CN104689804B - For adsorbing the phenylethylene resin series of AIDS virus molecule in blood - Google Patents

For adsorbing the phenylethylene resin series of AIDS virus molecule in blood Download PDF

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Publication number
CN104689804B
CN104689804B CN201510120605.9A CN201510120605A CN104689804B CN 104689804 B CN104689804 B CN 104689804B CN 201510120605 A CN201510120605 A CN 201510120605A CN 104689804 B CN104689804 B CN 104689804B
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resin
blood
aperture
phenylethylene
valence state
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CN104689804A (en
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于杰
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Weihai Weigaoyangquan Biological Co., Ltd.
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TIANJIN YANGQUAN MEDICAL DEVICES CO Ltd
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Priority claimed from CN201310347458.XA external-priority patent/CN103483487B/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26—Synthetic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES 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
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3621—Extra-corporeal blood circuits
    • A61M1/3627—Degassing devices; Buffer reservoirs; Drip chambers; Blood filters
    • A61M1/3633—Blood component filters, e.g. leukocyte filters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2220/00—Aspects relating to sorbent materials
    • B01J2220/40—Aspects relating to the composition of sorbent or filter aid materials
    • B01J2220/48—Sorbents characterised by the starting material used for their preparation
    • B01J2220/4812—Sorbents characterised by the starting material used for their preparation the starting material being of organic character

Abstract

For adsorbing the phenylethylene resin series of AIDS virus molecule in blood, it is characterized in that: the carbochain of cancellated styrene-divinyl benzene resin skeleton embeds metallic element X.

Description

For adsorbing the phenylethylene resin series of AIDS virus molecule in blood
Technical field
The present invention relates to phenylethylene resin series, particularly comprise the modified product of styrene-divinylbenzene, styrenic anion exchanger resin, the preparation method of this product and application thereof.
Background technology
Phenylethylene resin series in prior art, comprises styrene-divinylbenzene, and styrenic anion exchanger resin etc., as adsorbent and ion-exchanger, are widely used.
Use metallic compound such as FeCl 3catalyst as phenylethylene resin series post-crosslinking reaction has been routine techniques.But, all in prior art up to now functional modification or modification are carried out to phenylethylene resin series, all do not relate to and the constitute of the carbon chain backbone of resin or element are improved, after participating in post-crosslinking reaction, do not enter the report in resin structure about catalyst yet.In the report of prior art, after post-crosslinking reaction, cleaning solvent is usually used thoroughly to be removed by post-crosslinking reaction catalyst.
In medical resin adsorbent application, modern medicine is to " virulence factor " systematic achievement in research.And to adopt blood purification therapy to remove " virulence factor " from human peripheral blood be a kind of simple and effective approach.To remove for the purpose of " virulence factor ", development new construction adsorbent material is put on the agenda.
In life science, lack a kind of simple and effective live body Dynamic sampling technological means, with Dynamic Extraction active molecular species sample from biological living blood.
Summary of the invention
The object of the invention is to propose the new construction product of phenylethylene resin series, the technical scheme of preparation method and its usage.By changing phenylethylene resin series, comprise: styrene-divinyl benzene resin, and the structure of matter of polystyrene macroporous type anion exchange resin and gel-type anion exchanger resin, make it to have the New function being more suitable as blood-purifying adsorbing agent, can be used for intravital blood purification and Dynamic sampling from intravital blood.
The present invention includes three partial contents:
First: the new construction product of phenylethylene resin series, i.e. modified phenylethylene-divinylbenzene macroporous absorbent resin, and preparation method thereof.
This new construction product embeds metallic element X in the carbochain of cancellated styrene-divinyl benzene resin skeleton, and its structural formula is C-X-C; Wherein C is carbon, and X element is the metallic element with positive divalence or positive trivalent.
One of embodiment:
The metallic element X embedded is ferric iron element or trivalent aluminium element, and its structural formula is C-Fe-C or C-Al-C; Wherein the 3rd price of iron Fe or aluminium Al is avtive spot Y; Strong and weak according to the activity of element, Y site is element F (fluorine) or Elements C l (chlorine) or element B r (bromine) or I (iodine) successively; There is OH) time, be OH; Or there is the functional group of contraposition valence state.
Embodiment two:
The metallic element X embedded is divalent zinc element; Or described metallic element X is cupric element.
Divalent zinc element or cupric element do not have Y site.
