CN105709269A - Natural polymer liquid spray for wound protection - Google Patents

Abstract

The invention relates to a natural polymer liquid spray for wound protection, which aims to use non-toxic natural polymer material carboxymethyl chitosan as a raw material, supplemented by a low-concentration bifunctional siloxane coupling agent , the two solutions are sprayed onto the wound surface at the same time, and through the rapid cross-linking reaction of the two, a layer of polymer film is formed within 1 min. Promote wound healing to a great extent. This novel, efficient, safe and convenient drug for skin wounds has broad application prospects in acute wound treatment.

Description

A natural polymer liquid spray for wound protection

technical field

The invention relates to a natural polymer liquid bandage material used in the field of medical devices and a preparation method thereof, in particular to a novel liquid spray that can rapidly coagulate blood and promote wound healing.

Background technique

The key to wound treatment is rapid hemostasis, pain relief, infection prevention and tissue repair. Therefore, it is a clinical need to develop an external preparation that can stop bleeding, sterilize, promote healing and is easy to use. Liquid bandage is a new type of medical product that can form a polymer film on the skin surface to quickly stop bleeding, protect skin wounds from infection, and maintain a certain humidity on the skin surface.

Liquid bandages currently sold in the international market can be divided into two main types: the first category is volatile film-forming products, which usually dissolve synthetic polymers in a certain solvent, and some products also add preservatives and local anesthetic. After the liquid mixture containing the polymer is sprayed on the skin surface, a uniform polymer film can be formed on the skin surface through the volatilization of the solvent. In order to speed up the solvent evaporation process, many liquid bandage products usually use volatile hydrocarbon organic solvents. The use of such products will significantly increase the indoor volatile organic gas (VOC) content, which is not conducive to human health. The main component of another liquid bandage is siloxane monomer, which is condensed into a film on the skin surface after spraying. However, high concentrations of siloxanes may exhibit high cytotoxicity.

Contents of the invention

The object of the present invention is to provide a liquid spray film agent for wound protection which has the functions of rapid hemostasis, sterilization and disinfection, and promotion of wound healing. After the liquid spray film is sprayed on the surface of the wound, it can solidify within 1 minute to form a protective film with hemostatic effect, which has various functions such as antibacterial, hemostasis and pain relief, preventing wound infection, and promoting wound healing. It is very convenient to use and has good effect. Superior to traditional bandages.

The purpose of the present invention is achieved by the following technical solutions: a liquid spray for protecting skin wounds, composed of natural polymer solution A and low concentration bifunctional coupling agent solution B, during use, the two solutions are combined according to The ratio of 1:1 is sprayed onto the wound surface at the same time; in the natural polymer solution A, the solute is one of natural polymers such as chitosan, carboxymethyl chitosan, N-acetyl chitosan, and hyaluronic acid. One or more mixtures composed according to any ratio, the mass fraction of the solute is 1-2%; the solvent is a mixed solution of ethanol and water, and the mass content of ethanol is 10-60%; the low-concentration bifunctional coupling agent solution B Among them, the solute is a coupling agent with bifunctional groups, such as: γ-(2,3-glycidoxy)propyltrimethoxysilane, or 1,2-bis(triethoxysilyl) Ethane, or 4,4'bis(triethoxysilyl)-1,1'biphenyl, or bis[3-(trimethoxysilyl)propyl]amine, the mass fraction of solute is 1～ 3%; the coupling agent is ethanol as a solvent.

The beneficial effects of the present invention are: the present invention aims to use non-toxic natural polymer material carboxymethyl chitosan as raw material, supplemented by low concentration bifunctional siloxane coupling agent, and spray the two solutions to the wound at the same time On the surface, through the rapid cross-linking reaction of the two, a layer of polymer film is formed within 1 minute to achieve the effects of hemostasis, sterilization and wound healing. The film has many excellent properties such as hemostasis, antibacterial, anti-infection, breathable, waterproof, etc. This new, efficient, safe and convenient drug for skin wounds has broad application prospects in acute wound treatment.

Description of drawings

Fig. 1 is the dissolution rate curve of film in water;

Figure 2 is a graph showing the relationship between the NIH3T3 cell survival rate and the concentration of two kinds of liquid spray membrane soaking solutions;

Fig. 3 is the graph of the relationship between the survival rate of HaCaT cells and the concentration of two kinds of liquid spray membrane soaking solutions;

Fig. 4 is the inhibitory effect of 2 kinds of liquid sprays to the growth of escherichia coli;

Fig. 5 is the bacteriostatic rate of 2 kinds of liquid bandages to Escherichia coli.

specific implementation plan

Embodiment 1: the preparation and application method of liquid spray I

(1) Preparation method of liquid A: first dissolve carboxymethyl chitosan solid powder in a certain volume of water, stir to completely dissolve carboxymethyl chitosan, and slowly add a certain volume of ethanol dropwise to make the volume fraction of ethanol 50%, and the mass fraction of carboxymethyl chitosan solid powder is 1-2%; while stirring while adding dropwise, a light yellow transparent ethanol aqueous solution of carboxymethyl chitosan is obtained.

