CN114767653B - Preparation method of cellulose-zein-based drug delivery system - Google Patents
Preparation method of cellulose-zein-based drug delivery system Download PDFInfo
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- 229920002494 Zein Polymers 0.000 title claims abstract description 43
- 238000012377 drug delivery Methods 0.000 title claims abstract description 43
- 239000005019 zein Substances 0.000 title claims abstract description 43
- 229940093612 zein Drugs 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 73
- 229940079593 drug Drugs 0.000 claims abstract description 68
- 239000002105 nanoparticle Substances 0.000 claims abstract description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000001913 cellulose Substances 0.000 claims abstract description 26
- 229920002678 cellulose Polymers 0.000 claims abstract description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 18
- 239000000243 solution Substances 0.000 claims abstract description 16
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000004202 carbamide Substances 0.000 claims abstract description 6
- 238000005507 spraying Methods 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 9
- 239000006185 dispersion Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 230000001376 precipitating effect Effects 0.000 claims description 5
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 3
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 3
- 229960004622 raloxifene Drugs 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- 230000002209 hydrophobic effect Effects 0.000 abstract description 16
- 239000003995 emulsifying agent Substances 0.000 abstract description 12
- 238000013270 controlled release Methods 0.000 abstract description 11
- 238000013268 sustained release Methods 0.000 abstract description 11
- 239000012730 sustained-release form Substances 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 8
- 238000001704 evaporation Methods 0.000 abstract description 5
- 239000002245 particle Substances 0.000 abstract description 3
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000012876 carrier material Substances 0.000 description 5
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000001165 hydrophobic group Chemical group 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002356 single layer Substances 0.000 description 2
- 229940083466 soybean lecithin Drugs 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- YFGHCGITMMYXAQ-UHFFFAOYSA-N 2-[(diphenylmethyl)sulfinyl]acetamide Chemical compound C=1C=CC=CC=1C(S(=O)CC(=O)N)C1=CC=CC=C1 YFGHCGITMMYXAQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229960001165 modafinil Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5052—Proteins, e.g. albumin
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of a cellulose-zein-based drug delivery system, which comprises the steps of dissolving zein and a hydrophobic drug in an ethanol solution, evaporating to remove ethanol to obtain zein-drug micro-nano particles, dispersing the micro-nano particles in an aqueous solution containing an edible natural emulsifier to wrap the micro-nano particles, and spraying a sodium hydroxide/urea aqueous solution containing cellulose to prepare the cellulose-zein-based drug delivery system. The cellulose-zein-based drug delivery system prepared by the invention is flaky, has the size of about 30-40 mu m, can be used for oral administration after tabletting, and has good controlled and sustained-release effects on hydrophobic drugs, wherein the particle size of zein-drug micro-nano particles is about 30-40 nm.
Description
Technical Field
The invention relates to a drug delivery system, in particular to a preparation method of a cellulose-zein-based drug delivery system.
Background
The administration route of the medicine is various, including oral administration, intravenous injection, intramuscular injection, subcutaneous injection, sublingual administration, rectal administration, eye drop, nasal cavity spray, oral cavity spray and the like, wherein the oral administration is a very important administration route and a preferred administration route due to the simple administration mode, no direct damage to skin or mucous membrane, low production cost of tablets, relatively low price and the like. However, when some medicines are directly taken orally, there are still many problems, such as the concentrated decomposition and absorption of the medicines in the human body, the high concentration of the medicines has higher toxic and side effects on the human body and organs, the bitter taste of the medicines causes people to have interference to oral medicines, and the large quantity of concentrated release and decomposition of the medicines causes the medicines to be incapable of being continuously taken, so that the administration frequency is required to be increased, and a large amount of medicines are wasted. Therefore, the drug delivery system (Drug Delivery System, DDS) starts to appear, has a controlled and sustained release effect on the drug, reduces the contradiction emotion of a patient to the drug, can avoid the initial burst release of the drug, reduces the administration frequency and the toxic and side effects of the drug to human bodies and organs, and reduces the waste of the drug to the maximum extent.