The preparation method of the new construction product of this phenylethylene resin series: the preparation method being the modified phenylethylene-divinylbenzene macroporous absorbent resin embedding metallic element X in skeleton; Specifically, in styrene-divinylbenzene macroporous absorbent resin post-crosslinking reaction process, adopt dichloroethanes or liquid alcohols to make sweller, adopt metallic element X compound solution as catalyst; Under fully swelling condition, the boiling point making resin be warming up to sweller of heating, then the boiling point adding that catalyst solution continues to be warming up to catalyst solution, then add NaOH; Solution heats up tens of degree suddenly, make fully swelling resin under the condition exceeding swelling solution and the tens of degree temperature of catalyst boiling point and fierce boiling, catalyst adds reaction, in course of reaction, almost just make the particle of metallic element X in catalyst be embedded in the carbochain of resin matrix instantaneously; The addition of catalyst is relevant with the amount embedding metallic element X in carbochain, not by the restriction of insertion reaction.
Embodiment three:
In styrene-divinylbenzene macroporous absorbent resin post-crosslinking reaction process, adopt dichloroethanes or liquid alcohol to do resin swelling agent, adopt metallic element X compound solution as catalyst;
The first step: macroreticular resin is put into sweller and soaks, makes it fully swelling; Resin and the ratio of sweller addition be resin quality than sweller volume, i.e. Kg/L, its ratio is selected between 1:3 to 1:30; Soak time was selected between 12 hours to 120 hours;
Second step: the resin through fully soaking being filtered free swelling solution, adding in reactor, the newer swelling solution of resin volume adding 1/2 immersion, swelling solution boiling point is warming up to after stirring, adding catalyst makes temperature remain on sweller boiling point, continues to stir, and keeps two hours;
3rd step: again add catalyst and elevate the temperature, continues to stir; When temperature is increased to catalyst boiling point, stop adding;
4th step: continue to stir, keep temperature simultaneously, about two hours time, then add NaOH (NaOH), temperature of charge raises suddenly, stops adding NaOH, add water cooling when temperature is elevated to and exceeds catalyst boiling point 25-35 DEG C, and reactive material is released from reaction container bottom, continue cooling;
5th step: reacted resin is rinsed well.
In above-mentioned post-crosslinking reaction process, adopt liquor ferri trichloridi or aluminum trichloride solution as catalyst; Described metallic element X is metallic elements of ferrum, or metallic element aluminium.Adopt in the resin matrix obtained by liquor ferri trichloridi catalyst and embed ferro element, resin is red or kermesinus; When NaOH is excessive, resin also can be black.
In above-mentioned post-crosslinking reaction process, also can adopt copper chloride or adopt liquor zinci chloridi as catalyst.Copper and Zn-ef ficiency do not have Y site in resin matrix.
Embodiment four:
The preparation method of the new construction product of above-mentioned phenylethylene resin series can also be:
Its 3rd step: when catalyst to the temperature again added containing trivalent metallic element is elevated to 100 DEG C ± 5 DEG C instantaneously, add edible iodized salt and/or sugar defervescence, addition is 0.5 to 1.5 times of catalyst;
4th step: continue to stir, two hours time, then add NaOH (NaOH), temperature of charge raises again suddenly, to stopping when 130 DEG C adding NaOH when raising to temperature, adding water cooling, and reactive material is released from reaction container bottom;
5th step: reacted resin is rinsed well.
The Y site that gold in resin prepared by the method belongs to element can be occupied by I (iodine), monose, monose loop chain and OH-root, and performance has stronger polarity and the compatibility to water.
The new construction product of the phenylethylene resin series of the second part of the present invention is modified phenylethylene series anion exchange resin, comprises modified macroporous type anion exchange resin, and modified gel type anion exchange resin, and preparation method thereof.
The carbochain of cancellated styrenic anion exchanger resin skeleton embeds metallic element X, and its structural formula is C-X-C; Wherein X element is the metallic element with positive divalence or positive trivalent.
Embodiment five:
The metallic element X embedded is ferric iron element, or trivalent aluminium element; Its structural formula is C-Fe-C, or C-AL-C; Wherein the 3rd price of iron Fe or aluminium Al is avtive spot Y; Strong and weak according to the ripple alive of element, Y site is element F (fluorine) or Elements C l (chlorine) or element B r (bromine) or element I (iodine) successively; When there is OH, also can be OH; Or there is the functional group of pairing valence state.
Embodiment six:
The metallic element X embedded is divalent zinc element; Or cupric element.Its structural formula is: C-Zn-C, or: C-Cu-C.Zinc and copper do not have Y site in skeleton.
