CN101954087A - Fucoidan medicinal carrier and preparation method thereof - Google Patents
Fucoidan medicinal carrier and preparation method thereof Download PDFInfo
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- CN101954087A CN101954087A CN 201010281414 CN201010281414A CN101954087A CN 101954087 A CN101954087 A CN 101954087A CN 201010281414 CN201010281414 CN 201010281414 CN 201010281414 A CN201010281414 A CN 201010281414A CN 101954087 A CN101954087 A CN 101954087A
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a fucoidan medicinal carrier and a preparation method thereof. Microspheres are prepared from fucoidan and cationic polymers by an electrostatic cross-linking action by utilizing the polyanionic characteristic of the fucoidan, wherein the grain diameters of the microspheres are between 200 nm and 50 mu m. The preparation method of the invention has the characteristics of simple process and convenience operation, does not relate to a toxic organic solvent, is suitable for keeping the activities of small-molecular medicaments and polypeptide protein medicaments, and is an environmental-friendly carrier; and simultaneously, the carrier has an interventional therapy effect because of the materials per se have various biological activities such as coagulation resistance, blood fat reduction, tumor resistance, virus resistance, body immune function enhancement and the like. Therefore, the carrier has the characteristics of high practicability and wide application prospect.
Description
Technical field
The present invention relates to a kind of fucoidan pharmaceutical carrier and preparation method thereof, belong to bio-medical pharmaceutical carrier technical field.
Background technology
The research of pharmaceutical carrier is one of focus of field of medicaments always, and wherein the exploitation of new material occupies critical role with use in pharmaceutical carrier research.
Fucoidan (Fucoidan) has another name called fucoidan, is a kind of special sulfated polysaccharide that is present in the Brown algae.Fucoidan is a kind of outstanding wholesome food, pharmaceutical raw material, because of the natural sulfate radical that contains, thereby has the characteristic of anionic polymer chemical compound.Studies show that fucoidan has anticoagulation, blood fat reducing, anti-chronic kidney hypofunction, antitumor, antiviral, promotion tissue regeneration, suppresses multiple physiologically actives such as gastric ulcer, enhancing human body immunity function.Fucoidan is a kind of macrophage, T cell to be had direct acting immunomodulator; Pharmacological activity with tangible anticoagulation and fibrinolysis enhancing; Comprise fucoidan or its degradation product energy cancer cell specific induction of apoptosis of sulfate, can be used as inducer of apoptosis and anticarcinogen; Can bring out the generation of cell growth factor, thereby promote various cell growths, reparation is damaged or hypothyroid organ and tissue; Because it has anticoagulant effect,, can be used as thrombotic medicine of prevention or health product so be applicable to the patient that blood viscosity is high; It also has the effect of good blood fat reducing, blood sugar lowering, cholesterol reducing, can overcome some side effect of fat-reducing medicament; Can treat chronic kidney hypofunction, the early stage renal failure effect of centering is remarkable, and to improving renal function, it is particularly remarkable to the creatinine clearance rate effect to improve kidney especially; Can be used as the bonding agent and the resistance vapor of metal ion, reduce more than 70% to the absorption of lead as making human body.
Summary of the invention
The object of the present invention is to provide a kind of fucoidan pharmaceutical carrier and preparation method thereof.Preparation method technology of the present invention is simple, easy to operate, does not relate to poisonous organic solvent, is applicable to that the activity of small-molecule drug and polypeptide protein class medicine keeps, and is a kind of environmentally friendly novel carriers; Simultaneously, because material self has various biological activity such as anticoagulation, blood fat reducing, antitumor, antiviral, enhancing human body immunity function, have the interventional therapy effect, thereby have practical and wide application prospect.
In order to reach above-mentioned purpose, solution of the present invention is:
A kind of fucoidan pharmaceutical carrier utilizes the polyanion characteristic of fucoidan, makes the static crosslinked action of itself and cationic polymer prepare microsphere, and described microspherulite diameter is between 200nm～50 μ m.
