterization of adsorbent material
The Pore Characterization of more than 4. batches of LDL resins of table
The resin name of an article Specific surface area m2/g Flat diameter bore dia nm Total pore volume ml/g
MR20170601 489.4 4.214 1.147
MR20170620 496.3 4.265 1.165
MR20170714 501.4 4.367 1.028
Note: BET pore structure detection method is used.
Embodiment 2
The absorption property of adsorbent material
The absorption property of more than 5. batches of LDL resins of table
The resin name of an article Yellow Jackets VB12 β2-MG
MR20170601 99.98% 92.45% 85.47%
MR20170620 100.02% 91.59% 86.54%
MR20170714 99.55% 92.15% 84.98%
Embodiment 3
The security performance of adsorbent material
Being made of the preferable MR20170601 resin progress small lot production and processing tinning of absorption property early period is disposably made After blood perfusion device, safety animal's whole blood perfusion experimen is carried out;
Adsorption rate of the table 6.MR20170601 resin to each ingredient of blood plasma
Albumin Total protein Blood platelet Leucocyte Red blood cell
3.8% 1.7% 14.8% 5.9% 6.1%
3.8% 1.8% 14.5% 6.1% 6.2%
3.9% 1.5% 14.7% 5.4% 6.4%
The electrolyte adsorption rate of 7. MR20170601 resin pair of table
Potassium Calcium Sodium Magnesium Chlorine Phosphorus
2.8% 5.4% -0.2% 1.7% 0.9% 6.7%
2.9% 5.5% 0.1% 1.8% 0.5% 6.5%
2.6% 5.4% 0.3% 1.7% 0.6% 6.3%

Claims (6)

1. it is a kind of for blood perfusion removal LDL absorption resin adsorption material, it is characterised in that: its specific surface area be 400~ 600m2/ g, pore-size distribution 1-5nm, total pore volume > 1ml/g, resin partial size are about 300~450 μm.
2. a kind of absorption resin adsorption material for blood perfusion removal LDL, absorption property and security performance requirement: 1. pressing YY0464-2009 standard operation answers >=90% to the adsorption rate of yellow Jackets, VB12;2. by resin/external Plasma volumes than 1/ The adsorption rate of 10 couples of LDL answers >=80%;3. answering >=60% to the absorption of patient LDL when clinical verification;4. in safety animal perfusion In verification experimental verification, influence of the LDL resin absorbing column to blood formed element should meet: the influence to albumin, total protein answers≤ 10%;Influence to blood formed element blood platelet etc. answers≤15%;Influence to each electrolyte answers≤10%.
3. a kind of preparation method of the gel type resin material for blood perfusion removal LDL, it is characterised in that according to the following steps It carries out:
Step 1: acrylic acid, divinylbenzene monomers to be mixed to join to the water of dispersing agent containing gelatin and atoleine pore-foaming agent In solution, while glycerine crosslinking agent is added, reaction is crosslinked white polypropylene acid phenylethylene micro ball before obtaining;
Step 2: carrying out test tube of hepari to preceding cross linked polyacrylate phenylethylene micro ball using heparin, test tube of hepari acrylic acid benzene second is obtained Alkene microballoon;
Step 3: carrying out the removal and alcohol extracting of pore-foaming agent respectively to polyacrylic acid phenylethylene micro ball using petroleum ether and dehydrated alcohol Purifying obtains final resin cleaner and without chloromethyl ether etc..
4. the preparation method according to claim 3. for the resin material of blood perfusion removal LDL, it is characterised in that In step 1, the ratio of acrylic acid and divinylbenzene is mass ratio 1:2, and the additional amount of the pore-foaming agent is between styrene-diethyl The 40-60%wt of alkene benzol mixture.
5. the preparation method according to claim 3. for the resin material of blood perfusion removal LDL, it is characterised in that: In the step 1, the pore-foaming agent is atoleine, using benzoyl peroxide as initiator.
6. the preparation method according to claim 3. for the resin material of blood perfusion removal LDL, it is characterised in that: In the step 2, the modifying agent is heparin.
CN201810111001.1A 2018-02-05 2018-02-05 Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof Active CN110117379B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810111001.1A CN110117379B (en) 2018-02-05 2018-02-05 Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201810111001.1A CN110117379B (en) 2018-02-05 2018-02-05 Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof

Publications (2)

Publication Number Publication Date
CN110117379A true CN110117379A (en) 2019-08-13
CN110117379B CN110117379B (en) 2021-11-12

Family

ID=67519167

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201810111001.1A Active CN110117379B (en) 2018-02-05 2018-02-05 Adsorbing material for removing LDL (low density lipoprotein) in blood perfusion and preparation method thereof

Country Status (1)