The preparation method of the modified styrene macroporous type anion exchange resin of metallic element X is embedded in skeleton:
The method and the aforementioned method embedding metallic element x in styrene-divinyl benzene resin skeleton similar.Specifically, in resin post-crosslinking reaction process, adopt dichloroethanes or liquid alcohols to make sweller, adopt metallic element X compound solution as catalyst; Heat under fully swelling condition, raise the temperature to sweller boiling point, keep temperature, add catalyst, then be warming up to the boiling point of catalyst solution, then add NaOH, make temperature rising 25-35 DEG C suddenly, when fully swelling resin being in exceed the tens of degree temperature of its solution boiling point and catalyst reaction, in course of reaction, almost just the particle of metallic element X is made to be embedded in the carbochain of resin matrix instantaneously.
Embodiment seven:
The present embodiment and styrene-divinylbenzene method of modifying have a little difference part, are in macroporous type anion exchange resin post-crosslinking reaction process:
The first step: resin is put into sweller and soaks, makes it fully swelling; Resin and the ratio of sweller addition be resin quality than sweller volume, i.e. Kg/L, its ratio is selected between 1:6 to 1:60; Soak time was selected between 8 hours to 120 hours;
Second step: the resin through fully soaking is filtered free swelling solution, add in reactor, add the new swelling solution of the resin volume of 1/2 immersion again, heat after stirring, elevate the temperature to sweller boiling point, add catalyst, and remain on sweller boiling temperature continuation stirring, keep two hours;
3rd step: again add catalyst solution, elevates the temperature to during catalyst boiling point, continues stir about two hours;
4th step: then add NaOH (NaOH), reactant heats up suddenly, stops adding NaOH, and immediately cools when temperature is elevated to and exceeds catalyst boiling point 25-35 DEG C;
5th step: reacted resin is rinsed well.
Adopt ferric trichloride solvent or aluminum trichloride solution as catalyst in said method.Or adopt liquor zinci chloridi or copper chloride solution as catalyst.
Embodiment eight:
In above-mentioned post-crosslinking reaction process, adopt dichloroethanes or liquid alcohol to do resin swelling agent, adopt ferric trichloride or alchlor solvent as catalyst;
Its 3rd step: again adding when catalyst to temperature is elevated to sweller boiling point, continues to stir; Keep temperature and add edible iodized salt and/or sugar defervescence, addition is 0.5 to 1.5 times of catalyst;
4th step: continue to stir, two hours time, then add NaOH (NaOH), temperature of charge raises suddenly, stops adding NaOH, adds water cooling, and released from reaction container bottom by reactive material when temperature raises about 30 degree;
5th step: rinsed well by reacted resin, adopts liquor ferri trichloridi to be red, kermesinus as the resin that catalyst obtains; When NaOH is excessive, can be black.
The Y site that gold in resin prepared by the method belongs to element can be occupied by I (iodine), monose, monose loop chain and OH, and performance has stronger polarity and the compatibility to water.
The preparation method of metallic element X is embedded: in polystyrene gel-type anion exchanger resin post-crosslinking reaction process in polystyrene gel-type anion exchanger resin skeleton, adopt dichloroethanes or liquid alcohols as sweller, use in the form of a solution as the metallic element iron compound of catalyst or metallic element aluminium compound.
Embodiment nine:
The first step: sweller makes resin fully swelling at normal temperatures, resin is resin quality with the ratio of sweller addition: sweller volume, i.e. the ratio of Kg/L, and its ratio is 1:6 to 1:60; Soak time is 8 hours to 120 hours;
Second step: add catalyst when sweller is heated to boiling point, temperature is kept after four hours, to add NaOH (NaOH), make resin suddenly be warming up to 92 to 96 DEG C and produce fierce boiling, metallic element x reactant heat up and in fierce boiling process embedded resin skeleton carbochain in, add water immediately and be cooled to normal temperature.
Embodiment ten:
In said method second step, the catalyst added accounts for swellable resins ratio 1/10 and fully mixing, heat to during sweller boiling point and stop heating, keep temperature four hours, add again and account for the NaOH that resin reaction object amasss 20%, when making resin be warming up to reactant fierceness boiling (92 to 96 DEG C), immediately add and account for resin reaction object and amass the edible iodized salt of 20% and/or account for the sugar that resin reaction object amasss 20%, rapid defervescence, cooling, and release from reactor.
The Y site that gold in resin prepared by the method belongs to element can be occupied by I (iodine), monose loop chain and OH, and performance has stronger polarity and the compatibility to water.
11 of embodiment:
In above-mentioned post-crosslinking reaction process, also copper chloride solution can be adopted, or liquor zinci chloridi is as catalyst.The metallic element X embedded is divalent zinc element; Or cupric element.Its structural formula is: C-Zn-C, or: C-Cu-C.Zinc and copper do not have Y site in resin matrix.