Currently, drug delivery systems mainly include forms such as directly compressing a drug into a common tablet, loading a drug into a film (single-layer film or multi-layer film sustained release), loading a drug into a matrix material (matrix sustained release), covering a drug surface with one or more coatings (single-layer or multi-layer coatings), and the like. The drug delivery system can realize controlled and sustained release of drugs to a certain extent, but the controlled and sustained release effects of different drug carrier materials are different. Therefore, the selection of DDS drug carrier materials and the design of internal microstructures are key to the excellent controlled-release performance of the drug delivery system.
Based on the characteristics of drug delivery systems during oral administration, the carrier materials are required to have the following characteristics: 1) Cannot be rapidly decomposed or even not decomposed by intestines and stomach; 2) Preferably in a gradually distended state within the stomach so as to allow for slow release of the drug; 3) Is beneficial to intestines and stomach and body; 4) The source is wide, the acquisition is easy and the price is low; 5) The biocompatibility is good, and the absorptivity of the hydrophobic drug can be improved; (6) biodegradable; (7) The DDS can be conveniently and rapidly carried in the medicine bag during the preparation of the DDS. Based on the above requirements, researchers are continuously expanding the scope of exploration of carrier materials. Natural biopolymer materials are attracting great interest and attention as an emerging carrier functional material, such as fats, proteins, polypeptides and polysaccharides, especially proteins. However, if a drug-loaded protein delivery system is directly administered orally, the drug is rapidly decomposed in the gastrointestinal tract and is released explosively, and thus, researchers have considered that a drug delivery system having more excellent controlled-release performance is produced by combining a protein with a polysaccharide having high water solubility or hydrophilicity. However, the main problems faced by this drug delivery system for oral administration are: although the complex application of the polysaccharide with strong water solubility or hydrophilicity and the protein can meet a plurality of requirements of the carrier material, the drug delivery system taking the natural polymer material as the carrier still releases the drug in human intestines and stomach relatively quickly due to the water solubility or the strong hydrophilicity, thereby greatly compromising the controlled and sustained release effect. Meanwhile, considering that the hydrophobic drugs account for 60% of all drugs, entrapment for the hydrophobic drugs must also be studied. Therefore, a proper carrier material needs to be selected and the internal structure of the drug delivery system needs to be designed more reasonably so as to meet all requirements on the carrier material and realize excellent controlled and sustained release of the hydrophobic drug by using the drug delivery system.
Disclosure of Invention
The invention aims to overcome the problems in the prior art and provide a preparation method of a cellulose-zein-based drug delivery system with good controlled and sustained release effects on a hydrophobic drug.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a method of preparing a cellulose-zein-based drug delivery system comprising the steps of:
(1) Under the condition of room temperature, zein and a hydrophobic drug are dissolved in ethanol solution, and then ethanol is distilled out by a rotary evaporator to prepare Zein-drug micro-nano particles;
(2) Dispersing the Zein-drug micro-nano particles in an aqueous solution containing an edible natural emulsifier to wrap the micro-nano particles;
(3) Spraying sodium hydroxide/urea aqueous solution containing cellulose into the dispersion liquid obtained in the step (2), precipitating the cellulose, and encapsulating Zein-drug micro-nano particles, thereby preparing the cellulose-Zein-based drug delivery system with good controlled and sustained release effects on the hydrophobic drug.
The dosage of the hydrophobic drug in the step (1) is 0.1-20% of the mass of Zein, and the volume concentration of the ethanol solution is 65% -95%.
The content of the edible natural emulsifying agent in the aqueous solution containing the edible natural emulsifying agent in the step (2) is 4-10g/L, and the dosage of the aqueous solution is converted according to the condition that the mass of the edible natural emulsifying agent is 10-90% of the mass of zein. The edible natural emulsifier comprises one or more of soybean lecithin, sodium alginate and pluronic f-68 (PF-68).
In the step (3), the mass concentration of cellulose in the cellulose-containing sodium hydroxide/urea aqueous solution is 3-20%, the mass concentration of sodium hydroxide is 4-15%, and the mass concentration of urea is 4-15%; the amount of the aqueous solution is converted by 5-95% of the mass of the cellulose in the aqueous solution.
