CN104258829A - Serum phosphate adsorbing agent and preparation method thereof and adsorption column for blood perfusion - Google Patents
Serum phosphate adsorbing agent and preparation method thereof and adsorption column for blood perfusion Download PDFInfo
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- CN104258829A CN104258829A CN201410494396.XA CN201410494396A CN104258829A CN 104258829 A CN104258829 A CN 104258829A CN 201410494396 A CN201410494396 A CN 201410494396A CN 104258829 A CN104258829 A CN 104258829A
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- JMUQZLDSTQTIPX-UHFFFAOYSA-N OCCNC(COS)=O Chemical compound OCCNC(COS)=O JMUQZLDSTQTIPX-UHFFFAOYSA-N 0.000 description 2
- YMURLKIIDQPXRE-UHFFFAOYSA-N OCCNC(CCl)=O Chemical compound OCCNC(CCl)=O YMURLKIIDQPXRE-UHFFFAOYSA-N 0.000 description 1
- IWIYATDSSVMHEQ-UHFFFAOYSA-N OCCNC(C[ClH]C1CC1)=O Chemical compound OCCNC(C[ClH]C1CC1)=O IWIYATDSSVMHEQ-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
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- 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
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
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- 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
- A61M1/3687—Chemical treatment
-
- 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
- A61M1/38—Removing constituents from donor blood and storing or returning remainder to body, e.g. for transfusion
-
- 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
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/3085—Chemical treatments not covered by groups B01J20/3007 - B01J20/3078
-
- 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
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/58—Use in a single column
Abstract
The invention provides a serum phosphate adsorbing agent; a hydrophilic carrier is immobilized by ligands capable of capturing phosphate ions to obtain the serum phosphate adsorbing agent; the hydrophilic carrier is selected from one or more out of cellulose, agarose and polyvinyl alcohol microsphere, and the ligands capable of capturing phosphate ions refer to amino polymers. The invention also provides a preparation method of the serum phosphate adsorbing agent and an adsorption column for blood perfusion, prepared by the serum phosphate adsorbing agent. Compared with medicines which are orally taken to act on the human body, the serum phosphate adsorbing agent can directly remove the phosphate ions in blood through blood circulation, so as to immediately alleviate the illness state of a patient; and the serum phosphate adsorbing agent can be combined with hemodialysis, oral taking pain of the patient each day can be reduced, and the result caused by a situation that the patient forgets to take the medicine can be avoided.
Description
Technical field
The present invention relates to medical field, particularly relate to a kind of serium inorganic phosphorus adsorbent and preparation method thereof, and a kind of adsorption column for blood perfusion.
Background technology
Phosphorus, as one of human body base substance, take part in the regulation and control and acid-base balance adjustment etc. of the composition of the many vital tissues of life entity, human body energy metabolism, large biological molecule activity.In normal human, the phosphorus of 85% is present in bone, tooth, and 14.9% is present in cell, also has few fraction to be present in blood plasma.Plasma P concentration and diet, age, sex are relevant, and the fluctuation of normal plasma phosphorus is between 2.5 ~ 4.5mg/dl (0.81 ~ 1.45mmol/L).The phosphorus intake of normal person every day is approximately 1g, and 60% ~ 70% by intestinal absorption.In blood plasma, free phosphorus can be leached by glomerulus, and the phosphorus 80% ~ 90% leached heavily is absorbed at renal tubule, only 10% ~ 20% is excreted by urine.Work as renal hypofunction, kidney can not normal excretion phosphorus, just there will be hyperphosphatemia.
Hyperphosphatemia is the common complication of CKD (CKD), the key factor causing the change of SHPT, calcium phosphorus precipitation, vitamin D metabolism obstacle, renal osteodystrophy, closely related with the serious cardiovascular such as coronary artery, valvular calcification complication.Normal person suppresses renal tubule to absorb phosphorus again due to parathyroid hormone, calcitonin, and both play antagonism in intestines, bone, kidney are to the adjustment of alcium and phosphor metabolization, and therefore serium inorganic phosphorus maintains normal level and not easily rises.But to be transferred to blood, vitamin D excessive and hyperphosphatemia can occur under taking in the situation such as too much for phosphorus after renal failure row phosphorus difficulty, hypoparathyroidism, cell damage.
