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Complex and preparation method thereof as well as hydrogel

A complex and hydrogel technology, applied in the field of its preparation, complex and hydrogel, can solve problems such as large side effects, psychological and physiological damage to patients, etc.

Active Publication Date: 2017-06-13
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to its large side effects, it often causes huge psychological and physical harm to patients.

Method used

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  • Complex and preparation method thereof as well as hydrogel
  • Complex and preparation method thereof as well as hydrogel
  • Complex and preparation method thereof as well as hydrogel

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preparation example Construction

[0048] Correspondingly, the present invention provides a kind of preparation method of complex, comprises the following steps:

[0049] The drug reacts with the polymer having the structure of formula (I) or formula (II) in an aqueous medium to form a complex;

[0050]

[0051] where the R 1 Independently selected from -CH 2 -, -(CH 2 ) 2 ; 2 independently selected from H ions, metal cations or organic cations;

[0052] m is the degree of polymerization, 10≤m≤227, preferably 20≤m≤185, more preferably 30≤m≤115;

[0053] n is the degree of polymerization, 10≤n≤226; preferably 20≤n≤180, more preferably 30≤n≤112;

[0054] x is the degree of polymerization, 1≤x≤100; preferably 5≤x≤80; more preferably 3≤x≤50;

[0055] y is the degree of polymerization, 1≤y≤50; preferably 2≤y≤40; more preferably 3≤y≤30;

[0056] p is the degree of polymerization, 2≤p≤50; preferably 2≤p≤40; more preferably 3≤p≤30;

[0057] q is the degree of polymerization, 2≤q≤50; preferably 2≤q≤40; more ...

Embodiment 1

[0126] Azeotrope 6.0 g of aminated polyethylene glycol monomethyl ether with a number average molecular weight of 2000 and 200 mL of toluene at 130 ° C for 3 h to remove water, then vacuum the remaining toluene to dryness; dissolve the obtained solid in 100 mL In dried N,N-dimethylformamide, the first solution was obtained; 9.0 g of γ-ethyl-L-glutamic acid ester-N-carboxylic acid internal anhydride and 4.75 g of γ-benzyl-L-glutamine Amino acid ester-N-carboxylic acid internal acid anhydride was dissolved in 160mL of dry N,N-dimethylformamide to obtain a second solution; in a nitrogen atmosphere, the first solution was mixed with the second solution, at room temperature , stirring and reacting for 80 hours under the protection of nitrogen; after the reaction, drain N,N-dimethylformamide under reduced pressure, then dissolve the obtained solid in chloroform, settle with ether, filter with suction, and dry to obtain Polyethylene glycol monomethyl ether-polyamino acid ester block ...

Embodiment 2

[0129] Azeotrope 3.1 g of aminated polyethylene glycol monomethyl ether with a number average molecular weight of 2000 and 100 mL of toluene at 120 ° C for 3 h to remove water, and then drain the remaining toluene under reduced pressure; dissolve the obtained solid in 30 mL In dried N,N-dimethylformamide, the first solution was obtained; 4.7g of γ-ethyl-L-glutamic acid ester-N-carboxylate and 1.2g of γ-benzyl-L-glutamine Amino acid ester-N-carboxylic acid internal acid anhydride was dissolved in 62mL of dry N,N-dimethylformamide to obtain a second solution; in a nitrogen atmosphere, the first solution was mixed with the second solution, at room temperature , stirring and reacting for 70 hours under nitrogen protection; after the reaction, drain N,N-dimethylformamide under reduced pressure, then dissolve the obtained solid in chloroform, settle with ether, filter with suction, and dry to obtain Polyethylene glycol monomethyl ether-polyamino acid ester block polymer. Undeprotec...

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Abstract

The invention provides a complex which is formed by matching a drug and a polymer with a formula (I) or formula (II) structure. The complex provided by the invention contains polyamino acid with a formula (I) structure obtained by initiating terminal-aminated polyethylene glycol monomethyl ether or polyamino acid with a formula (II) structure obtained by initiating terminal-aminated polyethylene glycol. A PEG chain segment and a polyamino acid chain segment of the polyamino acid have different degrees of polymerization, and block polymers with different structures and hydrogel with different phase change temperatures can be obtained through adjusting the block ratio and the ratio of an ethyl ester group to a carboxyl group. The block polymer provided by the invention has a variety of adjusting methods, so that the adjustability of the formed temperature sensitive hydrogel is good, the adjusting methods for the phase change behavior of the temperature sensitive hydrogel are extended, and the further application of the temperature sensitive hydrogel is facilitated.

Description

technical field [0001] The invention relates to the technical field of polymer materials, in particular to complexes, their preparation methods and hydrogels. Background technique [0002] Due to the rapid growth of solid tumors, the interstitial pressure and fluid pressure are higher than those of normal physiological tissues, which makes it difficult to form effective drug concentrations locally during chemotherapy; in addition, the microenvironment of tumor tissues is complex, which also affects drug diffusion. important reason. However, due to the high toxicity and side effects of chemotherapy drugs in the method of intravenous injection, it is impossible to maintain the effective concentration of drugs in the lesion only by increasing the drug dose. Local tumor chemotherapy is an effective method to increase the effective concentration of drugs at the lesion site and overcome physiological drug delivery barriers. It has received extensive research and attention in rece...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/64A61K31/282A61K33/24A61K9/06A61K47/10A61K47/36A61K47/38A61K47/42C08G69/40A61P35/00
CPCA61K9/0002A61K9/06A61K31/282A61K33/24A61K47/10A61K47/36A61K47/38A61K47/42C08G69/40
Inventor 贺超良于双江陈学思
Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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