Need to propose, styrene series anion exchange resin, comprises macroporous type and gel type resin, and after employing the inventive method modification, its ion-exchange performance is tending towards disappearing, and polarization absorption property obtain significant lifting.Gel type resin creates hole in modifying process, and in reality detects, the specific area of modified gel type resin can reach 1900M unexpectedly 2/ gram.
Part III content of the present invention is the purposes of the new construction product of phenylethylene resin series:
The pore diameter range of the polystyrene new construction resin adopted is 0-200nm, and pore volume and specific area are not limit; The Y site of the trivalent metallic element embedded in its skeleton is by OH occupy-place and/or by the occupy-place of monose loop chain and/or by the functional group occupy-place with contraposition valence state; Its purposes is used as Medical Adsorbents, for blood perfusion device; Or be used as oral resin sorbent; Or be used as the absorption sampling agent to molecule living matter in intravital blood; By Peripheral Circulation system or gi system, adsorption removal virulence factor wherein, or live body Dynamic sampling is carried out to virulence factor and living matter.
Resin aperture is prepared when resin polymerization reacts, relevant with the pore-foaming agent material adopted.The inventive method, when participating in insertion reaction with metallic catalyst, has dilating effect to resin aperture.Such as aforementioned, there is not hole in gel shape resin anion (R.A.), but creates hole originally in course of reaction, also defines by process the space that specific area reaches 1900 square meters/every grammes per square metre.
According to the needs that clinical diagnosis proposes, the new construction product of medical phenylethylene resin series according to its pore diameter range, following differentiation can be done:
12 of embodiment:
The aperture 0-20nm of the polystyrene new construction resin adopted, the resin wherein containing 5-20nm aperture is not less than 60%.
13 of embodiment:
The aperture 0-40nm of the polystyrene new construction resin adopted, the resin wherein containing 20-40nm aperture is not less than 60%.
14 of embodiment:
The aperture 0-60nm of the polystyrene new construction resin adopted, the resin wherein containing 40-60nm aperture is not less than 60%.
15 of embodiment:
The aperture 0-80nm of the polystyrene new construction resin adopted, the resin wherein containing 60-80nm aperture is not less than 60%.
16 of embodiment:
The aperture 0-100nm of the polystyrene new construction resin adopted, the resin wherein containing 80-100nm aperture is not less than 60%.
17 of embodiment:
The aperture 0-140nm of the polystyrene new construction resin adopted, the resin wherein containing 100-140nm aperture is not less than 60%.
18 of embodiment:
The aperture 0-200nm of the polystyrene new construction resin adopted, the resin wherein containing 140-200nm aperture is not less than 60%.
19 of embodiment:
When making adsorbent for blood perfusion device and using, select according to the valence state attribute of virulence factor of absorption and particle diameter the resin that there is contraposition valence state functional group and be suitable for aperture, fill blood perfusion device; The mode of filling is that a kind of resin of pore diameter range loads a tank, and blood perfusion device is according to the material valence state attributive classification in in-built resin aperture and Y site;
Or according to the direction arrangement flowed through along blood, the large resin filling in aperture is at upstream position; Be loaded in perfusion device according to the order layering that aperture is descending is mixed, and according to the material valence state delamination classification that the element or functional group that occupy Y point have.
20 of embodiment:
Use for doing oral adsorbent agent, the resin of the different valence state material function that has with Y site group and different pore size is distinguished or hybrid packed in medicinal spansule in proportion.
21 of embodiment:
When using as intravital blood Middle molecule state living matter sampling agent, the different valence state material function group had with Y site and the resin of different pore size are loaded in sampler respectively.The similar blood perfusion device of structure of this sampler, using method also roughly the same.After completing sampling, sampler is extractd from blood extracorporeal circulation system, will the living beings wash-out in sampler resin be adsorbed on by the method for cleaning.Because resin of the present invention is the living matter adopting physical absorption principle separation and Extraction blood Middle molecule state, be adsorbed in resin voids of the present invention and resin surface living matter can in nutrient environment for a long time in keep its vital activity, for life science provides a kind of important technological means.
In such use embodiment of the present invention, the pore diameter range of resin is from " 0 ", and refer to that aperture is " 0 ", namely resin particle does not have hole.But in a perfusion device or sampler, the gap between resin particle also can be regarded as in " aperture ", then " aperture " even should cannot measure concrete data, it perhaps can be very large, the aperture that serious offense resin particle can have.