1, renal failure row phosphorus difficulty: when the glomerular filtration rate seeing many reasons reduces to below 30ml/min, serium inorganic phosphorus retention and rising, normal companion's azotemia or uremia and acid poisoning.
2, hypoparathyroidism: urine phosphorus resorption is received and increased, and serium inorganic phosphorus often increases and blood calcium reduces.
3, after cell damage, phosphorus is transferred to blood: see the metabolic acidosis caused such as hot, poisoning in height of cell damage that many reasons causes, hyperfunction and the disintegration of normal companion cell catabolism, Several Kinds of Malignancy is lymthoma especially, and during leukemia chemotherapy, due to cell disruption, phosphorus escapes into blood circulation.
4, vitamin D is excessive: because intestines and renal tubule absorb, calcium phosphorus increases, bone mobilization calcium phosphorus enters blood and can cause that serium inorganic phosphorus and blood calcium raise.
5, take in intestinal absorption too much: see baby feed with cow's milk time, due to phosphorus calcium content in cow's milk far beyond human milk be height (cow's milk phosphorous 940mg/L calcium 1220mg/L; Human milk is phosphorous 150mg/L and calcium 340mg/L only), therefore baby's serium inorganic phosphorus can reach 2.3mmol/L.Be grown up oral potassium phosphate or vitamin D time also cause a disease because of hyperabsorption.
The current primary treatments of hyperphosphatemia has: 1. aluminium porcelain enamelling: gel aluminum hydroxide can combine with phosphorus in enteron aisle, but can cause constipation, and long-term prescription can cause aluminium accumulate poisoning; 2. calcium preparation: calcium carbonate: this medicine is inexpensive, containing calcium component up to 40%, easily tolerates, determined curative effect, but easily causes hypercalcinemia and blood vessel, periarticular calcification; Calcium acetate: the improvement formulation being calcium carbonate, by often absorbing calcium amount and calculating in conjunction with the effect of phosphorus, calcium acetate is greater than 1 times, calcium carbonate.But also can there is hypercalcinemia.3. magnesium preparation: magnesium acetate is oral can be controlled in normal range (NR) for a long time by serium inorganic phosphorus concentration, also hypermagnesemia can not occur, but heavy dose of magnesium salts can cause diarrhoea.Be dialysis process again, dialysis process eliminates that phosphorus is unsatisfactory also needs oral phosphate binder.The phosphorus in medical charcoal removing blood is adopted in patent CN101904868A " application of medical charcoal in treatment hyperphosphatemia medicine ".Composition of medicine is utilized to treat hyperphosphatemia in patent CN102342995A " a kind of Pharmaceutical composition of hyperphosphatemia and preparation thereof ".But these methods are all utilize medicine indirectly in conjunction with the phosphorus in blood, the object directly removing phosphorus in blood cannot be reached.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of serium inorganic phosphorus adsorbent is provided, by this serium inorganic phosphorus absorbent filling in cylinder, is prepared into the adsorption column for blood perfusion, by blood circulation, directly remove phosphate radical in blood and reach the object of serum phosphate lowering.
First aspect of the present invention is to provide a kind of serium inorganic phosphorus adsorbent, described serium inorganic phosphorus adsorbent be adopt hydrophilic carrier immobilized can catch phosphate anion aglucon and the serium inorganic phosphorus adsorbent that obtains.Wherein, one or more preferably in cellulose, agarose, polyvinyl alcohol microparticles of described hydrophilic carrier, the described aglucon catching phosphate anion preferably refers to containing amino polymer.
Preferably, the described aglucon catching phosphate anion is selected from one or more in polyglutamic acid, poly-aspartate, polylysine, poly allylamine.
Further preferably, the described aglucon catching phosphate anion is poly allylamine.
Wherein, polyglutamic acid also can use the polyglutamic acid of acidifying, such as hydrochloric acid polyglutamic acid, hydrogen bromide polyglutamic acid etc.Poly-aspartate also can use the poly-aspartate of acidifying, such as hydrochloric acid poly-aspartate, hydrogen bromide poly-aspartate etc.Polylysine also can use the polylysine of acidifying, such as hydrochloric acid polylysine, hydrogen bromide polylysine etc.Poly allylamine also can use the poly allylamine of acidifying, such as hydrochloric acid poly allylamine, hydrogen bromide poly allylamine etc.
