CN108976428A - A kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial - Google Patents
A kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial Download PDFInfo
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Abstract
The invention discloses a kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial, which passes through sonic oscillation dispersion for raw materials such as ethylene glycol, polylactic acid, polypropylene-base ammonia, poly- hydroxyl valerate, phosphatidylinositols, calcium chloride, sodium alginate, phosphatidyl serine, glycine, dithiothreitol (DTT)s respectively, sieving sorting, heating in vacuum reaction, injection molding pressing mold, cooling fixed, ultrasonic cleaning, positive and negative polyelectrolyte adsorption from aqueous solution balance, washing are dried, nitrogen protection solidify and etc. high molecular degradable pharmaceutical carrier biomaterial is prepared.The high molecular degradable pharmaceutical carrier biomaterial being prepared, condition degradation property with higher are stablized nontoxic, are suitable for the application of the relevant material of a variety of pharmaceutical carriers.
Description
Technical field
The present invention relates to this technical fields of biomaterial, are related specifically to a kind of high molecular degradable pharmaceutical carrier biology
The preparation method of material.
Background technique
Pharmaceutical carrier, drug can be changed by, which referring to, enters the mode of human body and the release speed of distribution, control drug in vivo
Spend and conduct drugs to the system of target organs.Drug carrier material plays very important work in the research of controlled release preparation
With since the sixties in 20th century, the research of controlled drug delivery system causes people widely to pay attention to.Drug controlled release
Utilization rate, safety and the validity of drug can be improved in system, so as to reduce administration frequency, therefore attracts attention.In drug
In carrier, from animal and plant and the boiomacromolecule of microorganism, because of its good biocompatibility, biodegradable and can
Reproducibility becomes a kind of important drug carrier material.The material for preparing pharmaceutical carrier mainly has two major classes: 1. natural polymers
Material, such as lipid, carbohydrate, protein;2. high molecular material is synthesized, such as polyalkylcyanoacrylate, PLA and PLGA.Furthermore
There are also the lipid of synthesis such as stearic acid etc..Currently, the carrier material that U.S. FDA approval can be used for drug administration by injection is PLA and PLGA.
Pharmaceutical carrier has some special functional characteristics: 1. lymphatic system taxises: anticancer drug is encapsulated in liposome, can be made
It kills to drug selectivity cancer cell or inhibits the breeding of cancer cell, increasing drug reduces anticancer drug to the directionality of lymph
Damage or inhibiting effect to normal cell and tissue change the distribution of drug in the tissue.2. passive targeting: in entity
Tumor growth site, infection, inflammation part, lesion cause the permeability of hair cell blood vessel to increase, the load medicine in appropriate particle size range
Long circulating liposome shows EPR effect in these diseased regions.3. active targeting: liposome itself is without special active targeting
Property, it is necessary to antibody, hormone, saccharide residue and receptors ligand etc. are modified on lipid bilayer.Active targeting is to utilize target device
The structure and function feature of official, artificially designs and prepares the lipidosome drug carrier that can be selectively distributed in target organ, by drug
It is transported to specific histoorgan, cell or subcellular organelle.4. physical chemistry targeting: physical chemistry targeting refers in rouge
Certain special lipids are mixed in plastid or contain magnetisable material, make liposome that there is response to the variation in bait, temperature, magnetic field etc.
Property so that liposome carry drug effect in target site, such as pH sensitive liposome, thermo-responsive liposome, photaesthesia lipid
Body, magnetic liposome etc. have physics Targeting Performance.Simultaneously with the development of science and technology, therapeutic effect and treatment of the people to disease
The requirement of means also increasingly improves.The bioavilability of drug is improved, extends drug treating time, realize that targeting is fixed in drug body
Position reduces the emphasis that toxic side effect is always pharmaceutical carrier field research.From the point of view of present circumstances, many pharmaceutical carriers there are still
The problems such as development cost is high, encapsulation rate is low, narrow application range, not high clinical application rate.Research direction from now on should be further
Improve the controllable degree of pharmaceutical carrier, improve load pharmacological property, reduce toxic side effect, raising biodegradability and targeting positioning etc..
It is believed that in the near future, the intelligent pharmaceutical carrier such as reduction response type will clinically be widely used, become the mankind
The powerful mean to conquer a stubborn disease.
