CN104258829B - Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion - Google Patents
Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion Download PDFInfo
- Publication number
- CN104258829B CN104258829B CN201410494396.XA CN201410494396A CN104258829B CN 104258829 B CN104258829 B CN 104258829B CN 201410494396 A CN201410494396 A CN 201410494396A CN 104258829 B CN104258829 B CN 104258829B
- Authority
- CN
- China
- Prior art keywords
- hydrophilic carrier
- inorganic phosphorus
- preparation
- serium inorganic
- phosphorus adsorbent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- YMURLKIIDQPXRE-UHFFFAOYSA-N OCCNC(CCl)=O Chemical compound OCCNC(CCl)=O YMURLKIIDQPXRE-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Anesthesiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Analytical Chemistry (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- External Artificial Organs (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
The invention provides a kind of serium inorganic phosphorus adsorbent, it is to use the immobilized aglucon that can capture phosphate anion of hydrophilic carrier and the serium inorganic phosphorus adsorbent that obtains, one or more in cellulose microsphere, agarose microbeads, polyvinyl alcohol microparticles of described hydrophilic carrier, the described aglucon that can capture phosphate anion refers to the polymer containing amino.Present invention also offers the preparation method of above-mentioned serium inorganic phosphorus adsorbent, and a kind of adsorption column for blood perfusion using this serium inorganic phosphorus adsorbent to prepare.The present invention, compared to acting on human body after drug oral, can directly remove the phosphate anion in blood by blood circulation, alleviate patient's state of an illness at once；Can be used in combination with haemodialysis, reduce patient's misery that every day, drug administration brought, and will not produce because patient forgets the impact produced of taking medicine.
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 use
Adsorption column in blood perfusion.
Background technology
Phosphorus, as one of human body base substance, take part in the composition of the many vital tissues of life entity, human body energy generation
Thank, the regulation and control of large biological molecule activity and acid-base balance regulation etc..In normal human, the phosphorus of 85% is present in
Bone, tooth, 14.9% is present in intracellular, and the most few fraction is present in blood plasma.Plasma P concentration with
Diet, age, sex are relevant, and normal plasma phosphorus fluctuates in 2.5～4.5mg/dl (0.81～1.45mmol/L)
Between.The phosphorus intake of normal person every day is about 1g, and 60%～70% by intestinal absorption.Dissociate in blood plasma
Phosphorus can be leached by glomerulus, and the phosphorus 80%～90% leached heavily is absorbed at renal tubule, only 10%～20% by
Urine ejection is external.Work as renal hypofunction, kidney can not normal excretion phosphorus, arise that hyperphosphatemia.
Hyperphosphatemia is the common complication of CKD (CKD), is to cause Secondary cases parathyroid function
Hyperfunction, calcium phosphorus precipitation change, vitamin D metabolism obstacle, the key factor of renal osteodystrophy, with coronary artery,
The serious cardiovascular complication such as valvular calcification are closely related.Normal person presses down due to parathyroid hormone, calcitonin
Renal tubule re-absorption phosphorus processed, and both play antagonism, therefore in intestines, bone, the kidney regulation to alcium and phosphor metabolization
Serium inorganic phosphorus maintains normal level and is difficult to rise.But renal failure arrange phosphorus difficulty, hypoparathyroidism,
After cell damage, phosphorus is transferred to blood, vitamin D excess and hyperphosphatemia can occur when taking in too much.
1, renal failure row phosphorus difficulty: the glomerular filtration rate seeing many reasons reduces to below 30ml/min
Time, serium inorganic phosphorus retention and rise, often companion's azotemia or uremia and acid poisoning.
2, hypoparathyroidism: urine phosphorus resorption is received and increased, serium inorganic phosphorus often increases and blood calcium reduces.
3, after cell damage, phosphorus is transferred to blood: see cell damage such as high heat, poisoning etc. that many reasons causes
The metabolic acidosis caused, normal companion cell catabolism is hyperfunction and is disintegrated, Several Kinds of Malignancy especially lymph
Knurl, during leukemia chemotherapy, due to cell disruption, phosphorus escapes into blood circulation.
