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CN-122005821-A - Starch-based nanoscale drug-carrying system and preparation method thereof

CN122005821ACN 122005821 ACN122005821 ACN 122005821ACN-122005821-A

Abstract

The invention relates to a starch-based nanoscale drug-carrying system and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. The technical problems to be solved are to solve the problems of non-uniform particle size and morphology, potential toxicity caused by using a chemical cross-linking agent, complex operation, poor universality of the preparation process and the like of the product of the existing preparation method. The technical scheme is that the preparation method of the starch-based nano-scale drug-carrying system comprises the following steps of starch debranching treatment, namely adding water into starch to prepare suspension, gelatinizing, cooling and carrying out enzymolysis on the suspension to obtain debranched starch solution, adding alcohol solution of alcohol-soluble drugs into the debranched starch solution, uniformly mixing to obtain hydrophilic phase, emulsion preparation, namely mixing and emulsifying the hydrophilic phase with oil phase to obtain emulsion, wherein the oil phase is grease containing surfactant, and freeze-drying, centrifuging and separating the emulsion to obtain the starch-based nano-scale drug-carrying system.

Inventors

  • LI TAO
  • QIU DAN
  • CHEN XINGZHU
  • Pei Zhiduo
  • Zhuang Xuechen
  • ZHANG ZHIGUO
  • MAO LIKE
  • YU XINA
  • YUAN TAO

Assignees

  • 浙大宁波理工学院
  • 嘉兴顶晟健康科技有限公司

Dates

Publication Date
20260512
Application Date
20260213

Claims (9)

  1. 1. The preparation method of the starch-based nanoscale drug-carrying system is characterized by comprising the following steps of: (1) Starch debranching treatment, namely adding water into starch to prepare suspension, gelatinizing, cooling and carrying out enzymolysis on the suspension to obtain debranched starch solution; (2) Adding the medicine, namely uniformly mixing the debranched starch solution obtained in the step (1) with the alcohol solution of the alcohol-soluble medicine to obtain a hydrophilic phase; (3) The preparation of emulsion, namely mixing the hydrophilic phase obtained in the step (2) with an oil phase, and emulsifying to obtain emulsion, wherein the oil phase is grease containing a surfactant; (4) And (3) freeze-drying, centrifuging and separating the emulsion obtained in the step (3) to obtain the starch-based drug-carrying system.
  2. 2. The method according to claim 1, wherein the starch comprises at least one of corn starch, waxy corn starch, bean starch, potato starch, sweet potato starch, wheat starch, tapioca starch, amaranth starch, rice starch, water chestnut starch, lotus root starch, kudzuvine root starch, and chufa starch.
  3. 3. The process according to claim 1, wherein the starch content of the suspension of step (1) is 1-25w/v%.
  4. 4. The method of claim 1, wherein the gelatinization in step (1) is carried out by heating the suspension at 60-100 ℃ for 0.2-3 hours, and the cooling in step (1) is carried out at 40-80 ℃.
  5. 5. The preparation method according to claim 1, wherein the enzymolysis in the step (1) is the enzymolysis and enzyme deactivation by using isoamylase, preferably the enzymolysis and enzyme deactivation by using pullulanase; The enzymolysis of the isoamylase comprises adding 10-100U/g isoamylase based on starch dry basis, stirring at 45-75deg.C for 4-24 hr, and/or The pullulanase is prepared by adding 20-150U/g pullulanase based on starch dry basis, and stirring for 2-24h at 45-75 ℃.
  6. 6. The method of claim 1, wherein the alcohol-soluble drug of step (2) comprises at least one of vitamin E acetate, vitamin E, paclitaxel, curcumin, vitamin D3, vitamin a acetate, vitamin a, fish oil; And/or The alcohol in the step (2) comprises at least one of methanol, ethanol, isopropanol and tertiary butanol.
  7. 7. The method according to claim 1, wherein the alcohol-soluble drug in step (2) is contained in an alcohol solution at a concentration of 2-20mg/ml, and/or The volume ratio of the debranched starch solution to the alcohol solution of the alcohol-soluble medicine is (2.5-9): 1.
  8. 8. The process according to claim 1, wherein the oil or fat in the step (3) is an organic medium which is not miscible with water, and/or The surfactant in the step (3) comprises nonionic surfactant and/or zwitterionic surfactant, wherein the surfactant comprises at least one of sorbitan fatty acid ester, polyglycerol fatty acid ester, sucrose fatty acid ester and lecithin, and/or The concentration of the surfactant in the grease in the step (3) is 0.5 to 10 weight percent, and/or The volume ratio of the hydrophilic phase to the oil phase in the step (3) is 1 (2-10), preferably 1 (4-8), and/or The emulsification in the step (3) is carried out by high-speed shearing emulsification for 1-30min at 5000-20000rpm, and/or The condition of freeze drying in the step (4) is that the freeze drying is carried out for 2-12 hours at the temperature of minus 85 ℃ to minus 10 ℃, and the freeze drying is carried out for 20-72 hours in a freeze dryer with the cold trap temperature of minus 80 ℃ to minus 50 ℃ and the vacuum degree of 5-150 pa.
  9. 9. The starch-based nano-scale drug delivery system prepared by the preparation method of any one of claims 1-8.

