CN114100589A - Method for modifying blood perfusion resin adsorbent for acute and chronic poisoning of medicine - Google Patents

Method for modifying blood perfusion resin adsorbent for acute and chronic poisoning of medicine Download PDF

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CN114100589A
CN114100589A CN202110005257.6A CN202110005257A CN114100589A CN 114100589 A CN114100589 A CN 114100589A CN 202110005257 A CN202110005257 A CN 202110005257A CN 114100589 A CN114100589 A CN 114100589A
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pva
adsorbent
acute
resin
cross
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刘志远
张婷芳
张伟元
崔景强
杨娅楠
闫立论
崔淑洁
郑迎莹
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Henan Tuoren Medical Technology Co ltd
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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26Synthetic macromolecular compounds
    • B01J20/265Synthetic macromolecular compounds modified or post-treated polymers
    • B01J20/267Cross-linked polymers
    • 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
    • A61M1/3679Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption

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  • Medicinal Preparation (AREA)
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Abstract

The invention relates to the technical field of medical materials, and particularly discloses a method for modifying a blood perfusion resin adsorbent for acute and chronic drug poisoning.

Description

Method for modifying blood perfusion resin adsorbent for acute and chronic poisoning of medicine
Technical Field
The invention relates to the field of medical materials, in particular to a method for modifying a blood perfusion resin adsorbent for acute and chronic poisoning of a medicine.
Background
Drug intoxication includes both acute and chronic types, including systemic diseases in which the drug enters the human body and accumulates to a certain extent at the site of effect to cause physical damage. The drug poisoning phenomenon comprises excessive intake poisoning of the sedative-hypnotic drugs such as pentobarbital, and is followed by drug anaphylaxis poisoning. The former chemical drugs such as pentobarbital are common in small molecules, while the latter drug anaphylaxis is usually caused by macromolecular substances. Although the phenomenon of drug anaphylaxis is rare but fatal, in general, macromolecular drugs such as protein, polysaccharide and polypeptide, such as serum, crude drug preparations, vaccines and the like, have complete antigenicity, can enable the body to generate corresponding antibodies, but are easy to sensitize the body. Meanwhile, poisoning of patients is usually accompanied by damage of kidney functions, which causes toxin accumulation of macromolecular substances such as beta 2-microglobulin and the like to cause a series of complications. With regard to poisoning, current clinical treatment and rescue measures include emetic and gastric lavage, and for patients with severe coma, blood purification is a more appropriate measure.
Clinically, as a novel blood purification technology, blood perfusion is applied to the treatment and rescue of patients suffering from acute and chronic poisoning of drugs. During the blood perfusion treatment process, the blood of a patient is directly treated with the adsorbent through extracorporeal circulation, certain endogenous or exogenous harmful substances are selectively adsorbed from the blood, the operation is simple, the cost is low, and the design requirement on the adsorbent is higher. At present, the commercially available resin adsorbent for hemoperfusion has good adsorption performance on toxic substances in blood, but has poor effect on removing macromolecular substances which can cause anaphylaxis.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for modifying a hemoperfusion resin adsorbent for acute and chronic drug poisoning, wherein the obtained modified resin has good adsorption performance on substances causing acute and chronic drug poisoning in blood, and the modified resin adsorbent has good blood compatibility, high safety, economic and convenient preparation method, and can be widely applied in the field of medical materials.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for modifying blood perfusion resin adsorbent for acute and chronic poisoning of medicine comprises the following steps:
1) stirring purified water, adding a certain amount of PVA, continuously stirring to obtain a uniform PVA solution, heating to raise the temperature of the PVA solution to 80 ℃, and continuously keeping the temperature of 80 ℃ and stirring for 2-3 hours;
2) adding a cross-linking agent and a catalyst into the PVA aqueous solution obtained in the step 1) to carry out cross-linking reaction to obtain a PVA cross-linking solution;