4, vitamin D excess: increase owing to intestines and renal tubule absorb calcium phosphorus, bone is mobilized calcium phosphorus to enter blood and can be caused
Serium inorganic phosphorus and blood calcium raise.
5, take in too much with intestinal absorption: see baby hello with cow's milk time, due in cow's milk phosphorus calcium content far beyond
Human milk is high (cow's milk phosphorous 940mg/L calcium 1220mg/L；The most phosphorous 150mg/L of human milk and calcium
340mg/L), thus baby's serium inorganic phosphorus is up to 2.3mmol/L.Also because inhaling when the oral potassium phosphate of adult or vitamin D
Receive and too much cause a disease.
Hyperphosphatemia currently mainly methods for the treatment of has: 1. aluminium porcelain enamelling: gel aluminum hydroxide can be tied with phosphorus in enteron aisle
Closing, but can cause constipation, long-term prescription can cause aluminium and accumulate poisoning；2. calcium preparation: calcium carbonate: this medicine is inexpensive, contains
Calcium component is up to 40%, easy-tolerated, determined curative effect, but easily causes hypercalcinemia and blood vessel, periarticular calcification；
Calcium acetate: be the improvement formulation of calcium carbonate, by often absorbing calcium amount and combining the effect calculating of phosphorus, calcium acetate is more than
1 times of calcium carbonate.But hypercalcinemia also can occur.3. magnesium preparation: magnesium acetate is oral can be controlled for a long time by serium inorganic phosphorus concentration
System, in normal range (NR), also will not occur hypermagnesemia, but heavy dose of magnesium salts can cause diarrhoea.It is dialysis process again,
Dialysis process eliminates unsatisfactory also need of phosphorus and phosphate binder is administered orally." medical charcoal exists patent CN101904868A
Application in treatment hyperphosphatemia medicine " the middle phosphorus used in medical charcoal removing blood.Patent
CN102342995A " Pharmaceutical composition of a kind of hyperphosphatemia and preparation thereof " utilizes composition of medicine treatment height
Phosphoremia.But these methods are all the phosphorus utilizing medicine indirectly to combine in blood, it is impossible to reach directly to remove blood
The purpose of middle phosphorus.
Summary of the invention
It is an object of the invention to overcome the deficiencies in the prior art, it is provided that a kind of serium inorganic phosphorus adsorbent, this serium inorganic phosphorus is inhaled
Attached dose is filled in cylinder, is prepared as the adsorption column for blood perfusion, by blood circulation, directly removes blood
Phosphate radical in liquid and reach the purpose of serum phosphate lowering.
The first aspect of the invention is to provide a kind of serium inorganic phosphorus adsorbent, and described serium inorganic phosphorus adsorbent is to use hydrophily
The immobilized aglucon that can capture phosphate anion of carrier and the serium inorganic phosphorus adsorbent that obtains.Wherein, described hydrophilic carrier
It preferably is selected from one or more in cellulose microsphere, agarose microbeads, polyvinyl alcohol microparticles, described can capture phosphorus
The aglucon of acid ion preferably refers to the polymer containing amino.
Preferably, the described aglucon of phosphate anion that can capture is selected from polyglutamic acid, poly-aspartate, poly-bad ammonia
One or more in acid, polypropylene amine.
It is further preferred that the described aglucon that can capture phosphate anion is polypropylene amine.
Wherein, polyglutamic acid can also be with the polyglutamic acid of acidifying, such as hydrochloric acid polyglutamic acid, the poly-paddy of hydrogen bromide
Propylhomoserin etc..Poly-aspartate can also be with the poly-aspartate of acidifying, such as hydrochloric acid poly-aspartate, hydrogen bromide
Poly-aspartate etc..Polylysine can also be with the polylysine of acidifying, such as hydrochloric acid polylysine, hydrogen bromide
Polylysine etc..Polypropylene amine can also be with the polypropylene amine of acidifying, and such as hydrochloric acid polypropylene amine, hydrogen bromide are poly-
Allylamine etc..