Also any restriction is not done to " pore volume " and " specific area " in such use embodiment.Because for macroporous absorbent resin, the most important condition that restriction adsorbed material enters resin voids is aperture.After aperture is determined, pore volume and specific area are proportional with Adsorbent rate respectively.And adsorption rate and aperture, proportionate relationship between pore volume and specific area are more statistics contents, not there is disruptive technology invention meaning of the present invention.
In a word, the new construction product of phenylethylene resin series of the present invention is used in blood perfusion device He in sampler makes adsorbent, due to the existence of avtive spot Y point, and can with multiple virulence factor in its polarity adsorption function absorption blood; And can be occupied by monose loop chain due to Y point, all kinds of surface have glycan molecule, glycoprotein molecule virulence factor can because of compatibility docile wound on it; This polarity absorption and compatibility are wound around, also can produce to clash into or paste to virocyte shell in any case and tear effect, make intracellular virulence factor, such as small molecular virokine, viral RNA etc., waterfall type sprays and enters peripheral blood in cell, is just received by the large, medium and small aperture of polymeric adsorbent of the present invention and resin surface.
The effect of the avtive spot Y point that resin material of the present invention has, also be that Y point can by corresponding modification, occupied by the molecular function group with required function, thus for the polymeric adsorbent of all kinds of virulence factor is adsorbed in preparation targetedly, provide technology platform.
Arthus Claude Bernard proposes the theory about biotic environment balance; " in the external environment that biological existence is accustomed at it, and various in organism organize move in biological ˋ environment ' inner.The stable prerequisite being life and existing of environment; Environment is wanted often to keep balance with external environment, otherwise biological phenomena will get muddled." resin of the present invention set up with " competitive Adsorption " rule biotic environment balance order in play a role.
The feature structure of resin of the present invention comprises: the salience(-cy) of Y point on skeleton, and the particle level film formed by the monose loop chain occupying Y point, and is wrapped in the cellulose coating on resin balls surface.The osmolality power utilizing resin balls surface and resin structure space to produce, effectively can pull out intracellular viral Small molecular outside cell membrane when not destroying cell, and be adsorbed onto easily in resin.After hemoperfusion treatment terminates, the Small molecular in cell and in peripheral blood, Middle molecule, large molecule virus all can be adsorbed by perfusion device, indwelling, and takes out of in body; And reach and purify the blood, solve the disease that blood environment causes because of imbalance.
Based on the above material property that the present invention has, all kinds of medical polymeric adsorbent can be prepared pointedly, be applicable to following all kinds of illness:
1, AIDS, i.e. acquired immunodeficiency syndrome; Human immunodeficiency virus is RNA virus, comprising: human immunodeficiency virus type 1 (HIV-1) and human immunodeficiency virus 2 type (HIV-2).
1.1, the rounded particle of electric Microscopic observation HIV-1, diameter is about 110nm; Adventitia has outer membrane glycoprotein (Env).
HIV-1 viral genome is about 10kb, and respectively there is a RNA sequence being called long end repetition (1ongterminalrepeat, LTR) at two ends, are about 634bp.
New construction resin sorbent of the present invention is in HIV-1 virus replication regrouping process, to the virokine in each stage, all there is good suction-operated, can blocks protein virus pass on, the a large amount of progeny virus produced in adsorption removal peripheral blood, stop virus fast-developing, and then remaining virokine is run its course in its life cycle.
1.2, the ultra microstructure of HIV-2 and cell tropism similar to HIV-1.Resin sorbent of the present invention can infect virus by adsorption removal HIV-2 equally, blocks the inflammatory factor outburst of waterfall type.
2, resin sorbent of the present invention is to the virion of viral liver disease and Non-viral liver disease, has suction-operated.
2.1, hepatitis A virus: be a kind of RNA virus, belonging to pico+ribonucleic acid+virus section, is the spheric granules that diameter is about 27nm, forms symmetrical 20 body nucleocapsids by 32 shell particulates, includes line style single-stranded RNA.This viral material is in the suction-operated scope of resin of the present invention.
2.2, hepatitis type B virus: be a kind of DNA virus, belonging to Hepadnaviridae (hepadnavividae), is the spheric granules of diameter 42nm.
2.3, serum of hepatitis B Patients can be looked into and see three kinds of particles under microscopical observation:
2.3.1, the pellet shapes particle of diameter 22nm;
2.3.2, tubular particle, be about 100 ~ 700nm, wide about 22nm;
2.3.3, diameter is the large spheric granules of 42nm, pellet shapes particle.
