阅读说明：本技术 一种治疗肝脏缺血再灌注损伤的药物组合物及其制备方法 (Pharmaceutical composition for treating liver ischemia reperfusion injury and preparation method thereof ) 是由 姜力群 王云 白玉婷 王子尧 杨玲 张咪 周峰 张召辉 于 2019-11-25 设计创作，主要内容包括：本发明公开了一种治疗肝脏缺血再灌注损伤的药物组合物及其制备方法,其中,一种治疗肝脏缺血再灌注损伤的药物组合物,其包括,壳聚糖、醛类、阿魏酸；按质量份数计,所述壳聚糖、醛类、阿魏酸的组成比例为：(20～40)：(0.1～5)：(2～40)；一种治疗肝脏缺血再灌注损伤的药物组合物的制备方法,其包括,将醛类搅拌溶解；加入壳聚糖搅拌；加入阿魏酸搅拌；按质量份数计,所述壳聚糖、醛类、阿魏酸的组成比例为：(20～40)：(0.1～5)：(2～40)。该药物组合物可直接用于口服和静脉注射,可有效调控肝脏巨噬细胞分型,将M1型巨噬细胞诱导为M2型,对肝缺血再损伤具有明显的治疗作用。(The invention discloses a pharmaceutical composition for treating liver ischemia-reperfusion injury and a preparation method thereof, wherein the pharmaceutical composition for treating liver ischemia-reperfusion injury comprises chitosan, aldehydes and ferulic acid; the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40); a preparation method of a pharmaceutical composition for treating liver ischemia reperfusion injury comprises dissolving aldehydes under stirring; adding chitosan and stirring; adding ferulic acid and stirring; the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40). The pharmaceutical composition can be directly used for oral administration and intravenous injection, can effectively regulate and control liver macrophage typing, induces M1 type macrophage to M2 type macrophage, and has obvious therapeutic effect on liver ischemia re-injury.)

1. A pharmaceutical composition for treating hepatic ischemia-reperfusion injury, which is characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

chitosan, aldehydes and ferulic acid;

the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40).

2. The pharmaceutical composition for treating hepatic ischemia reperfusion injury of claim 1, wherein: the chitosan is 1-500 kDa chitosan, chitosan oligosaccharide and various salt forms thereof, and the aldehyde comprises one or more of formaldehyde, paraformaldehyde, glutaraldehyde and other mono-aldehyde or multi-aldehyde.

3. The pharmaceutical composition for treating hepatic ischemia reperfusion injury according to claim 1 or 2, wherein: also comprises a nano-scale magnetic substance,

the nano-scale magnetic substance, the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (20-40): (0.1-5): (2-40).

4. The pharmaceutical composition for treating hepatic ischemia reperfusion injury according to claim 3, wherein: the nanoscale magnetic substance is nanoscale iron oxide, and the particle size range of the nanoscale iron oxide is 2-50 nm.

5. The pharmaceutical composition for treating hepatic ischemia reperfusion injury according to claim 3, wherein: the nanoscale magnetic substance nanoscale iron oxide comprises gamma-Fe₂O₃、β-Fe₂O₃Or Fe₃O₄One or more of them, the particle size range is 2-50 nm.

6. A method for preparing a pharmaceutical composition for treating hepatic ischemia-reperfusion injury according to any one of claims 1 to 5, wherein the pharmaceutical composition comprises: comprises the steps of (a) preparing a mixture of a plurality of raw materials,

aldehyde is stirred and dissolved;

adding chitosan and stirring;

adding ferulic acid and stirring;

the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40).

7. The method of preparing a pharmaceutical composition for the treatment of hepatic ischemia reperfusion injury of claim 6, wherein: also comprises the following steps of (1) preparing,

firstly, preparing a nano-scale magnetic substance dispersion liquid, and then stirring and dissolving the aldehydes in the dispersion liquid;

the nano-scale magnetic substance, the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (20-40): (0.1-5): (2-40).

8. The method for preparing a pharmaceutical composition for treating ischemia-reperfusion injury of the liver according to claim 6 or 7, wherein: the nanoscale magnetic substance nanoscale iron oxide comprises gamma-Fe₂O₃、β-Fe₂O₃Or Fe₃O₄One or more of them, the particle size range is 2-50 nm.

9. The method for preparing a pharmaceutical composition for treating ischemia-reperfusion injury of the liver according to claim 6 or 7, wherein: the aldehydes are stirred and dissolved for 0.5-1.5 hours, the chitosan is added and stirred for 0.1-2 hours, and the ferulic acid is added and stirred for 0.1-2 hours.

10. The use of the pharmaceutical composition for treating hepatic ischemia-reperfusion injury according to any one of claims 1 to 5, wherein: the composition can be directly used for oral administration and intravenous injection.

Technical Field

The invention belongs to the technical field of medicines for treating hepatic ischemia-reperfusion injury, and particularly relates to a pharmaceutical composition for treating hepatic ischemia-reperfusion injury and a preparation method thereof.

Background

The ischemia reperfusion injury of the liver refers to the phenomenon that when the liver is subjected to ischemia and hypoxia for a certain time and degree, cells are pathologically changed, and after the blood supply is recovered, the diseased cells can not recover the function necessarily, but the injury is further aggravated. Liver surgery often requires partial or complete blockage of liver blood flow clinically, and thus the occurrence of ischemia-reperfusion injury of the liver is often unavoidable. Multiple studies show that in the liver ischemia-reperfusion occurrence process, a large number of liver macrophages have M1 polarization, the M2 type polarization of the liver macrophages is induced by a specific method, the proportion of the M1 type macrophages in the liver is reduced, and the liver ischemia-reperfusion injury can be effectively relieved.

