CN103751149A - Gamma-polyglutamic acid/gelatin nanoparticles loaded with water-insoluble drug and preparation method thereof - Google Patents
Gamma-polyglutamic acid/gelatin nanoparticles loaded with water-insoluble drug and preparation method thereof Download PDFInfo
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Abstract
The invention discloses gamma-polyglutamic acid/gelatin nanoparticles loaded with water-insoluble drug and a preparation method thereof. The method comprises the following steps: preparing an aqueous solution of gamma-polyglutamic acid, an aqueous solution of gelatin and an ethanol solution of water-insoluble drugs; mixing the ethanol solution of water-insoluble drugs with the aqueous solution of gamma-polyglutamic acid to obtain an aqueous solution of gamma-polyglutamic acid containing the water-insoluble drugs; dripping the aqueous solution of gamma-polyglutamic acid containing the water-insoluble drugs into the aqueous solution of gelatin under stirring conditions, continuing to stir for 30 minutes after the dripping operation is ended, and performing vacuum freeze drying on the obtained gamma-polyglutamic acid/gelatin nanoparticle solution loaded with the water-insoluble drugs to obtain the gamma-polyglutamic acid/gelatin nanoparticles loaded with the water-insoluble drugs, wherein the average particle size of the nanoparticles is 298.4-375.3nm, and the polydispersity index is 0.267-0.382. The preparation method is performed under normal temperature and normal pressure, the conditions are mild, and large-scale expanded production is promoted.
Description
Technical field
The present invention relates to the field of nanoparticle load water-insoluble drug, be specifically related to a kind of gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug and utilize gamma-polyglutamic acid-and gelatin carries out by the mode of polyelectrolyte self assembly the method that complex coacervation is prepared the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug for raw material.
Background technology
Gamma-polyglutamic acid-is a kind ofly by D-or Pidolidone, by alpha-amido and γ-carboxyl, to form gamma-glutamyl amine key and be combined into, in gamma-polyglutamic acid-molecular structure, exist a large amount of activated free carboxies because of but a kind of anionic polymer.
Gamma-polyglutamic acid-is a kind of polymer substance of water-soluble biodegradable, has the features such as edibility, avirulence, caking property, moisture retention, and its application is very extensive.In current research report, gamma-polyglutamic acid-is mainly for the higher field of medicaments of added value as pharmaceutical carrier, biological adhesive, secondly gamma-polyglutamic acid-also can be used as flocculating agent, heavy metal chelant for water treatment aspect, can also be as the antifreezing agent of water-retaining agent and fruit, vegetable, antistaling agent for food, health product and cosmetics.
Gamma-polyglutamic acid-has two kinds of modes conventionally as pharmaceutical carrier: a kind of is to utilize the modification to gamma-polyglutamic acid-such as Polyethylene Glycol, L-Phe, benzylamine and alcohol; Another kind of mode is to be directly combined with the medicine such as camptothecine, taxol, penicillamine and cisplatin, and the gamma-polyglutamic acid--medicinal composition making in this way has certain improvement to the water solublity of medicine, half-life, toxicity and slow-releasing etc.
Gelatin is a kind of natural high molecular polymer, has good bio-compatibility and biological degradability, is as the more satisfactory material of microcapsule wall material.Gelatin is protein, in aqueous solution, on strand, contains-NH
2with-COOH and the corresponding group-NH that dissociates thereof
3 +with-COO
-.And contain-NH
3 +with-COO
-ion is how many, is subject to the impact of PH values.When pH value is during lower than the isoelectric point, IP of gelatin ,-NH
3 +number is more than-COO
-, solution is positively charged; When pH value of solution is during higher than the electricity such as gelatin ,-COO
-one number is more than-NH
3 +, solution bear electric charge.Gelatin has good biocompatibility, safety and immunostimulatory activity, is a kind of good natural biological medical material.
Having the microsphere of slow release or control-release function or the research of microcapsule is current focus, and it can also can be for food and essence and flavoring agent field for field of medicaments.The method that is usually used at present preparing microcapsule has emulsion process, spray drying method and complex coacervation etc.The technique of these methods is relatively complicated, and preparation condition is harsher, simultaneously owing to there is plurality of raw materials in reaction system, easily causes that certain side reaction brings by-product.
In sum, gamma-polyglutamic acid-and gelatin are grouped together and make Nano capsule and will have (1) extra small volume and can pass through the thinnest blood capillary, avoid macrophage to remove rapidly, so greatly extend its persistent period in blood; (2) can penetration cell and interstice arrive target organ, as liver, spleen, lung, spinal cord and lymph; (3) can control its release by the temperature sensitivity of biodegradability, pH value, ion and material; (4) can improve drug effect and reduce the character such as toxic and side effects, can be for delivery of medicine, polypeptide, protein, vaccine, nucleic acid, gene etc.