The second aspect of the invention is to provide the preparation side of the serium inorganic phosphorus adsorbent described in first aspect of the present invention
Method, comprises the following steps:
Step 1, hydrophilic carrier and hydroxyethyl acetamide carry out graft reaction under the conditions of catalyst and alkalescence；
Step 2, the hydrophilic carrier Epichlorohydrin activation after grafting is processed；
Step 3, by immobilized for the hydrophilic carrier after the activation process aglucon that can capture phosphate anion, both.
Preferably, described hydroxyethyl acetamide by monoethanolamine and chloracetyl chloride under conditions of alkaline, inorganic salts exists
It is prepared from according to following reaction equation:
Wherein, alkaline, inorganic salts can be the one in sodium carbonate, sodium acid carbonate, saleratus or potassium carbonate etc.
Or it is multiple.
Specifically, in toluene, add monoethanolamine and 10wt% sodium carbonate liquor, at 20-30 DEG C, drip chloroethene
Acyl chlorides 1h, at 20-30 DEG C, insulated and stirred reaction 3-6h, obtains hydroxyethyl acetamide, wherein toluene, second
The mass ratio of hydramine, 10wt% sodium carbonate liquor and chloracetyl chloride is (40-100): (1-8): (3-7):
(2-18), wherein, sodium carbonate replaceable one-tenth sodium acid carbonate, saleratus, potassium carbonate etc..
Preferably, in step 1, described catalyst is TBAB.
Preferably, the one during described alkaline, inorganic salts is sodium carbonate, sodium acid carbonate, saleratus, potassium carbonate
Or it is multiple.
Preferably, step 1 particularly as follows:
S is hydrophilic carrier；
By Anhydrous potassium carbonate joins DMF and acetone mixed solution, add hydrophily
Carrier and catalyst TBAB, be subsequently adding hydroxyethyl acetamide, reacts 12-24h under room temperature,
Hydrophilic carrier after processing to grafting, wherein, Anhydrous potassium carbonate, DMF, acetone, parent
The mass ratio of aqueous carrier, TBAB and hydroxyethyl acetamide is (5-25): (5-90): (10-50):
(1-5):(0.05-0.15):(1-5)。
Preferably, step 2, particularly as follows: take the hydrophilic carrier after grafting processes and epoxychloropropane, joins
In the sodium hydroxide solution of 1-2mol/L, it is stirred at room temperature and reacts 2-4h, the hydrophilic carrier after being activated,
Hydrophilic carrier after wherein grafting processes, the mass ratio of the sodium hydroxide solution of epoxychloropropane 1-2mol/L
For (1-5): (1-10): (1-20)
Preferably, step 3 is particularly as follows: hydrophilic carrier after taking activation, and the training base joining 3%-10% is molten
In liquid, at 30-50 DEG C, react 6-20h, both obtained, wherein, the hydrophilic carrier after activation, 3%-10%
Training based sols weight ratio be (1-5): (2-10).
Preferably, the described aglucon of phosphate anion that can capture is selected from polyglutamic acid, poly-aspartate, poly-bad ammonia
One or more in acid, polypropylene amine.
It is further preferred that the described aglucon that can capture phosphate anion is polypropylene amine.
Wherein, polyglutamic acid can also be with the polyglutamic acid of acidifying, such as hydrochloric acid polyglutamic acid, the poly-paddy of hydrogen bromide
Propylhomoserin etc..Poly-aspartate can also be with the poly-aspartate of acidifying, such as hydrochloric acid poly-aspartate, hydrogen bromide
Poly-aspartate etc..Polylysine can also be with the polylysine of acidifying, such as hydrochloric acid polylysine, hydrogen bromide
Polylysine etc..Polypropylene amine can also be with the polypropylene amine of acidifying, and such as hydrochloric acid polypropylene amine, hydrogen bromide are poly-
Allylamine etc..
Preferably, step 4 is also included: product hydrochloric acid step 3 obtained is acidified.Preferably, step 4
Join in the hydrochloric acid solution of 0.05-0.2mol/L soak particularly as follows: take the serium inorganic phosphorus adsorbent that step 3 prepares
2-5h, cleans up hydrochloric acid with water for injection, and wherein, serium inorganic phosphorus adsorbent is with 0.05-0.2mol/L's
The mass ratio of hydrochloric acid solution is (1-5): (2-10).