The invention discloses a composition with the effect of treating liver ischemia-reperfusion injury and a preparation method thereof, wherein the composition can effectively act on liver macrophages, and the liver macrophages are induced from proinflammatory M1 type to inflammation-inhibiting M2 type. Animal experiments show that the mixture can obviously reduce liver injury indexes such as glutamic-oxaloacetic transaminase (AST), glutamic-pyruvic transaminase (ALT) and the like in blood after ischemia reperfusion in liver operation by intravenous injection, and has obvious treatment effect on liver ischemia-reperfusion.

Disclosure of Invention

This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.

The present invention has been made in view of the above-mentioned technical drawbacks.

Therefore, as one aspect of the present invention, the present invention overcomes the disadvantages in the prior art, and provides a pharmaceutical composition for treating ischemia-reperfusion injury of liver and a preparation method thereof.

In order to solve the technical problems, the invention provides the following technical scheme: a pharmaceutical composition for treating ischemia reperfusion injury of liver comprises chitosan, aldehydes, ferulic acid; the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40).

The preferable scheme of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury provided by the invention is as follows: the chitosan is 1-500 kDa chitosan, chitosan oligosaccharide and various salt forms thereof, and the aldehyde comprises one or more of formaldehyde, paraformaldehyde, glutaraldehyde and other mono-aldehyde or multi-aldehyde.

The preferable scheme of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury provided by the invention is as follows: the nano-scale magnetic material, the chitosan, the aldehydes and the ferulic acid are prepared from the following components in parts by weight: (20-40): (20-40): (0.1-5): (2-40).

The preferable scheme of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury provided by the invention is as follows: the nanoscale magnetic substance is nanoscale iron oxide, and the particle size range of the nanoscale iron oxide is 2-50 nm.

As the inventionThe preferable scheme of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury is as follows: the nanoscale magnetic substance nanoscale iron oxide comprises gamma-Fe₂O₃、β-Fe₂O₃Or Fe₃O₄One or more of them, the particle size range is 2-50 nm.

In one aspect, the present invention overcomes the disadvantages of the prior art and provides a method for preparing a pharmaceutical composition for treating ischemia-reperfusion injury of liver, which comprises dissolving aldehydes in a stirring manner; adding chitosan and stirring; adding ferulic acid and stirring; the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (0.1-5): (2-40).

The preferable scheme of the preparation method of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury comprises the following steps: preparing a nano-scale magnetic substance dispersion liquid, and stirring and dissolving the aldehydes in the dispersion liquid; the nano-scale magnetic substance, the chitosan, the aldehydes and the ferulic acid comprise the following components in parts by weight: (20-40): (20-40): (0.1-5): (2-40).

The preferable scheme of the preparation method of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury comprises the following steps: the nanoscale magnetic substance nanoscale iron oxide comprises gamma-Fe₂O₃、β-Fe₂O₃Or Fe₃O₄One or more of them, the particle size range is 2-50 nm.

The preferable scheme of the preparation method of the pharmaceutical composition for treating the hepatic ischemia-reperfusion injury comprises the following steps: the aldehydes are stirred and dissolved for 0.5-1.5 hours, the chitosan is added and stirred for 0.1-2 hours, and the ferulic acid is added and stirred for 0.1-2 hours.

In one aspect, the present invention overcomes the deficiencies in the prior art and provides a pharmaceutical composition for treating ischemia-reperfusion injury of liver, wherein the composition can be directly used for oral administration and intravenous injection.

The invention has the beneficial effects that:

the composition disclosed by the invention can effectively regulate and control liver macrophage typing, and induces M1 type macrophages into M2 type macrophages, and particularly shows that the composition can obviously improve the gene expression level of macrophage IL-10 and obviously improve the cell surface CD206 expression. The composition can be administered intravenously, and can be concentrated in liver after administration, and can be used for reducing liver injury indexes such as AST and ALT in blood after ischemia reperfusion in liver operation by regulating and controlling liver macrophage typing, and has obvious therapeutic effect on liver ischemia reperfusion injury.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:

FIG. 1 is a graph of the particle size of the composition prepared in example 1;

FIG. 2 is a potential diagram of the composition prepared in example 1;

FIG. 3 shows the effect of RT-PCR detection on IL-10 gene expression in M1 type RAW264.7 cells of the composition prepared in example 1;

FIG. 4 shows the results of the uptake of the composition prepared in example 1 by RAW264.7 cells M1 in example 3;

FIG. 5 is a graph showing the effect of the composition prepared in example 1 on the expression of CD206, a surface marker for M1 type RAW264.7 cell typing;

FIG. 6 shows the results of the effect of the composition prepared in example 1 on the ALT and AST indicators of the ischemia-reperfusion injury of the liver of a mouse;

FIG. 7 is a graph of the particle size of the composition prepared in example 6;

FIG. 8 is a potential diagram of the composition prepared in example 6;

FIG. 9 is a particle size plot of the composition prepared in example 7.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with examples are described in detail below.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.

Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.