Pellet shapes particle and tubular particle are superfluous virus coat, containing surface antigen; Large spheric granules and virion, have solid and hollow two kinds, and hollow bead lacks nucleic acid.Three kinds of particles are all in the adsorbing scope of application of adsorbent of the present invention:
2,4, resin of the present invention has absorption corrective action to antigen-antibody:
The form of hepatitis B surface antigen and surface antibody:
2.4.1, hepatitis B surface antibody (HBsAg) and surface antibody (anti--HBs) HBsAg is present in the shell of virion and pellet shapes particle and tubular particle.
2.4.2, hepatitis BcAg (HBcAg) and core antibody (anti-HBc)
2.4.3, hepatitis B e antigen (HBeAg) and e antibody-(HBe).
Three kinds of antigen-antibodies are all in resin adsorption sphere of action of the present invention.
2.5, resin of the present invention has compatibility and specific adsorption effect to HCV (HCV):
HCV (HCV) is a kind of RNA virus with lipidic shell, and diameter 50-60nm, its genome is 10kb single strand RNA molecule.
2.6, resin of the present invention has compatibility and specific adsorption effect to Hepatitis D virus (HDV):
Hepatitis D virus (HDV) be a kind of defect addicted to liver single strand RNA virus, need the auxiliary of HBV just can copy, therefore the existing HBV of HDV is simultaneously or superinfection.HDV is the little garden spherical particle of diameter 35-37nm, and its shell is HBsAg, and inside is made up of the RNA molecule of a HDAg and 1.7kb.
2.7, resin of the present invention has compatibility and specific adsorption effect to HEV (HEV):
The picornavirus that HEV (HEV) is diameter 27-34nm.
2.8, resin of the present invention has compatibility and specific adsorption effect to HGV RNA (HGV):
3, resin of the present invention has suction-operated to the inflammatory factor causing blood pressure to increase in patient body.
Vascular hypertension is divided into: a primary, b Secondary cases, and the vascular hypertension that the pathogenic factors such as c is viral are different is all relevant to the effect of excessive inflammatory factor.The inflammatory factor of vascular hypertension is small molecular, belongs to the scope of application of resin adsorption effect of the present invention.
4, hyperinsulinemia is by the sufferer of the excessive initiation of insulin.
Resin of the present invention has obvious polar adsorption to insulin molecule excessive in patient body, insulin storage in control agent, may be used for treating hyperinsulinemia.
5, the autoimmune disease etc. such as pernicious swollen, systemic loupus erythematosus, the hemolytic anemia such as uremia, hepatopathy, Hematopoietic Malignancies, primary carcinoma of liver, lung cancer, myeloma, all show increasing of serum beta-2-microglobulin content to reduce with glomerular filtration rate(GFR (GFR), synthesizing acceleration with B2M has substantial connection.Due to β 2the Middle molecular toxins accumulations such as microglobulin cause the incidence of dialysis related amyloidosis, renal osteodystrophy, Secondary Hyperparathyroidism etc. to increase, and cause all kinds of complication of patient thus, admission rate, the death rate also increase thereupon.
Resin of the present invention has the effect of adsorbing excessive B2-microglobulin, the excessive synthesis of β 2-microballoon egg in body can be blocked, remove the excessive Middle molecule toxicant being representative with B2-microglobulin, the biotic environment of the Diseases such as uremia, hepatopathy, lupus erythematosus, malignant tumour can be improved, improve Quality of Life of Patients.
6, drug dependence patient body internal cause is taken drugs and produces toxicity neuropeptide, blocks normal nerve signals conduction function.
Toxicity neuropeptide molecule in resin human peripheral blood of the present invention has suction-operated, and patient can be made in several tens minutes to cross over the abstinence reaction phase fast, and the body broken away from causing addiction medicine relies on.
7, acute drugs poisoning is rescued.
Resin of the present invention, to the suction-operated of toxicity neuropeptide material, can be applied to equally in the rescue to acute drugs poisoning patient, and have clinical verification case.
8, mental patient is given treatment to.
Resin of the present invention, to the suction-operated of neuropeptide material, also can be used in giving treatment to mental patient, and has had clinical verification case.
9, hypertriglyceridemia (hypertriglyceridemia, HTG) is the synthesis of a kind of different race's property triglycerides albumen or degraded obstacle.HTG refers to that the triglycerides in blood is excessive with content in chylomicron and prebeta-lipoprotein, it and be atheroscleroticly formed with very large relation.Be called as " reticent killer "
Resin of the present invention can excessive chylomicron in the blood of adsorption removal Hypertriglyceridemia (HTG) patient and beta lipoprotein, alleviates and even cures HTG sufferer.