The third aspect of the invention is to provide a kind of adsorption column for blood perfusion, the cylinder of described adsorption column
Inside it is filled with the serium inorganic phosphorus adsorbent described in first aspect of the present invention.
The present invention, compared to acting on human body after drug oral, can directly remove the phosphorus in blood by blood circulation
Acid ion, alleviates patient's state of an illness at once；Can be used in combination with haemodialysis, reduce patient's drug administration every day
The misery brought, and will not produce because patient forgets the impact produced of taking medicine.
Accompanying drawing explanation
The action principle figure of the serium inorganic phosphorus adsorbent that Fig. 1 provides for the present invention；
The structural representation of the adsorption column for blood perfusion that Fig. 2 provides for the present invention, wherein, 1 cylinder,
2 serium inorganic phosphorus adsorbents.
Detailed description of the invention
The serium inorganic phosphorus adsorbent that the present invention provides is to use the immobilized aglucon that can capture phosphate anion of hydrophilic carrier
And the serium inorganic phosphorus adsorbent obtained.Described hydrophilic carrier preferably is selected from cellulose microsphere, agarose microbeads, polyethylene
One or more in alcohol microballoon, the described aglucon that can capture phosphate anion preferably refers to the polymerization containing amino
Thing.
The mechanism of action of serium inorganic phosphorus adsorbent of the present invention includes aperture absorption and chemisorbed, and wherein chemisorbed plays master
Act on.Hydrophilic carrier used by the present invention is porous carrier, and the aperture of carrier and phosphate radical molecule
Diameter is suitable, when absorbent interior aperture limb is interlocked, and phosphate radical molecule is hindered by aperture limb after entering adsorbent
Gear, it is impossible to by adsorbent, thus be physically adsorbed at absorbent interior.
The aglucon that serium inorganic phosphorus adsorbent of the present invention uses is amino polymer, as it is shown in figure 1, the amino on aglucon
Cation and the oxygen generation ion exchange on phosphate radical, produce ionic bond and combine.NH in amido link and side chain
In CH2 and phosphate radical on oxygen produce hydrogen bond action.Both the above power combines, by phosphate radical firmly
Adsorb at adsorbent surface, thus reach to remove the purpose of serium inorganic phosphorus.And containing multiple in amino polymer strand
Amino and-NH-key, relative to single amino-compound, increase the binding site with phosphate radical in blood,
Amino and-NH-key are easily and phosphate radical is many with ionic bond with Hydrogenbond, can remove phosphate radical in blood efficiently,
Thus reduce patient's serum phosphorus levels.And other ion, if calcium, magnesium, iron etc. are positive charge, will not with on aglucon
Cation generation ionic bond combine, thus realize the relative specificity of phosphate radical is adsorbed.
Below in conjunction with specific embodiment, the invention will be further described, to be more fully understood that the present invention.
Embodiment 1
1. the synthesis of hydroxyethyl acetamide
Equipped with constant pressure funnel, agitator there-necked flask in add 40g toluene add 1g monoethanolamine, 3g
10wt% sodium carbonate liquor, at 20-30 DEG C drip 2g chloracetyl chloride, at 30 DEG C insulated and stirred reaction 3h.
Wherein toluene is solvent, and monoethanolamine, sodium carbonate liquor are reaction promoter.Sodium carbonate liquor in the present embodiment
The solution such as the most replaceable one-tenth sodium acid carbonate, saleratus, potassium carbonate.After having reacted, stirring cooling, filter,
It is dried, obtains product hydroxyethyl acetamide:
2. carrier graft reaction
In 100mL there-necked flask, add 5g Anhydrous potassium carbonate, be subsequently adding the N of 50g, N-dimethyl formyl
Amine and 10g acetone mixed solution, add 1g agarose microbeads and 0.05g TBAB, and 2g walks
The hydroxyethyl acetamide of synthesis in rapid 1, reacts 12h, is steamed by acetone, use respectively after having reacted under room temperature
Water, saturated aqueous common salt wash, and 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 urging
Agent.
