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Gel-in-oil-in-water emulsion as well as preparation method and application thereof

A gel emulsion and oil-in-water technology, which is applied in the field of biomedicine, can solve the problems of no environmental responsiveness, irritative response, restriction, etc., achieve good biocompatibility and safety, reduce material exchange, and significantly concentration Effect

Pending Publication Date: 2019-03-15
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, double emulsion has the following problems as a delivery carrier: (1) double emulsion is a thermodynamically unstable system, and slight changes in the external environment will lead to emulsion breaking. Therefore, strict control of transportation and storage conditions is required, which greatly limits its use as a delivery carrier. (2) Although the two-step emulsification method is easier to control the ratio of the inner and outer water phases and the distribution of hydrophilic substances than the one-step emulsification method, the re-agglomeration ratio of the inner and outer water phases of the emulsion is large during the preparation process, resulting in complex The embedding rate of milk to hydrophilic substances is not high (generally no more than 60%); (3) in order to obtain stable double emulsion as much as possible, it needs to contain a large amount of self-emulsifying surfactant, which is usually The toxicity is higher than that of ordinary surfactants, and it is easy to cause irritation after a large dose of administration; (4) The drug loaded in the water phase is easily inactivated by contact with the oil-water interface, which is not conducive to embedding drugs, especially biomacromolecules Activity retention of active substances; (5) Surfactant-stabilized emulsions are usually not environmentally responsive
For example, some studies have used high temperature to denature the protein in the internal phase to stabilize the water-in-oil-in-water emulsion, but this preparation method is obviously not suitable for the embedding of active substances
[0006] On the other hand, there are currently few reports reporting the development of oil-in-water gel emulsions and their application as human or animal pharmaceutical preparations.

Method used

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  • Gel-in-oil-in-water emulsion as well as preparation method and application thereof
  • Gel-in-oil-in-water emulsion as well as preparation method and application thereof
  • Gel-in-oil-in-water emulsion as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0120] This example prepares a sol with temperature-stimulated phase transition characteristics

[0121] Adopt electronic balance to accurately weigh 0.3g of matrix material chitosan quaternary ammonium salt (molecular weight is 700,000, deacetylation degree is 90%, quaternary ammonium substitution degree 40%) and 1.4g sodium glycerophosphate. Chitosan quaternary ammonium salt was added into 8 mL of 0.25M lactic acid solution, and magnetically stirred at 25°C overnight to dissolve to obtain chitosan quaternary ammonium salt solution. Dissolve sodium glycerophosphate in 2 mL of deionized water, vortex to dissolve it completely, and obtain sodium glycerophosphate solution. Chitosan quaternary ammonium salt solution and sodium glycerophosphate solution were mixed evenly at 4°C to prepare a solution with temperature-sensitive phase transition characteristics. The prepared sol is tested by a rheometer to obtain the corresponding rheological performance curve, wherein the elastic m...

Embodiment 2

[0127] This example prepares a sol with pH-stimulated phase transition properties

[0128] Accurately weigh 1.5g of Carbomer 971P with an electronic balance and add it to 100mL deionized water to obtain a carbomer solution; accurately weigh 18g of Poloxamer 407 with an electronic balance and add it to 100mL of deionized water, and dissolve completely at 4°C Standby to obtain a poloxamer solution. Take 1mL carbomer solution and 1mL poloxamer solution with a pipette gun, mix and stir evenly, and then a sol with pH-sensitive stimulus phase transition characteristics can be prepared. The prepared sol was tested with a rheometer to detect the critical phase transition pH. Prepare buffer solutions with pH = 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 7.4, 8.0, 9.0, mix the gel with the buffer solution at a volume ratio of 1:9, stir magnetically at a stirring speed of 20 rpm at 25°C, After equilibrating for 10 minutes, the gel viscosity was detected with a rheometer, and the influence of pH on t...

Embodiment 3

[0130] This example prepares a sol with ionic strength-stimulated phase transition characteristics

[0131] Accurately weigh 0.6g of deacetylated gellan gum with an electronic balance and slowly add it to 100mL of deionized water, heat until a clear solution is formed, and cool naturally to room temperature to obtain a gellan gum solution; accurately weigh 10g of poloxa with an electronic balance Poloxamer 407 was added to 100 mL of deionized water and placed at 4°C to completely dissolve for later use to obtain a poloxamer solution. Take 1 mL of gellan gum solution and 1 mL of poloxamer solution with a pipette gun, mix and stir evenly, and then a sol with ionic strength-stimulated phase transition characteristics can be prepared. The prepared sol is tested with a rheometer for critical phase transition ionic strength, and the specific steps are as follows: prepare simulated body fluid (Na + ~150mmol / L, K + ~41mmol / L, Ca 2+ ~8mmol / L) and an electrolyte solution equivalent t...

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Abstract

The invention provides gel-in-oil-in-water emulsion as well as a preparation method and an application thereof. The gel-in-oil-in-water emulsion comprises an internal gel phase, an oil phase and an external water phase, wherein the internal gel phase is coated with the oil phase which is coated with the external water phase. The gel-in-oil-in-water emulsion can be used as a delivery carrier for human or animals, the internal gel phase has good biocompatibility, can be prepared under mild conditions and has environmental stimulus response, a multiple emulsion structure is prepared under mild conditions, and poor stability of multiple emulsion is improved greatly; efficient loading and activity retention of hydrophilic and hydrophobic substances especially bioactive substances can be realized, the condition that in-situ gel can only realize local drug delivery is improved, and the gel-in-oil-in-water emulsion can realize targeted delivery and intelligent controllable release on human andanimals and has extensive application prospects in the fields of vaccine adjuvant preparation, sustained and controlled drug release, targeted drug delivery, disease diagnosis and daily chemical products.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a gel-in-oil-in-water emulsion and its preparation method and application, in particular to a gel-in-oil-in-water emulsion used as a delivery carrier for humans or animals, its preparation method and application . Background technique [0002] In recent years, co-loading multiple drugs into a delivery vehicle for combined administration can achieve excellent synergistic therapeutic effects, so it has broad application prospects in the field of pharmacy. Drugs to be loaded often have different hydrophilicity and hydrophobicity. At present, many carriers have been developed for co-loading hydrophilic drugs and hydrophobic drugs, such as biodegradable polymer particles, liposomes, water-in-oil-in-water complex emulsions, gels, etc. glue system. [0003] Among them, the water-in-oil-in-water composite emulsion has a unique "two-membrane three-phase" structure, which can jointly load hydrop...

Claims

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Application Information

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IPC IPC(8): A61K9/113A61K39/39
CPCA61K39/39A61K9/0009A61K9/113A61K2039/55511A61K2039/575Y02A50/30
Inventor 马光辉吴颉邹勇娟吴楠苗春宇周炜清
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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