(2) Preparation method of liquid B: Dissolve γ-(2,3-glycidoxy)propyltrimethoxysilane in corresponding volume of ethanol, so that γ-(2,3-glycidoxy ) The mass fraction of propyltrimethoxysilane is 1-3%, and the mixture is evenly stirred.

(3) How to use the liquid spray: put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S1.

Embodiment 2: the preparation and use method of liquid spray II:

(1) The preparation method of A liquid: dissolve the carboxymethyl chitosan solid powder in a certain volume of water, stir to make the carboxymethyl chitosan dissolve completely, slowly add a certain volume of ethanol dropwise, so that the volume fraction of ethanol is 30%, and the mass fraction of the carboxymethyl chitosan solid powder is 1-2%; while stirring while adding dropwise, a light yellow transparent ethanol aqueous solution of carboxymethyl chitosan is obtained.

(2) The preparation method of B liquid: [3-(trimethoxysilyl) propyl] amine is dissolved in the ethanol of corresponding volume, makes [3-(trimethoxysilyl) propyl] amine The mass fraction is 1%, and it is evenly stirred.

(3) How to use the liquid spray: Put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S6.

Embodiment 3: the preparation and application method of liquid spray III

(1) Preparation method of liquid A: Carboxymethyl chitosan solid powder is dissolved in a certain volume of water, stirred to completely dissolve carboxymethyl chitosan, slowly add a certain volume of ethanol, so that the volume fraction of ethanol is 60 %, the mass fraction of carboxymethyl chitosan solid powder is 1-2%, and it is added dropwise while stirring to obtain light yellow transparent carboxymethyl chitosan ethanol aqueous solution.

(2) The preparation method of liquid B: dissolve 1,2-bis(triethoxysilyl)ethane in ethanol, so that the mass of 1,2-bis(triethoxysilyl)ethane The fraction is 1-3%, stir evenly.

(3) How to use the liquid spray: put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S3.

Embodiment 4: the preparation and use method of liquid spray IV:

(1) Preparation method of liquid A: first dissolve carboxymethyl chitosan solid powder in a certain volume of water, stir to completely dissolve carboxymethyl chitosan, and slowly add a certain volume of ethanol dropwise to make the volume fraction of ethanol 10%, and the mass fraction of carboxymethyl chitosan solid powder is 1-2%; while stirring while adding dropwise, a pale yellow transparent ethanol aqueous solution of carboxymethyl chitosan is obtained.

(2) Preparation method of liquid B: Dissolve 4,4'bis(triethoxysilyl)-1,1'biphenyl in corresponding volume of ethanol, so that 4,4'bis(triethoxymethyl The mass fraction of silane)-1,1'biphenyl is 1-3%, and the mixture is evenly stirred.

(3) How to use the liquid spray: put liquid A and liquid B into spray bottles with double nozzles, and then spray them onto the wound surface, and wait for less than 1 minute to form a film S4.

Embodiment 5: the preparation and application method of liquid spray V:

(1) The compound method of A liquid: dissolve chitosan solid powder in the water of certain volume, stir to make chitosan dissolve completely, slowly add the ethanol of certain volume, make the volume fraction of ethanol be 20%, chitosan The mass fraction of the solid powder is 1-2%, and it is added dropwise while stirring to obtain light yellow transparent chitosan ethanol aqueous solution.

(2) Preparation method of liquid B: Dissolve γ-(2,3-glycidoxy)propyltrimethoxysilane in corresponding volume of ethanol, so that γ-(2,3-glycidoxy ) The mass fraction of propyltrimethoxysilane is 1-3%, and the mixture is evenly stirred.

(3) How to use the liquid spray: Put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S5.

Embodiment 6: Preparation and usage of liquid spray VI:

(1) The preparation method of A liquid: N-acetyl chitosan solid powder is dissolved in the water of certain volume, stirs and N-acetyl chitosan is dissolved completely, slowly adds the ethanol of certain volume dropwise, makes the volume fraction of ethanol be 30%, and the mass fraction of the N-acetyl chitosan solid powder is 1-2%; stirring while adding dropwise, to obtain light yellow transparent ethanol aqueous solution of N-acetyl chitosan.

(2) Preparation method of liquid B: Dissolve γ-(2,3-glycidoxy)propyltrimethoxysilane in corresponding volume of ethanol, so that γ-(2,3-glycidoxy ) The mass fraction of propyltrimethoxysilane is 1%, and the mixture is evenly stirred.