10, hypercholesterolemia refers to that in the blood of patient, plasma cholesterol concentration is too high.1/3 of total plasma cholesterol exists in a free form, and 2/3 is the cholesteryl ester be combined with aliphatic acid.Plasma cholesterol is primarily of liver and small intestine synthesis.China is healthy between twenty and fifty many in 1400 ~ 1600 mg/litre, and the elderly is no more than 2000 mg/litre, more American-European artificially low.As treated more than 2500 mg/litre.
Resin sorbent of the present invention has suction-operated to plasma cholesterol, and plasma cholesterol that can be excessive in adsorption removal body, alleviates and even cure hypercholesterolemia.
11, the suction-operated of resin of the present invention is in the physical environment balance order set up with " competitive Adsorption " rule, all kinds of lipoprotein that can exist in human peripheral blood, the PC comprising high and low density lipoprotein etc. carries out appropriateness and regulates, thus alleviates and cure hyperlipoprotememia.
12, resin of the present invention has good equilibrium adsorption effect to lipid material excessive in Metabolic Syndrome Patients body.At use resin of the present invention as in the clinical testing of blood-purifying adsorbing agent, the triglycerides average rate of decrease of patient is not less than 50%, the insulin average rate of decrease of hyperinsulinemia is not less than 60%, the rate of descent of LDL is not less than 35%, the average rate of decrease of VLDL is not less than 55%, the rate of descent of T-CHOL is not less than 35%.30% is not less than to the rate of descent of the angiotensins of hypertension Metabolic syndrome patient, adjustable metabolic syndrome patient blood pressure.
13, resin of the present invention can effectively remove excessive in patient body in, large molecule poisonous substance, to Middle molecule and in macromolecular viral H-N in clinical verification, obtain good effect, to rescuing the sudden pandemic (H1N1 caused by virus, H7N9, SARS) be very effective methods for the treatment of, and emergency measures.There is the case of clinical case.
14, resin of the present invention is to the interleukin-11 in Uveitis Patients blood, 6,18, has suction-operated, can alleviate and even cure uveitis illness.
15, resin of the present invention to comprise high endotoxemia, septicopyemia crush syndrome blood samples of patients in Small molecular, Middle molecule and large molecule virulence factor have and well remove and suction-operated.Effectively can rescue, alleviate and cure crush syndrome patient, patients with sepsis.
16, resin of the present invention can to the excessive inflammatory factor in blood; Interleukin, TNF, parathormone, Endothelin, feritin, angiotensins, hyperinsulinism etc. have adsorption removal effect targetedly.
17, resin of the present invention is to DIABLO through system balancing, hinders the newborn virulence factor of neural normal conduction effect to have suction-operated, hypogona dism and impotence is had to the effect alleviated and cure in the process of Clinical practice, and its mechanism still requires study summary.
18, with resin of the present invention, blood purification treatment is done, the facial reddish brown in its postpartum and abdominal spot patterns to fertility puerpera, black can be alleviated fast; Present smooth belly and pale skin.
19, resin of the present invention can adsorb the virulence factor of various venereal disease, comprises bacterium and virus; For gonorrhoea in the process of clinical verification, condyloma acuminatum, the venereal diseases such as syphilis have the effect alleviated and cure.
20, resin of the present invention is used for the agent of living matter living body sampling, and its using method is identical with the using method as blood-purifying adsorbing agent in blood perfusion device, for life science provides a kind of simple and effective sampling technique means.
Preparation method's technical scheme that naval stores new construction technical scheme of the present invention and the present invention propose, all never sees the report of any open source literature before this, is unprecedented technical innovation in this area, compared with prior art has outstanding substantive distinguishing features.
The new construction product of phenylethylene resin series of the present invention uses as adsorbent in blood perfusion device, and adsorption effect is more excellent than the resin sorbent of prior art, and the scope of application is more extensive, is verified in test.The present invention has significant progress than prior art resin sorbent.
Adopt the blood perfusion device of material of the present invention and oral adsorbent agent to list the supporting technology of National 863 key project in, be incorporated into state science think tank a few days ago.

Claims (3)

1. for removing the phenylethylene resin series adsorbent of AIDS virus molecule in blood, it is characterized in that: be modified phenylethylene-divinylbenzene macroporous absorbent resin, the carbochain of cancellated styrene-divinyl benzene resin skeleton embeds metallic element X, and its structural formula is C-X-C; Wherein C is carbon; The metallic element X that the carbochain of cancellated styrene-divinyl benzene resin skeleton embeds be ferric iron element or trivalent aluminium element time, its structural formula is C-Fe-C or C-Al-C; Wherein the 3rd price of iron Fe or aluminium Al is avtive spot Y; The Y point of the trivalent metallic element embedded in its carbochain is by OH occupy-place and/or by the occupy-place of monose loop chain and/or by the functional group occupy-place with contraposition valence state; the aperture 0-140nm of described phenylethylene resin series, the resin wherein containing 100-140nm particle diameter is not less than 60%.