Description

Starch-based nanoscale drug-carrying system and preparation method thereof Technical Field The invention provides a starch-based nanoscale drug-carrying system and a preparation method thereof, belonging to the technical field of pharmaceutical preparations. Background Starch is a natural, renewable biopolymer that has received great attention in the field of drug delivery vehicles because of its good biocompatibility, degradability and low cost. The structure is mainly composed of amylose (linear chain linked by alpha-1, 4-glycosidic bond) and amylopectin (branched by alpha-1, 6-glycosidic bond). However, natural starch has strong crystallinity, poor solubility and dispersibility, and is difficult to be directly used for constructing a high-efficiency and uniform drug-carrying system. At present, various preparation methods of starch-based drug-carrying systems are developed, and mainly comprise a physical method, an acid hydrolysis method, a self-assembly method, an emulsion crosslinking method and the like. The physical method (such as mechanical grinding, ultrasonic treatment and high-pressure homogenization) is simple and convenient to operate, but the particle size of the product is larger and the distribution is uneven, the acid hydrolysis method utilizes sulfuric acid or hydrochloric acid to erode the amorphous region of starch particles, but has the problems of low recovery rate and easy particle aggregation, the self-assembly method can form regular molecular structures, but natural starch is not modified and is difficult to directly construct effective drug-carrying particles, and the emulsion crosslinking method is used for forming microspheres by emulsifying starch solution in an oil phase and then curing the microspheres through a crosslinking agent, but chemical crosslinking agent used in the process possibly remains and introduces potential cytotoxicity risks. The traditional microsphere preparation method often has the limitations of difficult regulation and control of particle size, wide particle distribution size and the like. The Zhi and the like realize the preparation of nanospheres with uniform particle size (100-150 nm) through chemical modification (such as hydroxypropylation), but the introduction of non-natural components (Dual-modified starch nanospheres encapsulated with curcumin by self-assembly: Structure, physicochemical properties and anti-inflammatory activity." International Journal of Biological Macromolecules,2021, 191: 305–314.）;Zhuang and the like which directly wrap fat-soluble drugs （Preparation, characterisation and evaluation of loading paclitaxel into debranched corn starch." Industrial Crops and Products,2025, 229: 120969.）, by debranched starch are limited by specific crystallization behaviors of the drugs, and have insufficient universality and morphology controllability. The methods can not simultaneously meet the key requirements of green safety, strong universality and accurate and controllable morphology and particle size. Literature Enzymatic Debranching of Starch: Techniques for Improving Drug Delivery and Industrial Applications（doi.org/10.1002/star.202400224） discloses that the enzymatic debranching modified starch has great potential in the field of drug delivery, can be used as an auxiliary material of oral solid preparations (such as tablets and capsules), improves the dissolution rate of insoluble drugs, enhances the stability of the drugs and realizes controlled release, but does not relate to direct drug loading and particle size regulation of a drug loading system. The related patent documents: Publication No. CN101439183B, publication No. 2008.12.19, discloses a method for preparing pharmaceutical excipients from starch, comprising the steps of: (1) Dispersing starch in water to obtain starch milk with a mass of 5-40%, heating the starch milk to 90-95deg.C, adding high temperature resistant alpha-amylase at the temperature of 10-25 activity units/g dry starch, and liquefying for 10-20min; (2) Adding acetic acid-sodium acetate buffer solution to adjust the pH of the solution obtained in the step (1) to be acidic, adding pullulanase or isoamylase at 40-70 ℃ with the dosage of 1-12 activity units/g dry starch, and preserving the temperature for 1-24h; (3) Heating the solution obtained in the step (2) to 80-90 ℃ and maintaining for 20min to inactivate enzymes; (4) Adding NaOH solution, adjusting pH to 6.5-7.0, standing at 4deg.C for coagulating sedimentation for 24-48 hr; (5) Filtering, drying and pulverizing. But adopts the method of enzymolysis of alpha-amylase and then pullulanase, starch is directly changed into dextrin with complex structure, and the drug carrying capacity is lost. Therefore, the starch-based nano drug-carrying system capable of effectively loading the alcohol-soluble drug is constructed through non-chemical modification of starch and simple process, and has important innovation significance and application value. Disclosure of