3. Epichlorohydrin activation
Take reacted carrier 1g in above-mentioned 2, add 1g epoxychloropropane, be subsequently adding 1g 2mol/L's
Sodium hydroxide solution, under room temperature, stirring reaction 2h, is washed till neutrality by purified water by carrier, then will with ethanol
Epoxychloropropane washes clean in adsorbent, washes away ethanol by purified water.Described epoxychloropropane is as connection
Carrier and the spacerarm of aglucon, sodium hydroxide solution is as reaction promoter.
4. aglucon is immobilized
Take the above-mentioned 3 carrier 1g prepared, add the polyglutamic acid solution of 2g 3%, react at 30 DEG C
6h, is washed till neutrality by adsorbent purified water after having reacted.
5. adsorbent is acidified
Take the adsorbent 1g of preparation in above 4, the hydrochloric acid solution of the 0.05mol/L adding 2g soak 2h,
With water for injection, hydrochloric acid is cleaned up, the adsorbent that must have prepared.The acting as of hydrochloric acid makes ammonia in aglucon
Base cation becomes salinization, enables the existence that aglucon is more stable, is unlikely to oxidized.
6. adsorbent dress post
By in above 5, the absorbent filling of preparation is in cylinder, the adsorption column that must have prepared, such as Fig. 2
Shown in.
Embodiment 2
1. the synthesis of hydroxyethyl acetamide
Equipped with constant pressure funnel, agitator there-necked flask in add 100g toluene add 8g monoethanolamine,
7g10wt% sodium carbonate liquor, at 20-30 DEG C drip 18g chloracetyl chloride, at 30 DEG C, insulated and stirred is anti-
Answer 6h.After having reacted, stirring cool down, filters, dry, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
In 250mL there-necked flask, add 25g Anhydrous potassium carbonate, be subsequently adding the N of 90g, N-dimethyl methyl
Acid amides and 50g acetone mixed solution, add 5g cellulose microsphere and 0.15g TBAB, 5g
The hydroxyethyl acetamide of synthesis in step 1, reacts 24h, is steamed by acetone after having reacted, respectively under room temperature
With water, saturated aqueous common salt washing, wash DMF with ethanol:
S is hydrophilic carrier, represents cellulose microsphere in the present embodiment.
3. Epichlorohydrin activation
Take reacted carrier 5g in above-mentioned 2, add 10g epoxychloropropane, be subsequently adding 20g 2mol/L
Sodium hydroxide solution, under room temperature stirring reaction 4h, by purified water, carrier is washed till neutrality, then uses ethanol
By the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.
4. aglucon is immobilized
Take the above-mentioned 3 carrier 1g prepared, add the hydrochloric acid polypropylene amine solution of 2g 3%, anti-at 50 DEG C
Answer 6h, after having reacted, adsorbent purified water is washed till neutrality.
5. adsorbent is acidified
Take the adsorbent 1g of preparation in above 4, the hydrochloric acid solution of the 0.05mol/L adding 2g soak 2h,
With water for injection, hydrochloric acid is cleaned up, the adsorbent that must have prepared.
6. adsorbent dress post
By in above 5, the absorbent filling of preparation is in cylinder, the adsorption column that must have prepared, such as Fig. 2
Shown in.
Embodiment 3
1. the synthesis of hydroxyethyl acetamide
Equipped with constant pressure funnel, agitator there-necked flask in add 60g toluene add 3g monoethanolamine,
3g10wt% sodium carbonate liquor, dropping 8g chloracetyl chloride, insulated and stirred reaction at 30 DEG C at 20-30 DEG C
4h.After having reacted, stirring cool down, filters, dry, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
In 250mL there-necked flask, add 10g Anhydrous potassium carbonate, be subsequently adding the N of 60g, N-dimethyl methyl
Acid amides and 30g acetone mixed solution, add 3g polyvinyl alcohol microparticles and 0.1g TBAB, 3g
The hydroxyethyl acetamide of synthesis in step 1, reacts 16h, is steamed by acetone after having reacted, respectively under room temperature
With water, saturated aqueous common salt washing, wash DMF with ethanol:
S is hydrophilic carrier, represents polyvinyl alcohol microparticles in the present embodiment.
