CN102847521A - Macro-porous adsorption resin and its application - Google Patents
Macro-porous adsorption resin and its application Download PDFInfo
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- CN102847521A CN102847521A CN201110195335XA CN201110195335A CN102847521A CN 102847521 A CN102847521 A CN 102847521A CN 201110195335X A CN201110195335X A CN 201110195335XA CN 201110195335 A CN201110195335 A CN 201110195335A CN 102847521 A CN102847521 A CN 102847521A
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Abstract
The invention relates to a macro-porous adsorption resin. The macro-porous adsorption resin treats styrene-divinylbenzen material resin balls as an adsorbent resin frame, the resin balls densely cover micro-pores, the pore widths of the resin balls are in a range of 22-100nm, the specific surface area of the resin balls is greater than 1000m<2>/g, and the pore volume of the resin balls is greater than 6.000e-01cc/g. The resin surface can be coated with a protein membrane as needed, and the resin surface or its coating can be processed to have a polarity as needed.
Description
Invent described technical field
The invention belongs to medical macromolecular materials and application thereof.
The prior art background
This ethene-divinylbenzene resin has been widely used in the Medical Adsorbents material, but up to the present people still well do not explain the absorption principle of material in this adsorbent human peripheral blood; Therefore its range of application is very narrow, mostly be confined to in the late stage of uremia patient treatment as the auxiliary curing mode of dialysis treatment.For in the application in other illness field then seldom, even do not make inquiries.
In depositing at present the difficult sufferer of generation, such as the disease of AIDS, cerebral infarction and the classes such as hypertension, hyperthyroidism, adopt operation of the prior art and drug treatment all to be difficult to remarkable and lasting curative effect.Blood purification comes out for many years as the third illness therapeutic modality, does not pioneer and keep forging ahead in the difficult illness treatment field to these harm humans health but be based on previous reasons.
The content of invention
The present invention be resin balls with styrene-divinylbenzene material as the resin framework, its aperture (Pore Size) scope is between the 22-100 nanometer; Specific area (Snrface Area) is greater than 1000 square metres/g, between 1000 square metres/g to 3000 square metre/g; Pore volume (Pore volume) is greater than 6.000e-01cc/g, between 6.000e-01cc/g to 9.000e-01cc/g.
Macroporous absorbent resin of the present invention can take the sublimate processing to reach medical grade, adsorbent as blood perfusion device, absorption surpasses 10,000 except all kinds of in the blood side by side in people's extracorporal circulatory system bloody path, until surpass the exogenous and endogenous poisonous substance of the large molecule of 2,000,000 d, virus protein molecule, complex virus material, and excessive molecular weight surpass 10,000 d, until surpass the macromolecular components that 2,000,000 d, diameter surpass 100 nanometers; Blood samples of patients is purified, reach and alleviate and even cure all kinds of illness that cause because of septicemia.
A kind of concrete scheme of resin of the present invention can be: aperture (Pore width) scope is in the 22-25 nanometer; Specific area (Snrface Area Date) is greater than 1100 square metres/g; Pore volume (Pore volume) is greater than 6.500e-01cc/g.
The another kind of concrete scheme of resin of the present invention can be: its aperture (Pore width) scope is in the 30-35 nanometer; Specific area (Snrface Area Date) is greater than 1900 square metres/g; Pore volume (Pore volume) is greater than 6.000e-01cc/g.
Another concrete scheme of resin of the present invention can be: its aperture (Pore width) scope 92-100 nanometer; Specific area (Snrface Area Date) is greater than 1000 square metres/g; Pore volume (Pore volume) is greater than 7.000e-01cc/g.
The above-mentioned performance indications data of resin of the present invention are taken under the dry state state, and when doing the polymeric adsorbent use, resin is in hygrometric state.According to calculating, the aperture ratio dry state of resin can enlarge about 2 to 6 times during hygrometric state.That is, the maximum diameter of hole can reach about 600 nanometers.
Macroporous absorbent resin of the present invention surface can coat protein film as required.
Macroporous absorbent resin of the present invention surface or its coating can also be done the polarity processing as required makes it with polarity.
Embodiments of the invention
One of embodiment:
Resin of the present invention uses as the adsorbent of blood perfusion device, and blood perfusion device is placed in AIDS patient's the extracorporeal circulation blood circuit, and absorption is also got rid of AIDS virus, complex immunity virus and inflammatory factor in the blood samples of patients, to such an extent as to alleviate treatment of AIDS.
