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Drug-loaded hydrogel with enzyme and temperature dual responsibility and preparation method and application of drug-loaded hydrogel

A responsive, liquid medicine technology, applied in the fields of medical formula, medical science, capsule delivery, etc., can solve the problems of collapsed dissolution, loss of drug molecules, inconvenience, etc., to achieve prolonged action time, reduce patient pain, and easy to use Effect

Active Publication Date: 2017-08-04
FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In order to avoid toxic and side effects on the body caused by the peak concentration of the drug in a short period of time, and the inconvenience and pain caused by multiple dressing changes caused by too fast drug metabolism, there is an urgent need for a drug molecule to be encapsulated in a stable carrier to form a sustained release system. , a wound dressing that releases gradually at the wound site
[0003] However, at present, wound dressings with drug sustained-release systems cannot be widely used for the following reasons: First, when the drug is entrapped in a stable carrier to form a suspension, it is not easy to fit on the wound surface, and it is easy to cause the loss of drug molecules, resulting in the inability of the drug. Reaching the lesion, eventually resulting in a single dose that cannot be maximized, still unable to solve the problem of multiple dressing changes
Secondly, due to the poor water solubility of many drug molecules, it is difficult to effectively dissolve in the water-soluble liquid environment in the body and reach the effective concentration, thus failing to exert clinical pharmacological effects
Thirdly, the effect of disintegration and release of drug molecules in the body of the carrier containing the drug molecules is not ideal. For example, the carrier cannot be dissolved in the body, so that the drug molecules cannot be released and exert pharmacological effects; the carrier will collapse and dissolve when it enters the body, and the drug molecules The release is uncontrollable; after the drug particle molecules are locally enriched from the wound surface, they will enter the microcirculation and then enter the systemic circulation system, resulting in the inability of the drug to reach an effective therapeutic concentration in the local lesion, and the distribution to other tissues of the body may cause unexpected toxic side effects

Method used

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  • Drug-loaded hydrogel with enzyme and temperature dual responsibility and preparation method and application of drug-loaded hydrogel
  • Drug-loaded hydrogel with enzyme and temperature dual responsibility and preparation method and application of drug-loaded hydrogel
  • Drug-loaded hydrogel with enzyme and temperature dual responsibility and preparation method and application of drug-loaded hydrogel

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preparation example Construction

[0038] In the preparation process of the carrier, the inventor tried to select natural materials or clinically approved materials as raw materials, such as gelatin, chitosan, modified starch, etc. The combination of these raw materials and nano-sized drugs can ensure that the drug has better clinical safety; and it is finally determined that when the particle size of the carrier is 1-20 μm, it can be enriched around the lesion and not enter the blood in the case of local application. circulatory system.

[0039] Gelatin is an analogue of the extracellular matrix obtained from acid-denatured pig skin. Due to the evolutionary conservation of the extracellular matrix of vertebrates (even including some invertebrates) (for example, collagen maintains the structural pattern of Gly-X-Y from lower animals to humans), the possibility of causing immune rejection in organisms lower. Gelatin is a denatured extracellular matrix, which can be used as a substrate for matrix metalloprotein...

Embodiment 1

[0087] (1) Nano-drugs: Dissolve curcumin as a drug in tetrahydrofuran to form a drug solution with a concentration of 0.1 mg / ml, stir physiological saline at a speed of 2000 rpm, then slowly add the drug solution therein, and stir evenly After 30 minutes, a curcumin nanoparticle solution was formed; after standing still for 24 hours, the THF was removed by rotary evaporation, and then freeze-dried at a vacuum degree of 9 Pa at a temperature lower than -50° C. to obtain curcumin nanoparticles. The average particle diameter of curcumin nanoparticles is 50-100nm.

[0088] (2), forming drug-loaded gelatin microspheres: adding gelatin to double-distilled water, stirring at 55° C. at 800 rpm to obtain a 10wt% gelatin solution; slowly adding the curcumin nanoparticles obtained in step (1) to the gelatin solution, fully Stir for 2h to form an aqueous phase. Take 4.5ml of liquid paraffin, add 45μl of Span-80 (Span-80), stir evenly at 55°C and 800rpm to form an oil phase. Slowly and e...

Embodiment 2

[0091] (1), nano-ization of medicine: dissolving curcumin as medicine in ethanol to form a medicine solution with a concentration of 5 mg / ml, stirring physiological saline under the condition of 700 rpm, then slowly adding medicine solution therein, and stirring evenly for 2 hours , forming a curcumin nanoparticle solution; after standing still for 24 hours, the ethanol was removed by rotary evaporation, and then freeze-dried at a vacuum degree of 7 Pa at a temperature lower than -50° C. to obtain curcumin nanoparticles. The average particle diameter of curcumin nanoparticles observed under scanning electron microscope is 100nm.

[0092] (2), forming drug-loaded gelatin microspheres: adding gelatin to double-distilled water, stirring at 55°C at 1500rpm to obtain a 10wt% gelatin solution; slowly adding the curcumin nanoparticles obtained in step (1) to the gelatin solution, fully Stir for 0.5h to form an aqueous phase. Take 4.5ml of liquid paraffin, add 45μl of Span-80 (Span-8...

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Abstract

The invention discloses a drug-loaded hydrogel with enzyme and temperature dual responsibility and a preparation method and application of the drug-loaded hydrogel. The drug-loaded hydrogel comprises the following raw materials: 0.01-1% of a nano-crystallized drug, 0.5-25% of gelatin, 10-30% of poloxamer F127, 2-15% of poloxamer F68 and the balance of solvent. The drug-loaded hydrogel can be gathered on the periphery of a focus; and the nano-crystallized drug is gradually released hierarchically and gathered on a target site under the action of a focus characteristic molecule MMP9, plays a pharmacologic effect and can be used for treatment of diseases such as a burn, a war injury, an operative wound, a cold injury, skin-related tumors, a skin infection disease, a sexually transmitted disease, an oral disease, baldness and panneuritis epidemica, and the action time can be prolonged. The drug-loaded hydrogel is convenient to use and simple in operation, frequent dressing change is not needed and the pain of a patient is reduced.

Description

technical field [0001] The invention relates to the technical field of wound dressings, in particular to an enzyme- and temperature-responsive drug-loaded hydrogel and a preparation method and application thereof. Background technique [0002] Commonly used wound dressings are in the form of hydrogels, which can directly act on the lesion, act on the corresponding receptors, exert pharmacological effects, and produce clinical curative effect. However, after the hydrogel-like wound dressing contacts the lesion, the drug loaded will quickly enter the body, making the drug concentration exceed the concentration of the drug effect, reaching a toxic concentration; in addition, because the drug enters the body too quickly and is metabolized, The time to produce clinical curative effect is too short, so that the lesion has not recovered, and the drug has been metabolized and excreted, which needs to be solved by frequent replacement of wound dressings. In order to avoid toxic and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L26/00
CPCA61L26/0019A61L26/0038A61L26/0066A61L26/008A61L2300/602A61L2300/622C08L71/02
Inventor 王韫芳柳娟陈志强施艳霞闫舫
Owner FIELD OPERATION BLOOD TRANSFUSION INST OF PLA SCI ACAD OF MILITARY
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