CN113230450A

CN113230450A - Chitosan antibacterial gel and preparation method thereof

Info

Publication number: CN113230450A
Application number: CN202110496031.0A
Authority: CN
Inventors: 丁宁
Original assignee: Individual
Current assignee: Individual
Priority date: 2021-05-07
Filing date: 2021-05-07
Publication date: 2021-08-10

Abstract

The application provides a chitosan bacteriostatic gel and a preparation method thereof, wherein the chitosan bacteriostatic gel comprises the following components in parts by weight: 0.5-6 parts of micromolecular chitosan, 0.5-1 part of bacteriostatic agent, 0.1-0.8 part of carbomer, 0.05-0.3 part of gamma-polyglutamic acid and 0.1-3 parts of lubricant. The gel preparation is uniform, fine, smooth and beneficial to smearing, has cool feeling when being smeared, can be better used for irregular and difficultly-operated parts such as joints, folds and the like, and can move freely after being smeared.

Description

Chitosan antibacterial gel and preparation method thereof

Technical Field

The invention belongs to the technical field of antibacterial gel, and particularly relates to chitosan antibacterial gel and a preparation method thereof.

Background

As a means for treating wounds, the conventional dressing plays an important role in wound treatment, and the dressing mainly covers the wound to isolate the wound from the outside, thereby preventing the wound from being further polluted by the outside and the like. In recent years, novel dressings meeting the requirements of wound treatment are developed on the basis of the traditional dressings which only cover the wound surface and play a role in protecting and isolating the wound surface, and mainly refer to bioactive dressings which have the effects of moisturizing and promoting repair compared with traditional gauze (dry dressings, also called inert dressings), including alginate dressings, hydrocolloid dressings, hydrogel dressings and the like.

The novel dressing can further meet the requirement of treating wounds and mainly comprises the following aspects: facilitating and accelerating the release of a variety of growth factor proteins or polypeptides involved in tissue repair and regeneration; the formation of granulation tissue can be remarkably accelerated; the labor of doctors and nurses is reduced, the life is convenient, for example, the frequency of dressing change is reduced, and the bath can be performed under the condition of using the dressing. The gel liquid dressing can meet the requirements, has the characteristics of good biocompatibility, air permeability, no adhesion to wounds, transparent appearance, easiness in observation of wound repair conditions and the like, and can be thinly coated on the skin as a protective layer by adopting a spraying, brushing or other methods. Most of the existing liquid dressings in the market are still in a liquid state after being sprayed, dust is easy to adhere to the dressings, and the dressings are also easy to adhere to clothes. It is needed to develop a gel liquid dressing which can form a breathable film after being sprayed on an affected part, protect a wound surface, and simultaneously has good effects of stopping bleeding, easing pain, inhibiting bacteria, promoting wound healing and the like.

Disclosure of Invention

In order to solve the problems, the application provides a chitosan antibacterial gel and a preparation method thereof, wherein the chitosan antibacterial gel comprises the following components in parts by weight: 0.5-6 parts of micromolecular chitosan, 0.5-1 part of bacteriostatic agent, 0.1-0.8 part of carbomer, 0.05-0.3 part of gamma-polyglutamic acid and 0.1-3 parts of lubricant.

Preferably, the pH value of the chitosan bacteriostatic gel is 5.5-8.0.

Preferably, the pH value regulator is one of sodium hydroxide, potassium hydroxide and triethanolamine.

Preferably, the bacteriostatic agent is one or more of chlorhexidine acetate, chlorhexidine gluconate, tea tree oil, and eucalyptus oil.

Preferably, the bacteriostatic agent is chlorhexidine acetate, tea tree oil and eucalyptus oil, and the mass ratio of the three components is 1: (0.5-0.8): (0.2-0.5).

Preferably, the carbomer is one or more of carbomer 980, carbomer 981, carbomer 940.

Preferably, the lubricant is one or more of glycerol, propylene glycol and polyethylene glycol.

Preferably, the lubricant is glycerol and polyethylene glycol, and the mass ratio of the two components is 1: (1.5-3).

Preferably, the preparation method of the small molecule chitosan comprises the following steps:

1) wetting chitosan powder with 30% sodium hydroxide solution;

2) performing electron irradiation on the wetted chitosan powder, wherein the irradiation dose is 300-450kGy, so that the chitosan powder is degraded;

3) dissolving the irradiated chitosan powder in 3 wt% acetic acid solution, and introducing ozone for 5-8min for decolorizing;

4) neutralizing the decolorized chitosan solution with 30% sodium hydroxide solution until the pH value is 7, filtering to remove precipitate, adding ethanol to precipitate, and drying to remove ethanol to obtain the micromolecular chitosan.

