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Use of glycine in aspect of preparation of drug delivery reinforcer and cell transplantation reagent

A technology for enhanced delivery and preparation of drugs, applied in the field of biomedicine, can solve the problems of ineffective effect and low transplantation rate in aging muscle atrophy mice

Active Publication Date: 2019-08-23
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The prior art discloses a new type of transport auxiliary agent-hexose, which can efficiently improve the transport efficiency of nucleic acid drugs in muscle tissue, but it has no obvious effect on aging mice with muscle atrophy; and in some patients with muscular dystrophy , patients with late insulin resistance
In addition, the biggest problem facing cell therapy is the low rate of transplantation

Method used

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  • Use of glycine in aspect of preparation of drug delivery reinforcer and cell transplantation reagent
  • Use of glycine in aspect of preparation of drug delivery reinforcer and cell transplantation reagent
  • Use of glycine in aspect of preparation of drug delivery reinforcer and cell transplantation reagent

Examples

Experimental program
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Effect test

experiment example 1

[0129] Different small molecular compounds were mixed with PMO, the total volume was 40 μl, the final concentration of small molecular compounds was 5% (mass volume ratio), and the dose of PMO was 2 μg. Injected into the tibialis anterior muscle, the control group was a mixture of normal saline and PMO, administered once to adult mdx mice at 6-8 weeks, and samples were taken for detection two weeks later. Immunohistochemistry (IHC) and western-blot were used to detect the expression level of dystrophin protein. figure 1 It is the IHC result, and the red part is the dystrophin protein. From the IHC results, it can be seen that the positive regions of the dystrophin protein in the glycine group are more than those in other small molecule compound groups. figure 2 It is a western-blot result and a quantitative statistical chart. It can be seen from the results that the expression level of dystrophin protein in the glycine group is higher than that in other groups.

experiment example 2

[0131] 2.5%, 5% and 10% glycine were mixed with 2 μg PMO respectively, and the total volume was 40 μl, wherein, the final concentration of glycine was 2.5%, 5% or 10%, respectively, and were injected locally once in the tibialis anterior muscle of mdx mice, Samples were taken after two weeks. Immunohistochemistry (IHC) was used to detect the expression level of dystrophin protein. image 3 IHC staining results and quantitative statistical results, the red part is dystrophin protein, from the IHC results, it can be seen that the 5% glycine group has more dystrophin protein positive areas in the nucleic acid drug mixture than 2.5%; similar to the 10% glycine group. Figure 4 It is the result of western blot and quantitative statistics. The quantitative analysis results also show that glycine improves the drug activity of PMO, and the 5% glycine group is better than the 2.5% group, and the effect is close to that of the 10% glycine group.

experiment example 3

[0133] Mix glycine with 2'Ome RNA, B-MSP-PMO, PNA and Pip5e-PMO respectively in a total volume of 40 μl, wherein the final concentration of glycine is 5%, containing 5 μg of 2'Ome or 1 μg of B-MSP-PMO or PNA 5 μg or Pip5e-PMO 1 μg were injected locally in the tibialis anterior muscle. In the control group, normal saline was mixed with respective nucleic acid drugs, and the others were the same as the glycine group, only glycine was replaced with normal saline. They were injected into the tibialis anterior muscle of mdx mice once, and samples were taken two weeks later. Immunohistochemistry (IHC) was used to detect the expression level of dystrophin protein. Figure 5 It is the result of IHC staining and quantitative statistics. The red part is the dystrophin protein. From the IHC results, it can be seen that the glycine group has more dystrophin protein positive areas in different nucleic acid drug mixtures than the control group. Figure 6 It is the result of western blot a...

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Abstract

The invention relates to use of glycine in the aspect of preparation of a drug delivery reinforcer and a cell transplantation reagent and belongs to the field of biomedicines. The use of the glycine in the aspect of preparation of the drug delivery reinforcer is characterized in that drug delivery is reinforced through activating mTORC1 by the glycine; meanwhile, based on new use of the glycine, the invention further provides a novel drug for treating muscular diseases, use of the glycine in preparation of anti-aging drugs, use of the glycine in the aspect of preparation of drugs for muscularfrozen injury and a composition for reinforcing the drug delivery. According to the use, a novel mechanism for reinforcing the drug delivery by the glycine is discovered, the efficiency of drug delivery can be effectively increased, the drug effect is improved, the dosage of drugs is lowered, and the treatment effect is improved.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the use of glycine in the preparation of drug delivery enhancers and cell transplantation reagents. Background technique [0002] The low efficacy of the drug system is the bottleneck of its clinical transformation, especially for nucleic acid drugs. At present, there is a lack of safe and effective methods and systems to improve its systemic efficacy. Especially for muscle tissue, which accounts for one-third of the human body, systemic treatment is the only effective method. Therefore, there is an urgent need to develop new enhancers that can improve the systemic efficiency of drugs (including nucleic acid drugs). In the prior art, different research groups have made a lot of attempts to improve the transport efficiency of nucleic acid drugs in muscle tissue, including the use of polymers, nanomaterials, cell shuttle peptides, etc., but the system effect or safety needs ...

Claims

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Application Information

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IPC IPC(8): A61K47/18A61K31/7088A61K35/34A61P21/00
CPCA61K31/7088A61K35/34A61K47/183A61P21/00
Inventor 尹海芳林曹瑞韩刚
Owner TIANJIN MEDICAL UNIV
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