Summary of the invention
In order to solve the above-mentioned technical problem, the invention discloses a kind of systems of high molecular degradable pharmaceutical carrier biomaterial
Preparation Method, the technique is by ethylene glycol, polylactic acid, polypropylene-base ammonia, poly- hydroxyl valerate, phosphatidylinositols, calcium chloride, alginic acid
The raw materials such as sodium, phosphatidyl serine, glycine, dithiothreitol (DTT) pass through sonic oscillation dispersion, sieving sorting, heating in vacuum respectively
It reacts, injection molding pressing mold, cooling fixed, ultrasonic cleaning, positive and negative polyelectrolyte adsorption from aqueous solution balances, washing is dried, nitrogen protection
Solidification and etc. high molecular degradable pharmaceutical carrier biomaterial is prepared.The high molecular degradable pharmaceutical carrier being prepared
Biomaterial, condition degradation property with higher are stablized nontoxic, are suitable for answering for the relevant material of a variety of pharmaceutical carriers
With.
Technical solution: to solve the above-mentioned problems, the invention discloses a kind of high molecular degradable pharmaceutical carrier biology materials
The preparation method of material, comprising the following steps:
(1) by 5-10 parts of ethylene glycol, 22-25 parts of polylactic acid, 4-8 parts of polypropylene-base ammonia, hydroxyl valerate 7-15 parts poly-, coupling agent
It 2-5 parts, is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare；
(2) solution of step (1) is added in vacuum reaction kettle, phosphatidylinositols 2-4 is sequentially added after being heated to 60 DEG C
Part, 2-6 parts of calcium chloride, 1-3 parts of sodium alginate, 3-6 parts of phosphatidyl serine, 1-4 parts of glycine, 1-2 parts of dithiothreitol (DTT), so
Temperature rises to 100-105 DEG C again afterwards, vacuumizes, and sustained response 2-5h, air pressure returns back to normal pressure in furnace after reaction, reaction
Object heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30-50min, with sterile steaming
Distilled water washing, naturally dry；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30-50min, with sterile steaming
Distilled water washing, naturally dry；
(7) material is carried out under 75-80 DEG C of nitrogen protection atmosphere then with being dried with nitrogen with the moulding of ethyl alcohol cleaning step (6)
Material solidification 90-150min, is then packed to get finished product.
Preferably, the ultrasonic power in the step (1) is 250KW, sonic oscillation 30-50min.
Preferably, the mesh size of crossing in the step (1) is 2000 mesh.
Preferably, the coupling agent in the step (1) is selected from tetra isopropyl two (phosphorous acid dilauryl) titanate esters, two
(dioctyl pyrophosphoryl base) oxygen-containing acetic acid esters titanium, isopropyl three (isostearoyl base) titanate esters, two (dioctyl pyrophosphoryl base) second
Support one or more of titanate esters.
Preferably, the vacuum pressure in the step (2) is 5*10-8Pa。
Preferably, it is 150-180 DEG C that the injecting condition in the step (3), which is nozzle temperature, the temperature in an area and 2nd area
It is 150-180 DEG C, the temperature in 3rd area and 4th area is 130-150 DEG C, and the temperature in 5th area and 6th area is 130-150 DEG C, injection mold
Mould temperature be 90-95 DEG C, injection pressure 100-150MPa, injection speed 220-300mm/s.
Preferably, the composition of the positive polyelectrolyte aqueous solution in the step (5) is w/v: collagen 10%,
Lactalbumin 3%, legumelin 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water.
Preferably, the composition of the negative polyelectrolyte aqueous solution in the step (6) is w/v: hyaluronic acid 6%,
Kayexalate 8%, sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water.
Preferably, the nitrogen pressure in the step (7) is 2Mpa.
Compared with prior art, the present invention has the advantages that:
(1) a kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial of the invention is by ethylene glycol, polylactic acid, poly- third
Alkenyl ammonia, poly- hydroxyl valerate, phosphatidylinositols, calcium chloride, sodium alginate, phosphatidyl serine, glycine, dithiothreitol (DTT)
Equal raw materials pass through respectively sonic oscillation dispersion, sieving sorting, heating in vacuum reaction, injection molding pressing mold, cooling fixed, ultrasonic cleaning,
Positive and negative polyelectrolyte adsorption from aqueous solution balance, washing dry, nitrogen protection solidification and etc. high molecular degradable medicine is prepared
Object carrier organism material.The high molecular degradable pharmaceutical carrier biomaterial being prepared, condition degradability with higher
It can, stablize nontoxic, be suitable for the application of the relevant material of a variety of pharmaceutical carriers.
(2) high molecular degradable pharmaceutical carrier biomaterial raw material of the invention be easy to get, simple process, be suitable for extensive work
Industryization is used, practical.