On the other hand, the invention discloses a preparation method of chitosan antibacterial gel, which comprises the following steps:

1) preparation of chitosan solution:

weighing micromolecular chitosan and a bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

weighing carbomer, uniformly scattering the carbomer into ultrapure water, standing for natural swelling for 1-6 h, adding a pH value regulator into the solution after swelling to a gel state, and uniformly stirring to obtain a solution B;

3) preparing the antibacterial composite gel:

mixing the solutions A, B, adding gamma-polyglutamic acid and lubricant, stirring thoroughly to mix well, adding pH regulator to obtain stable transparent gel, vacuum degassing, sterilizing, and packaging to obtain chitosan antibacterial gel.

This application can bring following beneficial effect:

1. the gel preparation is uniform, fine, smooth and beneficial to smearing, has cool feeling when being smeared, can be better used for irregular and difficultly-operated parts such as joints, folds and the like, and can move freely after being smeared;

2. the synergistic effect of the bacteriostatic agent and the micromolecular chitosan can achieve the effects of long-acting bacteriostasis and excellent healing promotion, and a soft and transparent protective film can be formed on the wound surface to protect the wound surface, so that the wound surface is more beneficial to healing, the wound surface repairing condition is easy to observe in real time, and the wound surface healing process is intuitively and clearly mastered;

3. the micromolecular chitosan has the molecular weight of less than 10000, can be better dissolved in water, has simple preparation method and low preparation cost, and has better bacteriostatic effect after being irradiated;

4. the addition of the gamma-polyglutamic acid not only improves the moisture retention of the gel and improves the use feeling of users, but also improves the film forming property of the gel and reduces the adhesive feeling.

Detailed Description

The preparation method of the micromolecule chitosan comprises the following steps:

1) wetting chitosan powder with 30% sodium hydroxide solution;

Example 1: the preparation process of the chitosan antibacterial gel comprises the following steps:

1) preparation of chitosan solution:

weighing 0.5kg of micromolecular chitosan and 1kg of bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

weighing 0.1kg of carbomer, uniformly scattering the carbomer into ultrapure water, standing for natural swelling for 1h, adding a pH value regulator into the solution after swelling to a gel state, and uniformly stirring to obtain a solution B;

3) preparing the antibacterial composite gel:

mixing the solutions A, B, adding 0.3kg of gamma-polyglutamic acid and 0.1kg of lubricant, fully stirring until the mixture is completely and uniformly mixed, adding the pH value regulator again to a stable transparent gel state, vacuum degassing, sterilizing and filling to obtain the chitosan antibacterial gel.

Wherein the pH regulator is sodium hydroxide, the bacteriostatic agent is chlorhexidine acetate, the carbomer is carbomer 980, and the lubricant is glycerol

Example 2: the preparation process of the chitosan antibacterial gel comprises the following steps:

1) preparation of chitosan solution:

weighing 6kg of micromolecular chitosan and 0.5kg of bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

weighing 0.8kg of carbomer, uniformly scattering the carbomer into ultrapure water, standing for natural swelling for 6h, adding a pH value regulator into the solution after swelling to a gel state, and uniformly stirring to obtain a solution B;

3) preparing the antibacterial composite gel:

mixing the solutions A, B, adding 0.05kg of gamma-polyglutamic acid and 3kg of lubricant, fully stirring until the mixture is completely and uniformly mixed, adding the pH value regulator again to a stable transparent gel state, degassing in vacuum, sterilizing and filling to obtain the chitosan antibacterial gel.

Wherein the pH value regulator is potassium hydroxide, the bacteriostatic agent is chlorhexidine gluconate, tea tree oil and eucalyptus oil, and the mass ratio is 1: 1: 1. carbomer 981, lubricant propylene glycol and polyethylene glycol, and the mass ratio is 1: 1.

example 3: the preparation process of the chitosan antibacterial gel comprises the following steps:

1) preparation of chitosan solution:

weighing 3kg of micromolecular chitosan and 0.8kg of bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

weighing 0.5kg of carbomer, uniformly scattering the carbomer into ultrapure water, standing for natural swelling for 3h, adding a pH value regulator into the mixture after swelling to be in a gel state, and uniformly stirring to obtain a solution B;

3) preparing the antibacterial composite gel:

mixing the solution A, B, adding 0.2kg of gamma-polyglutamic acid and 2kg of lubricant, fully stirring until the mixture is completely and uniformly mixed, adding the pH value regulator again to a stable transparent gel state, degassing in vacuum, sterilizing and filling to obtain the chitosan antibacterial gel.