The invention uses the hydrophobic protein Zein to encapsulate the hydrophobic drug, and uses the cellulose to further encapsulate the drug-encapsulated particles, so as to finally prepare the Zein-cellulose composite drug delivery system. Because Zein is a hydrophobic protein and cellulose is hydrophilic, in order to enhance the molecular acting force of Zein and cellulose, an emulsifier plays a vital role in the design, preparation and research of a novel Zein-cellulose composite carrier. Hydrophobic Zein wraps the hydrophobic drug inside, the hydrophobic group of the emulsifier interacts with the hydrophobic group on the surface of Zein, and the hydrophilic group of the emulsifier can exist stably in cellulose, and the Zein-cellulose composite drug delivery system with the structure shown in figure 1 can be prepared through final vacuum freeze drying.
Compared with the prior art, the invention has the following advantages:
(1) From the raw material, the invention directly applies cellulose instead of cellulose derivatives, thereby realizing the optimization of the technological process;
(2) From the perspective of the solvent, the ethanol is a relatively environment-friendly and easily available substance, is basically harmless to human bodies, evaporates quickly in subsequent treatment, can be removed from the solution quickly, and has no residue; the emulsifier is food grade, and the application is safe;
(3) From the aspects of the preparation method and the operation process, the method is simple, each step is simple and easy to implement, and the energy consumption is low;
(4) From the view of the used equipment, the instruments involved in the invention are all common instruments, and the cost is low;
(5) From the application, the invention has universality on hydrophobic drugs and can prepare a composite carrier with excellent controlled and sustained release performance;
(6) From the degradation process, zein, cellulose and other additives belong to natural substances, and the natural biodegradable cellulose is beneficial to human bodies when being directly used, can be naturally biodegraded, and has no pollution to the environment.
Drawings
FIG. 1 is a schematic diagram of the internal structure of a cellulose-zein-based drug delivery system prepared in accordance with the present invention.
FIG. 2 is a scanning electron microscope image of a cellulose-zein-based drug delivery system prepared in example 1.
FIG. 3 is a scanning electron microscope image of a cellulose-zein-based drug delivery system prepared in comparative example without an emulsifier.
FIG. 4 is a graph comparing drug release of the cellulose-Zein-based drug delivery system with that of Zein-drug micro-nano-particles in example 2.
Detailed Description
In order to make the contents of the present invention more easily understood, the technical scheme of the present invention will be further described with reference to the specific embodiments, but the present invention is not limited thereto.
NaOH-Urea-H used 2 The content of NaOH and Urea in the O solution was 10%.
Example 1
A method of preparing a cellulose-zein-based drug delivery system comprising the steps of:
the first step: at room temperature, dissolving 1g of Zein (Zein) and 0.01g of hydroxycamptothecin into an ethanol solution with the volume concentration of 65%, and evaporating ethanol by a rotary evaporator to prepare Zein-medicine micro-nano particles;
and a second step of: dispersing the Zein-drug micro-nano particles in 50mL of aqueous solution containing 0.1g of soybean lecithin, so that the Zein-drug micro-nano particles are wrapped on the surfaces of the micro-nano particles;
and a third step of: 10mL of NaOH-Urea-H containing 0.3g of cellulose was added 2 Spraying O solution into the dispersion liquid obtained in the step (2), precipitating cellulose, and encapsulating Zein-drug micro-nano particles to obtain the cellulose-Zein-based drug delivery system.
As can be seen from the scanning electron microscope of FIG. 2, the cellulose-Zein-based drug delivery system prepared in this example is in the form of a tablet with a size of about 30-40 μm, wherein the Zein-drug micro-nano particles have a particle size of about 30-40 nm.
The drug delivery system prepared in the embodiment is placed in physiological saline with the temperature of 37 ℃ and the pH value of 7.0 for drug release experiments, and the result shows that the cellulose-Zein-based drug delivery system prepared in the embodiment only releases about 42% of the drug in the previous 4 hours, and is reduced by 16% compared with Zein-drug micro-nano particles.