Second aspect of the present invention is to provide the preparation method of the serium inorganic phosphorus adsorbent described in the present invention first aspect, comprises the following steps:
Step 1, hydrophilic carrier and hydroxyethyl acetamide carry out graft reaction under catalyst and alkali existent condition;
Step 2, by the hydrophilic carrier Epichlorohydrin activation after grafting process;
Step 3, by immobilized for the hydrophilic carrier after the activation process aglucon catching phosphate anion, both.
Preferably, described hydroxyethyl acetamide is prepared from according to following reaction equation under inorganic base existent condition by monoethanolamine and chloracetyl chloride:
Wherein, inorganic base can be one or more in sodium carbonate, sodium acid carbonate, saleratus or potash etc.
Particularly, monoethanolamine and 10wt% sodium carbonate liquor is added in toluene, chloracetyl chloride 1h is dripped at 20-30 DEG C, insulated and stirred reaction 3-6h at 20-30 DEG C, obtain hydroxyethyl acetamide, wherein the mass ratio of toluene, monoethanolamine, 10wt% sodium carbonate liquor and chloracetyl chloride is (40-100): (1-8): (3-7): (2-18), wherein, and the replaceable one-tenth sodium acid carbonate of sodium carbonate, saleratus, potash etc.
Preferably, in step 1, described catalyst is TBAB.
Preferably, described alkali is one or more in sodium carbonate, sodium acid carbonate, saleratus, potash.
Preferably, step 1 is specially:
S is hydrophilic carrier;
N is joined by Anhydrous potassium carbonate, dinethylformamide and acetone mixed solution, add hydrophilic carrier and catalyst TBAB again, then hydroxyethyl acetamide is added, 12-24h is reacted under room temperature, obtain the hydrophilic carrier after grafting process, wherein, the mass ratio of Anhydrous potassium carbonate, DMF, acetone, hydrophilic carrier, TBAB and hydroxyethyl acetamide is (5-25): (5-90): (10-50): (1-5): (0.05-0.15): (1-5).
Preferably, step 2 is specially: get the hydrophilic carrier after grafting process and epoxychloropropane, join in the sodium hydroxide solution of 1-2mol/L, stirring at room temperature reaction 2-4h, obtain the hydrophilic carrier after activating, the mass ratio of the hydrophilic carrier wherein after grafting process, the sodium hydroxide solution of epoxychloropropane 1-2mol/L is (1-5): (1-10): (1-20)
Preferably, step 3 is specially: get the hydrophilic carrier after activation, joins in the training based sols of 3%-10%, 6-20h is reacted at 30-50 DEG C, both, wherein, the weight ratio of the training based sols of the hydrophilic carrier after activation, 3%-10% is (1-5): (2-10).
Preferably, the described aglucon catching phosphate anion is selected from one or more in polyglutamic acid, poly-aspartate, polylysine, poly allylamine.
Further preferably, the described aglucon catching phosphate anion is poly allylamine.
Wherein, polyglutamic acid also can use the polyglutamic acid of acidifying, such as hydrochloric acid polyglutamic acid, hydrogen bromide polyglutamic acid etc.Poly-aspartate also can use the poly-aspartate of acidifying, such as hydrochloric acid poly-aspartate, hydrogen bromide poly-aspartate etc.Polylysine also can use the polylysine of acidifying, such as hydrochloric acid polylysine, hydrogen bromide polylysine etc.Poly allylamine also can use the poly allylamine of acidifying, such as hydrochloric acid poly allylamine, hydrogen bromide poly allylamine etc.
Preferably, also step 4 is comprised: product hcl acidifying step 3 obtained.Preferably, step 4 is specially: get the obtained serium inorganic phosphorus adsorbent of step 3 and join in the hydrochloric acid solution of 0.05-0.2mol/L and soak 2-5h, with water for injection by hydrochloric acid cleaning totally, wherein, the mass ratio of the hydrochloric acid solution of serium inorganic phosphorus adsorbent and 0.05-0.2mol/L is (1-5): (2-10).