3. Epichlorohydrin activation
Take reacted carrier 3g in above-mentioned 2, add 3g epoxychloropropane, be subsequently adding 6g 2mol/L's
Sodium hydroxide solution, under room temperature, stirring reaction 3h, is washed till neutrality by purified water by carrier, then will with ethanol
Epoxychloropropane washes clean in adsorbent, washes away ethanol by purified water.
4. aglucon is immobilized
Take the above-mentioned 3 carrier 3g prepared, add the poly-aspartate solution of 6g 3%, react at 40 DEG C
10h, is washed till neutrality by adsorbent purified water after having reacted.
5. adsorbent is acidified
Take the adsorbent 3g of preparation in above 4, the hydrochloric acid solution of the 0.1mol/L adding 6g soak 3h,
With water for injection, hydrochloric acid is cleaned up, the adsorbent that must have prepared.
6. adsorbent dress post
By in above 5, the absorbent filling of preparation is in cylinder, the adsorption column that must have prepared, such as Fig. 2
Shown in.
Embodiment 4
1. the synthesis of hydroxyethyl acetamide
Equipped with constant pressure funnel, agitator there-necked flask in add 80g toluene add 6g monoethanolamine,
5g10wt% sodium carbonate liquor, dropping 12g chloracetyl chloride, insulated and stirred reaction at 30 DEG C at 25 DEG C
5h.After having reacted, stirring cool down, filters, dry, obtain product hydroxyethyl acetamide:
2. carrier graft reaction
In 250mL there-necked flask, add 20g Anhydrous potassium carbonate, be subsequently adding the N of 80g, N-dimethyl methyl
Acid amides and 40g acetone mixed solution, add 4g cellulose microsphere and 0.12g TBAB, 4g
The hydroxyethyl acetamide of synthesis in step 1, reacts 20h, is steamed by acetone after having reacted, respectively under room temperature
With water, saturated aqueous common salt washing, wash DMF with ethanol:
S is hydrophilic carrier, represents cellulose microsphere in the present embodiment.
3. Epichlorohydrin activation
Take reacted carrier 4g in above-mentioned 2, add 8g epoxychloropropane, be subsequently adding 16g 1.5mol/L
Sodium hydroxide solution, under room temperature stirring reaction 4h, by purified water, carrier is washed till neutrality, then uses ethanol
By the epoxychloropropane washes clean in adsorbent, wash away ethanol by purified water.
4. aglucon is immobilized
Take the above-mentioned 3 carrier 4g prepared, add the Poly-L-Lysine Solution of 8g 8%, react at 35 DEG C
16h, is washed till neutrality by adsorbent purified water after having reacted.
5. adsorbent is acidified
Take the adsorbent 4g of preparation in above 4, the hydrochloric acid solution of the 0.2mol/L adding 8g soak 4h,
With water for injection, hydrochloric acid is cleaned up, the adsorbent that must have prepared.
6. adsorbent dress post
By in above 5, the absorbent filling of preparation is in cylinder, the adsorption column that must have prepared, such as Fig. 2
Shown in.
Absorption property detects
The adsorbent 3mL addition 30mL blood plasma that respectively prepared by Example 1-4,37 DEG C of constant temperature oscillation 2h,
Take upper plasma, albumen and ion concentration in detection blood plasma.
In embodiment 1-4, the adsorbent of preparation is as shown in the table to the adsorption levels of albumen and ion
| 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, the serium inorganic phosphorus adsorbent that the present invention provides to the absorption of serium inorganic phosphorus up to more than 15%,
Absorption to other benefit materials is less, the suction to serium inorganic phosphorus of the serium inorganic phosphorus adsorbent of the most immobilized hydrochloric acid polypropylene amine
Attached the highest, can reach more than 50%, and the absorption to other benefit materials is less.
Being described in detail the specific embodiment of the present invention above, but it is intended only as example, the present invention is also
It is not restricted to particular embodiments described above.To those skilled in the art, any the present invention is carried out
Equivalent modifications and substitute the most all among scope of the invention.Therefore, without departing from the spirit of the present invention and model
Enclose lower made impartial conversion and amendment, all should contain within the scope of the invention.