Specific embodiment
Embodiment 1
(1) by 5 parts of ethylene glycol, 22 parts of polylactic acid, 4 parts of polypropylene-base ammonia, 7 parts of poly- hydroxyl valerate, two (phosphorous acid of tetra isopropyl
Dilauryl) 2 parts of titanate esters, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein
Ultrasonic power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, sequentially added after being heated to 60 DEG C 2 parts of phosphatidylinositols,
2 parts of calcium chloride, 1 part of sodium alginate, 3 parts of phosphatidyl serine, 1 part of glycine, 1 part of dithiothreitol (DTT), then temperature rises again
It to 100-105 DEG C, vacuumizes, vacuum pressure 5*10-8Pa, sustained response 2h, air pressure returns back to normal pressure in furnace after reaction,
Reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then with being dried with nitrogen, at 75-80 DEG C, the nitrogen that pressure is 2MPa is protected
It protects and carries out material solidification 90min under atmosphere, then pack to get finished product.
Embodiment 2
(1) by 7 parts of ethylene glycol, 23 parts of polylactic acid, 5 parts of polypropylene-base ammonia, 9 parts of poly- hydroxyl valerate, two (dioctyl pyrophosphoryls
Base) it is 3 parts of acetic acid esters titanium oxygen-containing, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein
Ultrasonic power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, sequentially added after being heated to 60 DEG C 3 parts of phosphatidylinositols,
4 parts of calcium chloride, 2 parts of sodium alginate, 4 parts of phosphatidyl serine, 2 parts of glycine, 1 part of dithiothreitol (DTT), then temperature rises again
It to 100-105 DEG C, vacuumizes, vacuum pressure 5*10-8Pa, sustained response 3h, air pressure returns back to normal pressure in furnace after reaction,
Reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 35min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 35min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then with being dried with nitrogen, at 75-80 DEG C, the nitrogen that pressure is 2MPa is protected
It protects and carries out material solidification 100min under atmosphere, then pack to get finished product.
Embodiment 3
(1) by 9 parts of ethylene glycol, 24 parts of polylactic acid, 7 parts of polypropylene-base ammonia, 13 parts of poly- hydroxyl valerate, (the different tristearin of isopropyl three
Acyl group) 4 parts of titanate esters, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein ultrasound
Power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, sequentially added after being heated to 60 DEG C 3 parts of phosphatidylinositols,
5 parts of calcium chloride, 2 parts of sodium alginate, 5 parts of phosphatidyl serine, 3 parts of glycine, 2 parts of dithiothreitol (DTT), then temperature rises again
It to 100-105 DEG C, vacuumizes, vacuum pressure 5*10-8Pa, sustained response 4h, air pressure returns back to normal pressure in furnace after reaction,
Reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 45min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 45min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then with being dried with nitrogen, at 75-80 DEG C, the nitrogen that pressure is 2MPa is protected
It protects and carries out material solidification 120min under atmosphere, then pack to get finished product.
Embodiment 4
(1) by 10 parts of ethylene glycol, 25 parts of polylactic acid, 8 parts of polypropylene-base ammonia, 15 parts of poly- hydroxyl valerate, two (dioctyl pyrophosphoryls
Base) 5 parts of ethylene titanate esters, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein surpassing
Acoustical power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, sequentially added after being heated to 60 DEG C 4 parts of phosphatidylinositols,
6 parts of calcium chloride, 3 parts of sodium alginate, 6 parts of phosphatidyl serine, 4 parts of glycine, 2 parts of dithiothreitol (DTT), then temperature rises again
It to 100-105 DEG C, vacuumizes, vacuum pressure 5*10-8Pa, sustained response 5h, air pressure returns back to normal pressure in furnace after reaction,
Reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 50min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 50min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then with being dried with nitrogen, at 75-80 DEG C, the nitrogen that pressure is 2MPa is protected
It protects and carries out material solidification 150min under atmosphere, then pack to get finished product.
Comparative example 1
(1) by 5 parts of ethylene glycol, 22 parts of polylactic acid, 4 parts of polypropylene-base ammonia, 7 parts of poly- hydroxyl valerate, two (phosphorous acid of tetra isopropyl
Dilauryl) 2 parts of titanate esters, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein
Ultrasonic power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, 1 part of sodium alginate, sweet is sequentially added after being heated to 60 DEG C
1 part of propylhomoserin, 1 part of dithiothreitol (DTT), then temperature rises to 100-105 DEG C again, vacuumizes, vacuum pressure 5*10-8Pa continues
2h is reacted, air pressure returns back to normal pressure in furnace after reaction, and reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then with being dried with nitrogen, at 75-80 DEG C, the nitrogen that pressure is 2MPa is protected
It protects and carries out material solidification 90min under atmosphere, then pack to get finished product.
