CN112972757A

CN112972757A - Perfluorodecalin hydrogel healing-promoting dressing and preparation method and application thereof

Info

Publication number: CN112972757A
Application number: CN202110245136.9A
Authority: CN
Inventors: 程宇豪; 孟帅; 杨沛峥
Original assignee: Jiangsu Junjunjun Biotechnology Co ltd
Current assignee: Jiangsu Junjunjun Biotechnology Co ltd
Priority date: 2021-03-05
Filing date: 2021-03-05
Publication date: 2021-06-18
Also published as: WO2022184150A1

Abstract

The invention provides a hydrogel healing-promoting dressing containing perfluorodecalin, which, in parts by weight, comprises the following components: PBS buffer, sodium hyaluronate, perfluorodecalin, stabilizer, and emulsifier. The preparation method includes the following steps: a. first dissolving sodium hyaluronate in a PBS buffer, then adding an emulsifier and stirring at a constant speed to obtain a sodium hyaluronate hydrogel containing an emulsifier; b. dissolving the perfluorodecalin liquid The sodium hyaluronate hydrogel containing the emulsifier obtained in step a is added, stirred at a constant speed at room temperature, and finally a stabilizer is added, and stirred until uniform to obtain a hydrogel-promoting healing dressing containing perfluorodecalin. The perfluorodecalin hydrogel dressing of the present invention is a novel smart hydrogel wound dressing with both accelerated healing and safety, and can be applied to chronic wounds, trauma, burns, scalds, ulcers, bedsores and other wounds.

Description

Perfluorodecalin hydrogel healing-promoting dressing and preparation method and application thereof

Technical Field

The invention belongs to the technical field of hydrogel, and particularly relates to a perfluorodecalin hydrogel healing-promoting dressing as well as a preparation method and application thereof.

Background

With the growing aging population and the increasing number of diabetic patients, chronic wounds have become a major challenge in the global medical field; one important reason for the difficulty in healing chronic wounds, such as diabetic feet, is that local hypoxia at the wound site is an important factor limiting wound healing; currently, oxygen therapy is mainly divided into two types, one is hyperbaric oxygen therapy, and the other is local oxygen therapy. Local oxygen therapy is a novel wound treatment technology, and can realize low-cost and portable oxygen delivery to wounds.

Research shows that perfluorodecalin is a compound with high safety, is colorless, tasteless and nontoxic transparent liquid at normal temperature, has high density, low surface tension and stable chemical property, and does not metabolize in vivo. More importantly, the perfluorodecalin has good gas carrying capacity, the solubility to oxygen is about 20 times that of water and 2-3 times that of whole blood, and the solubility to carbon dioxide is more than 3 times that of water; and has wound repairing, antibacterial, antioxidant, and antiinflammatory effects. Perfluorodecalin has good histocompatibility and biological inertia, and has been used in the biomedical field for a long time, but because perfluorodecalin is insoluble in water, has poor stability, low bioavailability and other characteristics, it has great difficulty in being used in wound dressing.

Therefore, a hydrogel dressing which can actively supply oxygen and has a simple process is urgently needed at present, an oxygen-rich environment is provided for wounds, and the problem that wound cells are slowly healed due to oxygen deficiency is solved.

Disclosure of Invention

The invention aims to solve the defects in the prior art, and provides a perfluorodecalin hydrogel healing-promoting dressing which is simple in process, controllable in cost and capable of accelerating wound healing, a preparation method and application thereof.

The technical scheme adopted by the invention is as follows: a hydrogel healing-promoting dressing containing perfluorodecalin comprises the following components in parts by weight: 100 parts of PBS buffer solution, 1-2 parts of sodium hyaluronate, 1-3 parts of perfluorodecalin, 1-2 parts of stabilizer and 1-3 parts of emulsifier.

Preferably, the composition comprises the following components in parts by weight: 100 parts of PBS buffer solution, 1.5-2 parts of sodium hyaluronate, 1.5-2 parts of perfluorodecalin, 1-1.5 parts of stabilizer and 2-3 parts of emulsifier.

Preferably, the molecular weight of the sodium hyaluronate is 200-600w, the stabilizer is xanthan gum, and the emulsifier is any one of poloxamer, tween-80 or tween-20.

The preparation method of the hydrogel healing-promoting dressing comprises the following steps:

a. firstly, dissolving sodium hyaluronate in a PBS buffer solution, then adding an emulsifier, stirring at a constant speed, and stirring at room temperature for 0.5-1 h to obtain sodium hyaluronate hydrogel containing the emulsifier;

b. and (b) adding perfluorodecalin liquid into the sodium hyaluronate hydrogel containing the emulsifier obtained in the step a, stirring at a constant speed at room temperature, finally adding a stabilizer, and stirring until the mixture is uniform, thus obtaining the perfluorodecalin-containing hydrogel healing-promoting dressing.

