The Preparation method and use of cm-chitosan and sodium alginate blend microcapsuleTechnical field
The present invention relates to the Preparation method and use of cm-chitosan and sodium alginate blend microcapsule.
Background technology
In recent years, be that the sustained release microballoon or the microcapsule of carrier are noticeable day by day with the natural macromolecular material.Lot of advantages such as that natural polymer has is nontoxic, degradable and biocompatibility, be widely used as bio-medical material, they can cover peculiar smell, raising stability of drug and the stomach of the medicine receptivity to medicine, can prolong the time of releasing of oral back medicine simultaneously.Chitosan has immune stimulating activity, resist coagulation, antimycotic and promote the ability of wound healing to be widely used in biomedical materials field (Int.J.Pharm.194,1).In addition, chitosan has opens combining closely of epidermic cell, improves the intercellular penetrating power of macromolecular drug.But the chitosan solubleness under the environment (pH7.4) in vivo is lower, has limited it as absorbing the application that promotes carrier, as the mouth and nose drug delivery system.Cm-chitosan can be dissolved in the aqueous solution, the neutral environment that is fit to human body, therefore can more convenient drug use and effectively improve the penetrating quality (Carbohydr.Polym.1988 of medicine, 8,1), it has also kept some characteristics of chitosan in addition, as biological degradability, biocompatibility, antifungal property etc.Sodium alginate is the sea-tangle processing byproduct, has adsorption function and biological activity.Found that outside surface at the sodium alginate micro gel capsule coats other superpolymer and can obtain a kind of new carrier, immunoprotection, immobilized enzyme and controlled delivery of pharmaceutical agents that it is widely used for as Transplanted cells discharge (Carbohydr.Polym.1998,36,81; Process Biochemistry, Vol 31,4, and 347).For example the alginates carrier has been used for materials (Macromol.chem.phys.1994,195,1557) such as inclusion release serum protein, bovine serum albumin.The blend film of cm-chitosan and alginates has the good mechanical performance, so cm-chitosan and sodium alginate all are the ideal natural polymers as slow-release material.
Summary of the invention
The Preparation method and use that the purpose of this invention is to provide a kind of water-soluble natural polymer cm-chitosan and sodium alginate blend microcapsule, prepared blend microcapsule have more sensitive response function to different pH, release rate is lower when pH＜2, and the solubleness under the environment (pH7.4) is higher in vivo, the medicine that can be used for inclusion treatment enteron aisle disease makes it discharge rapidly at the enteron aisle position and reaches the purpose that target discharges.
Technical scheme provided by the invention is: the preparation method of a kind of cm-chitosan and sodium alginate blend microcapsule, with mass percent be 1%～8% carboxymethyl chitosan sugar aqueous solution and mass percent be 1%～8% sodium alginate aqueous solution with 1: 1～1: 8 mass ratio mixed blended liquid I, again the sliding albumin 0.1～1.0g of inclusion medicine ox blood is dissolved in mix among the above-mentioned blend solution I of 20～60mL blended liquid II, then blended liquid II is dispersed in that to contain the emulsifying agent volume ratio be among whiteruss 30～60mL of 0.5%～3%, emulsifying agent is mixing in 1: 1～1: 2 by sorbitan mono-laurate (Span-20) and polyoxyethylene 20 sorbitan monolaurate (Tween-20) with mass ratio, stirs to make in 0.5～2.0 hour; Be 5%～20%CaCl with mass percent then2The aqueous solution and dehydrated alcohol are the CaCl that 1: 1～1: 2 mixed obtains with volume ratio2Solidification liquid 20～60mL was added dropwise in 0.5～1.5 hour among the above-mentioned blended liquid II that is dispersed in the whiteruss that contains emulsifying agent, stirred 0.5～2 hour, added 10～30mL Virahol at last and solidified and obtain microcapsule; Filtering or centrifugation collection microcapsule, is 3%～5%CaCl with mass percent respectively2The aqueous solution and washing with alcohol, dry cm-chitosan and the sodium alginate blend microcapsule of getting.
Zhi Bei cm-chitosan and sodium alginate blend microcapsule are as the application of slowly-releasing inclusion material in preparation bovine serum albumin slow releasing pharmaceutical of medicine bovine serum albumin as stated above.
