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Preparation method of liposome and product prepared by preparation method of liposome

A technology of liposomes and plastids, which is applied in liposome delivery, medical preparations containing active ingredients, pharmaceutical formulas, etc., and can solve problems such as uneven particle size distribution of liposomes

Active Publication Date: 2015-07-01
王海龙
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ultrasonic dispersion is a common method for preparing small liposomes, but the particle size distribution of the prepared liposomes is uneven, and a considerable part of the liposome particle size exceeds 100nm
Moreover, strong ultrasonic waves can easily cause the degradation of the drug, and the resulting solution will also be mixed with tiny metal residues produced by the ultrasonic probe.

Method used

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  • Preparation method of liposome and product prepared by preparation method of liposome
  • Preparation method of liposome and product prepared by preparation method of liposome
  • Preparation method of liposome and product prepared by preparation method of liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1 Preparation of very small liposomes of monophospholipid components (the molar ratio of guest molecule to host molecule is 1:5)

[0117] Dissolve 0.01 g of 1-stearoyl-2-oleoyl lecithin (chemical name 1-stearoyl-2-oleoyl-sn-glyceryl-3-phosphocholine, SOPC, molecular weight 788) with 25 ml of chloroform , into a 100 ml round bottom flask, and evaporate the solvent to dryness under reduced pressure. Add 50 mL of phosphate-buffered saline solution containing 1 mmol / L n-dodecyl-β-D-maltoside (nonionic surfactant) to the round bottom flask, pH 7.4. SOPC was completely dissolved in the nonionic surfactant phosphate buffered saline by shaking the round bottom flask. 0.33 g of γ-cyclodextrin (molecular weight 1297) was dissolved in 50 ml of water at room temperature (25° C.) to obtain a 5 mmol / L aqueous solution of γ-cyclodextrin. The SOPC solution was added to the aqueous γ-cyclodextrin solution and mixed under vigorous stirring for 15 minutes. In this way, the SOPC...

Embodiment 2

[0120] Example 2 Preparation of very small liposomes of monophospholipid components (the molar ratio of guest molecule to host molecule is 1:2)

[0121] Dissolve 0.16 g of 1-stearoyl-2-oleoyl lecithin in 50 ml of chloroform, put it into a 250 ml round bottom flask, and evaporate the solvent to dryness under reduced pressure. Into the round bottom flask was added 100 ml of pH 7.4 phosphate buffered saline solution containing 8 mmol / L of n-dodecyl-β-D-maltoside (non-ionic surfactant). SOPC was completely dissolved in the nonionic surfactant phosphate buffered saline by shaking the round bottom flask or applying magnetic stirring. 2.1 g of γ-cyclodextrin was dissolved in 100 ml of room temperature (25° C.) water. The resulting SOPC solution was mixed with the 100 ml aqueous solution of γ-cyclodextrin under vigorous stirring for 15 minutes at room temperature. In this way, the SOPC single-component ultrafine liposome solution is prepared. The particle size of the ultrafine lipo...

Embodiment 3

[0122] Embodiment 3 prepares solid single phospholipid component very small liposome

[0123] 0.32 g of 1-stearoyl-2-oleoyl lecithin (SOPC, molecular weight 788) was dissolved in 50 ml of chloroform, put into a 250 ml round bottom flask, and the solvent was evaporated to dryness under reduced pressure. Add 100 ml of phosphate buffered saline solution containing 16 mmol / L nonyl-β-D-glucoside (non-ionic surfactant) to the round bottom flask, pH 7.4, stir and warm the solution to 55°C , so that SOPC is completely dissolved in the non-ionic surfactant phosphate-buffered saline. Dissolve 4 g of β-cyclodextrin in 100 ml of water at 55°C and keep warm. Mix under vigorous stirring for 15 minutes. Thus, SOPC single-component extremely tiny liposomes are prepared. When standing to room temperature, a pale yellow cyclodextrin-nonylglucoside complex precipitated, and the precipitate was removed by filtration. Continue to lower the temperature to 4°C, precipitate the cyclodextrin-nonyl...

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Abstract

The invention relates to a preparation method of a liposome and the liposome prepared by the preparation method. The preparation method of the liposome comprises the following steps: (1) respectively preparing a lipoid molecule solution and a guest molecule solution; and (2) mixing the mixed lipoid molecule solution prepared in step (1) with a host molecule solution, so as to obtain the liposome. The liposome obtained by the preparation method is a single-compartment liposome of which the particle size is distributed in the range of 15-100nm, especially, in the range of 20-80nm. The invention also provides a preparation method of a drug-carrying liposome as well as the drug-carrying liposome obtained by the preparation method. The liposome or the drug-carrying liposome prepared by the preparation method is small in particle size and narrow in distribution, so that the liposome drug can be more rapidly administered to the lesion to improve curative effect; moreover, the micro-particle-size liposome prepared by the preparation method is capable of reaching the inside of the tumor tissue where the regular liposome cannot reach. Furthermore, the in-vivo transport time of the liposome drug is shortened by the rapid administration of the liposome drug, so that the degradation loss of the liposome drug by the organism enzyme system and the immune system is further reduced so as to reduce the toxic and side effects.

Description

technical field [0001] The invention relates to a preparation method of a liposome and a liposome drug delivery system and the prepared product, in particular to a very small liposome. Background technique [0002] Liposome is a supramolecular structure (microcapsule) similar to a biological membrane bilayer formed by the self-assembly of membrane-forming lipid molecules. It has a double-layer structure with a hydrophilic outer layer and a hydrophobic inner layer. Its size is usually tens of nanometers to tens of microns. Liposomes have been widely used as drug delivery carriers (eg patents CN 1237957C, CN 101371828B, CN 101579312B). Compared with non-drug-loaded liposome drug formulations, drug-loaded liposomes can improve the therapeutic effect of drugs and reduce the toxicity of drugs during in vivo delivery. It embeds, adsorbs or encapsulates drug molecules in liposomes, and delivers the drug to the lesion tissue through the enhanced penetration and retention effect (E...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K31/337A61K31/706A61K31/4709
Inventor 王海龙
Owner 王海龙
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