Comparative example
The first step: at room temperature, dissolving 1g of Zein (Zein) and 0.01g of hydroxycamptothecin into an ethanol solution with the volume concentration of 65%, and evaporating ethanol by a rotary evaporator to prepare Zein-medicine micro-nano particles;
and a second step of: dispersing the Zein-drug micro-nano particles in 10mL NaOH-Urea-H containing 0.3g cellulose 2 In the O solution, the cellulose-zein-based drug delivery system without the emulsifier is prepared.
As can be seen from the scanning electron microscope of FIG. 3, the product prepared in this comparative example is in the form of agglomerated crystals, and the Zein-drug micro-nano particles cannot be wrapped.
Example 2
A method of preparing a cellulose-zein-based drug delivery system comprising the steps of:
the first step: at room temperature, dissolving 1g of Zein (Zein) and 0.1g of raloxifene in an ethanol solution with the volume concentration of 80%, and evaporating ethanol by a rotary evaporator to prepare Zein-drug micro-nano particles;
and a second step of: dispersing the Zein-drug micro-nano particles in 50mL of aqueous solution containing 0.4g of sodium alginate, so that the Zein-drug micro-nano particles are wrapped on the surfaces of the micro-nano particles;
and a third step of: 10mL of NaOH-Urea-H containing 0.5g of cellulose was added 2 Spraying O solution into the dispersion liquid obtained in the step (2), precipitating cellulose, and encapsulating Zein-drug micro-nano particles to obtain the cellulose-Zein-based drug delivery system.
The drug delivery system prepared in the embodiment is placed in physiological saline with the temperature of 37 ℃ and the pH value of 7.0 for drug release experiments, and the result shows that the cellulose-Zein-based drug delivery system prepared in the embodiment only releases about 34% of the drug in the previous 4 hours, and is reduced by 50% compared with Zein-drug micro-nano particles.
Example 3
A method of preparing a cellulose-zein-based drug delivery system comprising the steps of:
the first step: at room temperature, dissolving 1g of Zein (Zein) and 0.2g of modafinil in an ethanol solution with the volume concentration of 90%, and evaporating ethanol by a rotary evaporator to prepare Zein-medicine micro-nano particles;
and a second step of: dispersing the Zein-drug micro-nano particles in 50mL of aqueous solution containing 0.9g of pluronic f-68 (PF-68) so as to wrap the surface of the micro-nano particles;
and a third step of: 10mL of NaOH-Urea-H containing 0.9g of cellulose was added 2 Spraying O solution into the dispersion liquid obtained in the step (2), precipitating cellulose, and encapsulating Zein-drug micro-nano particles to obtain the cellulose-Zein-based drug delivery system.
The drug delivery system prepared in the embodiment is placed in physiological saline with the temperature of 37 ℃ and the pH value of 7.0 for drug release experiments, and the result shows that the cellulose-Zein-based drug delivery system prepared in the embodiment only releases about 52% of the drug in the previous 4 hours, and is reduced by 31% compared with Zein-drug micro-nano particles.
The foregoing description is only of the preferred embodiments of the invention, and all changes and modifications that come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Claims (1)
1. A method of preparing a drug delivery system for raloxifene, comprising: the method comprises the following steps:
the first step: at room temperature, 1g of zein and 0.1g of raloxifene are dissolved in an ethanol solution with the volume concentration of 80%, ethanol is distilled out by a rotary evaporator, and the zein-drug micro-nano particles are prepared;
and a second step of: dispersing the zein-drug micro-nano particles in 50mL of aqueous solution containing 0.4g of sodium alginate, so that the zein-drug micro-nano particles are wrapped on the surfaces of the micro-nano particles;
and a third step of: 10mL of NaOH-urea-H containing 0.5g of cellulose was added 2 Spraying the O solution into the dispersion liquid obtained in the second step, precipitating the cellulose, and encapsulating the zein-drug micro-nano particles to prepare a cellulose-zein-based drug delivery system;
NaOH-urea-H used 2 The content of NaOH and urea in the O solution is 10 percent.
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| 魏东伟.玉米醇溶蛋白膜的改性制备及性能研究.《中国博士学位论文全文数据库 工程科技I辑》.2018,(第6期),第B018-14页. * |
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