The application of the perfluorodecalin-containing hydrogel healing-promoting dressing can improve the oxygen concentration and the humidity on the surface of a wound through oxygen evolution, and can be applied to chronic wounds, trauma, burns, scalds, ulcers or bedsore wounds.

Preferably, the dressing is suitable for wounds at the site of recurrent activity of the elbow, wrist, knee or ankle.

Preferably, the dressing is suitable for chronic wounds.

The beneficial effects obtained by the invention are as follows: the perfluorodecalin hydrogel dressing is white and viscous, is a novel intelligent hydrogel wound dressing with accelerated healing and safety, can be applied to wounds such as chronic wounds, trauma, burns, scalds, ulcers, bedsores and the like, and particularly has a better effect on diabetic foot type chronic wounds.

(1) The perfluorodecalin contained in the hydrogel dressing has strong oxygen dissolving capacity and good moisture retention and air permeability. After being applied to the wound surface, the dressing can isolate the wound surface from the external environment, so that the wound is not contacted with pathogens in the environment, the continuous oxygen supply environment of the wound surface is maintained, the epithelial regeneration is accelerated, and the safety is high; the oxygen concentration and the humidity on the surface of the wound can be effectively improved through oxygen evolution, the improvement of the oxygen concentration directly enhances the wound healing, the improvement of the humidity is favorable for the permeation and the diffusion of gas on the surface of the wound, and the wound healing is promoted through a wet healing mode.

(2) The emulsifier selected by the invention has good wetting dispersibility, can disperse perfluorodecalin in the hydrogel in an oil-in-water form, enables the perfluorodecalin to exist stably, overcomes the defects of water insolubility and poor stability of perfluorodecalin, and can slowly release oxygen when being applied to wounds.

(3) The stabilizing agent selected by the invention has good suspension effect on insoluble solids and oil drops, and can form a hydrogel dressing into a colloidal structure to form a stable gel form.

(4) The invention adopts an oil-in-water emulsion template method to prepare perfluorodecalin hydrogel dressing; firstly, the emulsifier is dissolved in the sodium hyaluronate as a water phase, the perfluorodecalin is dispersed in the gel containing the emulsifier, and the mixture is mixed to form an oil-in-water emulsion system.

(5) The perfluorodecalin hydrogel dressing has good mechanical property, good flexibility and elasticity, can form good adhesion with skin, and is suitable for wound surfaces of different parts of a body, in particular to frequently moving parts such as elbows, wrists, knees, ankles and the like.

Drawings

FIG. 1 is a therapeutic schematic of a wound repair dressing of the present invention;

FIG. 2 is a graph of an acute wound healing rate experiment in accordance with the present invention;

FIG. 3 is a graph of a chronic wound healing experiment according to the present invention;

FIG. 4 is a 400-fold magnified optical micrograph of a hydrogel sample according to example 1 of the present invention;

FIG. 5 is a 400-fold magnified optical micrograph of a perfluorodecalin-free hydrogel sample according to the present invention;

FIG. 6 is a photograph of a sample hydrogel dressing of the present invention applied to a skin surface;

figure 7 is a shape diagram of a sample perfluorodecalin hydrogel dressing of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments.

Example 1: a hydrogel healing-promoting dressing containing perfluorodecalin comprises the following components in parts by weight: 100 parts of PBS buffer solution, 1 part of sodium hyaluronate with molecular weight of 200w, 1 part of perfluorodecalin, 1 part of xanthan gum and 1 part of poloxamer.

The preparation method of the hydrogel healing-promoting dressing comprises the following steps: a. firstly, dissolving sodium hyaluronate in a PBS buffer solution, then adding an emulsifier, stirring at a constant speed, and stirring at room temperature for 0.5h to obtain sodium hyaluronate hydrogel containing the emulsifier; b. and (b) adding perfluorodecalin liquid into the emulsifier-containing sodium hyaluronate hydrogel obtained in the step (a), uniformly stirring at room temperature for 24 hours, finally adding a stabilizer, and manually stirring for 20 minutes or magnetically stirring at a rotating speed of 2000 rpm until the mixture is uniform, thus obtaining the perfluorodecalin-containing hydrogel healing-promoting dressing.

Example 2: a hydrogel healing-promoting dressing containing perfluorodecalin comprises the following components in parts by weight: 100 parts of PBS buffer solution, 2 parts of sodium hyaluronate with molecular weight of 200-.

The preparation method of the hydrogel healing-promoting dressing comprises the following steps: a. firstly, dissolving sodium hyaluronate in a PBS buffer solution, then adding an emulsifier, stirring at a constant speed, and stirring at room temperature for 1h to obtain sodium hyaluronate hydrogel containing the emulsifier; b. and (b) adding perfluorodecalin liquid into the emulsifier-containing sodium hyaluronate hydrogel obtained in the step a, stirring at a constant speed for 24 hours at room temperature, finally adding a stabilizer, and manually stirring for 20 minutes or magnetically stirring at a rotating speed of 5000 rpm until the mixture is uniform, thus obtaining the perfluorodecalin-containing hydrogel healing-promoting dressing.

