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Multifunctional liposome based on ROS sensitivity and H2S response as well as preparation method and application of multifunctional liposome

A liposome, multi-functional technology, applied in the field of medicine, to achieve the effect of delaying the release time, increasing the slow release time, and reducing ROS

Active Publication Date: 2021-07-09
YANTAI UNIV +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is no chemical drug that can significantly improve the body dysfunction caused by acute kidney injury

Method used

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  • Multifunctional liposome based on ROS sensitivity and H2S response as well as preparation method and application of multifunctional liposome
  • Multifunctional liposome based on ROS sensitivity and H2S response as well as preparation method and application of multifunctional liposome
  • Multifunctional liposome based on ROS sensitivity and H2S response as well as preparation method and application of multifunctional liposome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Synthesis of HSYA liposomes

[0043] 1, multi-function carrier PFC synthesis

[0044] The structural formula of the PFC carrier is formula 1:

[0045]

[0046] Synthetic route figure 1 As shown; the specific steps are as follows:

[0047] (1) Precision, 229 mg, EDC 764 mg, and NHS 661 mg, dissolved in 5 ml of DMSO, catalyzed at room temperature for 3 h, and obtained the first solution. Preciseral alkenyl cysteine ​​was 629 mg, dissolved in 30 ml DMSO. The allyl cysteine ​​solution was added dropwise to the first solution, and the reaction was 12 h.

[0048] After the reaction is completed, the reaction solution is 0.5 times CHCl. 3 3 times extraction, and 100ml H 2 O wash 2 times, 10% aqueous citrate solution 100ml washed once, 100ml H 2 O washed twice, saturated NaCl solution was washed once. CHCL 3 Layer, add a certain amount of waterless NA 2 SO 4After 4 hours, centrifugation was allowed to be centrifuged and the product was evaporated to extract the product...

Embodiment 2

[0053] Example 2: Structure of PFC New Carrier

[0054] Through FT-IR, 1 The H-NMR is characterized by the structure of the PFC to verify the success of the new multi-functional materials.

[0055] The PFC new carrier is synthesized by chemical bonds. 1 H-NMR, FT-IR is investigated for new vectors. figure 2 Display, 7.70ppm is NH-CH 2 -PO 3 NH proton absorption peak, 4.83 ppm and 4.68 ppm of ferrocetic acid C 5 Hide 5 Proton absorption peak, 3.58 ppm is Co-NH-CH 2 - NH proton absorption peak, 2.87ppm is S-CH 2 - Proton absorption peak, 1.56ppm is OH-PO 3 -OH proton absorption peak. image 3 Show, 3364.16cm -1 For N-H telescopic vibration peak, 2920.61cm -1 For C-N telescopic vibration peak, 1762cm -1 And 1731cm -1 C = O telescopic vibration peak, 1635cm -1 For C = C telescopic vibration peak, 1427cm -1 1377cm -1 The characteristic peak of the five-membered ring of ferrocetic acid. This verifies the synthesis of the PFC carrier.

Embodiment 3

[0056] Example 3: Study on the performance of HSYA liposomes

[0057] 1. Characterization of the particle diameter and zeta potential of the HSYA liposome by the particle size meter, characterized by the electron transmissive electron microscope (TEM) to characterize the morphology of the liposome.

[0058] Figure 4 The particle size, zeta potential, electron microscope map of the HSYA liposomes is shown. The particles are displayed by particle size, Zeta potential, and the particles are spherical, the size is uniform, the particle size is about 218 nm, the zeta potential is -17.48mV, and dispersion Good nature, better stability.

[0059] 2, HSYA lipid body external release experiment

[0060] The HSYA liposomes were placed in a dialysis bag, which was placed in a 20 mL pH 7.4PBS release medium, and in the shaker of 37 ° C and 120 rpm, in vitro drug release. The release medium of the sample is placed with an equal amount of fresh media, and 0.5 ml is exchanged each time. The resu...

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Abstract

The invention provides a multifunctional liposome based on ROS sensitivity and H2S response as well as a preparation method and application of the multifunctional liposome. The multifunctional liposome comprises a PFC carrier, phospholipid and cholesterol, wherein ROS reaction groups and H2S donors are introduced into the PFC carrier through chemical bonds; meanwhile, the invention also entraps hydroxysafflor yellow A; the mass ratio of the phospholipid to the hydroxysafflor yellow A is (2-4): 1; the molar ratio of the phospholipid to the PFC carrier is (4-8): 1. The ROS reactive group and the H2S donor are introduced into the PFC carrier, and the liposome prepared by using the PFC carrier has ROS sensitivity and H2S response functions. The liposome simultaneously entraps a strong water-soluble drug hydroxysafflor yellow A, so that the slow release time of HSYA is prolonged, the cell penetrating ability of HSYA is improved, and the renal ischemia reperfusion injury is treated in multiple aspects.

Description

Technical field [0001] The present invention belongs to the field of medical technology, and it is specifically related to ROS sensitive and H. 2 S-respond to multi-functional liposomes and preparation methods and applications thereof. Background technique [0002] Renal ischemia-reperfusion injury is one of the main reasons for acute kidney injury, which is characterized in that renal tubular epithelial cell death and loss of renal function. Effective measures for preventing or treating ischemic acute renal injury are: 1 inhibiting renal ischemia-reperfusion induced apoptosis; 2 renal tubular-interstitial inflammatory response; 3 promotes renal tubular epithelial cell proliferation repair. ROS is a series of superoxidized function generated by ROS, such as H. 2 O 2 , O 2 2- Wait. After renal ischemia-reperfusion injury, the inflammatory level reaction produces ROS, resulting in more severe renal tissue damage, wherein neutrophil and macrophage infiltration and inflammatory fact...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/24A61K47/28A61K31/351A61P13/12C07F17/02
CPCA61K9/1272A61K9/1277A61K47/24A61K47/28A61K31/351A61P13/12C07F17/02
Inventor 陈大全周绣棣郭春静陈强李毅于彩薇刘雪苏彦国郭慧敏王金秋弭淑琦刘海东陈小伟葛秀孙长岗衣晓娟
Owner YANTAI UNIV
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