CN1903366A - Targeted nanometer medicine carrier and its prepn. method - Google Patents
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- CN1903366A CN1903366A CNA2006100215564A CN200610021556A CN1903366A CN 1903366 A CN1903366 A CN 1903366A CN A2006100215564 A CNA2006100215564 A CN A2006100215564A CN 200610021556 A CN200610021556 A CN 200610021556A CN 1903366 A CN1903366 A CN 1903366A
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Abstract
A target medicine nano-carrier used for anti-neoplastic medicine, cancer suppressing gene and gene vaccine is prepared from sodium alginate and mannosan through polymerizing by solvent emulsifying and evaporating method, ultrasonic emulsifying method, or high-pressure emulsifying method to obtain nano-class sodium alginate-mannosan polymer.
Description
Technical field
The present invention relates to a kind of targeted nanometer medicine carrier and preparation method thereof, the novel targeted property Nano medication that particularly relates to a kind of sodium alginate-mannan polymer carries and preparation method thereof.
Background technology
In China, there are every year 1300000 people to die from malignant tumor approximately, estimate sickness rate between 1,800,000-2,000,000, total sickness rate is in continuous rising.In a plurality of at home big cities, malignant tumor has surpassed cardiovascular and cerebrovascular disease, comes first of all disease death reasons, and at 35-59 year age bracket, malignant tumor is first killer always.Tumor is the complex disease of multimachine system, and present Therapeutic Method still adopts comprehensive means treatments such as traditional early diagnosis, radiotherapy, chemotherapy.Adopt above-mentioned Therapeutic Method, its maximum defective is sick cell and Normocellular resolution lower, thereby causes the normal cell damage of human body too big.Therefore, develop drug delivery system and just seem particularly important with tumor-targeting.Along with illustrating of tumor development molecular mechanism, tumor cell and Normocellular difference will be clearer and more definite, the distinctive molecular target of some tumor cells will become the useful tool of screening anti-cancer herb medicine, and the drug delivery system with tumor-targeting is that target medicine carrier may make cancer therapy drug attack tumor cell specifically.These cancer therapy drugs are very little to normal primary cellular defect, thereby its better efficacy, also can be clinical heavy dose of for long periods the use, and therefore, the targeted therapy of tumor is the optimal route of administration of oncotherapy.
In China, nearly three during the last ten years applied chemistry Drug therapy malignant tumor had more rapidly development, the nearest report of International Union Against Cancer is thought can obviously prolong cancer patient life cycle after the chemotherapy.But can see that from another point of view chemotherapy has the not strong shortcoming of targeting,, easily produce multidrug resistance and treat failure so killing tumor cell on the one hand can obviously influence the function of patient's hemopoietic, immunity and some organ on the other hand.Therefore this just need take more efficient methods to alleviate or eliminate these side effect.Nano microsphere with degradable high molecular polymer preparation, it is the pharmaceutical carrier that late nineteen seventies grows up with slow release and targeting, it can arrive diseased region with the drug conveying of wrapping up according to the specificity of particle, improve the drug level of focus, the action time of prolong drug, and then obviously improve the therapeutic effect of medicine, reducing its toxic and side effects, thereby reach the purpose of in vivo drug targeting being put to the gentle slow release of diseased region.Nano meter biomaterial has become the focus of research at present, and is obtaining better basis and making substantive result aspect medicament nano carrier and the nano-particle gene transfer techniques.This technology is as medicine and gene transfer vector with nano-particle, be wrapped in gene therapy molecules such as chemotherapeutics, DNA and RNA among the nano-particle or be adsorbed on its surface, simultaneously also join specific targeted molecular at the particle surface coupling, as ligands specific, monoclonal antibody etc., combine with the cell surface specific receptor by targeted molecular, under the cellular uptake effect, enter in the cell, realize target medicine and gene therapy safely and effectively, promptly realize the principle of " combination among the strong ones ".
One of key character of pharmaceutical carrier or genophore is its biological degradability, and by Composition Control and structural design, biodegradable speed can be controlled, and part and their copolymer can be biodegradable into cell homergy material, promptly-and water and carbon dioxide.By degraded, carrier and medicine/genetic fragment orientation enters after the target cell, and the carrier on top layer is by biodegradation, and the drug release of core comes out to bring into play curative effect, has avoided medicine to discharge in its hetero-organization.The research of this class carrier polymer is mainly aspect pharmaceutical preparation and organizational project at present, and aspect pharmaceutical preparation, mostly be connected with medicine by chemical reaction, thereby reach the purpose of treatment, but its maximum defective of method that adopts above-mentioned chemosynthesis is such medicine and enters behind the human body not attacking tumor cell specifically, and is very big to normal primary cellular defect.Modify as regulating material surface hydrophilic/hydrophobic and electric charge, bioactie agents such as the cytoadherence factor and growth factor being fixed in material surface etc. for polymer surfaces, mostly adopt the method for modifying of physical absorption, be to keep effect between absorbing molecules and base material by Van der Waals force, so a little less than the adhesion, combined molecule easily comes off, influence the life-time service performance of material, can not satisfy application need.
Sodium alginate is the cell membrane constituent of Brown algae, is polysaccharide compound, is found in 1881, and nineteen sixty-five is determined its structural formula with nuclear magnetic resonance technique.Alginic acid is by poly-β-1,4-mannuronic acid (β-1,4-D-mannosyluronicacid, M) with poly-α-1-4-L-guluronic acid (α-1-4-L-gulosyluronic acid, G) bonded linear high polymer, diluted alkaline commonly used extracts from Brown algae and gets, and the structural formula of sodium alginate is as follows:
Sodium alginate be can be used as the biomaterial of external preparation such as wound dressing and drug release carrier by drugs approved by FDA, have biological degradability and biocompatibility, is widely used in medicine, cosmetics, food, fields such as weaving.In pharmaceutics, utilize dissolubility property, gel and the polyelectrolyte character of sodium alginate carrier as slow releasing preparation, embedding medium or bioadhesive polymer, utilize its film property, the preparation microcapsule, utilize itself and bivalent ions associativity, the viscosifier of Ceng Zuowei ointment base or suspensoid, it is particularly important as slow releasing preparation and microencapsulated material etc.Sodium alginate is used for the existing report of developmental research of pharmaceutical carrier, but will be used for the shortcoming that there is no targeting equally in pharmaceutical carrier.
As everyone knows, saccharide compound is the earn a bare living main sources of activity institute energy requirement of all organisms, is the base stock of synthetic other chemical compound of organism, or serves as the structure raw material of organism.The research of saccharide chemistry is morning, but is in the period of great prosperity in nucleic acid, proteinic research, and the research of saccharide compound was once treated coldly.After the seventies in 20th century, along with development of molecular biology, people progressively recognize, saccharide relates to one of biomacromolecule of vital movement essence, have a plurality of oh groups on the carbohydrate structure, sugar chain structure contains very abundant biological linguistic information, is highdensity information carrier.To studies show that of multiple polysaccharide antitumor action mechanism, polyose medicament is not direct kill cancer cell, but, body immune system being restored balance by stimulating maturation, differentiation and the breeding of the various immunologically competent cells of body, the resistance of performance body self removes to remove, engulf cancerous cell.Dendritic cell (dendriticcells in recent years, DCs) become one of focus that current tumor biotherapy field receives much concern, more and more evidences shows the activated cellular immunization by DC, the particularly immunoreation of cytotoxic T lymphocyte (CTL) mediation, resist at body and to bring into play crucial effect in malignant tumor and the infectious disease, mannan by the discovery of success it to dendritic cell (dendritic cells, effective submission such as DCs), thereby can evoke the effective antitumour reaction, its structural formula is as follows:
Therefore, with the modification group of mannan as sodium alginate micro ball, make up the novel targeted drug delivery system of tumour-specific, can be with the diseased region of delivering to of the medicine of microsphere parcel or gene orientation, thereby improve the drug effect of lesions position, having the effect of slow release simultaneously concurrently, is a kind of functional and practical novel drug delivery system.
Summary of the invention
The purpose of this invention is to provide a kind of targeted nanometer medicine carrier and preparation method thereof, this targeted nanometer medicine carrier is the synthetic target drug-carrying microsphere of sodium alginate and mannan; This method is with the modification group of mannan as sodium alginate, and through technologies such as esterifications, preparation has the Nano medication medicine carrying microballoons of targeting; Prepared medicine carrying microballoons can reach more than 80% the envelop rate of antitumor drug, has improved the affinity to the therapeutic goal cell.
The preparation method of targeted nanometer medicine carrier of the present invention, on the one hand, to have the modification group of the mannan of targeting to dendritic cell as sodium alginate, preparation sodium alginate-mannan polymer, on the other hand, with the sodium alginate for preparing-mannan polymer, adopt the solvent emulsion evaporation, or supersound method, or the equal method of high pressure breast, the sodium alginate micro ball of preparation mannan targeting, i.e. targeted nanometer medicine carrier, the preparation of sodium alginate-mannan polymer mainly comprises following processing step:
(1) at ambient temperature, sodium alginate and mannan are placed container, by weight mannan be sodium alginate 1-2 doubly, in being the acid solution HCl of 0.01-0.1mol/l, concentration carries out esterification, stir down, react after 0.5-2 hour, the pH value of reaction solution is transferred to neutrality;
(2) in above-mentioned reaction solution, add peroxide Ammonium Persulfate 98.5 1-5 weight portion as initiator, add surfactant sodium lauryl sulphate 1-5 weight portion as emulsifying agent, be warming up to 40 ℃-60 ℃, stir down response time 2-4 hour, use deionized water wash, after removing surfactant, dry in freeze dryer, it is standby promptly to make sodium alginate-mannan polymer.
Sodium alginate-mannan the polymer of the present invention's preparation adopts IR to carry out analyzing and testing, and its esterification reaches 100%.
In the preparation method of targeted nanometer medicine carrier of the present invention, described solvent emulsion evaporation, mainly through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere is between 200nm～300nm:
(1) with the sodium alginate-mannan polymer for preparing, be dissolved in the organic solvent, make it get the mixed solution that concentration is 0.1-5mg/ml, adding accounts for the cosolvent that mixed liquor volume percentage ratio is 0.01-0.1% in this mixed solution, gets composite solution;
(2) indissoluble or water-fast antitumor drug vincristine are dissolved in the above-mentioned composite solution, making its concentration is 1-5mg/ml, be added dropwise to slowly then and contain in the aqueous solution of surfactant that percentage ratio by volume is 1-10%, get emulsion, at room temperature, stirring reaction 4-12 hour, make the organic solvent evaporation in the emulsion;
(3) collect microsphere particle with the centrifuge high speed centrifugation, use distilled water wash microsphere particle at least three times, promptly obtain targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
In the such scheme, described organic solvent is a dichloromethane, or chloroform, or ethyl acetate; Better in the described organic solvent with the microsphere envelop rate of dichloromethane preparation.
In the such scheme, described surfactant is a sodium lauryl sulphate, or polyvinyl alcohol.
In the such scheme, described cosolvent is an acetone, or methanol, or dimethyl sulfoxine.
In the preparation method of targeted nanometer medicine carrier of the present invention, described supersound method, mainly through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere is between 50nm～150nm:
(1) with the sodium alginate-mannan polymer for preparing, is dissolved in the organic solvent, makes it get the mixed solution that concentration is 0.1-5mg/ml;
(2) use ultraemulsifier, with above-mentioned mixed solution and water-soluble antitumor drug, be scattered in and contain in the aqueous solution of surface active agent polyvinyl alcohol that percentage ratio by volume is 1-10%, the concentration that makes solution is 1-5mg/ml, carried out then ultrasonic emulsification 1-5 minute, ultrasonic power is 50-100W, gets emulsion, stir, remove the organic solvent in the emulsion;
(3) collect microsphere particle with the centrifuge high speed centrifugation, use distilled water wash microsphere particle at least three times, promptly make targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
In the such scheme, described organic solvent is an acetone, or dichloromethane.
In the such scheme, described antitumor drug is a paclitaxel, or DNA, or protein.
The present invention is littler and even with the microsphere particle of supersound method preparation, and the size of its Nano microsphere is between 50nm～150nm.
In the preparation method of targeted nanometer medicine carrier of the present invention, described high pressure breast is method all, and mainly through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere is between 50nm～150nm:
(1) sodium alginate-mannan polymer is dissolved in organic solvent dichloromethane, or chloroform, or in the ethyl acetate, make it get the mixed solution that concentration is 0.1-5mg/ml, with gene, or gene vaccine is dissolved in and contains in the distilled water of surface active agent polyvinyl alcohol that percentage ratio by volume is 1-10%
(2) use high pressure homogenizer, above-mentioned composite solution emulsifying is scattered in accounts in the aqueous solution of surface active agent polyvinyl alcohol that percent by volume is 1-10%, carry out the high-pressure emulsification circulation more than three times, each 2-3 minute, middling speed stirs again, gets emulsion, and the organic solvent evaporation in the emulsion is removed;
(3) collect Nano microsphere with the centrifuge high speed centrifugation, use distilled water wash Nano microsphere at least three times, promptly make targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
It is 50nm～150nm that the present invention adopts the sodium alginate Nano microsphere grain diameter of the mannan targeting of the equal method preparation of high pressure breast, microsphere disperses more even, and adopts the method, in preparation process, can not destroy the DNA segment of parcel, and the envelop rate of DNA is higher than 60%.
The sodium alginate Nano microsphere of the mannan targeting of the present invention's preparation adopts lyophilizing to preserve, and can further effectively remove the organic solvent that remains in the Nano microsphere.
The targeted nanometer medicine carrier of arbitrary described method preparation is characterized in that this targeted nanometer medicine carrier contains sodium alginate and mannan in the above-mentioned preparation method of the present invention, its content by weight, mannan be sodium alginate 1-2 doubly; The size of its Nano medication microspherulite diameter is between 50nm～300nm.
Nano-medicament carrier of the present invention is to have the targeting administration Nano microsphere medicine-carried system of the mannan of targeting as the modification group of sodium alginate; This Nano microsphere can wrap up chemotherapeutics, or antitumor drug, or antioncogene and gene vaccine etc., with the diseased region of delivering to of medicine or gene orientation, is the strong medicament-carrying nano-microsphere of a kind of targeting.
The present invention has following characteristics:
One, the safety of the sodium alginate-mannan polymer support of the selected material preparation of the present invention is good, and toxic and side effects is little, has stable and high targeting; Sodium alginate-mannan polymer has biological degradability and biocompatibility as the biomaterial of drug release carrier; Utilize the specificity of mannan, promptly it (dendriticcells DCs) waits effectively submission, reacts thereby can evoke effective antitumour to dendritic cell.
Two, mannan is connected on the sodium alginate by chemical modification, and then preparation has the Nano microsphere of targeting; This Nano microsphere can wrap up chemotherapeutics, or antitumor drug, or antioncogene and gene vaccine etc., be the strong medicament-carrying nano-microsphere of a kind of targeting, this medicament-carrying nano-microsphere can be with the diseased region of delivering to of medicine or gene orientation, thereby improves the drug effect of lesions position; Having the effect of slow release simultaneously concurrently, is a kind of functional and stronger novel targeted drug delivery system of practicality.
Three, targeted nanometer medicine carrier preparation method of the present invention is simple, easy to operate, and the reaction condition gentleness; Can also pass through adjusting reaction time, reactant concentration or control polymeric reaction temperature, come the hydrophobicity of telomerized polymer carrier material.
Description of drawings
Accompanying drawing is the infared spectrum of sodium alginate, in the accompanying drawing after sodium alginate and the mannan esterification, with the IR detection that performs an analysis, according to the characteristic absorption frequency of common group and chemical bond as can be known, the characteristic absorption frequency of the compound group of esterification is at 1720～1750cm
-1Scope, as can be seen from Figure, be 1748.976cm at adsorption frequency
-1The peak of the last one appears in the place, is the sodium alginate-mannan polymer that obtains.
The specific embodiment
Used instrument among the embodiment: freeze dryer, centrifuge,
The preparation example of sodium alginate of the present invention-mannan polymer
Embodiment 1
In reaction bulb, under the room temperature, add the sodium alginate of 20mg and the mannan of 24mg, add the HCl of the 0.1mol/L of 4ml, stir down, react 0.5 hour, use the NaOH of 0.1ml/L, the pH value of above-mentioned solution is transferred to 7; Add the Ammonium Persulfate 98.5 of 1mg and the sodium lauryl sulphate of 1mg again, rise to 60 ℃ with temperature this moment, stirs reaction down 2 hours, uses deionized water wash, the freeze dryer drying, and it is standby promptly to make sodium alginate-mannan polymer.
Embodiment 2
In reaction bulb, under the room temperature, add the sodium alginate of 10mg and the mannan of 20mg, add the HCl of the 0.05mol/L of 4ml, stir down, react 2 hours, use the NaOH of 0.1ml/L, the pH value of above-mentioned solution is transferred to 7; Add the Ammonium Persulfate 98.5 of 0.8mg and the sodium lauryl sulphate of 0.8mg again, rise to 40 ℃ with temperature this moment, stirs reaction down 4 hours, uses deionized water wash, and dry in freeze dryer, it is standby promptly to make sodium alginate-mannan polymer support.
Adopt the conversion ratio height of the sodium alginate-mannan polymer graft polymer of method for preparing, and can come the esterification degree 50%～100% of telomerized polymer, and then change the hydrophilic of polymer by the concentration that changes mannan.
Sodium alginate-mannan the polymer of the present invention's preparation adopts IR to carry out analyzing and testing, and its esterification reaches 100%.
The present invention is with the example of above-mentioned sodium alginate-mannan polymer manufacture targeted nanometer medicine carrier
Embodiment 3 adopts O/W solvent emulsion evaporation to prepare example
In reaction bulb, get sodium alginate-mannan polymer of 1mg, get indissoluble or water-fast antitumor drug vincristine 5mg, be dissolved in the CH of 5ml
2CI
2In, be added dropwise to slowly and contain in the 10ml aqueous solution that percent by volume is 1% surface active agent polyvinyl alcohol (PVA), get emulsion, under the room temperature, stir, reacted 8 hours, make organic solvent evaporation in the emulsion, collect Nano microsphere, use distilled water cyclic washing Nano microsphere more than three times then with the centrifuge high speed centrifugation, promptly make targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
Adopt O/W solvent emulsion evaporation, be applicable to the antitumor drug of or indissoluble insoluble to water, its size of Nano microsphere for preparing by this method is between 200nm～500nm; Can further remove the organic solvent that remains in the microsphere with the freeze dryer preservation; This medicament-carrying nano-microsphere can be with the diseased region of delivering to of antitumor drug vincristine orientation, thereby improves the treatment drug effect of vincristine at lesions position.
Embodiment 4 adopts supersound method to prepare example
In reaction bulb,, be dissolved in the CH of 5ml with sodium alginate-mannan polymer and indissoluble or the water-fast paclitaxel 3mg of 1mg
2Cl
2Get mixed solution in the organic solvent, with ultraemulsifier mixed solution is scattered in and contains in the aqueous solution of 10ml that percent by volume is 5% surface active agent polyvinyl alcohol (PVA), get emulsion, ultrasonic emulsification 5 minutes, ultrasonic power is 50W, stir, remove the organic solvent in the emulsion, reuse centrifuge high speed centrifugation is collected microsphere particle, uses distilled water cyclic washing microsphere particle three times, promptly get targeted nanometer medicine carrier, lyophilizing is preserved standby in freeze dryer.
Adopt supersound method, the microsphere particle of preparation is littler and more even, and its size of Nano microsphere for preparing by this method is between 50nm～200nm; Can further remove the organic solvent that remains in the microsphere with the freeze dryer preservation; This medicament-carrying nano-microsphere can be with the diseased region of delivering to of antitumor drug paclitaxel orientation, thereby improves the treatment drug effect of paclitaxel at lesions position.
Embodiment 5 adopts the equal legal system of high pressure breast to be equipped with example
In reaction bulb,, be dissolved in the CH of 5ml with sodium alginate-mannan polymer of 5mg
2Cl
2In the solvent, gene DNA is dissolved in contains in the 10ml distilled water that percent by volume is 3% surfactant PVA, above-mentioned emulsifying soln is scattered in the aqueous solution of PVA with the high-pressure emulsification machine, emulsion, carry out high-pressure emulsification circulation three times, middling speed stirs, and reacts 2 hours, and the organic solvent evaporation in the emulsion is removed, collect Nano microsphere with high speed centrifugation, with distilled water wash Nano microsphere three times, promptly get targeted nanometer medicine carrier, lyophilizing is preserved standby in freeze dryer.
Adopting its particle diameter of Nano microsphere of the equal method preparation of high pressure breast is 50nm～150nm, and disperses more even; And adopt this method, in preparation process, can not destroy the DNA segment of parcel, and the envelop rate of DNA is higher than 60%; This medicament-carrying nano-microsphere can be with the diseased region of delivering to of antitumor drug gene orientation, thereby improves the treatment drug effect of gene at lesions position.
The present invention adopts the modification group of mannan as sodium alginate micro ball, makes up the novel targeted drug delivery system of tumour-specific, has improved the affinity to the therapeutic goal cell; Prepared medicine carrying microballoons can reach more than 80% the envelop rate of antitumor drug, can be with the diseased region of delivering to of the medicine of microsphere parcel or gene orientation, thus improve the drug effect of lesions position; Having the effect of slow release simultaneously concurrently, is a kind of functional and practical novel drug delivery system.
Claims (10)
1. the preparation method of a targeted nanometer medicine carrier, it is characterized in that, to have the modification group of the mannan of targeting to dendritic cell as sodium alginate, preparation sodium alginate-mannan polymer with the sodium alginate-mannan polymer for preparing, adopts the solvent emulsion evaporation, or supersound method, or the equal method of high pressure breast, the preparation targeted nanometer medicine carrier, the preparation of sodium alginate-mannan polymer comprises following processing step:
(1) at ambient temperature, sodium alginate and mannan are placed container, by weight mannan be sodium alginate 1-2 doubly, in being the acid solution HCl of 0.01-0.1mol/l, concentration carries out esterification, stir down, react after 0.5-2 hour, the pH value of reaction solution is transferred to neutrality;
(2) in above-mentioned reaction solution, add peroxide Ammonium Persulfate 98.5 1-5 weight portion as initiator, add surfactant sodium lauryl sulphate 1-5 weight portion as emulsifying agent, be warming up to 40 ℃-60 ℃, stir down response time 2-4 hour, use deionized water wash, after removing surfactant, dry in freeze dryer, it is standby promptly to make sodium alginate-mannan polymer.
2. preparation method according to claim 1 is characterized in that, described solvent emulsion evaporation, and through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere is between 200nm～300nm:
(1) with the sodium alginate-mannan polymer for preparing, be dissolved in the organic solvent, make it get the mixed solution that concentration is 0.1-5mg/ml, adding accounts for the cosolvent that mixed liquor volume percentage ratio is 0.01-0.1% in this mixed solution, gets composite solution;
(2) indissoluble or water-fast antitumor drug vincristine are dissolved in the above-mentioned composite solution, making its concentration is 1-5mg/ml, be added dropwise to slowly then and contain in the aqueous solution of surfactant that percentage ratio by volume is 1-10%, get emulsion, at room temperature, stirring reaction 4-12 hour, make the organic solvent evaporation in the emulsion;
(3) collect microsphere particle with the centrifuge high speed centrifugation, use distilled water wash microsphere particle at least three times, promptly obtain targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
3. preparation method according to claim 2 is characterized in that, described organic solvent is a dichloromethane, or chloroform, or ethyl acetate; Better in the described organic solvent with the microsphere envelop rate of dichloromethane preparation.
4. preparation method according to claim 2 is characterized in that, described surfactant is a sodium lauryl sulphate, or polyvinyl alcohol.
5. preparation method according to claim 2 is characterized in that, described cosolvent is an acetone, or methanol, or dimethyl sulfoxine.
6. preparation method according to claim 1 is characterized in that, described supersound method, and through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere is between 50nm～150nm:
(1) with the sodium alginate-mannan polymer for preparing, is dissolved in the organic solvent, makes it get the mixed solution that concentration is 0.1-5mg/ml;
(2) use ultraemulsifier, with above-mentioned mixed solution and water-soluble antitumor drug, be scattered in and contain in the aqueous solution of surface active agent polyvinyl alcohol that percentage ratio by volume is 1-10%, the concentration that makes solution is 1-5mg/ml, carried out then ultrasonic emulsification 1-5 minute, ultrasonic power is 50-100W, gets emulsion, stir, remove the organic solvent in the emulsion;
(3) collect microsphere particle with the centrifuge high speed centrifugation, use distilled water wash microsphere particle at least three times, promptly make targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
7. preparation method according to claim 5 is characterized in that, described organic solvent is an acetone, or dichloromethane.
8. preparation method according to claim 5 is characterized in that, described antitumor drug is a paclitaxel, or DNA, or protein.
9. preparation method according to claim 1 is characterized in that, described high pressure breast is method all, and through the targeted nanometer medicine carrier of following processing step preparation, the size of its Nano microsphere particle diameter is between 50nm～150nm:
(1) sodium alginate-mannan polymer is dissolved in the described organic solvent of claim 3, make it get the mixed solution that concentration is 0.1-5mg/ml, with gene, or gene vaccine is dissolved in and contains in the distilled water of surface active agent polyvinyl alcohol that percentage ratio by volume is 1-10%
(2) use high pressure homogenizer, above-mentioned composite solution emulsifying is scattered in accounts in the aqueous solution of surface active agent polyvinyl alcohol that percent by volume is 1-10%, carry out the high-pressure emulsification circulation more than three times, each 2-3 minute, middling speed stirs again, gets emulsion, and the organic solvent evaporation in the emulsion is removed;
(3) collect Nano microsphere with the centrifuge high speed centrifugation, use distilled water wash Nano microsphere at least three times, promptly make targeted nanometer medicine carrier, it is standby to place the freeze dryer lyophilizing to preserve.
10. the targeted nanometer medicine carrier of arbitrary described method preparation among the claim 1-9, it is characterized in that, this targeted nanometer medicine carrier contains sodium alginate and mannan, its content by weight, mannan is 1-2 a times of sodium alginate, this pharmaceutical carrier is to have the targeting administration Nano microsphere medicine-carried system of the mannan of targeting as the modification group of sodium alginate, and the size of its Nano medication microspherulite diameter is between 50nm～300nm.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105396140A (en) * | 2015-12-02 | 2016-03-16 | 浙江医药高等专科学校 | Anti-tumor immunotherapy nano-drug delivery system and construction method thereof |
| CN108096212A (en) * | 2017-12-25 | 2018-06-01 | 河北科技大学 | Preparation method of drug microspheres with hydroxyethyl starch 200/0.5 as carrier |
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| CN1313156C (en) * | 2004-02-06 | 2007-05-02 | 北京圣医耀科技发展有限责任公司 | Sodium alginate microglobule blood vessel suppositery containing gynecoiatry medicine and its preparation method |
| CN1319525C (en) * | 2004-09-16 | 2007-06-06 | 北京圣医耀科技发展有限责任公司 | Taxinol-sodium alginate micro ball vascular embolism agent and its preparation |
| CN1698901A (en) * | 2005-06-15 | 2005-11-23 | 蒋斯扬 | Chitosan or its derivative as drug carrier for carrying red sage root extract |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105396140A (en) * | 2015-12-02 | 2016-03-16 | 浙江医药高等专科学校 | Anti-tumor immunotherapy nano-drug delivery system and construction method thereof |
| CN105396140B (en) * | 2015-12-02 | 2019-07-02 | 浙江医药高等专科学校 | Anti-tumor immunotherapy administration nano-drug administration system and its construction method |
| CN108096212A (en) * | 2017-12-25 | 2018-06-01 | 河北科技大学 | Preparation method of drug microspheres with hydroxyethyl starch 200/0.5 as carrier |
| CN108096212B (en) * | 2017-12-25 | 2020-06-09 | 河北科技大学 | Preparation method of drug microspheres with hydroxyethyl starch 200/0.5 as carrier |
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