Two of embodiment:
Resin of the present invention uses as the adsorbent of blood perfusion device, and blood perfusion device is placed in cerebral infarction patient's the extracorporeal circulation blood circuit, and absorption is also got rid of B2-microglobulin and inflammatory factor in the blood samples of patients, cures the cerebral infarction illness to such an extent as to alleviate.
Three of embodiment:
Resin of the present invention uses as the adsorbent of blood perfusion device, and blood perfusion device is placed in the extracorporeal circulation blood circuit of patients with hypertension, and absorption is also got rid of the parathormone high pressure factor and inflammatory factor in the blood samples of patients, cures the hypertension illness to such an extent as to alleviate.
Four of embodiment:
Resin of the present invention uses as the adsorbent of blood perfusion device, blood perfusion device is placed in hyperthyroid's the extracorporeal circulation blood circuit, absorption is also got rid of the excessive thyroxine factor and inflammatory factor in the blood samples of patients, cures the hyperthyroidism illness to such an extent as to alleviate.
In conjunction with the embodiments the present invention is described in detail:
The material absorption principle of macroporous absorbent resin of the present invention is physical absorption, and active force mainly is the Van der Waals force that material surface exists.For surpassing the large molecule of 10,000 d or greater than the super large Molecular Adsorption active force of the 2000000 d Van der Waals force that also to be material surface produce when the contact.Can adsorb large molecule and super macromolecular key and be that resin of the present invention has the aperture of super large, pore volume and specific area.When the large molecule that is adsorbed touches resin of the present invention, model ylid bloom action power can be drawn into these large molecules and the super large molecule aperture by super large in the resin balls, and the pore volume of resin balls super large and specific area can retain and be included on the resin balls surfaces externally and internally separating its peripheral blood that passes through from resin balls or the body fluid; When treatment finishes, extract blood perfusion device and will be attracted to external that super large molecular substance on the resin abandons at leisure, reach the purpose that purifies the blood and treat illness.
Because most super large molecular toxicity materials belong to toxic protein, the present invention coats protein film at resin surface, makes it have compatibility to the protein type poisonous substance, can strengthen the suction-operated to toxicant.
And most of toxicants surface comprises negative electrode or anode all with strong or weak polarity; Perhaps or irregular reverse regular with environmental factor.For the adsorbed material surface with polarity, can be correspondingly with resin surface polarity of the present invention processing.The surface contacts with resin surface under fluid pressure with large molecule or the super large molecule of polarity, little active force of homopolar-repulsion can squeeze brokenly the Polar Crystal Slab that may be coated on large molecule or super large molecular surface, it is deflected at the volley, cause its surface polarity and change; Heteropole is inhaled mutually and can be strengthened resin to large molecule or super large Adsorbed molecular power.
Body fluid under the health status in the human body is a kind of equilibrium state; Illness state servant's body fluid is uneven attitude, presents on the whole acid attitude more.Resin of the present invention is affected by the poised state of body fluid on the suction-operated of material in the body fluid, then have the situation of so-called " competitive Adsorption " for adsorbed material, and the material of overbalance state preferentially is adsorbed, the attitude so that body fluid tends to balance.Therefore the material overwhelming majority of being peeled off absorption by resin of the present invention from peripheral blood or body fluid is the toxicant that affects blood and/or isohydria, or affect the excessive composition of blood and/or isohydria, thereby make blood or the body fluid state that restores balance; In this separation adsorption process, can be carried secretly absorption to human body beneficial's material, but its amount of being carried secretly absorption is not understood manyly under the state of " competitive Adsorption " yet, and the recovery capability of human body self can make these losses be compensated very soon.