Comparative example 2
(1) by 10 parts of ethylene glycol, 25 parts of polylactic acid, 8 parts of polypropylene-base ammonia, 15 parts of poly- hydroxyl valerate, two (dioctyl pyrophosphoryls
Base) 5 parts of ethylene titanate esters, it is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare, wherein surpassing
Acoustical power is 250KW, sonic oscillation 30min, and crossing mesh size is 2000 mesh；
(2) solution of step (1) is added in vacuum reaction kettle, sequentially added after being heated to 60 DEG C 4 parts of phosphatidylinositols,
6 parts of calcium chloride, 3 parts of sodium alginate, 6 parts of phosphatidyl serine, 4 parts of glycine, 2 parts of dithiothreitol (DTT), then temperature rises again
It to 100-105 DEG C, vacuumizes, vacuum pressure 5*10-8Pa, sustained response 5h, air pressure returns back to normal pressure in furnace after reaction,
Reactant heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding, wherein infusing
Modeling condition is that nozzle temperature is 150-180 DEG C, and the temperature in an area and 2nd area is 150-180 DEG C, and the temperature in 3rd area and 4th area is
130-150 DEG C, the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, injection pressure 100-
150MPa, injection speed 220-300mm/s；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 50min uses sterile distilled water
The composition of washing, naturally dry, positive polyelectrolyte aqueous solution is w/v: collagen 10%, lactalbumin 3%, beans are clear
Albumen 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 50min uses sterile distilled water
Washing, naturally dry, the composition of negative polyelectrolyte aqueous solution are w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water；
(7) moulding of ethyl alcohol cleaning step (6) is used, then naturally dry solidification is packed to get finished product.
The high molecular degradable pharmaceutical carrier biomaterial obtained of embodiment 1-4 and comparative example 1-2 is carried out carefully respectively
Cellular toxicity experiment, targets this several performance tests of site degradation rate at antioxygenic property, and test result is shown in Table 1.
Table 1
| Cytotoxicity experiment | Antioxygenic property | Target site degradation rate/drug half-life test | |
| Embodiment 1 | It is non-stimulated | Well | 87.50% |
| Embodiment 2 | It is non-stimulated | Well | 86.40% |
| Embodiment 3 | It is non-stimulated | Well | 85.00% |
| Embodiment 4 | It is non-stimulated | Well | 86.10% |
| Comparative example 1 | It is non-stimulated | Generally | 38.50% |
| Comparative example 2 | It is non-stimulated | Generally | 23.60% |
A kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial of the invention is by ethylene glycol, polylactic acid, polypropylene
Base ammonia, poly- hydroxyl valerate, phosphatidylinositols, calcium chloride, sodium alginate, phosphatidyl serine, glycine, dithiothreitol (DTT) etc.
Raw material pass through respectively sonic oscillation dispersion, sieving sorting, heating in vacuum reaction, injection molding pressing mold, cooling fixed, ultrasonic cleaning, just,
Negative polyelectrolyte adsorption from aqueous solution balance, washing dry, nitrogen protection solidification and etc. high molecular degradable drug is prepared
Carrier organism material.The high molecular degradable pharmaceutical carrier biomaterial being prepared, condition degradation property with higher,
Stablize nontoxic, is suitable for the application of the relevant material of a variety of pharmaceutical carriers.High molecular degradable pharmaceutical carrier biology of the invention
Material feedstock is easy to get, simple process, is suitable for heavy industrialization and uses, practical.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Equivalent structure or equivalent flow shift made by bright description is applied directly or indirectly in other relevant technology necks
Domain is included within the scope of the present invention.
Claims (9)
1. a kind of preparation method of high molecular degradable pharmaceutical carrier biomaterial, which comprises the following steps:
(1) by 5-10 parts of ethylene glycol, 22-25 parts of polylactic acid, 4-8 parts of polypropylene-base ammonia, hydroxyl valerate 7-15 parts poly-, coupling agent
It 2-5 parts, is added in ultrasonator and is dispersed, is coupled, obtained solution sieving sorting is spare；
(2) solution of step (1) is added in vacuum reaction kettle, phosphatidylinositols 2-4 is sequentially added after being heated to 60 DEG C
Part, 2-6 parts of calcium chloride, 1-3 parts of sodium alginate, 3-6 parts of phosphatidyl serine, 1-4 parts of glycine, 1-2 parts of dithiothreitol (DTT), so
Temperature rises to 100-105 DEG C again afterwards, vacuumizes, and sustained response 2-5h, air pressure returns back to normal pressure in furnace after reaction, reaction
Object heat preservation is spare；
(3) injection molding pressing mold will be carried out in the reaction solution injection injection molding machine of step (2), then cooling, fixed, demoulding；
(4) moulding of step (3) is put into sterile distilled water and is cleaned by ultrasonic, removal surface organic impurities residual is dried in the air
It is dry；
(5) moulding of step (4) is put into positive polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30-50min, with sterile steaming
Distilled water washing, naturally dry；
(6) moulding of step (5) is put into negative polyelectrolyte aqueous solution and is carried out, adsorption equilibrium 30-50min, with sterile steaming
Distilled water washing, naturally dry；
(7) material is carried out under 75-80 DEG C of nitrogen protection atmosphere then with being dried with nitrogen with the moulding of ethyl alcohol cleaning step (6)
Material solidification 90-150min, is then packed to get finished product.
2. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
Stating the ultrasonic power in step (1) is 250KW, sonic oscillation 30-50min.
3. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
The mesh size of crossing stated in step (1) is 2000 mesh.
4. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
The coupling agent stated in step (1) contains selected from tetra isopropyl two (phosphorous acid dilauryl) titanate esters, two (dioctyl pyrophosphoryl bases)
One of fluoroacetic acid ester titanium, isopropyl three (isostearoyl base) titanate esters, two (dioctyl pyrophosphoryl base) ethylene titanate esters or
It is several.
5. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
Stating the vacuum pressure in step (2) is 5*10-8Pa。
6. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
It is 150-180 DEG C that state the injecting condition in step (3), which be nozzle temperature, and the temperature in an area and 2nd area is 150-180 DEG C, 3rd area and
The temperature in 4th area is 130-150 DEG C, and the temperature in 5th area and 6th area is 130-150 DEG C, and the mould temperature of injection mold is 90-95 DEG C, note
Injection pressure 100-150MPa, injection speed 220-300mm/s.
7. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
The composition for stating the positive polyelectrolyte aqueous solution in step (5) is w/v: collagen 10%, lactalbumin 3%, the clear egg of beans
White 8%, chitin 4%, glucan 1%, magnesium sulfate 1%, potassium chloride 1%, water.
8. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
State the negative polyelectrolyte aqueous solution in step (6) composition be w/v: hyaluronic acid 6%, kayexalate 8%,
Sodium alginate 10%, mannitol 1%, heparin 1%, ethyl alcohol 1%, water.
9. the preparation method of high molecular degradable pharmaceutical carrier biomaterial according to claim 1, which is characterized in that institute
Stating the nitrogen pressure in step (7) is 2MPa.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109942903A (en) * | 2019-02-11 | 2019-06-28 | 赵延延 | A kind of preparation method of antibacterial type blood compatibility biological material |
| CN112011161A (en) * | 2020-09-07 | 2020-12-01 | 河南应用技术职业学院 | Composite biodegradable synthetic polymer material and processing method thereof |
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| CN1943565A (en) * | 2006-10-24 | 2007-04-11 | 中山大学 | Biological degradable nano medicinal capsule with MRI tracer effect and its preparing method |
| CN1973832A (en) * | 2006-10-24 | 2007-06-06 | 中山大学 | Biodegradable nanometer medicine capsule with CT trace effect and its prepn process |
| CN102238943A (en) * | 2008-10-01 | 2011-11-09 | Nurim-Mwellness株式会社 | Solid microstructure that enables multiple controlled release and method of manufacturing same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1943565A (en) * | 2006-10-24 | 2007-04-11 | 中山大学 | Biological degradable nano medicinal capsule with MRI tracer effect and its preparing method |
| CN1973832A (en) * | 2006-10-24 | 2007-06-06 | 中山大学 | Biodegradable nanometer medicine capsule with CT trace effect and its prepn process |
| CN102238943A (en) * | 2008-10-01 | 2011-11-09 | Nurim-Mwellness株式会社 | Solid microstructure that enables multiple controlled release and method of manufacturing same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109942903A (en) * | 2019-02-11 | 2019-06-28 | 赵延延 | A kind of preparation method of antibacterial type blood compatibility biological material |
| CN112011161A (en) * | 2020-09-07 | 2020-12-01 | 河南应用技术职业学院 | Composite biodegradable synthetic polymer material and processing method thereof |
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