3rd aspect of the present invention is to provide a kind of adsorption column for blood perfusion, is filled with the serium inorganic phosphorus adsorbent described in the present invention first aspect in the cylinder of described adsorption column.
The present invention acts on human body compared to after drug oral, directly can be removed the phosphate anion in blood by blood circulation, alleviates patient's state of an illness at once; Can with haemodialysis conbined usage, reduce the patient misery that every day, drug administration brought, and can not produce because patient forgets the impact of taking medicine and producing.
Accompanying drawing explanation
Fig. 1 is the action principle figure of serium inorganic phosphorus adsorbent provided by the invention;
Fig. 2 is the structural representation of the adsorption column for blood perfusion provided by the invention, wherein, and 1 cylinder, 2 serium inorganic phosphorus adsorbents.
Detailed description of the invention
Serium inorganic phosphorus adsorbent provided by the invention be adopt hydrophilic carrier immobilized can catch phosphate anion aglucon and the serium inorganic phosphorus adsorbent that obtains.One or more preferably in cellulose, agarose, polyvinyl alcohol microparticles of described hydrophilic carrier, the described aglucon catching phosphate anion preferably refers to containing amino polymer.
The mechanism of action of serium inorganic phosphorus adsorbent of the present invention comprises aperture absorption and chemisorbed, and wherein chemisorbed plays a major role.The present invention's hydrophilic carrier used is porous carrier, and the diameter of the aperture of carrier and phosphate radical molecule is suitable, when absorbent interior aperture limb is interlocked, stop by aperture limb after phosphate radical molecule enters adsorbent, cannot adsorbent be passed through, thus be physically adsorbed at absorbent interior.
The aglucon that serium inorganic phosphorus adsorbent of the present invention adopts is amino polymer, and as shown in Figure 1, the amino cation on aglucon and the oxygen generation ion-exchange on phosphate radical, produce ionic bond and combine.NH in amido link and the CH2 in side chain and the oxygen on phosphate radical produce hydrogen bond action.Above two kinds of power combine, and phosphate radical is adsorbed on adsorbent surface firmly, thus reach the object removing serium inorganic phosphorus.And containing multiple amino and-NH-key in amino polymer strand, relative to single amino-compound, increase the binding site with phosphate radical in blood, amino and-NH-key easily and phosphate radical mainly with ionic bond and Hydrogenbond, phosphate radical in blood can be removed efficiently, thus reduce patient's serum phosphorus levels.And other ion, if calcium, magnesium, iron etc. are positive charge, the cation generation ionic bond on aglucon can not be combined, thus realize adsorbing the relative specificity of phosphate radical.
Below in conjunction with specific embodiment, the invention will be further described, to understand the present invention better.
Embodiment 1
1. the synthesis of hydroxyethyl acetamide
Add in the there-necked flask that constant pressure funnel, agitator are housed in 40g toluene and add 1g monoethanolamine, 3g10wt% sodium carbonate liquor, at 20-30 DEG C, drip 2g chloracetyl chloride, insulated and stirred reaction 3h at 30 DEG C.Wherein toluene is solvent, and monoethanolamine, sodium carbonate liquor are reaction promoter.Sodium carbonate liquor in the present embodiment is the solution such as replaceable one-tenth sodium acid carbonate, saleratus, potash also.After having reacted, stir cooling, filtration, drying, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
5g Anhydrous potassium carbonate is added in 100mL there-necked flask, then the N of 50g is added, dinethylformamide and 10g acetone mixed solution, add 1g agarose microbeads and 0.05g TBAB again, the hydroxyethyl acetamide of synthesis in 2g step 1, reacts 12h under room temperature, after having reacted, acetone is steamed, use water, saturated common salt water washing respectively, wash DMF with ethanol:
S is hydrophilic carrier, represents agarose microbeads in the present embodiment.
Wherein, DMF and acetone mixed solution are as solvent, and TBAB is as catalyst.
3. Epichlorohydrin activation
Get reacted carrier 1g in above-mentioned 2, add 1g epoxychloropropane, then add the sodium hydroxide solution of 1g 2mol/L, stirred at ambient temperature reaction 2h, by purified water, carrier is washed till neutrality, then with ethanol by the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.Described epoxychloropropane is as the spacerarm of connection carrier and aglucon, and sodium hydroxide solution is as reaction promoter.