The inventor executes the mechanism of controlling for the illness that relates among the embodiment and is described as follows based on the study to modern cell, molecule and gene medical knowledge:
AIDS is century property illness, there is no at present the method treatment.Analyze its reason and be because AIDS virus HIV and with CD4 molecule and the HHV series complex virus of HIV virus coexistence, all in 100,000 d level scopes, diameter about about 200 nanometers, belongs to the super large molecule to their itself molecular weight mostly.And this HIV virus at body fluid, comprise that the mode that exists in the peripheral blood is to be coated by the CD4 in macrophage or the immune system T cell first, HIV attacks and captures the CD4 in macrophage or the immune system T cell, makes the immune system forfeiture to the recognition function of HIV virus; Then HIV enters amount reproduction in the immune T-CD4 lymphocyte, and the DNA gene strand in the while attack cells, disintegrates the human immune system until make its collapse, and various opportunistic diseases will be invaded without barrier human body and be caused death.Medicine can't penetrate the adventitia of infected macrophage in the immune system that coats HIV virus and/or T-CD4, thereby up to the present, does not have medicine substantial kill activity directly or indirectly to occur to HIV.Comprise the HIV that exists in the blood for body fluid, take the way that exchanges blood transfusion also of no avail.Because can't the instantaneously changing whole blood, even the instantaneously changing whole blood also can't all be removed infected T-CD4 from immune system; And the stimulation of new blood can make HIV and the infected T-CD4 ground fast breeding that is further intensified after the change-blood, and consequence is the process of having accelerated the healthy body of virus infraction.
Adopt resin of the present invention to body fluid, comprise that the suction-operated of HIV in the blood and various composite toxicity materials is based on the Van der Waals force of material surface; And whether coated irrelevant by the CD4 molecule of infected macrophage or immune t-cell with HIV or other toxicant surfaces.Separate absorption HIV and infected macrophage or T-CD4 and composite toxicity material, and with blood purification, relevant with aperture, pore volume and the specific area of resin.The ultra-large aperture that resin of the present invention has, pore volume and specific area, can separate absorption HIV, comprise viral complex virus and infected macrophage or the T-CD4 of HHV system, and can and remain in the resin nearly all large molecule and the absorption of super large molecular toxicity material, simultaneously with blood purification.
Resin of the present invention shows that in the Various types of data such as aperture, pore volume and specific area of carrying out measuring when species analysis detects this resin can adsorb and contain the super large molecular substance of millions of grades of d fully, for example: blue Buddhist nun's alkali.So absorption only have relative molecular weight the HIV of hundreds thousand of d level scopes virus, infected macrophage, T-CD4 molecule, HHV be complex virus and comprise B2-microglobulin, TNF, parathormone inflammatory mediator, interleukin-11,1B, 6, etc. inflammatory factor all be not a problem.
Resin surface of the present invention can coat protein film to increase the affinity to virus protein, is conducive to its absorption.The polarity processing can also be done in the surface of this resin surface or coating film, also can increase effects on surface with the physical absorption function of viruses molecule or the toxicant of polarity.
The inventor obtained blood sample in a specific aim clinical testing, to its detection: the AIDS check is positive before the art; Through adopting resin of the present invention to carry out blood purification, postoperative AIDS detects to become and transfers feminine gender to.Owing to lack the comprehensive detection means of the material that is adsorbed, this detection is so that CD4 and the detection of related substances HIV infection index are as the criterion.And the in addition inflammatory factors such as B2-microglobulin, interleukin-11 B, interleukin 6, TNF that can detect in the material that is adsorbed, and the numerical exception that is adsorbed ground is high.
" many CD40 (relative molecular weight 4-5 ten thousand d) and CD40L (relative molecular weight 3.3 ten thousand d) express in the artery congee shape lump in the cerebral infarction blood samples of patients.
The CD40-CD40L system all plays an important role in the atherosclerotic stages.In human artery's AP, all express CD40 and CD40L on endothelial cell, macrophage and the smooth muscle cell, and in normal arterial tissue, do not express.Cerebral atherosclerosis is the main pathogenic factor of acute cerebral ischemia, in the lesion growth process, cytokine profiles such as interleukin-1 beta (IL-1 β). interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interferon gamma (IFN-γ) can promote endothelial cell monocytes CD40L
], can excite that CD40 and CD40L's is interconnected
]Thereby promoting E-selectin (CD62E), ICAM-1 (ICAM-1) and vascular adhesion molecules-1 (VCAM-1) to express increases.And then mediation activated blood platelet or endothelial cell and neutrophil leucocyte and monocytes adhesion, further cause vascular dysfunctions and tissue damage.Since going down of inner skin cell function, the enhancing of neutrophil adhesion function, and ischemic tissue of brain discharges TXA2, LTB4, PAF, LTB46, the chemotactic factor (CF)s such as COX-2 and complement
[8], cause Vascular diseases and vasomotor dysfunction.Matrix metalloproteinase (MMPS) mediation connective tissue degradation, removing and the reconstruction that produce after CD40 and CD40L interact simultaneously, destroy the collagen in the fibrous cap, cause plaque rupture, cause thrombus, arterial occlusion, participated in generation and the development of cerebral atherosclerosis." (annotating 1)
Resin of the present invention is interleukin-11 B, interleukin 6, TNF A and B2-microglobulin in the adsorption stripping blood for the embodiment of cerebral infarction illness.Separate above-mentioned toxicant through resin adsorption of the present invention, interrupted the evolution of cerebral infarction pathology, to such an extent as to delay to cure the cerebral infarction illness.