3) adding neutral macroporous resin into the PVA cross-linking liquid prepared in the step 2), stirring to enable the PVA cross-linking liquid to be coated on the surface layer of the neutral macroporous resin to form a film, performing suction filtration to enable the residual PVA cross-linking liquid to be separated from the neutral macroporous resin to obtain the neutral macroporous resin with the PVA coated film as an adsorbent, then adding absolute ethyl alcohol into the adsorbent to fully disperse the adsorbent, washing with purified water until the pH value of the adsorbent is neutral, and finally obtaining the PVA film coated blood perfusion resin adsorbent for acute and chronic poisoning of the medicine.
Preferably, the PVA is medical grade polyvinyl alcohol, the alcoholysis degree is 88%, the polymerization degree is 500, 1700 and 2400 respectively, and the concentration of the PVA aqueous solution is 0.1-5%.
Preferably, the cross-linking agent is any one or any combination of formaldehyde, glutaraldehyde, oxalic acid, malonic acid and succinic acid.
Preferably, the catalyst is a 0.5mol/L sulfuric acid solution, and the volume ratio of the sulfuric acid solution to the PVA aqueous solution is 1: 50-1: 30.
preferably, the crosslinking reaction time is 20-60 min.
Preferably, the volume ratio of the PVA aqueous solution to the resin is 10: 1-5: 4.
preferably, the coating time is 5-10 min.
The invention has the beneficial effects that:
the blood perfusion modified resin adsorbent provided by the invention has excellent adsorption effect on substances causing acute and chronic poisoning of medicines and excellent blood purification effect; has good blood compatibility and high safety; the preparation method is economical, convenient and convenient, and convenient for application and production; the modified hemoperfusion resin adsorbent is used for adsorbing substances causing acute and chronic poisoning of medicines in blood and removing macromolecular toxin substances in the blood.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a scanning electron micrograph of an uncoated resin adsorbent.
FIG. 2 is a scanning electron micrograph of the coated resin adsorbent.
Detailed Description
The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
1) Preparation of 2% PVA aqueous solution:
and (3) adding 490g of purified water weighed by an electronic balance into a 500ml beaker, carrying out magnetic stirring, weighing 10g of PVA, adding the PVA into the beaker, raising the temperature from 25 ℃ to 80 ℃ after uniform dispersion, and stirring for 3 hours to obtain a PVA aqueous solution fully dissolved.
2) Taking a 1000mL beaker, adding 400mL of prepared 2% PVA aqueous solution to the beaker at the normal temperature of 25 ℃, placing the beaker in a magnetic stirrer for stirring, then adding 2.09mL of formaldehyde by using a liquid transfer gun, and then dropwise adding 8.8 mL of 0.5mol/L sulfuric acid solution for crosslinking reaction for 1h to obtain PVA crosslinking solution;
3) 320 mL of neutral macroporous resin is measured by a measuring cylinder and added into the prepared PVA cross-linking liquid, stirring and coating are carried out for 5min, suction filtration is carried out to obtain a crude product adsorbent, then 1000mL of absolute ethyl alcohol is added to fully disperse the obtained adsorbent, purified water is used for washing to be neutral, and finally the blood perfusion resin adsorbent coated with the PVA film and used for acute and chronic poisoning of the medicine is obtained. The scanning electron micrograph of the modified resin adsorbent prepared in this example is shown in fig. 2.
Test method
An in vitro static adsorption experiment (a disposable hemoperfusion apparatus is used according to the standard YYT 0464-2019) is carried out, and the adsorption performance of the modified resin on sodium pentobarbital, vitamin B12 and cytochrome C is detected. The data obtained are shown in Table 1.
Example 2
1) Preparation of 2% PVA aqueous solution:
and (3) adding 490g of purified water weighed by an electronic balance into a 500ml beaker, carrying out magnetic stirring, weighing 10g of PVA, adding the PVA into the beaker, raising the temperature from 25 ℃ to 80 ℃ after uniform dispersion, and stirring for 3 hours to obtain a PVA aqueous solution fully dissolved.
2) Taking a 1000mL beaker, adding prepared 400mL of 2% PVA aqueous solution into the beaker, placing the beaker in a magnetic stirrer for stirring, then adding 2.74mL of glutaraldehyde by using a liquid transfer gun, and then dropwise adding 8.8 mL of 0.5mol/L sulfuric acid solution for carrying out crosslinking reaction for 1h to obtain PVA crosslinking solution;
3) 320 mL of neutral macroporous resin is measured by a measuring cylinder and added into the prepared PVA cross-linking liquid, stirring and coating are carried out for 5min, suction filtration is carried out to obtain a crude product adsorbent, then 1000mL of absolute ethyl alcohol is added to fully disperse the obtained adsorbent, purified water is used for washing to be neutral, and finally the blood perfusion resin adsorbent coated with the PVA film and used for acute and chronic poisoning of the medicine is obtained. The scanning electron micrograph of the modified resin adsorbent prepared in this example is shown in fig. 2. The test method was in accordance with example 1, and the data obtained are shown in Table 1.