4. aglucon is immobilized
Get the above-mentioned 3 carrier 1g prepared, add the polyglutamic acid solution of 2g 3%, at 30 DEG C, react 6h, after having reacted, adsorbent purified water is washed till neutrality.
5. adsorbent is acidified
Get the adsorbent 1g of preparation in above 4, add in the hydrochloric acid solution of the 0.05mol/L of 2g and soak 2h, with water for injection, hydrochloric acid cleaning is clean, the adsorbent that must have prepared.Acting as of hydrochloric acid makes amino cation in aglucon become salinization, enables the existence that aglucon is more stable, is unlikely to oxidized.
6. adsorbent dress post
By the absorbent filling of preparation in above 5 in cylinder, the adsorption column that must have prepared, as shown in Figure 2.
Embodiment 2
1. the synthesis of hydroxyethyl acetamide
Add in the there-necked flask that constant pressure funnel, agitator are housed in 100g toluene and add 8g monoethanolamine, 7g10wt% sodium carbonate liquor, at 20-30 DEG C, drip 18g chloracetyl chloride, insulated and stirred reaction 6h at 30 DEG C.After having reacted, stir cooling, filtration, drying, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
25g Anhydrous potassium carbonate is added in 250mL there-necked flask, then the N of 90g is added, dinethylformamide and 50g acetone mixed solution, add 5g cellulose microsphere and 0.15g TBAB again, the hydroxyethyl acetamide of synthesis in 5g step 1, reacts 24h under room temperature, after having reacted, acetone is steamed, use water, saturated common salt water washing respectively, wash DMF with ethanol:
S is hydrophilic carrier, represents cellulose microsphere in the present embodiment.
3. Epichlorohydrin activation
Get reacted carrier 5g in above-mentioned 2, add 10g epoxychloropropane, then add the sodium hydroxide solution of 20g 2mol/L, stirred at ambient temperature reaction 4h, by purified water, carrier is washed till neutrality, then with ethanol by the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.
4. aglucon is immobilized
Get the above-mentioned 3 carrier 1g prepared, add the hydrochloric acid poly allylamine solution of 2g 3%, at 50 DEG C, react 6h, after having reacted, adsorbent purified water is washed till neutrality.
5. adsorbent is acidified
Get the adsorbent 1g of preparation in above 4, add in the hydrochloric acid solution of the 0.05mol/L of 2g and soak 2h, with water for injection, hydrochloric acid cleaning is clean, the adsorbent that must have prepared.
6. adsorbent dress post
By the absorbent filling of preparation in above 5 in cylinder, the adsorption column that must have prepared, as shown in Figure 2.
Embodiment 3
1. the synthesis of hydroxyethyl acetamide
Add in the there-necked flask that constant pressure funnel, agitator are housed in 60g toluene and add 3g monoethanolamine, 3g10wt% sodium carbonate liquor, at 20-30 DEG C, drip 8g chloracetyl chloride, insulated and stirred reaction 4h at 30 DEG C.After having reacted, stir cooling, filtration, drying, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
10g Anhydrous potassium carbonate is added in 250mL there-necked flask, then the N of 60g is added, dinethylformamide and 30g acetone mixed solution, add 3g polyvinyl alcohol microparticles and 0.1g TBAB again, the hydroxyethyl acetamide of synthesis in 3g step 1, reacts 16h under room temperature, after having reacted, acetone is steamed, use water, saturated common salt water washing respectively, wash DMF with ethanol:
S is hydrophilic carrier, represents polyvinyl alcohol microparticles in the present embodiment.
3. Epichlorohydrin activation
Get reacted carrier 3g in above-mentioned 2, add 3g epoxychloropropane, then add the sodium hydroxide solution of 6g 2mol/L, stirred at ambient temperature reaction 3h, by purified water, carrier is washed till neutrality, then with ethanol by the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.
4. aglucon is immobilized
Get the above-mentioned 3 carrier 3g prepared, add the poly-aspartate solution of 6g 3%, at 40 DEG C, react 10h, after having reacted, adsorbent purified water is washed till neutrality.
