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Injectable thermosensitive physical hydrogel and preparation method thereof

A technology of hydrogel and physical water, which is applied in the fields of pharmaceutical formulation, drug delivery, medical science, etc. It can solve the problems of excessive modulus, unsuitable for embedding cells, hindering application, etc., and achieve good biocompatibility and wide application Foreground, effect of improving stability

Inactive Publication Date: 2016-03-16
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] However, when these PEG-PCL block copolymers are used as in-situ hydrogel materials, due to the strong crystallinity and hydrophobicity of the PCL segment, it is not suitable for embedding cells, the solution is unstable, and it is easy to form gel spontaneously at room temperature, and it is not suitable for loading protein drugs.
In addition, the strong crystallinity and hydrophobicity of the PCL segment will also make the hydrogel formed by this material, the viscosity in the sol state is too high to be easy to inject, the modulus in the gel state is too large, and the degradation rate is too slow, etc. , which seriously hinders the application of this material

Method used

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  • Injectable thermosensitive physical hydrogel and preparation method thereof
  • Injectable thermosensitive physical hydrogel and preparation method thereof
  • Injectable thermosensitive physical hydrogel and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0032] Example 1: Poly(caprolactone-co-gamma-benzyl carbamate caprolactone)-polyethylene glycol-poly(caprolactone-co-gamma-benzyl carbamate caprolactone) (P Synthesis of (CL-co-CABCL)-PEG-P(CL-co-CABCL))

[0033] In the state of vacuuming, bake a 10ml polymerization bottle (a glass bottle with a suction device that can be sealed after vacuuming) on ​​a gas lamp for three times to fully remove water. Then feed argon, under the protection of argon, the polyethylene glycol (PEG, 1g) that molecular weight is 1500, caprolactone (CL, 1.2g) and gamma-benzyl carbamate caprolactone (CABCL, 0.05g) into the polymerization bottle. Then put the polymerization bottle in a constant temperature oil bath at 60°C to stir and evacuate for 2 hours to fully mix the raw materials and remove traces of toluene, water and other small molecular impurities that may exist in the raw materials. Next, the catalyst Sn(Oct) was added in an atmosphere protected by argon 2 (one-thousandth of the amount of m...

Embodiment 2

[0034] Example 2: Poly(caprolactone-co-γ-aminocaprolactone)-polyethylene glycol-poly(caprolactone-co-γ-aminocaprolactone) (P(CL-co-ACL)- Synthesis of PEG-P(CL-co-ACL))

[0035]1 g of P(CL-co-CABCL)-PEG-P(CL-co-CABCL) was completely dissolved in 25 mL of tetrahydrofuran, and 0.2 g of palladium on carbon (Pd / C, 10%) was added. The round bottom flask was bubbled three times with dry nitrogen, then hydrogen was continuously bubbled into the flask. After stirring at room temperature for 72 hours, the reaction was stopped, and the Pd / C was filtered out with a floxacin funnel, most of the tetrahydrofuran was removed by rotary evaporation, settled in excess ether, and vacuum-dried for 2 days to constant weight to obtain pure and dry poly(hexyl) Ester-copoly-γ-aminocaprolactone)-polyethylene glycol-poly(caprolactone-copoly-γ-aminocaprolactone) (P(CL-co-ACL)-PEG-P(CL-co- ACL)) polymers. It is 5200 by 1HNMR measurement copolymer relative molecular mass, and the content of the epsilon-...

Embodiment 3

[0036] Embodiment 3: Poly(caprolactone-copoly-4-methylcaprolactone)-polyethylene glycol-poly(caprolactone-copoly-4-methylcaprolactone) (P(CL-co-MeCL )-PEG-P(CL-co-MeCL)) Synthesis

[0037] Under vacuum, bake the 10ml polymerization bottle on the gas lamp three times to fully remove the water. Then pass through argon, under the protection of argon, the polyethylene glycol (PEG, 1g) that molecular weight is 1000, caprolactone (CL, 1.4g) and 4-methyl caprolactone (MCL, 0.2g) Add to the polymerization bottle. Then put the polymerization bottle in a constant temperature oil bath at 60°C to stir and evacuate for 2 hours to fully mix the raw materials and remove traces of toluene, water and other small molecular impurities that may exist in the raw materials. Next, the catalyst Sn(Oct) was added in an atmosphere protected by argon 2 (one-thousandth of the amount of monomer), vacuumize and seal the polymerization bottle. After reacting at 130° C. for 24 hours under sufficient magn...

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Abstract

The invention relates to the technical field of biomedical polymer materials, in particular to injectable thermosensitive physical hydrogel with functional side groups and a preparation method thereof. Polyethylene glycol serves as a hydrophilic block (B), polycaprolactone serves as a hydrophobic block (A), a polymer composition with the functional side groups is connected, an aqueous solution, with a certain mass percentage, of the composition is in a free flowing sol state when the temperature of the aqueous solution is lower than that of a human body and is in a non-flowing gel state when the temperature of the aqueous solution is equal to that of the human body, and conversion from sol to gel is achieved when the low temperature is raised to the high temperature. The hydrogel is injectable and biodegradable, has good biocompatibility and can be widely applied to medicine conveying, cell encapsulation and tissue repair.

Description

technical field [0001] The invention relates to the technical field of biomedical polymer materials, in particular to an injectable temperature-sensitive physical hydrogel with functional side groups and a preparation method thereof. Background technique [0002] Traditional drug administration methods have many limitations, such as: intravenous injection, which does not have a specific targeting effect, and the drug cannot be effectively gathered near the lesion; at the same time, due to blood circulation and multiple When injected, the drug will continue to accumulate in healthy tissues and organs, bringing serious toxic side effects to patients. In response to these problems, the use of drug carriers is very necessary. Excellent drug carriers can control drug release and targeted drug delivery, avoid repeated drug administration, and reduce drug side effects. [0003] In recent years, topical drug delivery based on thermosensitive in situ gels has found application in c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/34A61K9/06A61L27/18A61L27/52A61L27/58C08G63/685C08G63/664
CPCA61K47/34A61K9/0024A61K9/06A61L27/18A61L27/52A61L27/58A61L2300/604C08G63/664C08G63/6852
Inventor 张琰王淼郎美东傅雨桐
Owner EAST CHINA UNIV OF SCI & TECH
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