When curing the hypertension illness, adopt resin of the present invention also be affect blood pressure take adsorption stripping from blood large molecular toxicity material for example molecular weight as the parathormone high pressure factor of 9000d, to participate in simultaneously in malignant change all kinds of, large molecular toxicity material comprises that toxic protein and other endotoxin adsorb in the lump, thereby interrupt the evolution of hypertension pathology, to such an extent as to delay to cure the hypertension illness.The inventor has obtained numerical example success case in clinical treatment.Patient Wang suffers from essential hypertension (family history is arranged), and blood pressure index 160/100 before the art is taken depressor throughout the year.Adopted resin of the present invention to carry out blood purification treatment on February 25th, 2009, postoperative blood pressure is recovered normal index and is remained on 120/80, postoperative 2 years so far, and the withdrawal blood pressure is bounce-back not.
Resin of the present invention is the excessive thyroxine factor and inflammatory factor in absorption and the eliminating blood samples of patients for hyperthyroid's treatment, cures the hyperthyroidism illness to such an extent as to alleviate.A routine clinical case that adopts the present invention to treat the hyperthyroid, patient Wang, 65 years old age, the male sex.Suffer from hypertension, (blood pressure is 100-120/180-200) and hyperthyroidism for many years.Take depressor every day, morning and afternoon each once, each ten multi-discs.The eyes evagination, facial congested.Successively through twice blood purification treatment of the present invention, between two weeks of interval.Through about one month self adjusting, adjustment period, do not take medicine after the two treatments.Postoperative surpasses 1 year at present, and hyperthyroid symptom disappears substantially.Hypertension is obviously alleviated.Substantially no longer take now depressor, blood is stabilized between 80/120 substantially.
Each single index restricted portion of resin of the present invention can have variation slightly, and this variation must follow the correspondence of other index to change; This corresponding relation comprises: an index descends and causes that another index rises, and perhaps an index rises and causes that another index rises simultaneously; But do not comprise that three indexs descend simultaneously; Excursion greatly floating about 10-20% does not affect its application, and these variations also should be included in protection scope of the present invention.There is certain inverse relation each other in the indices of resin of the present invention, and for example enlarging pore volume can affect specific area decline.But the relation that also exists two indexs of correlation to rise simultaneously simultaneously, when for example specific area enlarged, pore volume also increased.The variation of the indices of resin of the present invention is relevant with molecular weight and the molecular diameter of the material of want specific aim absorption.The adsorbent molecular weight is large, and what at first consider is the aperture of resin.
Resin of the present invention can also be applied in the treatment of other difficult illness, for example as Medical Adsorbents: hyperlipemia, tumour etc.; Everyly relate to the illness that the virus relevant with blood conduction causes, perhaps accumulating illness that the endotoxin material in blood causes can be in clinical middle employing, and all certain curative effect can be arranged.
The present invention is in for example being applied to the treating AIDS process time, its generation to all toxicants that causes a disease, to comprising the absorption kill activity of virocyte, not only be expressed as the just separation of movable virus absorption in blood, also be expressed as the removing to related compound virus or toxicant, thereby cut off the needed energy supply chains of virus transcription process such as being hidden in intracellular HIV; And then cause hiding virus in the life cycle when termination natural apoptosis of himself.
In addition, industry is particularly paid close attention in academic discussion: when being subjected to HIV to infect macrophage and T-CD4 death the HIV virokine occurs and spread explosively, so that cause the situation of large-scale infection, when adopting the present invention to treat, can not occur.HIV virokine blast process occurs in the blood, when it is blasted, and the chance that adopts just the technology of the present invention that the HIV virokine that is hidden in infected macrophage and the T-CD4 cell is thoroughly removed from blood.