Claims (9)
1. a serium inorganic phosphorus adsorbent, it is characterised in that be use hydrophilic carrier immobilized can capture phosphate radical from
The aglucon of son and the serium inorganic phosphorus adsorbent that obtains, described hydrophilic carrier selected from cellulose microsphere, agarose microbeads,
One or more in polyvinyl alcohol microparticles, the described aglucon that can capture phosphate anion is selected from polyglutamic acid, gathers
One or more in aspartic acid, polylysine, polypropylene amine.
Serium inorganic phosphorus adsorbent the most according to claim 1, it is characterised in that described can capture phosphate radical from
The aglucon of son is polypropylene amine.
3. a preparation method for serium inorganic phosphorus adsorbent described in any one in claim 1-2, its feature exists
In, comprise the following steps:
Step 1, hydrophilic carrier and hydroxyethyl acetamide carry out graft reaction under the conditions of catalyst and alkalescence；
Step 2, the hydrophilic carrier Epichlorohydrin activation after grafting is processed；
Step 3, by immobilized for the hydrophilic carrier after the activation process aglucon that can capture phosphate anion, both.
Preparation method the most according to claim 3, it is characterised in that hydroxyethyl acetamide is by monoethanolamine
It is prepared from according to following reaction equation under conditions of alkaline, inorganic salts exists with chloracetyl chloride:
Preparation method the most according to claim 3, it is characterised in that in step 1, described catalyst
For TBAB, described alkaline, inorganic salts is in sodium carbonate, sodium acid carbonate, saleratus, potassium carbonate
One or more.
Preparation method the most according to claim 3, it is characterised in that step 1 is particularly as follows: by anhydrous
Potassium carbonate joins DMF and acetone mixed solution, adds hydrophilic carrier and catalysis
Agent TBAB, is subsequently adding hydroxyethyl acetamide, reacts 12-24h under room temperature, obtains grafting and processes
After hydrophilic carrier, wherein, Anhydrous potassium carbonate, DMF, 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, particularly as follows: take the hydrophilic carrier after grafting processes and epoxychloropropane, joins 1-2mol/L
Sodium hydroxide solution in, be stirred at room temperature reaction 2-4h, the hydrophilic carrier after being activated, be wherein grafted
Hydrophilic carrier, the mass ratio of the sodium hydroxide solution of epoxychloropropane 1-2mol/L after process are (1-5):
(1-10):(1-20)；
Step 3, particularly as follows: hydrophilic carrier after taking activation, joins in the ligand solution of 3%-10%,
Reacting 6-20h at 30-50 DEG C, both obtained, wherein, the hydrophilic carrier after activation, the aglucon of 3%-10% are molten
The weight ratio of liquid is (1-5): (2-10).
Preparation method the most according to claim 6, it is characterised in that also include step 4: by step
The product hydrochloric acid that 3 obtain is acidified.
Preparation method the most according to claim 6, it is characterised in that the ligand solution described in step 3
For polypropylene amine solution.