Example 3
1) Preparation of 2% PVA aqueous solution:
and (3) adding 490g of purified water weighed by an electronic balance into a 500ml beaker, carrying out magnetic stirring, weighing 10g of PVA, adding the PVA into the beaker, raising the temperature from 25 ℃ to 80 ℃ after uniform dispersion, and stirring for 3 hours to obtain a PVA aqueous solution fully dissolved.
2) Taking a 1000mL beaker, adding 400mL of prepared 2% PVA aqueous solution into the beaker at the normal temperature of 25 ℃, placing the beaker in a magnetic stirrer for stirring, then weighing and adding 3.44g of oxalic acid by using an electronic balance, and then dropwise adding 8.8 mL of 0.5mol/L sulfuric acid solution for crosslinking reaction for 1h to obtain PVA crosslinking solution;
3) 320 mL of neutral macroporous resin is measured by a measuring cylinder and added into the prepared PVA cross-linking liquid, stirring and coating are carried out for 5min, suction filtration is carried out to obtain a crude product adsorbent, then 1000mL of absolute ethyl alcohol is added to fully disperse the obtained adsorbent, purified water is used for washing to be neutral, and finally the blood perfusion resin adsorbent coated with the PVA film and used for acute and chronic poisoning of the medicine is obtained. The scanning electron micrograph of the modified resin adsorbent prepared in this example is shown in fig. 2. The test method was in accordance with example 1, and the data obtained are shown in Table 1.
Example 4
1) Preparation of 2% PVA aqueous solution:
and (3) adding 490g of purified water weighed by an electronic balance into a 500ml beaker, carrying out magnetic stirring, weighing 10g of PVA, adding the PVA into the beaker, raising the temperature from 25 ℃ to 80 ℃ after uniform dispersion, and stirring for 3 hours to obtain a PVA aqueous solution fully dissolved.
2) Taking a 1000mL beaker, adding 400mL of prepared 2% PVA aqueous solution into the beaker at the normal temperature of 25 ℃, placing the beaker in a magnetic stirrer for stirring, then weighing and adding 2.84g of malonic acid by using an electronic balance, and then dropwise adding 8.8 mL of 0.5mol/L sulfuric acid solution for carrying out crosslinking reaction for 1h to obtain PVA crosslinking solution;
3) 320 mL of neutral macroporous resin is measured by a measuring cylinder and added into the prepared PVA cross-linking liquid, stirring and coating are carried out for 5min, suction filtration is carried out to obtain a crude product adsorbent, 1000mL of absolute ethyl alcohol is added to fully disperse the obtained adsorbent, purified water is used for washing to be neutral, and finally the PVA film-coated blood perfusion resin adsorbent for acute and chronic poisoning of the medicine is obtained. The scanning electron micrograph of the modified resin adsorbent prepared in this example is shown in fig. 2. The test method was in accordance with example 1, and the data obtained are shown in Table 1.
Example 5
1) Preparation of 2% PVA aqueous solution:
and (3) adding 490g of purified water weighed by an electronic balance into a 500ml beaker, carrying out magnetic stirring, weighing 10g of PVA, adding the PVA into the beaker, raising the temperature from 25 ℃ to 80 ℃ after uniform dispersion, and stirring for 3 hours to obtain a PVA aqueous solution fully dissolved.
2) Taking a 1000mL beaker, adding 400mL of prepared 2% PVA aqueous solution into the beaker at the normal temperature of 25 ℃, placing the beaker in a magnetic stirrer for stirring, then weighing and adding 3.22g of succinic acid by using an electronic balance, and then dropwise adding 8.8 mL of 0.5mol/L sulfuric acid solution for crosslinking reaction for 1h to obtain PVA crosslinking solution;
3) 320 mL of neutral macroporous resin is measured by a measuring cylinder and added into the prepared PVA cross-linking liquid, stirring and coating are carried out for 5min, suction filtration is carried out to obtain a crude product adsorbent, 1000mL of absolute ethyl alcohol is added to fully disperse the obtained adsorbent, purified water is used for washing to be neutral, and finally the PVA film-coated blood perfusion resin adsorbent for acute and chronic poisoning of the medicine is obtained. The scanning electron micrograph of the modified resin adsorbent prepared in this example is shown in fig. 2. The test method was in accordance with example 1, and the data obtained are shown in Table 1.
TABLE 1
Figure 413915DEST_PATH_IMAGE002
It should be understood that the detailed description of the present invention is only for illustrating the present invention and is not limited by the technical solutions described in the embodiments of the present invention, and those skilled in the art should understand that the present invention can be modified or substituted equally to achieve the same technical effects; as long as the use requirements are met, the method is within the protection scope of the invention.