(3) How to use the liquid spray: Put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S6.

Embodiment 7: the preparation and application method of liquid spray VII:

(1) The preparation method of A liquid: dissolve the hyaluronic acid solid powder in a certain volume of water, stir to dissolve the hyaluronic acid completely, slowly add a certain volume of ethanol dropwise, so that the volume fraction of ethanol is 10%, and the hyaluronic acid The mass fraction of the solid powder is 1-2%, and it is added dropwise while stirring to obtain a pale yellow transparent hyaluronic acid aqueous solution in ethanol.

(2) Preparation method of liquid B: Dissolve γ-(2,3-glycidoxy)propyltrimethoxysilane in corresponding volume of ethanol, so that γ-(2,3-glycidoxy ) The mass fraction of propyltrimethoxysilane is 1-3%, and the mixture is evenly stirred.

(3) How to use the liquid spray: Put liquid A and liquid B into spray bottles with double nozzles, then spray them onto the wound surface, and wait for less than 1 minute to form a film S7.

Membrane performance test

(1) Adopt the stripping rate of the film formed in water by ultraviolet absorbance photometry test embodiment 1, the stripping rate curve of this film in water is shown in Figure 1, after the film is immersed in water for 15 minutes, the solubility in water reaches equilibrium, The dissolution rate after stabilization was 3.75%. From this, it was proved that the film has good water repellency.

(2) prepare the DMEM leachate of the film that embodiment 1,2 obtains, and adopt MTT colorimetric method to the cytotoxicity of leachate (mouse embryo skin fibroblast-NHI3T3 cell and human skin epidermal keratinocyte -HaCaT cells) were tested. Figures 2 and 3 are graphs showing the relationship between the survival rate of NIH3T3 and HaCaT cells and the concentrations of the two liquid spray membrane immersion solutions. As can be seen from Figures 2 and 3, within the scope of 0 to 1000ppm, the toxicity of the two liquid bandages is all very low to the toxicity of NIH3T3 cells and HaCaT cells (the cell survival rate is all greater than 80%), thus proving that under the normal action concentration , The liquid spray impregnation solution has no obvious toxicity to cells.

(3) The sprays of Examples 1 and 2 are evenly sprayed on the surface of the culture medium, and then plated to observe whether the bacteria can grow. All experiments were set up with a negative control group (blank), a positive control group (the antibiotic ciprofloxacin), and two different bacterial dilutions, 10 ^-5 and 10 ^-6 , respectively. The experimental results are shown in Figures 4 and 5. It can be seen from the chart that S1 and S2 have antibacterial properties, and the antibacterial rates are 80% and 60% respectively, while the antibacterial rate of the positive control antibiotic ciprofloxacin is nearly 100%. %. This experiment shows that this liquid spray has certain bacteriostasis property indeed.

Example 8

The composition of liquid A is: the solute is carboxymethyl chitosan, and the mass fraction of the solute is 1%; the solvent is a mixed solution of ethanol and water; ) Propyltrimethoxysilane, the mass fraction of solute is 3%, and the solvent is ethanol.

In the solvent of liquid A, the volume fraction of ethanol and the film forming speed are shown in the table below

10% 20% 30% 40% 50% 60% Film forming speed 2min35s 2min 1min40s 1min25s 50s 35s

It can be seen from the above table that as the volume fraction of ethanol increases, the film forming speed increases. Considering that the concentration of medical alcohol is 75%, and too high concentration of ethanol is easy to cause skin irritation. At the same time, too high ethanol concentration will reduce the solubility of carboxymethyl chitosan, so the ethanol concentration is controlled at 10%-60%. At the same time, according to the stoichiometric relationship, the concentration of the B liquid coupling agent is controlled to be 1-3%.

Claims (1)

1. the natural polymer liquid sprays for Wound protection, it is characterised in that it is made up of natural polymer solution A and low concentration difunctional coupling agent's solution B, during use, according to the ratio of 1:1, two kinds of solution is ejected into wound surface simultaneously；In described natural polymer solution A, solute is the mixture according to any ratio composition of the one or more of which in the natural polymers such as chitosan, carboxymethyl chitosan, N-acetyl chitosan, hyaluronic acid, and the mass fraction of solute is 1～2%；Solvent is ethanol water mixed solution, and the mass content of ethanol is 10～60%；In described low concentration difunctional coupling agent's solution B, solute is the coupling agent being connected to difunctional, such as: γ-(2,3-glycidoxy) propyl trimethoxy silicane, or 1,2-bis-(triethoxysilyl) ethane, or 4,4 ' two (triethoxy-silicane)-1,1 ' biphenyl, or double; two [3-(trimethoxysilyl) propyl group] amine, the mass fraction of solute is 1～3%；Described coupling agent is solvent is ethanol.