Country Link
CN (1) CN110117379B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114230718A (en) * 2022-01-27 2022-03-25 河北利江生物科技有限公司 Preparation method and application of resin for adsorbing low-density lipoprotein in blood
CN114426653A (en) * 2022-01-26 2022-05-03 河北利江生物科技有限公司 For adsorbing beta2Preparation method and application of resin of (E) -MG
CN116586048A (en) * 2023-07-17 2023-08-15 江苏恰瑞生物科技有限公司 Modified polystyrene adsorption resin for blood perfusion device and preparation method thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11332981A (en) * 1998-05-25 1999-12-07 Tosoh Corp Method for removing low-density lipoprotein in blood
CN104174386A (en) * 2014-07-28 2014-12-03 南开大学 Adsorbent for removing BETA-2 microglobulin in blood
CN104492402A (en) * 2014-12-31 2015-04-08 珠海健帆生物科技股份有限公司 Preparation method of adsorbent for adsorbing low-density lipoprotein (LDL) for whole blood perfusion

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH11332981A (en) * 1998-05-25 1999-12-07 Tosoh Corp Method for removing low-density lipoprotein in blood
CN104174386A (en) * 2014-07-28 2014-12-03 南开大学 Adsorbent for removing BETA-2 microglobulin in blood
CN104492402A (en) * 2014-12-31 2015-04-08 珠海健帆生物科技股份有限公司 Preparation method of adsorbent for adsorbing low-density lipoprotein (LDL) for whole blood perfusion

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114426653A (en) * 2022-01-26 2022-05-03 河北利江生物科技有限公司 For adsorbing beta2Preparation method and application of resin of (E) -MG
CN114426653B (en) * 2022-01-26 2023-12-19 河北利江生物科技有限公司 Be used for adsorbing beta 2 Preparation method and application of resin of-MG (polyethylene glycol)
CN114230718A (en) * 2022-01-27 2022-03-25 河北利江生物科技有限公司 Preparation method and application of resin for adsorbing low-density lipoprotein in blood
CN114230718B (en) * 2022-01-27 2023-11-21 河北利江生物科技有限公司 Preparation method and application of resin for adsorbing low-density lipoprotein in blood
CN116586048A (en) * 2023-07-17 2023-08-15 江苏恰瑞生物科技有限公司 Modified polystyrene adsorption resin for blood perfusion device and preparation method thereof
CN116586048B (en) * 2023-07-17 2023-09-08 江苏恰瑞生物科技有限公司 Modified polystyrene adsorption resin for blood perfusion device and preparation method thereof

Also Published As

Publication number Publication date
CN110117379B (en) 2021-11-12

Similar Documents

Publication Publication Date Title
CN105418946B (en) The preparation method of secondary cross-linking polymeric adsorbent
CN103483487B (en) Novel structure product, preparation method and use of styrenic resin
CN110117379A (en) One kind is for blood perfusion removal LDL adsorbent material and preparation method thereof
CN105561950B (en) Macroporous absorbent resin and preparation method thereof
CN102049242B (en) Anion resin for bilirubin absorption and preparation method thereof
US8138289B2 (en) Imprinted polymeric materials for binding various targets such as viruses
CN105085829B (en) The preparation method of the macroporous absorbent resin adsorbed for toxic substance
CN105126784B (en) Adsorbent and preparation method thereof, the adsorbent equipment for blood perfusion
US4140652A (en) Method of preparing blood-compatible sorbents for recovering exo- and endogenic poisons
CN108031454A (en) Possesses blood-purifying adsorbing agent of physics specific selectivity and preparation method thereof
CN101224415A (en) Low density lipoprotein adsorbent for extrinsic blood perfusion and preparing method thereof
CN102212177B (en) Porous resin with surface hydrophily
JPS59182802A (en) High molecular weight carbonyl group-containing substance useful as absorbent for nitrogen compound
CN105749886A (en) Medical polymeric microsphere adsorbent for hemoperfusion apparatus and preparation method of medical polymeric microsphere adsorbent
CN104667897B (en) For adsorbing high endotoxic phenylethylene resin series in blood
CN105709705A (en) Molecular imprinting adsorbent for eliminating blood bilirubin and preparation method thereof
CN108191804B (en) The method of purification of Flavonoid substances Quercetin in a kind of Guava Leaf
CN109513429A (en) A kind of preparation method of modified adsorbent for bilirubin
CN107200804A (en) A kind of inflammatory factor macroporous adsorbent and preparation method thereof
Pan et al. Experimental investigation of a natural favonoid adsorption on macroporous polymers with intrinsic cis-diol moieties recognition function: Static and dynamic methods
CN104587979B (en) A kind of efficient blood-purifying adsorbing agent and preparation method thereof
CN103224590B (en) Glabridin molecularly imprinted polymer, as well as preparation method and application thereof
CN111282555B (en) Macroporous adsorption resin and preparation method thereof
CN105289546B (en) A kind of preparation method of liquaemin Special adsorbent
CN107513126A (en) A kind of opaque polymer resin and its application in serum separation gel

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
PE01 Entry into force of the registration of the contract for pledge of patent right
PE01 Entry into force of the registration of the contract for pledge of patent right

Denomination of invention: A material for removing LDL during blood perfusion and its preparation method

Effective date of registration: 20231214

Granted publication date: 20211112

Pledgee: Societe Generale Limited by Share Ltd. Chongqing branch

Pledgor: CHONGQING XIERKANG BLOOD PURIFICATION EQUIPMENT RESEARCH DEVELOPMENT CO.,LTD.

Registration number: Y2023500000103