Example 3: a hydrogel healing-promoting dressing containing perfluorodecalin comprises the following components in parts by weight: 100 parts of PBS buffer solution, 1.5 parts of sodium hyaluronate with molecular weight of 200-.

The preparation method of the hydrogel healing-promoting dressing comprises the following steps: a. firstly, dissolving sodium hyaluronate in a PBS buffer solution, then adding an emulsifier, stirring at a constant speed, and stirring at room temperature for 0.8h to obtain sodium hyaluronate hydrogel containing the emulsifier; b. and (b) adding perfluorodecalin liquid into the emulsifier-containing sodium hyaluronate hydrogel obtained in the step (a), stirring at a constant speed for 24 hours at room temperature, finally adding a stabilizer, and manually stirring for 20 minutes or magnetically stirring at a rotating speed of 3000 rpm until the mixture is uniform, thus obtaining the perfluorodecalin-containing hydrogel healing-promoting dressing.

The shape of perfluorodecalin hydrogel dressings of the present invention was tested as exemplified in example 3

The blank control group was a non-diabetic group and healed naturally; the diabetic group was diabetic mice and healed naturally; the hydrogel group is a diabetic mouse and wound is coated with a dressing which does not contain perfluorodecalin gel; the perfluorodecalin hydrogel group was diabetic mice and wounds were coated with the dressing containing perfluorodecalin gel of example 3 of the present invention.

An animal assay method for a control hydrogel healing-promoting dressing comprising the steps of: a. the aged mice are firstly bred to adapt to the environment for 7 days, and the acute wound group feed is high-fat and high-sugar; b. cutting a wound with the diameter of about 1cm on the back of the mouse, and coating a hydrogel dressing and a control group reagent; c. preparation of hydrogel without perfluorodecalin: firstly, dissolving sodium hyaluronate in PBS buffer solution, then adding emulsifier and uniformly stirring, uniformly stirring at room temperature for 24h, finally adding stabilizer, manually stirring for 20 min or magnetically stirring at the rotating speed of 3000 r/min until the mixture is uniform, thus obtaining the hydrogel dressing without perfluorodecalin. d. The wound healing curves were prepared by changing the dressing on time each day, measuring the wound length on time and recording, as shown in fig. 2.

The acute wound healing rate experiment of example 3 was compared to the comparative example described above, as shown in figure 2; and example 3 was compared to the above comparative example for a chronic wound healing rate experiment, as shown in figure 3.

Experiments show that the wound healing speed of the dressing is obviously superior to that of gel products without perfluorodecalin and natural healing speed.

The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.

Claims

1. a hydrogel healing dressing containing perfluorodecalin is characterized in that: in parts by weight, comprising the following components: 100 parts of PBS buffers, 1-2 parts of sodium hyaluronate, perfluoronaphthalene 1-3 parts of alkane, 1-2 parts of stabilizer, 1-3 parts of emulsifier.

2. a kind of hydrogel healing-promoting dressing containing perfluorodecalin according to claim 1 is characterized in that: in parts by weight, comprising the following components: 100 parts of PBS buffers, 1.5-1.5 parts of sodium hyaluronate 2 parts, 1.5-2 parts of perfluorodecalin, 1-1.5 parts of stabilizer, 2-3 parts of emulsifier.

3. a kind of hydrogel healing-promoting dressing containing perfluorodecalin according to claim 1 and 2 is characterized in that: the molecular weight of the sodium hyaluronate is 200-600w, and the stabilizer is xanthan gum , the emulsifier is any one of poloxamer, Tween-80 or Tween-20.

4. the preparation method of hydrogel promoting healing dressing is characterized in that: comprise the steps:

a. First dissolve sodium hyaluronate in PBS buffer, then add an emulsifier and stir at a constant speed, and stir at room temperature for 0.5-1 h to obtain a sodium hyaluronate hydrogel containing an emulsifier;

b. Add the perfluorodecalin liquid into the emulsifier-containing sodium hyaluronate hydrogel obtained in step a, stir at a constant speed at room temperature, and finally add a stabilizer and stir until uniform to obtain a perfluorodecalin-containing hydrogel Healing dressings.

5. The purposes of the hydrogel healing-promoting dressing containing perfluorodecalin is characterized in that: the perfluorodecalin in the dressing improves the oxygen concentration and humidity of the wound surface through oxygen evolution, and can be applied to chronic wounds, trauma, Burns, scalds, ulcers or bedsores.

6 . The use of the hydrogel-promoting healing dressing containing perfluorodecalin according to claim 5 , wherein the dressing is suitable for wounds on the frequently moving parts of the elbow, wrist, knee or ankle. 7 .

7 . The use of the perfluorodecalin-containing hydrogel healing-promoting dressing according to claim 5 , wherein the dressing is suitable for chronic wounds. 8 .