2. as claimed in claim 1 for removing the purposes of the phenylethylene resin series adsorbent product of AIDS virus molecule in blood, it is characterized in that:when making adsorbent for blood perfusion device and using, select according to the valence state attribute of AIDS virus molecule of absorption and particle diameter and there is contraposition valence state functional group, and the resin being suitable for aperture is to fill blood perfusion device; The mode of filling is that a kind of resin of pore diameter range loads a tank, and blood perfusion device is according to the material valence state attributive classification in in-built resin aperture and Y site; Or according to the direction arrangement flowed through along blood, the large resin filling in aperture is at upstream position; Be loaded in perfusion device according to the order layering that aperture is descending is mixed, and according to the material valence state delamination classification that the element or functional group that occupy Y point have.
3. as claimed in claim 2 for removing the purposes of the phenylethylene resin series adsorbent product of AIDS virus molecule in blood, it is characterized in that:for do oral adsorbent agent use, the resin of the different valence state attribute that different pore size and Y point have, distinguish or hybrid packed in medicinal spansule in proportion.
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CN201510120761.5A Active CN104667897B (en) 2013-08-12 2013-08-12 For adsorbing high endotoxic phenylethylene resin series in blood
CN201510291602.1A Active CN104941607B (en) 2013-08-12 2013-08-12 Styrene resin adsorption agent for clearing high beta2 microglobulin in blood
CN201510120428.4A Active CN104689803B (en) 2013-08-12 2013-08-12 For adsorbing the phenylethylene resin series of hepatitis viruse in blood
CN201510291617.8A Pending CN104857015A (en) 2013-08-12 2013-08-12 Styrene type novel-structure adsorption resin for de-addiction and detoxification
CN201510291604.0A Active CN104923185B (en) 2013-08-12 2013-08-12 Medical polymeric adsorbent for removing H N macromoleculars virus
CN201510291616.3A Pending CN104887700A (en) 2013-08-12 2013-08-12 Medical adsorptive resin for eliminating syphilis and sexual disease pathogenic factors
CN201510156544.1A Active CN104815628B (en) 2013-08-12 2013-08-12 A kind of purposes of modified phenylethylene-divinylbenzene macroporous absorbent resin
CN201510291618.2A Pending CN104922147A (en) 2013-08-12 2013-08-12 New structure medical resin for eliminating high cholesterol
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CN201510291602.1A Active CN104941607B (en) 2013-08-12 2013-08-12 Styrene resin adsorption agent for clearing high beta2 microglobulin in blood
CN201510120428.4A Active CN104689803B (en) 2013-08-12 2013-08-12 For adsorbing the phenylethylene resin series of hepatitis viruse in blood
CN201510291617.8A Pending CN104857015A (en) 2013-08-12 2013-08-12 Styrene type novel-structure adsorption resin for de-addiction and detoxification
CN201510291604.0A Active CN104923185B (en) 2013-08-12 2013-08-12 Medical polymeric adsorbent for removing H N macromoleculars virus
CN201510291616.3A Pending CN104887700A (en) 2013-08-12 2013-08-12 Medical adsorptive resin for eliminating syphilis and sexual disease pathogenic factors
CN201510156544.1A Active CN104815628B (en) 2013-08-12 2013-08-12 A kind of purposes of modified phenylethylene-divinylbenzene macroporous absorbent resin
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CN104887699A (en) * 2013-08-12 2015-09-09 天津市阳权医疗器械有限公司 Medical adsorptive resin for clearing away factors blocking nerve conduction
WO2017005090A1 (en) * 2015-07-09 2017-01-12 于杰 Micro-nano medical adsorbent resin powder material
CN107789691A (en) * 2016-09-07 2018-03-13 天津市阳权医疗器械有限公司 It is exclusively used in treating the disposable blood perfusion device of endotoxemia
CN108031454B (en) * 2017-12-19 2021-08-13 陈荣胜 Blood purification adsorbent with physical specificity selectivity and preparation method thereof
CN113262762B (en) * 2021-05-06 2023-04-21 西安蓝深新材料科技股份有限公司 Adsorption material for blood perfusion and preparation method thereof
CN114085829B (en) * 2021-11-18 2023-08-11 军事科学院军事医学研究院环境医学与作业医学研究所 Efficient enrichment method for viruses in environmental medium

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CN104857015A (en) 2015-08-26
CN104923185B (en) 2017-10-24
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