Current gamma-polyglutamic acid-/gelatin nanparticles about load water-insoluble drug and preparation method thereof has no report.
Summary of the invention
One of object of the present invention is to provide a kind of gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
Two of object of the present invention is to provide a kind of mode by polyelectrolyte self assembly to carry out the method that complex coacervation is prepared the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
Technical scheme of the present invention
Gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug, first, compound concentration is that 0.05～5.0g/L gamma-polyglutamic acid-aqueous solution and concentration are 0.1～10.0g/L aqueous gelatin solution;
Then, water-insoluble drug is dissolved in to ethanol, obtains the alcoholic solution of the water-insoluble drug of 0.25～1.5g/L; Described water-insoluble drug is rifampicin, ibuprofen or nifedipine;
Then, again by the alcoholic solution of water-insoluble drug and gamma-polyglutamic acid-aqueous solution by volume, be the alcoholic solution of water-insoluble drug: after the ratio that gamma-polyglutamic acid-aqueous solution is 5:95 is mixed, it is 6.0～9.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug;
Then, under the condition that is 300r/min by the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug in stir speed (S.S.) again, controlling drop rate is that 2.0mL/h is added dropwise in the aqueous gelatin solution that concentration is 0.1～10.0g/L, it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
Finally, by gamma-polyglutamic acid-/gelatin nanparticles solution for vacuum lyophilization of the load water-insoluble drug of above-mentioned gained, obtain the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
The preparation method of the gamma-polyglutamic acid-/gelatin nanparticles of above-mentioned a kind of load water-insoluble drug, specifically comprises the steps:
(1), the preparation of solution
1., the alcoholic solution of water-insoluble drug
Water-insoluble drug is dissolved in to ethanol, obtains the alcoholic solution of the water-insoluble drug of 0.25～1.5g/L;
Described water-insoluble drug is rifampicin, ibuprofen or nifedipine;
2., the preparation of gamma-polyglutamic acid-aqueous solution
Gamma-polyglutamic acid-solid is dissolved in ultra-pure water, and obtaining mass concentration is the gamma-polyglutamic acid-aqueous solution of 0.05～5.0g/L;
3., the preparation of aqueous gelatin solution:
Gelatin solid is dissolved in ultra-pure water, obtains the aqueous gelatin solution that mass concentration is 0.1～10.0g/L, the salt acid for adjusting pH value that is then 1mol/L by concentration is 2.0～5.0;
(2) preparation of the gamma-polyglutamic acid-aqueous solution that, contains water-insoluble drug
By the 2. described gamma-polyglutamic acid-aqueous solution in the alcoholic solution of the 1. described water-insoluble drug in step (1) and step (1) with volume ratio 5:95 mix homogeneously after, it is 6.0～9.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value, be preferably pH8.0, obtain the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug;
(3) under the condition that is, 300r/min by the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug of step (2) gained in stir speed (S.S.), controlling drop rate and be 2.0mL/h is added dropwise in the 3. described aqueous gelatin solution in step (1), it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
(4), by gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug of step (3) gained, in vacuum, be 0.2MPa, temperature is vacuum lyophilization at-55 ℃, obtains the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
Gamma-polyglutamic acid-/the gelatin nanparticles of the load water-insoluble drug of above-mentioned gained, its mean diameter is 250～380nm, and polydispersity coefficient is 0.25～0.40, and preferably mean diameter is 298.4-375.3nm, and polydispersity coefficient is 0.267～0.382.
Further, gamma-polyglutamic acid-/the gelatin nanparticles of the load water-insoluble drug of above-mentioned gained, pass through transmission electron microscope observing, because there is hole its inside, and particle diameter is nanoscale, uniform and stable, and in simulated gastric fluid, intestinal juice environment lentamente, the non-water-insoluble drug by inner at the uniform velocity discharges, and therefore can be used for the water-insoluble drugs such as coated rifampicin, ibuprofen, nifedipine.
Beneficial effect of the present invention
Gamma-polyglutamic acid-/the gelatin nanparticles of a kind of load water-insoluble drug of the present invention, because being mainly utilizes the product gamma-polyglutamic acid-of biofermentation and natural extract product gelatin to prepare load water-insoluble drug nanoparticle for raw material, the two is all through the natural product of modifying, not have good biocompatibility and biodegradability, nontoxic to human body and environment, its mean diameter is 250～380nm, polydispersity coefficient is 0.25～0.40, can be used as ibuprofen, the carrier of the medicines such as nifedipine, also can be for the embedding of functional food and essence, be specially adapted to food and field of medicaments.
In addition, the preparation method of Nano capsule of the present invention is to carry out at normal temperatures and pressures, and condition is gentleer, is more conducive to extensive expanding production.Owing to preparing the system of Nano capsule, be aqueous solution simultaneously, do not need other reagent, so environmentally safe, further can reduce production cost.
The specific embodiment
Below by specific embodiment, the present invention is set forth, but do not limit the present invention.
In various embodiments of the present invention, the specification of raw material used and the information of manufacturer are as follows:
Gelatin: extract approximately 225 wawter blooms, biochemical reagents, Pu Boxin bio tech ltd, Beijing from Corii Bovis seu Bubali skin;
The laser particle analyzer that the present invention is used: Nano-ZS nano particle size laser device, Britain Ma Erwen.
The gamma-polyglutamic acid-that the present invention is used: utilize bacillus subtilis (
bacillus subtilisgIM1.286) by fermenting and producing, obtain gamma-polyglutamic acid-.
Above-mentioned fermenting and producing fermentation medium used is: in 500mL water, and sucrose 20.0g, Carnis Bovis seu Bubali cream 4.0g, sodium glutamate 20.0g, K
2hPO
4﹒ 3H
2o1.0g, MgSO
4﹒ 7H
2o 0.125g is 7.5 with the dilute hydrochloric acid adjusting pH of 1mol/L;
Above-mentioned fermentation production process is as follows:
By in the conical flask of fermentation medium subpackage and 500mL, every bottle of 50mL, with 121 ℃, 0.1MPa sterilizing 20min, be that 5% inoculum concentration is inoculated into seed culture fluid in fermentation medium by volume, 37 ℃, 220r/min condition is cultivated 24h, fermentation liquid through centrifugal, using isopropyl alcohol as organic solvent precipitate, dialysis, lyophilization obtain gamma-polyglutamic acid-solid, purity >=99%;
Above-mentioned seed culture fluid production process is:
(a), picking one ring bacillus subtilis (
bacillus subtilis) be inoculated in slant medium, in constant incubator, cultivate 12 hours for 35～40 ℃, as activated spawn; Wherein said slant medium (LB culture medium) composition is as follows: peptone 1.0g, and Carnis Bovis seu Bubali cream 0.5g, NaCl 0.5g, glucose 0.1g, agar 2.0g, yeast powder 0.2g, distilled water 100ml, pH 7.4～7.5;
(b), strain picking one ring after (a) activation is inoculated in seed culture medium, shaking speed is 180～220r/min, and 35～40 ℃ of shaken cultivation 5～15 hours are as seed liquor;
Wherein said seed culture based component is as follows: sucrose 10～15g, Carnis Bovis seu Bubali cream 2.0～1.8g, sodium glutamate 10～15g, MgSO
47H
2o 0.10～0.15g, K
2hPO
43H
2o 0.4～0.8g, water 300ml, pH 7.0～7.5.
embodiment 1
A preparation method for the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug, specifically comprises the steps:
(1), the preparation of solution
1., the alcoholic solution of water-insoluble drug
Water-insoluble drug ibuprofen 0.0025g is dissolved in to 10ml ethanol, obtains the alcoholic solution of the water-insoluble drug ibuprofen of 0.25g/L;
2., the preparation of gamma-polyglutamic acid-aqueous solution
Gamma-polyglutamic acid-solid 0.0050g is dissolved in 100ml ultra-pure water, and obtaining mass concentration is the gamma-polyglutamic acid-aqueous solution of 0.05g/L;
3., the preparation of aqueous gelatin solution:
Gelatin solid 0.0100g is dissolved in super 100ml pure water, obtains the aqueous gelatin solution that mass concentration is 0.1g/L, the salt acid for adjusting pH value that is then 1mol/L by concentration is 3.0;
(2), by the alcoholic solution of 5ml water-insoluble drug ibuprofen and 95ml gamma-polyglutamic acid-aqueous solution with after volume ratio 5:95 mix homogeneously, it is 8.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug ibuprofen;
(3) under the condition that the gamma-polyglutamic acid-aqueous solution that, 4ml is contained to water-insoluble drug ibuprofen is 300r/min in stir speed (S.S.), controlling drop rate is that 2.0mL/h is added dropwise in 4ml aqueous gelatin solution, it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug ibuprofen obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug ibuprofen that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
(4) by gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug ibuprofen of above-mentioned gained, in vacuum, be, 0.2MPa, temperature is vacuum lyophilization at-55 ℃, obtains the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug ibuprofen.
Gamma-polyglutamic acid-/the gelatin nanparticles of the load water-insoluble drug ibuprofen of above-mentioned gained, its mean diameter is 298.4nm, polydispersity coefficient is 0.267.
embodiment 2
A preparation method for the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug, specifically comprises the steps:
(1), the preparation of solution
1., the alcoholic solution of water-insoluble drug
Water-insoluble drug nifedipine 0.0150g is dissolved in to 10ml ethanol, obtains the alcoholic solution of the water-insoluble drug nifedipine of 1.5g/L;
2., the preparation of gamma-polyglutamic acid-aqueous solution
Gamma-polyglutamic acid-solid 0.5000g is dissolved in 100ml ultra-pure water, and obtaining mass concentration is the gamma-polyglutamic acid-aqueous solution of 5.0g/L;
3., the preparation of aqueous gelatin solution:
Gelatin solid 1.0000g is dissolved in 100ml ultra-pure water, obtains the aqueous gelatin solution that mass concentration is 10.0g/L, the salt acid for adjusting pH value that is then 1mol/L by concentration is 3.0;
(2) preparation of the gamma-polyglutamic acid-aqueous solution that, contains water-insoluble drug nifedipine
By the alcoholic solution of 5ml water-insoluble drug nifedipine and 95ml gamma-polyglutamic acid-aqueous solution evenly after, the sodium hydroxide that is 1mol/L with concentration adjusting pH value is pH8.0, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug nifedipine;
(3) under the condition that the gamma-polyglutamic acid-aqueous solution that, 4ml is contained to water-insoluble drug nifedipine is 300r/min in stir speed (S.S.), controlling drop rate is that 2.0mL/h is added dropwise in 4ml aqueous gelatin solution, it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug nifedipine obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug nifedipine that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
(4) by gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug nifedipine of above-mentioned gained, in vacuum, be, 0.2MPa, temperature is vacuum lyophilization at-55 ℃, obtains the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug nifedipine.
Utilize laser particle analyzer to measure the gamma-polyglutamic acid-/gelatin nanparticles of the load water-insoluble drug nifedipine of above-mentioned gained, its mean diameter is 375.3nm, and polydispersity coefficient is 0.382.
embodiment 3
A preparation method for the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug, specifically comprises the steps:
(1), the preparation of solution
1., the alcoholic solution of water-insoluble drug rifampicin
Water-insoluble drug rifampicin 0.0050g is dissolved in to 10ml ethanol, obtains the alcoholic solution of the water-insoluble drug rifampicin of 0.5g/L;
2., the preparation of gamma-polyglutamic acid-aqueous solution
Gamma-polyglutamic acid-solid 0.1000g is dissolved in 100ml ultra-pure water, and obtaining mass concentration is the gamma-polyglutamic acid-aqueous solution of 1.0g/L;
3., the preparation of aqueous gelatin solution:
Gelatin solid 0.1000g is dissolved in 100ml ultra-pure water, obtains the aqueous gelatin solution that mass concentration is 1.0g/L, the salt acid for adjusting pH value that is then 1mol/L by concentration is 3.0;
(2) preparation of the gamma-polyglutamic acid-aqueous solution that, contains water-insoluble drug rifampicin
By the alcoholic solution of 5ml water-insoluble drug rifampicin and 95ml gamma-polyglutamic acid-aqueous solution evenly after, the sodium hydroxide that is 1mol/L with concentration adjusting pH value is 8.0, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug rifampicin;
(3) under the condition that the gamma-polyglutamic acid-aqueous solution that, 4ml is contained to water-insoluble drug rifampicin is 300r/min in stir speed (S.S.), controlling drop rate is that 2.0mL/h is added dropwise in 4ml aqueous gelatin solution, it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug rifampicin obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug rifampicin that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
(4) by gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug rifampicin of above-mentioned gained, in vacuum, be, 0.2MPa, temperature is vacuum lyophilization at-55 ℃, obtains the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug rifampicin.
Utilize laser particle analyzer to measure the gamma-polyglutamic acid-/gelatin nanparticles of the load water-insoluble drug rifampicin of above-mentioned gained, its mean diameter is 314.8nm, and polydispersity coefficient is 0.279.
Foregoing is only the basic explanation of the present invention under conceiving, and according to any equivalent transformation that technical scheme of the present invention is done, all should belong to protection scope of the present invention.
Claims (4)
1. gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug, is characterized in that being prepared by a method comprising the following steps and obtains:
First, compound concentration is that 0.05～5.0g/L gamma-polyglutamic acid-aqueous solution and concentration are 0.1～10.0g/L aqueous gelatin solution;
Then, water-insoluble drug is dissolved in to ethanol, obtains the alcoholic solution of the water-insoluble drug of 0.25～1.5g/L; Described water-insoluble drug is rifampicin, ibuprofen or nifedipine;
Then, again by the alcoholic solution of water-insoluble drug and gamma-polyglutamic acid-aqueous solution by volume, be the alcoholic solution of water-insoluble drug: after the ratio that gamma-polyglutamic acid-aqueous solution is 5:95 is mixed, it is 6.0～9.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug;
Then, under the condition that is 300r/min by the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug in stir speed (S.S.) again, controlling drop rate is that 2.0mL/h is added dropwise in the aqueous gelatin solution that concentration is 0.1～10.0g/L, it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
Finally, by gamma-polyglutamic acid-/gelatin nanparticles solution for vacuum lyophilization of the load water-insoluble drug of above-mentioned gained, obtain the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
2. the preparation method of the gamma-polyglutamic acid-/gelatin nanparticles of a kind of load water-insoluble drug as claimed in claim 1, is characterized in that specifically comprising the steps:
(1), the preparation of solution
1., the alcoholic solution of water-insoluble drug
Water-insoluble drug is dissolved in to ethanol, obtains the alcoholic solution of the water-insoluble drug of 0.25～1.5g/L;
2., the preparation of gamma-polyglutamic acid-aqueous solution
Gamma-polyglutamic acid-solid is dissolved in ultra-pure water, and obtaining mass concentration is the gamma-polyglutamic acid-aqueous solution of 0.05～5.0g/L;
3., the preparation of aqueous gelatin solution:
Gelatin solid is dissolved in ultra-pure water, obtains the aqueous gelatin solution that mass concentration is 0.1～10.0g/L, the salt acid for adjusting pH value that is then 1mol/L by concentration is 2.0～5.0;
(2) preparation of the gamma-polyglutamic acid-aqueous solution that, contains water-insoluble drug
By the 2. described gamma-polyglutamic acid-aqueous solution in the alcoholic solution of the 1. described water-insoluble drug in step (1) and step (1) with volume ratio 5:95 mix homogeneously after, it is 6.0～9.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value, obtains the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug;
(3) under the condition that is, 300r/min by the gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug of step (2) gained in stir speed (S.S.), controlling drop rate and be 2.0mL/h is added dropwise in the 3. described aqueous gelatin solution in step (1), it is that 300r/min stirs 30min that dropping finishes rear continuation control stir speed (S.S.), gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug obtaining;
The gamma-polyglutamic acid-aqueous solution that contains water-insoluble drug that above-mentioned dropping is used and the amount of aqueous gelatin solution are calculated as by volume the ratio of 1:1 and calculate;
(4), by gamma-polyglutamic acid-/gelatin nanparticles solution of the load water-insoluble drug of step (3) gained, in vacuum, be 0.2MPa, temperature is vacuum lyophilization at-55 ℃, obtains the gamma-polyglutamic acid-/gelatin nanparticles of load water-insoluble drug.
3. the preparation method of the gamma-polyglutamic acid-/gelatin nanparticles of a kind of load water-insoluble drug as claimed in claim 2, while it is characterized in that aqueous gelatin solution preparation that the described concentration of step (1) is 0.1～10.0g/L, the salt acid for adjusting pH value that is 1mol/L by concentration is 3.0;
Described in step (2) by the alcoholic solution of water-insoluble drug and gamma-polyglutamic acid-aqueous solution by volume, be the alcoholic solution of water-insoluble drug: after the ratio that gamma-polyglutamic acid-aqueous solution is 5:95 is mixed, it is 8.0 that the sodium hydroxide that is 1mol/L by concentration regulates pH value.
4. the preparation method of the gamma-polyglutamic acid-/gelatin nanparticles of a kind of load water-insoluble drug as claimed in claim 1, is characterized in that the described vacuum lyophilization of step (4) controls temperature and be-55 ℃, under the condition that pressure is 0.2MPa, carries out.
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| CN109337948A (en) * | 2018-10-18 | 2019-02-15 | 江西师范大学 | Method for improving melting temperature and gel strength of fish gelatin |
| CN111378185A (en) * | 2020-03-31 | 2020-07-07 | 暨南大学 | Bionic proteoglycan nano material and preparation method and application thereof |
| CN115624157A (en) * | 2022-10-13 | 2023-01-20 | 上海暾昊餐饮有限公司 | Special meat pickling liquid and application |
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