5. adsorbent is acidified
Get the adsorbent 3g of preparation in above 4, add in the hydrochloric acid solution of the 0.1mol/L of 6g and soak 3h, with water for injection, hydrochloric acid cleaning is clean, the adsorbent that must have prepared.
6. adsorbent dress post
By the absorbent filling of preparation in above 5 in cylinder, the adsorption column that must have prepared, as shown in Figure 2.
Embodiment 4
1. the synthesis of hydroxyethyl acetamide
Add in the there-necked flask that constant pressure funnel, agitator are housed in 80g toluene and add 6g monoethanolamine, 5g10wt% sodium carbonate liquor, at 25 DEG C, drip 12g chloracetyl chloride, insulated and stirred reaction 5h at 30 DEG C.After having reacted, stir cooling, filtration, drying, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
20g Anhydrous potassium carbonate is added in 250mL there-necked flask, then the N of 80g is added, dinethylformamide and 40g acetone mixed solution, add 4g cellulose microsphere and 0.12g TBAB again, the hydroxyethyl acetamide of synthesis in 4g step 1, reacts 20h under room temperature, after having reacted, acetone is steamed, use water, saturated common salt water washing respectively, wash DMF with ethanol:
S is hydrophilic carrier, represents cellulose microsphere in the present embodiment.
3. Epichlorohydrin activation
Get reacted carrier 4g in above-mentioned 2, add 8g epoxychloropropane, then add the sodium hydroxide solution of 16g 1.5mol/L, stirred at ambient temperature reaction 4h, by purified water, carrier is washed till neutrality, then with ethanol by the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.
4. aglucon is immobilized
Get the above-mentioned 3 carrier 4g prepared, add the Poly-L-Lysine Solution of 8g 8%, at 35 DEG C, react 16h, after having reacted, adsorbent purified water is washed till neutrality.
5. adsorbent is acidified
Get the adsorbent 4g of preparation in above 4, add in the hydrochloric acid solution of the 0.2mol/L of 8g and soak 4h, with water for injection, hydrochloric acid cleaning is clean, the adsorbent that must have prepared.
6. adsorbent dress post
By the absorbent filling of preparation in above 5 in cylinder, the adsorption column that must have prepared, as shown in Figure 2.
Absorption property detects
The adsorbent 3mL that respectively prepared by Example 1-4 adds 30mL blood plasma, and 37 DEG C of constant temperature oscillation 2h, get upper plasma, detects albumen and ion concentration in blood plasma.
The adsorption levels of the adsorbent prepared in embodiment 1-4 to albumen and ion is as shown in the table
| Numbering | Representative species | Embodiment 1 | Embodiment 2 | Embodiment 3 | Embodiment 4 |
| 1 | Total protein | 8.2％ | 6.3％ | 7.8％ | 9.2％ |
| 5 | Blood iron | 3.2％ | 2.8％ | 4.2％ | 3.6％ |
| 6 | Blood potassium | 8.7％ | 6.5％ | 7.9％ | 6.6％ |
| 7 | The total calcium of blood | 8.1％ | 6.7％ | 9.2％ | 6.8％ |
| 8 | Serium inorganic phosphorus | 15％ | 58％ | 33％ | 18％ |
| 9 | Blood magnesium | 7.9％ | 7.1％ | 6.3％ | 7.8％ |
As can be seen from the above table, serium inorganic phosphorus adsorbent provided by the invention can reach more than 15% to the absorption of serium inorganic phosphorus, less to the absorption of other benefit materials, the absorption of serium inorganic phosphorus adsorbent to serium inorganic phosphorus of especially immobilized hydrochloric acid poly allylamine is the highest, can more than 50% be reached, and less to the absorption of other benefit materials.
Be described in detail specific embodiments of the invention above, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and substituting also all among category of the present invention.Therefore, equalization conversion done without departing from the spirit and scope of the invention and amendment, all should contain within the scope of the invention.
Claims (10)
1. a serium inorganic phosphorus adsorbent, it is characterized in that, be adopt hydrophilic carrier immobilized can catch phosphate anion aglucon and the serium inorganic phosphorus adsorbent that obtains, described hydrophilic carrier be selected from cellulose, agarose, polyvinyl alcohol microparticles one or more, the described aglucon catching phosphate anion refers to containing amino polymer.