Claims (7)

1. A method for modifying a hemoperfusion resin adsorbent for acute and chronic poisoning of a medicine is characterized by comprising the following steps:
1) stirring purified water, adding a certain amount of PVA, continuously stirring to obtain a uniform PVA solution, heating to raise the temperature of the PVA solution to 80 ℃, and continuously keeping the temperature of 80 ℃ and stirring for 2-3 hours;
2) adding a cross-linking agent and a catalyst into the PVA aqueous solution obtained in the step 1) to carry out cross-linking reaction to obtain a PVA cross-linking solution;
3) adding neutral macroporous resin into the PVA cross-linking liquid prepared in the step 2), stirring to enable the PVA cross-linking liquid to be coated on the surface layer of the neutral macroporous resin to form a film, performing suction filtration to enable the residual PVA cross-linking liquid to be separated from the neutral macroporous resin to obtain the neutral macroporous resin with the PVA coated film as an adsorbent, then adding absolute ethyl alcohol into the adsorbent to fully disperse the adsorbent, washing with purified water until the pH value of the adsorbent is neutral, and finally obtaining the PVA film coated blood perfusion resin adsorbent for acute and chronic poisoning of the medicine.
2. The method as claimed in claim 1, wherein the PVA is medical grade polyvinyl alcohol, the alcoholysis degree is 88%, the polymerization degree is 500, 1700 and 2400 respectively, and the concentration of the aqueous solution of PVA is 0.1-5%.
3. The method for modifying a hemoperfusion resin adsorbent for acute and chronic poisoning by drugs according to claim 1, wherein the cross-linking agent is any one or any combination of formaldehyde, glutaraldehyde, oxalic acid, malonic acid and succinic acid.
4. The method as claimed in claim 1, wherein the catalyst is 0.5mol/L sulfuric acid solution, and the volume ratio of the sulfuric acid solution to the PVA aqueous solution is 1: 50-1: 30.
5. the method for modifying a hemoperfusion resin adsorbent for acute and chronic poisoning of a drug as claimed in claim 1, wherein the cross-linking reaction time is 20-60 min.
6. The method for modifying a hemoperfusion resin adsorbent for acute and chronic poisoning of a drug as claimed in claim 1, wherein the volume ratio of the PVA aqueous solution to the resin is 10: 1-5: 4.
7. the method for modifying a hemoperfusion resin adsorbent for acute and chronic poisoning of a drug as claimed in claim 1, wherein the coating time is 5-10 min.
CN202110005257.6A 2021-01-05 2021-01-05 Method for modifying blood perfusion resin adsorbent for acute and chronic poisoning of medicine Pending CN114100589A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4728432A (en) * 1982-08-10 1988-03-01 Japan Medical Supply Co., Ltd. Method for decontaminating blood
CN2780207Y (en) * 2005-04-12 2006-05-17 浙江科锐生物科技有限公司 Disposable active carbon blood perfusion device
CN102671629A (en) * 2011-03-15 2012-09-19 上海翠屹新材料科技有限公司 Absorbent with high blood compatibility
CN105670021A (en) * 2016-01-23 2016-06-15 武汉理工大学 Method for wrapping semipermeable membrane on surface of solvent-impregnated resin
CN106268703A (en) * 2015-11-04 2017-01-04 珠海健帆生物科技股份有限公司 DNA immunization adsorbent and preparation method thereof
CN114106398A (en) * 2021-01-04 2022-03-01 河南省驼人医疗科技有限公司 Preparation method of macroporous resin

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4728432A (en) * 1982-08-10 1988-03-01 Japan Medical Supply Co., Ltd. Method for decontaminating blood
CN2780207Y (en) * 2005-04-12 2006-05-17 浙江科锐生物科技有限公司 Disposable active carbon blood perfusion device
CN102671629A (en) * 2011-03-15 2012-09-19 上海翠屹新材料科技有限公司 Absorbent with high blood compatibility
CN106268703A (en) * 2015-11-04 2017-01-04 珠海健帆生物科技股份有限公司 DNA immunization adsorbent and preparation method thereof
CN105670021A (en) * 2016-01-23 2016-06-15 武汉理工大学 Method for wrapping semipermeable membrane on surface of solvent-impregnated resin
CN114106398A (en) * 2021-01-04 2022-03-01 河南省驼人医疗科技有限公司 Preparation method of macroporous resin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
陈长治,俞耀庭: "医用吸附剂及发展概况", 生物医学工程学杂志, no. 03, pages 213 *

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