9. the adsorption column for blood perfusion, it is characterised in that be filled with in the cylinder of described adsorption column
Serium inorganic phosphorus adsorbent described in any one in claim 1-2.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410494396.XA CN104258829B (en) | 2014-09-24 | 2014-09-24 | Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410494396.XA CN104258829B (en) | 2014-09-24 | 2014-09-24 | Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104258829A CN104258829A (en) | 2015-01-07 |
| CN104258829B true CN104258829B (en) | 2016-08-31 |
Family
ID=52150477
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410494396.XA Active CN104258829B (en) | 2014-09-24 | 2014-09-24 | Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104258829B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN109125273B (en) * | 2018-09-28 | 2020-10-09 | 北京市中关村医院 | Phosphorus binding agent and preparation method and application thereof |
| TWI788647B (en) * | 2019-03-29 | 2023-01-01 | 日商旭化成醫療股份有限公司 | blood purifier |
| CN110975844B (en) * | 2019-12-17 | 2021-11-09 | 重庆科技学院 | Preparation method of polyaspartic acid grafted viscose adsorbent |
| CN115138337B (en) * | 2022-07-13 | 2023-09-12 | 河北大学 | Amination bio-based phosphorus adsorption material and preparation method and application thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2162658T3 (en) * | 1996-03-05 | 2002-01-01 | Mitsubishi Chem Corp | USE OF ANIONIC EXCHANGING RESINS FOR THE MANUFACTURE OF A MEDICINAL PRODUCT FOR THE TREATMENT OF HYPERPHOSPHATEMIA. |
| US6180094B1 (en) * | 1996-07-19 | 2001-01-30 | Nikken Chemicals Co., Ltd. | Remedies for hyperphosphatemia |
| DE602006020080D1 (en) * | 2006-06-29 | 2011-03-24 | Pharma Co Ltd J | PREVENTIVE AND THERAPEUTIC AGENT AGAINST PHOSPHORUS DISORDER, ORAL AGENT FOR ADSORPTION OF PHOSPHATIONS IN FOOD, BEVERAGES AND CHEMICALS AND METHOD OF MANUFACTURE |
| CN101904868A (en) * | 2010-08-19 | 2010-12-08 | 河北长天药业有限公司 | Application of medicinal carbon in preparation of medicaments for curing hyperphosphatemia |
-
2014
- 2014-09-24 CN CN201410494396.XA patent/CN104258829B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN104258829A (en) | 2015-01-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104258829B (en) | Serium inorganic phosphorus adsorbent and preparation method thereof, adsorption column for blood perfusion | |
| US6844372B2 (en) | Crosslinked anion-exchange resin or salt thereof and phosphorus adsorbent comprising the same | |
| CN102112221B (en) | Adsorbent, cleaning agent, treatment of kidney disease medicine and functional food | |
| CN101687961B (en) | Crosslinked polyallylamine or acid addition salt thereof, and use thereof for medical purposes | |
| CN101224415A (en) | Low density lipoprotein adsorbent for extrinsic blood perfusion and preparing method thereof | |
| US20220401634A1 (en) | Sorbent for a dialysis device and dialysis system | |
| CN1269535C (en) | Spherical amino acid adsorbent and its preparation method | |
| CN103720708A (en) | Dialysis agent a containing acetic acid and acetate salt, and a two-part dialysis agent using thereof | |
| CN109174033A (en) | A kind of blood lead ion scavenger and its preparation method and application that can pass in and out red blood cell safely | |
| CN103611504B (en) | A kind of sorbing material for blood perfusion removal rheumatoid factor and preparation method thereof | |
| CN106074440B (en) | A kind of capsule and preparation method thereof | |
| CN104000191A (en) | A novel chelated calcium | |
| CN102872462B (en) | Ambroxol hydrochloride composition and preparation thereof | |
| JPWO2006038603A1 (en) | Phosphate ion adsorbent | |
| CN103239434A (en) | Ornithine aspartate composition | |
| JP2004505923A (en) | "Sustained-release" pharmaceutical composition containing lithium carbonate | |
| CN208512533U (en) | A kind of organic phosphorus catalysis impurity removing device | |
| CN101745116B (en) | Preparation method for copper ion chelate adsorbing medium used for curing Wilson's disease | |
| CN102516116B (en) | Low-osmotic-pressure triiodo-benzene compound contrast agent | |
| CN205796182U (en) | A kind of air purification type intelligent breathing therapeutic instrument | |
| CN102527359A (en) | Method for modifying activated carbon for blood perfusion | |
| CN101375858A (en) | Solid formulation of urea nitrogen sorbent for compensating kidney function and preparation method thereof | |
| CN106701731A (en) | Preparation method of SBA-15 immobilized angiotensin converting enzyme | |
| CN209679144U (en) | A kind of adjustable speed Lavage tube | |
| CN107157947A (en) | A kind of 2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate piece and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 519000 No. 98 Science and Technology Sixth Road, Zhuhai High-tech Zone, Guangdong Province Patentee after: Jianfan Biotechnology Group Co., Ltd. Address before: 519000 No. 98 Science and Technology Sixth Road, Zhuhai High-tech Zone, Guangdong Province Patentee before: Jafron Biomedical Co., Ltd. |