The present invention has outstanding substantive distinguishing features and is that macroporous absorbent resin of the present invention has unprecedented aperture, pore volume and specific area; Substantially opened up macroporous absorbent resin at medical domain, particularly the application prospect of clinical medicine domain; And for adopting the blood purification mode to give treatment to the difficult illness that this prehuman feels simply helpless, such as AIDS, cerebral infarction and hypertension, tumour, hyperthyroidism etc. opened up bright future.
The present invention has significant progress and is, macroporous absorbent resin of the present invention is easy to use in clinical medicine, easy operating, and is easy to utilize, and its cost is also than present with low cost for other clinical technology of similar illness.
Application of the present invention is to technological progress and guarantee that human health has epoch-making meaning.
Annotate 1: this section literal draws doctor Xu Junfeng that instructs from the quick academician of the former president Shi Xue of No.1 Hospital Attached to Tianjin College of Traditional Chinese Medicine about the paper of " consciousness regaining acupuncture therapy treatment cerebral infarction ".
Claims (11)
1. macroporous absorbent resin is characterized in that: be resin balls with styrene-divinylbenzene material as the resin framework, its aperture (Pore Size) scope is in the 22-100 nanometer; Specific area (Snrface Area) is greater than 1000 square metres/g, between 1000 square metres/g to 3000 square metre/g; Pore volume (Pore volume) is greater than 6.000e-01cc/g, between 6.000e-01cc/g to 9.000e-01cc/g.
According to claim 1 with described macroporous absorbent resin, it is characterized in that: its aperture (Pore width) scope is in the 22-25 nanometer; Specific area (Snrface Area Date) is greater than 1100 square metres/g; Pore volume (Pore volume) is greater than 6.500e-01cc/g.
According to claim 1 with described macroporous absorbent resin, it is characterized in that: its aperture (Pore width) scope is in the 30-35 nanometer; Specific area (Snrface Area Date) is greater than 1900 square metres/g; Pore volume (Pore volume) is greater than 6.000e-01cc/g.
According to claim 1 with described macroporous absorbent resin, it is characterized in that: its aperture (Pore width) scope 92-95 nanometer; Specific area (Snrface Area Date) is greater than 1000 square metres/g; Pore volume (Pore volume) is greater than 7.000e-01cc/g.
According to claim 1 with described macroporous absorbent resin, it is characterized in that resin surface coats protein film.
According to claim 1 or 5 with described macroporous absorbent resin, it is characterized in that resin surface or its coating are with polarity.
7. the application process of macroporous absorbent resin as claimed in claim 1 is characterized in that the adsorbent as blood perfusion device, all kinds ofly in the absorption blood in people's extracorporal circulatory system bloody path approaches and surpasses the large molecule poisonous substance of 10,000 d and excessive macromolecular components; Blood samples of patients is purified.
8. the application process of a macroporous absorbent resin as claimed in claim 7 is characterized in that being placed in AIDS patient's the extracorporeal circulation blood circuit, AIDS virus HIV, complex immunity virus and inflammatory factor in absorption and the eliminating blood samples of patients.
9. the application process of a macroporous absorbent resin as claimed in claim 7 is characterized in that being placed in cerebral infarction patient's the extracorporeal circulation blood circuit, and absorption is also got rid of B2-microglobulin and inflammatory factor in the blood samples of patients.
10. the application process of a macroporous absorbent resin as claimed in claim 7 is characterized in that being placed in hyperpietic's the extracorporeal circulation blood circuit, and absorption is also got rid of the parathormone high pressure factor and inflammatory factor in the blood samples of patients.
11. the application process of a macroporous absorbent resin as claimed in claim 7, it is characterized in that being placed in hyperthyroid's the extracorporeal circulation blood circuit, absorption is also got rid of the excessive thyroxine factor and inflammatory factor in the blood samples of patients, cures the hyperthyroidism illness to such an extent as to alleviate.
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| CN 201110195335 CN102847521B (en) | 2011-06-28 | 2011-07-05 | Macro-porous adsorption resin and its application |
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| CN102848679A (en) | 2013-01-02 |
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