Wherein the pH regulator is triethanolamine, the bacteriostatic agent is tea tree oil or eucalyptus oil, the carbomer is carbomer 940, and the lubricant is polyethylene glycol.

Example 4: the preparation process of the chitosan antibacterial gel comprises the following steps:

1) preparation of chitosan solution:

weighing 4kg of micromolecular chitosan and 0.6kg of bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

weighing 0.4kg of carbomer, uniformly scattering the carbomer into ultrapure water, standing for natural swelling for 3h, adding a pH value regulator into the mixture after swelling to be in a gel state, and uniformly stirring to obtain a solution B;

3) preparing the antibacterial composite gel:

mixing the solutions A, B, adding 0.15kg of gamma-polyglutamic acid and 1kg of lubricant, fully stirring until the mixture is completely and uniformly mixed, adding the pH value regulator again to a stable transparent gel state, degassing in vacuum, sterilizing and filling to obtain the chitosan antibacterial gel.

Wherein the pH value regulator is sodium hydroxide, the bacteriostatic agent is chlorhexidine gluconate, the carbomer is carbomer 980 and carbomer 981, and the mass ratio is 1: 1. the lubricant is propylene glycol.

Example 5: the preparation process of the chitosan antibacterial gel comprises the following steps:

1) preparation of chitosan solution:

weighing 2kg of micromolecular chitosan and 0.9kg of bacteriostatic agent, adding into ultrapure water, and uniformly stirring until the micromolecular chitosan and the bacteriostatic agent are completely dissolved to obtain a solution A;

2) preparation of carbomer solution:

3) preparing the antibacterial composite gel:

mixing the solutions A, B, adding 0.25kg of gamma-polyglutamic acid and 2.5kg of lubricant, fully stirring until the mixture is completely and uniformly mixed, adding the pH value regulator again to a stable transparent gel state, vacuum degassing, sterilizing and filling to obtain the chitosan antibacterial gel.

Wherein the pH value regulator is sodium hydroxide, the bacteriostatic agent is chlorhexidine acetate, tea tree oil and eucalyptus oil, and the mass ratio of the three components is 1: 0.5: 0.3, carbomer is carbomer 980, the lubricant is glycerol and polyethylene glycol, and the mass ratio of the two components is 1: 2.

comparative example 1:

comparative example 1 contains no gamma-polyglutamic acid component compared to example 1.

Comparative example 2:

comparative example 2 in comparison with example 1, chitosan was not subjected to the irradiation treatment.

Comparative example 3:

comparative example 3 contains no bacteriostatic component compared to example 1.

Characterization of

1. Bacteriostasis experiments of the chitosan bacteriostasis gel:

0.1mL of the bacterial solution (bacterial concentration: 106cfu/mL) was applied evenly to LB agar plate. The bacteriostatic chitosan gel containing the bacteriostatic tablets prepared in examples 1-5 and comparative examples 1-3 was placed on the surface of agar plates (experimental group-test solution diluted one time with ultrapure water), 4 plates per group, and the plates were then incubated in a 37 ℃ incubator for 16 hours. The bacteriostatic performance of the sample is evaluated by measuring the size of the bacteriostatic ring, and the calculation method is as follows:

the diameter of the bacteriostatic ring (mm,

) Outer diameter of bacteriostatic circle-diameter of sample to be measured

Diameter of the antibacterial ring	Staphylococcus aureus	Escherichia coli	Candida albicans	Pseudomonas aeruginosa
					Example 1	20.3	19.6	18.9	25.7
Example 2	19.9	20.0	20.9	24.9
					Example 3	21.5	20.6	25.1	26.1
Example 4	24.6	22.4	19.7	23.6
					Example 5	30.0	25.8	26.1	32.8
Comparative example 1	12.6	10.3	9.9	13.2
					Comparative example 2	9.8	10.0	8.7	10.9
Comparative example 3	8.5	7.8	10.5	12.2

The chitosan bacteriostatic gel provided by the invention has good bacteriostatic activity, the effect is obviously better than that of a chitosan control group, and the chitosan bacteriostatic gel especially has good bacteriostatic action on pseudomonas aeruginosa.