A kind of fucoidan preparation of drug carriers method is characterized in that comprising following preparation process:
(1) fucoidan solution is mixed with cationic polymer solution, adopt ultrasonic disruption method and high-speed mixing method emulsifying to prepare the fucoidan microsphere;
(2) be the rate of release of further regulating microsphere, after microsphere and film material solution are blended in the microsphere surface overlay film, be the fucoidan pharmaceutical carrier.
Described cationic polymer solution is one or more the mixed solution in chitosan, poly arginine, polylysine, polyhistidyl, the poly ornithine.
When described cationic polymer was chitosan, solvent was aqueous acetic acid or lactic acid aqueous solution, and when cationic polymer was poly arginine, polylysine, polyhistidyl, poly ornithine, solvent was a water.
Described fucoidan solution concentration is 2% (m/v), and cationic polymer solution concentration is 0.5% (m/v), and described volume ratio is 5: 1-1: 10.
Described volume ratio is preferably 1: 1.
The supersonic frequency 300w of ultrasonic cell disruption instrument in the described step (1), work 3s, 3s intermittently, ultrasonic time 4min; The stir speed (S.S.) of high-speed stirred is not less than 10000rpm, time 5min.
The mixed solution of one or more in the described step (2) in film material solution employing chitosan, poly arginine, polylysine, polyhistidyl, poly ornithine, the polyvinyl alcohol.
Beneficial effect of the present invention is: with fucoidan with physiologically active with to have nutrition and pharmacological effect and biodegradable alkaline polyamino acid/chitosan be material, adopt high-speed mixing method, ultrasonic disruption legal system to be equipped with the fucoidan microsphere; Optimize the influence factor in the regulation and control preparation process; On this basis, at the microsphere surface overlay film, strengthen resistance to mass tranfer; Small-molecule drug and protein and peptide drugs with the different molecular weight representative is model at last, investigates the slow/controlled release performance of this medicine controlled releasing system to different pharmaceutical.
The fucoidan medicine controlled release carrier system of the present invention's preparation is characterised in that: on material is selected, fucoidan has anticoagulation, blood fat reducing, anti-chronic kidney hypofunction, antitumor, antiviral, promotion tissue regeneration, suppresses multiple physiologically actives such as gastric ulcer, enhancing human body immunity function, the catabolite of alkaline polyamino acid/chitosan has Nutrition and pharmacological effect simultaneously, and this product has tangible interventional therapy effect; In addition, owing to do not adopt deleterious organic solvent, environmental protection meets the requirement of current environmentally friendly section bar material in the preparation process of carrier.
The particle diameter of fucoidan microsphere of the present invention between 200nm～50 μ m, no burst effect, this method technology is simple, easy to operate, not relating to poisonous organic solvent, be applicable to that the activity of small-molecule drug and polypeptide protein class medicine keeps, is a kind of environmentally friendly novel carriers; Simultaneously, because material self has various biological activity such as anticoagulation, blood fat reducing, antitumor, antiviral, enhancing human body immunity function, have the interventional therapy effect, thereby have practical and wide application prospect.
The specific embodiment
Embodiment 1
A kind of fucoidan pharmaceutical carrier of present embodiment utilizes the polyanion characteristic of fucoidan, makes the static crosslinked action of itself and cationic polymer prepare microsphere, and described microspherulite diameter is between 200nm～50 μ m.It comprises following preparation process:
(1) preparation 2% (m/v) fucoidan solution mixes with the chitosan solution of 0.5% (m/v), wherein the solvent of fucoidan solution is a water, the solvent of chitosan solution is aqueous acetic acid or lactic acid aqueous solution, all behind 0.22 μ m filtering with microporous membrane, regulate the volume ratio of chitosan and fucoidan, present embodiment has taken turns doing a plurality of parallel tests, and promptly volume ratio was respectively 1: 5; 1: 3; 1: 1; 3: 1; 5: 1; Make suspension at 10: 1 o'clock respectively, carry out subsequent operation respectively.Suspension is put into ultrasonic cell disruption instrument, supersonic frequency 300w, work 3s, 3s intermittently, ultrasonic time 4min.With the emulsion 10 that makes, the centrifugal 5mi n of 000rpm, collecting precipitation, lyophilization 24h obtains the fucoidan microsphere.
(2) being the rate of release of further regulating microsphere, both had been the fucoidan pharmaceutical carrier by microsphere and film material solution being blended in behind the microsphere surface overlay film.Film material solution adopts chitosan solution.
SEM result shows that volume ratio is very big to the form and the grain diameter influence of microsphere.When volume ratio less than 1, along with the increase of chitosan and fucoidan volume ratio, it is spherical that the sample of preparation gradually becomes, the sphere rule that also becomes, when the profit phase volume ratio was 1: 1, the particle diameter of preparation microsphere was less, particle size distribution is comparatively even.But in the time of chitosan and fucoidan volume ratio continuation increase, the microsphere shape of preparation begins again to become irregular, volume ratio also has microsphere when being 3: 1 and 5: 1, and what form when volume ratio increases to 10: 1 is the bulk polymer, can't form micro-sphere structure.
Embodiment 2
A kind of fucoidan pharmaceutical carrier of present embodiment utilizes the polyanion characteristic of fucoidan, makes the static crosslinked action of itself and cationic polymer prepare microsphere, and described microspherulite diameter is between 200nm～50 μ m.It comprises following preparation process:
(1) preparation 2% (m/v) fucoidan solution mixes with the chitosan solution of 0.5% (m/v), wherein the solvent of fucoidan solution is a water, the solvent of chitosan solution is aqueous acetic acid or lactic acid aqueous solution, all behind 0.22 μ m filtering with microporous membrane, get 20mL chitosan solution, being added dropwise to 20mL rapidly is dissolved with the bovine hemoglobin model drug and (perhaps adopts bovine serum albumin, ovalbumin, trypsin, insulin, one or more any collocation of albumen such as superoxide dismutase or polypeptide class macromolecular drug) in the fucoidan solution, make suspension.The medicine concentration of initially offeing medicine is 0.5mg/mL, 1mg/mL, 2mg/mL.Suspension is put into ultrasonic cell disruption instrument, supersonic frequency 300w, work 3s, 3s intermittently, ultrasonic time 4min.With the emulsion 10 that makes, the centrifugal 5min of 000rpm, collecting precipitation, respectively with 40%, 60%, 80%, the dehydration of dehydrated alcohol gradient removes moisture, the electric filament lamp drying is obtained the fucoidan microsphere.
(2) be the rate of release of further regulating microsphere, after microsphere and film material solution are blended in the microsphere surface overlay film, be the fucoidan pharmaceutical carrier.Film material solution adopts chitosan aqueous solution (also can adopt in poly arginine, polylysine, polyhistidyl, the poly ornithine aqueous solution one or more).Get dry microspheres, place 150, film formation reaction 10min in the chitosan aqueous solution of 000Da, 10, the centrifugal 5min of 000rpm, collecting precipitation, respectively with 40%, 60%, 80%, the dehydration of dehydrated alcohol gradient removes moisture, electric filament lamp drying.
According to version Pharmacopoeia of the People's Republic of China drug release determination in 2005, adopt dissolution slurry method determinator to measure the release performance of microsphere.The result shows that microsphere is about 2.0% 0.5 hour burst size, and burst size is less than 30% the prominent amount of releasing requirement in half an hour far below the pharmacopeia regulation, and there is not burst effect in the fucosan microcapsule of visible preparation.The fucoidan microsphere is longer to the release time of bovine hemoglobin, the cumulative release rate of the concentration of respectively offeing medicine when 96h is respectively: 95.1%, 84.8%, 80.0%, dosage is that the microsphere release of 0.5mg/ml is slow than two other, and the cumulative release rate of 96h is 80.0%.
Embodiment 3
A kind of fucoidan pharmaceutical carrier of present embodiment utilizes the polyanion characteristic of fucoidan, makes the static crosslinked action of itself and cationic polymer prepare microsphere, and described microspherulite diameter is between 200nm～50 μ m.It comprises following preparation process:
(1) preparation 2% (m/v) fucoidan solution mixes with the chitosan solution of 0.5% (m/v), wherein the solvent of fucoidan solution is a water, the solvent of chitosan solution is aqueous acetic acid or lactic acid aqueous solution, all behind 0.22 μ m filtering with microporous membrane, get 20mL chitosan solution, be added dropwise to 20mL rapidly and be dissolved with capecitabine model drug (perhaps adopting one or more any collocation of small-molecule drug such as fluorouracil, heparin sodium, cytosine arabinoside, paclitaxel, ftorafur, mitoxantrone hydrochloride, methotrexate, mitomycin).Fucoidan solution in, make suspension.The medicine concentration of initially offeing medicine is 0.5mg/mL, 1mg/mL, 2mg/mL.Suspension is put into ultrasonic cell disruption instrument, supersonic frequency 300w, work 3s, 3s intermittently, ultrasonic time 4min.With the emulsion 10 that makes, the centrifugal 5min of 000rpm, collecting precipitation, respectively with 40%, 60%, 80%, the dehydration of dehydrated alcohol gradient removes moisture, the electric filament lamp drying is obtained the fucoidan microsphere.
(2) being the rate of release of further regulating microsphere, both had been the fucoidan pharmaceutical carrier by microsphere and film material solution being blended in behind the microsphere surface overlay film.Film material solution adopts chitosan and poly-vinyl alcohol solution.Get dry microspheres, place 150, film formation reaction 10min in the chitosan aqueous solution of 000Da, 10, the centrifugal 5min of 000rpm, collecting precipitation, respectively with 40%, 60%, 80%, the dehydration of dehydrated alcohol gradient removes moisture, electric filament lamp drying.Pass through drug release determination: behind the 180h, the cumulative release rate of the fucosan microcapsule of chitosan and polyvinyl alcohol is respectively 79.0% and 92.1%.
Claims (8)
1. fucoidan pharmaceutical carrier is characterized in that: utilize the polyanion characteristic of fucoidan, make the static crosslinked action of itself and cationic polymer prepare microsphere, described microspherulite diameter is between 200nm～50 μ m.
2. fucoidan preparation of drug carriers method as claimed in claim 1 is characterized in that comprising following preparation process:
(1) fucoidan solution is mixed according to a certain volume with cationic polymer solution, adopt ultrasonic disruption method and high-speed mixing method emulsifying to prepare the fucoidan microsphere;
(2) being the rate of release of further regulating microsphere, both had been the fucoidan pharmaceutical carrier by microsphere and film material solution being blended in behind the microsphere surface overlay film.
3. a kind of fucoidan preparation of drug carriers method as claimed in claim 2 is characterized in that: described cationic polymer solution is one or more the mixed solution in chitosan, poly arginine, polylysine, polyhistidyl, the poly ornithine.
4. a kind of fucoidan preparation of drug carriers method as claimed in claim 3, it is characterized in that: when described cationic polymer is chitosan, solvent is aqueous acetic acid or lactic acid aqueous solution, when cationic polymer was poly arginine, polylysine, polyhistidyl, poly ornithine, solvent was a water.
5. a kind of fucoidan preparation of drug carriers method as claimed in claim 2, it is characterized in that: described fucoidan solution concentration is 2% (m/v), cationic polymer solution concentration is 0.5% (m/v), and described volume ratio is 5: 1-1: 10.
6. a kind of fucoidan preparation of drug carriers method as claimed in claim 5, it is characterized in that: described volume ratio is 1: 1.
7. a kind of fucoidan preparation of drug carriers method as claimed in claim 2 is characterized in that: the supersonic frequency 300w of ultrasonic cell disruption instrument in the described step (1), work 3s, 3s intermittently, ultrasonic time 4min; The stir speed (S.S.) of high-speed stirred is not less than 10000rpm, time 5min.
8. a kind of fucoidan preparation of drug carriers method as claimed in claim 2 is characterized in that: the mixed aqueous solution of one or more in the described step (2) in film material solution employing chitosan, poly arginine, polylysine, polyhistidyl, poly ornithine, the polyvinyl alcohol.
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