2. serium inorganic phosphorus adsorbent according to claim 1, is characterized in that, the described aglucon catching phosphate anion be selected from polyglutamic acid, poly-aspartate, polylysine, poly allylamine one or more.
3. serium inorganic phosphorus adsorbent according to claim 2, is characterized in that, the described aglucon catching phosphate anion is poly allylamine.
4. a preparation method for the serium inorganic phosphorus adsorbent in claim 1-3 described in any one, is characterized in that, comprise the following steps:
Step 1, hydrophilic carrier and hydroxyethyl acetamide carry out graft reaction under catalyst and alkali existent condition;
Step 2, by the hydrophilic carrier Epichlorohydrin activation after grafting process;
Step 3, by immobilized for the hydrophilic carrier after the activation process aglucon catching phosphate anion, both.
5. preparation method according to claim 4, is characterized in that, hydroxyethyl acetamide is prepared from according to following reaction equation under inorganic base existent condition by monoethanolamine and chloracetyl chloride:
6. preparation method according to claim 4, is characterized in that, in step 1, described catalyst is TBAB, and described alkali is one or more in sodium carbonate, sodium acid carbonate, saleratus, potash.
7. preparation method according to claim 4, it is characterized in that, step 1 is specially: join N by Anhydrous potassium carbonate, dinethylformamide and acetone mixed solution, add hydrophilic carrier and catalyst TBAB again, then hydroxyethyl acetamide is added, 12-24h is reacted under room temperature, obtain the hydrophilic carrier after grafting process, wherein, Anhydrous potassium carbonate, N, dinethylformamide, acetone, hydrophilic carrier, the mass ratio of TBAB and hydroxyethyl acetamide is (5-25): (5-90): (10-50): (1-5): (0.05-0.15): (1-5),
Step 2 is specially: get the hydrophilic carrier after grafting process and epoxychloropropane, join in the sodium hydroxide solution of 1-2mol/L, stirring at room temperature reaction 2-4h, obtain the hydrophilic carrier after activating, the mass ratio of the hydrophilic carrier wherein after grafting process, the sodium hydroxide solution of epoxychloropropane 1-2mol/L is (1-5): (1-10): (1-20);
Step 3 is specially: get the hydrophilic carrier after activation, join in the ligand solution of 3%-10%, at 30-50 DEG C, react 6-20h, both, wherein, the weight ratio of the hydrophilic carrier after activation, the ligand solution of 3%-10% is (1-5): (2-10).
8. preparation method according to claim 4, is characterized in that, also comprises step 4: product hcl acidifying step 3 obtained.
9. preparation method according to claim 7, is characterized in that, the ligand solution described in step 3 is poly allylamine solution.
10. for an adsorption column for blood perfusion, it is characterized in that, in the cylinder of described adsorption column, be filled with the serium inorganic phosphorus adsorbent in claim 1-3 described in any one.
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| CN201410494396.XA CN104258829B (en) | 2014-09-24 | 2014-09-24 | Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion |
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| CN106140109A (en) * | 2015-03-31 | 2016-11-23 | 国药集团化学试剂有限公司 | A kind of phosphate ion adsorbent and application thereof |
| CN109125273A (en) * | 2018-09-28 | 2019-01-04 | 北京市中关村医院 | A kind of phosphate binder and its preparation method and application |
| CN110975844A (en) * | 2019-12-17 | 2020-04-10 | 重庆科技学院 | Preparation method of polyaspartic acid grafted viscose adsorbent |
| CN115138337A (en) * | 2022-07-13 | 2022-10-04 | 河北大学 | Aminated bio-based phosphorus adsorption material and preparation method and application thereof |
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| CN115138337A (en) * | 2022-07-13 | 2022-10-04 | 河北大学 | Aminated bio-based phosphorus adsorption material and preparation method and application thereof |
| CN115138337B (en) * | 2022-07-13 | 2023-09-12 | 河北大学 | Amination bio-based phosphorus adsorption material and preparation method and application thereof |
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| CN104258829B (en) | 2016-08-31 |
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