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Method for assembling multi-biological functional factor on micro-particle surface based on aldehyde group

A technology of functional factors and assembly methods, applied in the directions of pharmaceutical formulations, medical preparations of inactive ingredients, and bulk delivery, etc., can solve problems such as obstacles to reach the target site smoothly, and achieve the effect of simple operation.

Inactive Publication Date: 2006-05-10
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The monofunctional particles achieved by the above method cannot solve the problem well in some cases, such as the targeting effect of nanoparticles used for cancer treatment in vivo is affected by various biological barriers (such as the blood-brain barrier, BBB), Even if there are targeting substances on their surface, an effective solution is to introduce a variety of functional factors on the surface of the particles, some of which guide the particles through biological barriers such as BBB, while Other factors guide the particles to reach the target site smoothly; as mentioned above, the transport of epidermal growth factor, endothelial growth factor, and nerve growth factor requires targeting at the same time as the load. functionalization to solve

Method used

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  • Method for assembling multi-biological functional factor on micro-particle surface based on aldehyde group
  • Method for assembling multi-biological functional factor on micro-particle surface based on aldehyde group
  • Method for assembling multi-biological functional factor on micro-particle surface based on aldehyde group

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030]1. Preparation of cholesterol hydrophobically modified dextran (Chol-Dex-CHO): (1) Dissolve 1g of cholesterol and 1g of succinic anhydride in 30mL of dry pyridine, react at 70°C for 5h, and recrystallize twice from ethanol , vacuum-dried for 24 hours to obtain cholesterol-3-semisuccinic acid (Chol-Succ); (2) 1 g of cholesterol-3-succinic acid was dissolved in 20 mL of dry chloroform, and 2 mL of chloroform dichloride was added dropwise to the system at 70 ° C sulfone, reacted for 6 hours to generate cholesterol-3-succinic acid chloride (Chol-Succ-COCl), the reaction solution was evaporated to dryness, and then reconstituted by adding 20 mL of dry chloroform; (3) 2 g glucose Polysaccharides were dissolved in 20 mL of deionized water, followed by sodium periodate (NaIO 4 ) and the sugar unit in a molar ratio of 1:5 and reacted for 8 hours, and the reaction solution was dialyzed against deionization with a molecular weight cut-off of 14,000 for 48 hours, and then freeze-dri...

Embodiment 2

[0034] 1. Preparation of Cholic-Sta-CHO hydrophobically modified starch (Cholic-Sta-CHO): (1) Dissolve 1 g of cholic acid in 30 mL of ethanol, form ethyl cholic acid under the catalysis of 4 mL of concentrated hydrochloric acid at 78 ° C, and dissolve the cholic acid Slowly add the ethanol solution of ethyl ester to the ethanol solution dissolved in 5mL of hydrazine hydrate at 78°C, react for 8h, and recrystallize the cooled precipitate with ethanol to obtain cholic acid hydrazide (CAH); (2) Formylate 100mg Starch (the preparation process is the same as that of the aldoglucan in Example 1) was dissolved in 8 mL of water, CAH was dissolved in 16 mL of DMF, and the two solutions were mixed to obtain a homogeneous system, and the molar ratio of CAH to sugar units in the system was 1:10; The pH value of the system was adjusted to 4, reacted at room temperature for 8 hours, the reaction solution was poured into a large amount of methanol to precipitate the product, filtered, fully w...

Embodiment 3

[0038] 1. Preparation of phenoxy hydrophobically modified formaldehyde pullulan (Ph-Pull-CHO): 0.5g formaldehyde pullulan (preparation process is the same as the formaldehyde dextran in Example 1) was dissolved in 20mL 1M hydrogen In sodium oxide (NaOH) solution, feed phenylglycerol ether (1,2-epoxy-3-phenoxypropane) according to the molar ratio of phenylglycerol ether: formaldehyde pullulan unit at 1:10, and react at room temperature for 24 hours, The product was settled in ethanol, dialyzed against deionized water for 24 hours, and freeze-dried to obtain phenoxy-modified formaldehyde pullulan.

[0039] 2. Preparation of microspheres: (1) 2 mg rifampicin, 4 mg Ph-Pull-CHO and 8 mg polycaprolactone were co-dissolved in 4 mL DMSO; (2) at room temperature to pH=9.18 Na 2 CO 3 -NaHCO 4 The buffer solution was dialyzed for 48 hours to form a stable solution with cloudy light; (3) the solution was centrifuged and ultrasonically cleaned to remove unbound Ph-Pull-CHO, and then adde...

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Abstract

The invention discloses an aldehydo-based particle surface multiple biological functional factor assembly method, which comprises the following steps: subjecting gluglucosan, starch or Pullulan to hydroformylation and amphiphilic modification, preparing durg-carrying microballoons from amphiphilic modified hydroformylated polysaccharides and liposolubilc medicament and biologically degradable polymer, separating the microballoon aqueous solution and redispersing into the buffer solution to form microballoon solution, dropping the microballoon solution into buffer solution with dissolved biological factor for incubation, charging sodium borohydride solution into the hatching fluid to reduce unreacted aldehydo radicals and produced Schiff's base, scouring with deionized water, thus obtaining particles with surface assembly of multiple biological functional factors.

Description

technical field [0001] The invention relates to a method for assembling multiple biological function factors on the surface of aldehyde-based microparticles, which belongs to the multiple biological function factor assembly technology. Background technique [0002] Nanoparticles or microspheres are ideal carriers of drugs because of their small particle size, long circulation time in the body, and the protection, control and sustained release of drugs. However, the ideal disease treatment, such as cancer treatment, requires that the drug only acts on diseased tissues or cells, and has no effect on normal tissues, that is, the targeted release of drugs; It has good targeting, such as the transportation of epidermal growth factor, endothelial growth factor and nerve growth factor. The above-mentioned various functional factors need to be combined with carriers, while particles or microspheres based on biodegradable materials such as polylactic acid have good biocompatibility,...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K9/16
Inventor 原续波顾鸣岐田恩江董穆盛京
Owner TIANJIN UNIV