The cm-chitosan that the present invention makes has responsive response function with sodium alginate blend microcapsule to different pH, when pH＜2, discharge hardly, slow swelling takes place in the acidic medium of pH1.0, after about 3～4 hours, microcapsule have arrived colon, be in the environment of pH7.4, microcapsule wall generation erosion action and being partly dissolved, thus the BSA release rate is obviously increased.The medicine that can be used for inclusion treatment enteron aisle disease thus makes it discharge rapidly at the enteron aisle position and reaches the purpose that target discharges.And these microcapsule have the excellent drug slow-release function, and the variation of pH is had the sensitive response, and production technique is easy.These microcapsule can be widely used in medicine, foodstuff additive, the slowly-releasing inclusion material in fields such as essence and flavoring agent.
Embodiment
Embodiment 1: with mass percent be 5% carboxymethyl chitosan sugar aqueous solution and mass percent be 5% sodium alginate aqueous solution with 1: 1 mass ratio mixed blended liquid I.Again 0.5g bovine serum albumin (BSA) is dissolved in mix among the above-mentioned blend solution I 20mL blended liquid II, then blended liquid II is dispersed in that to contain the emulsifying agent volume ratio be 1% whiteruss 40mL.Emulsifying agent consists of sorbitan mono-laurate (Span-20) and polyoxyethylene 20 sorbitan monolaurate (Tween-20) mass ratio is 1: 1.Stirred 1.5 hours at high speed machine.Then with CaCl2(mass percent is 5%CaCl to solidification liquid2The aqueous solution and dehydrated alcohol are 1: 1 mixed with volume ratio) 60mL splashed in 0.5 hour in the above-mentioned system, stirred 2 hours, add at last the 20mL Virahol solidify microcapsule.Filtering and collect microcapsule, is 5%CaCl with mass ratio2The aqueous solution and absolute ethanol washing microcapsule, vacuum-drying makes cm-chitosan and sodium alginate blend microcapsule product then.The microcapsule of inclusion BSA are 5% at 5 hours release rates of acidic medium of pH1.0, and 5 hours release rate brings up to 50% in the alkaline medium of pH7.4.The BSA release rate is 20 hours above 95% time.
Embodiment 2: with mass percent be 1% carboxymethyl chitosan sugar aqueous solution and mass percent be 8% sodium alginate aqueous solution with 1: 3 mass ratio mixed blended liquid I.Again 0.1g bovine serum albumin (BSA) is dissolved in mix among the blend solution I 40mL blended liquid II, then blended liquid II is dispersed in that to contain the emulsifying agent volume ratio be among the 0.5% whiteruss 30mL.The mass ratio that emulsifying agent consists of sorbitan mono-laurate (Span-20) and polyoxyethylene 20 sorbitan monolaurate (Tween-20) is 1: 1.5.Stirred 0.5 hour at high speed machine.Then with CaCl2(mass percent is 20%CaCl to solidification liquid2The aqueous solution and dehydrated alcohol are 1: 1.5 mixed with volume ratio) 20mL was added dropwise in 1 hour in the above-mentioned system, stirred 0.5 hour, add at last the 10mL Virahol solidify microcapsule.Collecting microcapsule with centrifugation, is 3%CaCl with mass ratio respectively then2The aqueous solution and absolute ethanol washing microcapsule, vacuum-drying makes product then.The microcapsule of inclusion BSA are 10% at 5 hours release rates of acidic medium of pH1.0, and 5 hours release rate brings up to 60% in the alkaline medium of pH7.4.The BSA release rate is 18 hours above 95% time.
Embodiment 3: with mass percent be 8% carboxymethyl chitosan sugar aqueous solution and mass percent be 1% sodium alginate aqueous solution with 1: 8 mass ratio mixed blended liquid I.Again 1g bovine serum albumin (BSA) is dissolved in mix among the above-mentioned blend solution 60mL blended liquid II, then it is dispersed in that to contain the emulsifying agent volume ratio be 3% whiteruss 60mL.Emulsifying agent consists of sorbitan mono-laurate (Span-20) and polyoxyethylene 20 sorbitan monolaurate (Tween-20) mass ratio is 1: 2.Mechanical stirring 2 hours.Then with CaCl2(mass percent is 15%CaCl to solidification liquid2The aqueous solution and dehydrated alcohol are to mix at 1: 2 with volume ratio) 40mL was added dropwise in 1.5 hours in the above-mentioned system, stirred 2 hours, add at last the 30mL Virahol solidify microcapsule.Collecting microcapsule with filter method, is 4.5%CaCl with mass ratio respectively then2The aqueous solution, distilled water and absolute ethanol washing microcapsule, vacuum-drying makes product then.The microcapsule of inclusion BSA are 7% at 5 hours release rates of acidic medium of pH1.0, and 5 hours release rates are 65% in the alkaline medium of pH7.2.The BSA release rate is 17 hours above 95% time.