2. The healing promotion experiment of the chitosan bacteriostatic gel comprises the following steps:

the experimental animals adopt Wister rats, 10 animals in each group weigh 250-300 g, and the male and female animals are half in half respectively, and the wound healing conditions are observed at 3, 7 and 14 days after injury. Depilating the back of a rat by using 8% sodium sulfide liquid, administering sodium pentobarbital to the abdominal cavity after 24 hours, shearing 3 circular full-skin symmetrical incisions with the diameter of about 2.0cm at positions 2.0cm away from the two sides of the spine after anesthesia is successful, disinfecting by using 70% alcohol solution, respectively coating chitosan antibacterial gel prepared in examples 1-5 and comparative examples 1-3 on the wound, drying to form a film and protect the wound without binding. Normal saline was administered intraperitoneally after injury. In addition, a blank set was set, i.e., the wound was left untreated. Measuring the area of the wound surface after the wound and 3, 7 and 14d, covering the wound surface with a transparent film, drawing and cutting the film along the wound surface, weighing and converting into the area.

The chitosan antibacterial gel has obvious healing promoting effect, can form a wound protecting film without binding after the gel is used, has obviously higher wound healing speed than a control group, and has unobvious scars after wound healing.

3. Sensory evaluation

The antibacterial chitosan gels prepared in examples 1-5 and comparative examples 1-3 were applied to the skin of 30 persons, and each person scored the appearance and body sensation of the gel, wherein the appearance was transparent (1-10 points, 10 points are transparent), whether or not a breathable film was formed (1-10 points, 10 points are breathable), the feeling of adhesion, and smoothness (1-10 points, 10 points are smooth and non-sticky)

Scoring	The appearance is transparent	Whether or not to form a breathable film	Sticky feeling and smoothness
				Example 1	9	8	7
Example 2	9	6	6
				Example 3	8	7	8
Example 4	8	6	6
				Example 5	10	10	10
Comparative example 1	6	3	2
				Comparative example 2	5	4	4
Comparative example 3	6	7	6

The chitosan antibacterial gel has the advantages of good using effect, good using feeling of a user, transparent appearance, smooth and non-greasy property, and a breathable film is formed.

The embodiments in the present specification are described in a progressive manner, and the same and similar parts among the embodiments are referred to each other, and each embodiment focuses on the differences from the other embodiments. In particular, for the system embodiment, since it is substantially similar to the method embodiment, the description is simple, and for the relevant points, reference may be made to the partial description of the method embodiment.

The above description is only an example of the present application and is not intended to limit the present application. Various modifications and changes may occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.

Claims

1. The chitosan bacteriostatic gel is characterized by comprising the following components in parts by weight:

0.5-6 parts of micromolecular chitosan, 0.5-1 part of bacteriostatic agent, 0.1-0.8 part of carbomer, 0.05-0.3 part of gamma-polyglutamic acid and 0.1-3 parts of lubricant.

2. A chitosan bacteriostatic gel according to claim 1, wherein: the pH value of the chitosan antibacterial gel is 5.5-8.0.

3. A chitosan bacteriostatic gel according to claim 2, wherein: the pH regulator is one of sodium hydroxide, potassium hydroxide and triethanolamine.

4. A chitosan bacteriostatic gel according to claim 1, wherein: the bacteriostatic agent is one or more of chlorhexidine acetate, chlorhexidine gluconate, tea tree oil, and eucalyptus oil.

5. A chitosan bacteriostatic gel according to claim 4, wherein: the bacteriostatic agent is chlorhexidine acetate, tea tree oil and eucalyptus oil, and the mass ratio of the three components is 1: (0.5-0.8): (0.2-0.5).

6. A chitosan bacteriostatic gel according to claim 1, wherein: the carbomer is one or more of carbomer 980, carbomer 981 and carbomer 940.

7. A chitosan bacteriostatic gel according to claim 1, wherein: the lubricant is one or more of glycerol, propylene glycol and polyethylene glycol.

8. A chitosan bacteriostatic gel according to claim 7, wherein: the lubricant is glycerol and polyethylene glycol, and the mass ratio of the two components is 1: (1.5-3).

9. A chitosan bacteriostatic gel according to claim 1, wherein: the preparation method of the micromolecule chitosan comprises the following steps:

1) wetting chitosan powder with 30% sodium hydroxide solution;

10. A preparation method of chitosan bacteriostatic gel is characterized by comprising the following steps:

1) preparation of chitosan solution:

2) preparation of carbomer solution:

3) preparing the antibacterial composite gel: