Orally taken nanometer protein polypetide composition particle and its prepn

A technology of protein peptides and complexes, which is applied in the field of medicine, can solve the problems of phospholipid bilayer membrane instability, protein instability, and short half-life, and achieve the effects of improving oral bioavailability, ensuring biological activity, and mild preparation process

Inactive Publication Date: 2006-05-17
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the main problems faced by protein and polypeptide drug preparations are: the half-life is very short, and the stability is poor; active
Numerous literatures have reported that nanoscale liposomes can significantly improve the oral bioavailability of insulin ( Degim Z .The effect of various liposome formulations on insulin penetration across Caco-2 cellmonolayer.Life Sci.2004 Oct 22;75(23):2819-27. Spangler RS .Insulinadministration via liposomes.Diabetes Care.1990 Sep; 13(9):911-22.), but due to the instability of the phospholipid bilayer membrane, the encapsulation rate of the drug is very low, and it is easy to gather and leak after long-term placement; recently The emergence of solid lipid nanoparticles with high melting point lipid materials as carriers makes up for the membrane instability of liposomes, but the preparation process requires severe conditions such as high temperature and high shear force, and its hydrophobicity makes water-soluble proteins Drug encapsulation rate (<60%) is low (Almeida. Peptide-loaded solid lipid nanoparticles (SLN): influence of production parameters. Int JPharm. 1997 April 28; 149 (2): 255-6.)
Chinese patents CN1253018A, CN1562356A, and CN1579546 all use biodegradable polymer materials such as PLGA (lactic acid-glycolic acid copolymer) as carriers to make polymer nanoparticles that wrap insulin, but there are still low drug encapsulation rates and protein aggregation. Long-term instability problems in biomaterials

Method used

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  • Orally taken nanometer protein polypetide composition particle and its prepn
  • Orally taken nanometer protein polypetide composition particle and its prepn

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0010] Embodiment 1: Preparation of insulin-phospholipid complex by vacuum evaporation method

[0011] Take 50mg of porcine insulin powder and 1000mg of soybean lecithin for injection and dissolve in 5ml of acidic ethanol solution, and stir at 400r / min until a clear solution is formed. The solution was evaporated under reduced pressure at 35° C. for 2 hours, and then dried again with nitrogen gas for 15 minutes to obtain a golden-yellow phospholipid film of composite insulin.

Embodiment 2

[0012] Embodiment 2: Preparation of insulin-phospholipid complex by freeze-drying method

[0013] Take 30 mg of insulin and 800 mg of soybean lecithin for injection and dissolve them in 5 ml of dimethyl sulfoxide, and stir at 400 r / min until a clear solution is formed. This solution was lyophilized for 12 hours to obtain a dry white loose powder.

Embodiment 3

[0014] Example 3: Preparation of polylactic acid co-precipitated lipid complex nanoparticles containing insulin

[0015] Dissolve 500 mg of DL-polylactic acid with a molecular weight of 10,000 in 5 ml of dichloromethane-acetone mixed solvent (the ratio of the two is 1:5), and stir evenly. Add 50 mg of the insulin-containing phospholipid membrane prepared in Example 1 into the polymer solution, and stir until clear. The above solution was poured into an aqueous solution containing 2% polyvinyl alcohol, stirred at room temperature at 400 r / min for 6 h, and after the solvent was evaporated, a blue opalescent nanosuspension was obtained. SEM photo see figure 1 . The measured encapsulation efficiency was 92%.

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Abstract

The present invention is one kind of orally taken nanometer protein polypeptide composition particle with enveloping rate higher than 90 % and medicine carrying amount up to 3-10 %. The mild preparation process without high temperature, high speed shearing and other intense condition can ensure the bioactivity of the polypeptide medicine. The preparation process includes dissolving water soluble protein polypeptide medicine and amphiphilic lipid material in non-water solvent I, eliminating solvent to form protein-lipid composition, dissolving the composition and proper polymer material in non-water solvent II to coat the composition inside the polymer material through emulsified solvent diffusion in liquid phase, and volatilizing the solvent to form particles of size 10-500 nm. The present invention is suitable for preparing oral medicine preparation.

Description

technical field [0001] The invention relates to the technical field of medicine, specifically, it is a protein polypeptide complex nanoparticle for oral administration and its preparation method Background technique [0002] With the rapid development of biotechnology, there are more and more biotech drugs (mainly protein and polypeptide drugs), and will become one of the mainstream drugs in the future. For a long time, this type of drug has been clinically based on injections (water injection and powder injection), but frequent injections for a long time will bring a lot of inconvenience and pain to patients. Therefore, medical workers at home and abroad have been devoting themselves to the research of non-injection administration routes of protein and polypeptide drugs, among which oral administration has always been the most acceptable route of administration for patients. At present, the main problems faced by protein and polypeptide drug preparations are: the half-life...

Claims

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Application Information

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IPC IPC(8): A61K9/16A61K38/16A61K38/28A61P3/10
Inventor 崔福德石凯
Owner SHENYANG PHARMA UNIVERSITY
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