CN107693842B

CN107693842B - Medical water-resistant gel and preparation method thereof

Info

Publication number: CN107693842B
Application number: CN201711266345.1A
Authority: CN
Inventors: 童榆清; 赵红灵; 童和林
Original assignee: Hubei Meierli Biotechnology Co ltd
Current assignee: Hubei Meierli Biotechnology Co ltd
Priority date: 2017-12-05
Filing date: 2017-12-05
Publication date: 2020-05-05
Anticipated expiration: 2037-12-05
Also published as: CN107693842A

Abstract

The invention discloses a medical water-resistant gel and a preparation method thereof, wherein the formula of the medical water-resistant gel comprises the following raw materials: xanthan gum, sericin, Aristoflex AVC, citric acid, triethyl citrate, glycerol and deionized water; adding xanthan gum, sericin and Aristoflex AVC into water to dissolve to obtain a mixed solution A, heating the mixed solution A to 55-65 ℃, dropwise adding citric acid, stirring, preserving heat and reacting for 0.4-0.6 h to obtain a mixed solution B, dropwise adding triethyl citrate into the mixed solution B, stirring, preserving heat and reacting for 0.4-0.6 h to obtain a mixed solution C, adding glycerol into the mixed solution C, stirring uniformly, adjusting the pH value of gel to 4.5-6.0, defoaming, filling and sterilizing to obtain the gel; the film formed by smearing the medical water-resistant gel on skin has excellent waterproof performance and moisturizing performance, can block dust, prevent invasion of bacteria, viruses and fungi, and promote rapid healing of wounds.

Description

Medical water-resistant gel and preparation method thereof

Technical Field

The invention relates to the technical field of medical products, in particular to a medical water-resistant gel and a preparation method thereof.

Background

The liquid wound dressing used in clinic at present mainly adopts gel products, but the existing liquid wound dressings have the following three problems:

(1) the use of organic solvents: in order to improve the film forming property and the water resistance of the liquid dressing, organic solvents such as ethyl acetate, acetone and the like are usually added into the liquid dressing, and the organic solvents have good volatility, but have great irritation to human skin and certain damage to human bodies;

(2) the use of a cross-linking agent: in order to enable a gel product to have better water resistance and avoid the gel dressing from being dissolved in water, a cross-linking agent is usually used to improve the film forming property and the water resistance of the liquid wound dressing in the preparation process of the gel, the cross-linking agent which is most commonly used at present is glutaraldehyde and other raw materials, but glutaraldehyde has certain harm to human health and limits the wide application of the glutaraldehyde in clinic;

(3) poor water resistance, water-soluble: the liquid wound dressing which does not use organic solvent or glutaraldehyde as a cross-linking agent has poor water resistance and can be dissolved when meeting water, so that the liquid wound dressing can be only used for body parts which are not easy to adhere to water, and the wide clinical application of the liquid wound dressing is limited.

Therefore, the development of a medical water-resistant gel which has good water resistance and does not use irritant chemical raw materials becomes a problem to be solved urgently in the industry.

Disclosure of Invention

The invention aims to provide a medical waterproof gel and a preparation method thereof, aiming at the problems that the existing medical gel generally uses an irritant organic solvent or has poor water resistance and cannot be widely used; the medical water-resistant gel disclosed by the invention has no stimulation to wounds, is good in water resistance and has an obvious effect of promoting wound healing.

The invention relates to a medical water-resistant gel which is prepared from the following raw materials in parts by weight:

xanthan gum 0.1-5 sericin 0.1-1

Aristoflex AVC 0.1-1 citric acid 0.01-1

Triethyl citrate 0.01-1 glycerin 3-8

80-98 parts of deionized water.

The invention discloses a medical water-resistant gel, which preferably comprises the following raw materials in parts by weight:

xanthan gum 0.1-3 sericin 0.1-0.8

Aristoflex AVC 0.1-0.6 citric acid 0.1-0.5

Triethyl citrate 0.1-0.5 glycerin 4-6

And 85-95 parts of deionized water.

The most preferable formula of the medical water-resistant gel disclosed by the invention is composed of the following raw materials in parts by weight:

xanthan gum 2 sericin 0.5

Aristoflex AVC 0.25 citric acid 0.14

Triethyl citrate 0.14 Glycerol 5

And 91.65 parts of water.

The xanthan gum is a powdery raw material with the molecular weight of more than 100 ten thousand and the purity of more than 95 percent;

the sericin is water-soluble sericin powder with the purity of more than 99 percent;

the Aristoflex AVC, the Chinese name of which is acrylamide dimethyl ammonium taurate/VP copolymer, adopts powdery raw materials with the purity of more than 92 percent;

the citric acid is a citric acid aqueous solution with the mass fraction of 10%;

the triethyl citrate is prepared by adopting a food-grade liquid raw material with the purity of more than 99 percent;

the glycerol is medical pure glycerol.

The preparation method of the medical water-resistant gel sequentially comprises the following steps of:

(1) taking xanthan gum, sericin and Aristoflex AVC according to a formula proportion, sequentially adding the xanthan gum, sericin and Aristoflex AVC into water for dissolving, and stirring while adding to obtain a mixed solution A;

(2) heating the mixed solution A to 55-65 ℃, slowly dropwise adding 10% citric acid aqueous solution into the mixed solution A within 5 minutes, adding 1-10% citric acid by mass of the total mass of the solutes of the mixed solution A, keeping the temperature at 60 ℃, and uniformly stirring for 1-1.5 hours to obtain mixed solution B;

(3) adding triethyl citrate into the mixed solution B, wherein the mass of the added triethyl citrate is 1-10% of the mass of the solute of the mixed solution A, completing the dropwise addition within 5 minutes, keeping the temperature at 60 ℃, and uniformly stirring for 0.4-0.6 hour to obtain mixed solution C;

(4) adding glycerol into the mixed solution C, uniformly stirring, and adding 3-8% of glycerol by mass to obtain a gel coarse body;

(5) and (3) regulating the pH of the gel coarse body to 4.5-6.0 by using a sodium hydroxide solution with the mass fraction of 5% under stirring, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel.

The film-forming agent xanthan gum used in the invention is also called xanthan gum, xanthan gum and xanthomonas polysaccharide, and is extracellular microbial polysaccharide produced by fermenting saccharides with xanthomonas. Due to its macromolecular special structure and colloidal property, it has multiple functions, and is currently used in industry as a stabilizer, thickener and processing aid for multiple purposes, including making canned and bottled foods, bakery foods, dairy products, frozen foods, salad dressings, beverages, brewing, candies, pastry formulations, and the like. At present, xanthan gum is not used in medical water-resistant gel products, and is selected as a film forming agent in the invention based on the following excellent properties:

1. suspension and emulsification Properties

Xanthan gum has good suspension effect on insoluble solid and oil drops, and xanthan gum sol molecules can form a super-bonded banded spiral copolymer to form a fragile gel-like network structure, so that the xanthan gum can support the forms of solid particles, liquid drops and bubbles, and shows strong emulsification stability and high suspension capacity;

2. good water solubility

The xanthan gum can be quickly dissolved in water, has good water solubility, can be dissolved in cold water particularly, can save complicated processing procedures, is convenient to use, and is slowly added into the stirring water after being uniformly mixed with dry powder of the xanthan gum or dry powder auxiliary materials such as salt, sugar and the like to prepare solution for use;

3. thickening property

The xanthan gum solution has the characteristics of low concentration and high viscosity (the viscosity of a 1% aqueous solution is equivalent to 100 times that of gelatin), and is a high-efficiency thickening agent;

4. pseudoplasticity

The xanthan gum aqueous solution has high viscosity under static or low shearing action, shows that the viscosity is sharply reduced under the high shearing action, but the molecular structure is unchanged, when the shearing force is eliminated, the original viscosity is immediately recovered, the relation between the shearing force and the viscosity is completely plastic, the pseudoplasticity of the xanthan gum is very outstanding, and the pseudoplasticity is extremely effective for stabilizing suspension and emulsion;

5. stability to heat

The viscosity of the xanthan gum solution can not change greatly along with the change of temperature, the viscosity of general polysaccharide can change due to heating, but the viscosity of the xanthan gum aqueous solution is hardly changed between 10 ℃ and 80 ℃, even the low-concentration aqueous solution still shows stable high viscosity in a wide temperature range, and the 1% xanthan gum solution (containing 1% of potassium chloride) is heated from 25 ℃ to 120 ℃, and the viscosity is only reduced by 3%;

6. stability to acid and base

The xanthan gum solution is very stable to acid and alkali, the viscosity of the xanthan gum solution is not influenced when the pH is between 5 and 10, the viscosity of the xanthan gum solution is slightly changed when the pH is less than 4 and more than 11, the xanthan gum can also be dissolved in a sodium hydroxide solution, and the xanthan gum solution has a thickening characteristic;

7. stability to salt

The xanthan gum solution can be mixed with a plurality of salt solutions (potassium salt, sodium salt, calcium salt, magnesium salt and the like) and is not influenced in viscosity, the solubility of the xanthan gum solution can be kept even in a saturated salt solution under the condition of higher salt concentration without precipitation and flocculation, and the viscosity of the xanthan gum solution is hardly influenced;

8. stability to enzymatic reactions

The xanthan gum has extremely strong oxidation resistance and enzymolysis resistance due to the stable double-helix structure, and the xanthan gum cannot be degraded by a plurality of enzymes such as protease, amylase, cellulase, hemicellulase and the like;

the properties are helpful for the stability, hydrophilicity, drug-loading property and the like of the prepared water-resistant gel product.

The sericin used as a film forming agent in the invention is sericin which is globulin and accounts for about 20-30% of the total weight of silk, the sericin is composed of I, II, III and IV proteins from outside to inside, the overall molecular conformation is mainly random coil, the molecular space structure is loose and disordered, β structure exists but no α spiral structure exists, a plurality of amino acids with longer side chains, such as arginine, lysine, glutamic acid, methionine, tryptophan, tyrosine and the like, and a plurality of polar hydrophilic groups (such as-OH, -COOH, -NH 2, -NH and the like) are arranged on the surface of a polypeptide chain, and the structural characteristics endow the sericin with excellent humidity conditioning and moisture retention effects.

The film forming agent Aristoflex AVC used in the invention, named as acrylamide dimethyl ammonium taurate/VP copolymer in the Chinese, is mainly used in skin care products at present and is not used in medical water-resistant gel products. The film forming agent is selected as the film forming agent, and the film forming agent has good stability, special rheological property and excellent skin matching property, and a product prepared from the film forming agent is light, thin, not thick and low in viscosity, is used for wound protection, and has good moisturizing and skin pleasure feeling.

The cross-linking agent used in the invention is citric acid and triethyl citrate, and the citric acid is mainly used as an acidulant, a solubilizer, a buffering agent, an antioxidant, a deodorization agent, a flavor enhancer, a gelling agent, a toner and the like at present. In addition, citric acid has effects of inhibiting bacteria, protecting color, improving flavor, and promoting sucrose conversion. Triethyl citrate is currently used mainly as a plasticizer for adhesives and sealants. Its dissolving power is high, and it has good compatibility with many resins, and the product plasticized by it has good oil resistance, light resistance and mildew resistance. Is mainly used for preparing pharmaceutical excipients and capsule plasticizers. According to experimental data, it has no irritation to eyes and skin. At present, the citric acid and the triethyl citrate are not used as cross-linking agents and reported in documents, and through a large number of experiments, the inventor of the invention accidentally finds that the citric acid and the triethyl citrate can be used as cross-linking agents for preparing medical water-resistant gel, and both belong to safe and non-toxic chemical agents and have no irritation to skin.

The humectant used in the invention is glycerin, the moisturizing performance of the glycerin is excellent, and the humectant used in the medical water-resistant gel can also enhance the moisturizing performance of a water-resistant gel product.

The solvent used in the invention is water, the pH regulator is sodium hydroxide solution with the mass fraction of 5%, and the pH value of the gel is regulated to make the gel more suitable for the pH value of human skin and enhance the comfortable feeling of skin use.

The chemical principle of the medical water-resistant gel is as follows: the xanthan gum, the sericin and the Aristoflex AVC are used as film forming agents, firstly, the xanthan gum, the sericin and the Aristoflex AVC are sequentially added into water to be completely dissolved, then, the temperature is raised to 60 ℃, cross-linking agents of citric acid and triethyl citrate are respectively added, so that the xanthan gum, the sericin and the Aristoflex AVC are subjected to cross-linking reaction, linear or slightly branched macromolecules are converted into a three-dimensional network structure in the reaction process, the performances of the gel, such as strength, wear resistance, solvent resistance and the like, are improved, meanwhile, a stable gel state is kept, then, the pH value is adjusted, and filling and sterilization.

Compared with the prior art, the invention has the following advantages:

1. the brand-new film-forming agents of xanthan gum, sericin and Aristoflex AVC are safe and non-irritant raw materials for skin, have good contact affinity, stability and moisture retention with the skin, and provide a new idea for the existing medical water-resistant gel raw materials;

2. the brand new cross-linking agents of citric acid and triethyl citrate are used, have good cross-linking reaction with the film forming agent, belong to recognized safe and non-irritant compounds, and avoid the irritation and harm of the traditional cross-linking agent of glutaraldehyde to the skin;

3. the novel medical water-resistant gel is provided, the raw materials adopted by the product formula are all safe and non-irritant components, the gel is friendly to skin, the film forming property, the water resistance and the drug loading property of the product are good, and the application field of the water-resistant gel in medical occasions is expanded.

The medical water-resistant gel is a waterproof gel product prepared by using water as a solvent, xanthan gum, sericin and Aristoflex AVC as film-forming agents, and low-molecular organic compounds citric acid and triethyl citrate as cross-linking agents according to a specific process method. The film formed by smearing the gel product on skin has excellent waterproof performance and moisturizing performance, can block dust and prevent invasion of bacteria, viruses and fungi, and is favorable for growth and repair of epidermal cells, and can avoid adhesion of the film and the skin wound surface due to the good moisturizing performance of the film, so that the pain of a patient is relieved. The water-resistant gel can be widely used for small surface wounds such as burns, scalds and skin damages; skin damage of skin diseases such as dermatitis, eczema, psoriasis, tinea manus and pedis, etc.; the laser postoperative wound surface is cooled and moisturized, the invasion of bacteria, viruses and fungi is prevented, the skin is repaired due to various skin barrier insufficiency, the healing capability is improved, the skin barrier function is recovered, the formation of scar tissues is reduced, the pigmentation is avoided, and the healing of skin wounds is promoted.

Drawings

FIG. 1 is an image obtained by magnifying a gel product obtained in example 1 of the present invention by 100 times under a microscope.

Detailed Description

Example 1

The preparation method of the medical water-resistant gel comprises the following steps:

(1) taking 2kg of xanthan gum, 0.5kg of sericin and 0.25kg of Aristoflex AVC, sequentially adding 91.65kg of water while stirring to obtain a mixed solution A;

(2) heating the mixed solution A to 60 ℃, slowly dripping 0.14kg of citric acid aqueous solution with the mass fraction of 10% into the mixed solution A, finishing dripping within 5 minutes, keeping the temperature at 60 ℃, and uniformly stirring for 1.5 hours to obtain mixed solution B;

(3) adding 0.14kg of triethyl citrate into the mixed solution B, finishing the dropwise adding within 5 minutes, keeping the temperature at 60 ℃, and uniformly stirring for 0.5 hour to obtain mixed solution C;

(4) adding 5kg of glycerol into the mixed solution C, and uniformly stirring to obtain a gel coarse body;

(5) and (3) regulating the pH of the gel to 5.5 by using a sodium hydroxide solution with the mass fraction of 5% under stirring, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel.

the glycerol is medical pure glycerol;

the pH regulator is sodium hydroxide solution with the mass fraction of 5%.

The gel product obtained in example 1 was subjected to a performance test, as follows:

experiment I, microscope detection

The gel product prepared in example 1 was uniformly applied to a glass plate having a length of 10 cm and a width of 2 cm, with a thickness of 2mm, and after the application was completed, the gel was placed in a 37 ℃ incubator for 30 minutes, and the gel was dried to form a film, and a slide glass was observed under a microscope with a magnification of 100 times, and the obtained picture is shown in fig. 1. As can be seen from fig. 1, the gel product prepared in this example shows a dense network structure in a 100-fold microscopic picture, which illustrates that the gel product prepared in this example is a product with a stable network structure inside.

Experiment two:

simulation film forming waterproof experiment: the gel product prepared in example 1 was uniformly applied to a glass plate 10 cm in length and 2 cm in width to a thickness of 2mm, and after application, the gel product was placed in a 37 ℃ incubator for 30 minutes, and the gel was dried to form a film, which was completely removed, and then placed in 40 ℃ warm water to be soaked for 1 hour, and the structural integrity of the film was still maintained. The gel product prepared by the embodiment has excellent waterproof performance.

Experiment three:

skin filming waterproof test: the gel product prepared in the example 1 is uniformly smeared on the back of the hand of a subject, the smearing thickness is 2mm, the gel is dried into a film after 10-30 minutes, the hand is soaked in warm water at 40 ℃, and the film still keeps the complete structure after being soaked in the warm water for 15 minutes, which shows that the gel product prepared in the example has excellent waterproof performance.

Example 2

(1) taking 3kg of xanthan gum, 0.8kg of sericin and 0.1kg of Aristoflex AVC, sequentially adding 95kg of water while stirring to obtain a mixed solution A;

(2) heating the mixed solution A to 65 ℃, slowly dripping 0.5kg of citric acid aqueous solution with the mass fraction of 10% into the mixed solution A, finishing dripping within 5 minutes, keeping the temperature at 65 ℃, and uniformly stirring for 1.3 hours to obtain mixed solution B;

(3) adding 0.8kg of triethyl citrate into the mixed solution B, finishing the dropwise adding within 5 minutes, keeping the temperature at 65 ℃, and uniformly stirring for 0.6 hour to obtain mixed solution C;

(4) adding 3kg of glycerol into the mixed solution C, and uniformly stirring to obtain a gel coarse body;

(5) and (3) regulating the pH of the gel to 5.0 by using a sodium hydroxide solution with the mass fraction of 5% under stirring, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel.

All raw material requirements were the same as in example 1.

Example 3

(1) taking 0.1kg of xanthan gum, 0.11kg of sericin and 0.6kg of Aristoflex AVC, sequentially adding into 98kg of water while stirring to obtain a mixed solution A;

(2) heating the mixed solution A to 55 ℃, slowly dripping 0.01kg of citric acid aqueous solution with the mass fraction of 10% into the mixed solution A, finishing dripping within 5 minutes, keeping the temperature at 55 ℃, and uniformly stirring for 1.0 hour to obtain mixed solution B;

(3) adding 0.04kg of triethyl citrate into the mixed solution B, finishing the dropwise adding within 5 minutes, keeping the temperature at 55 ℃, and uniformly stirring for 0.4 hour to obtain mixed solution C;

(4) adding 8kg of glycerol into the mixed solution C, and uniformly stirring to obtain a gel coarse body;

(5) and (3) regulating the pH of the gel to 6.0 by using a sodium hydroxide solution with the mass fraction of 5% under stirring, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel.

All raw material requirements were the same as in example 1.

Example 4

(1) taking 5kg of xanthan gum, 1kg of sericin and 1kg of Aristoflex AVC, sequentially adding 85kg of water while stirring to obtain a mixed solution A;

(2) heating the mixed solution A to 65 ℃, slowly dripping 1kg of citric acid aqueous solution with the mass fraction of 10% into the mixed solution A, finishing dripping within 5 minutes, keeping the temperature at 65 ℃, and uniformly stirring for 1.0 hour to obtain mixed solution B;

(3) adding 1kg of triethyl citrate into the mixed solution B, finishing the dropwise adding within 5 minutes, keeping the temperature at 65 ℃, and uniformly stirring for 0.6 hour to obtain mixed solution C;

(4) adding 6kg of glycerol into the mixed solution C, and uniformly stirring to obtain a gel coarse body;

(5) and (3) adjusting the pH of the gel to 4.5 by using a sodium hydroxide solution with the mass fraction of 5%, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel.

All raw material requirements were the same as in example 1.

The above examples are merely illustrative of the specific processes for preparing the present invention and are not intended to limit the invention in any way, and it is within the scope of the claims to anyone who can produce and prepare products related to the products of the present invention based on the compositions and principles of the claims.

Claims

1. The medical water-resistant gel is characterized by comprising the following raw materials in parts by weight:

2. the medical water-resistant gel according to claim 1, which is characterized by comprising the following raw materials in parts by weight:

3. the medical water-resistant gel according to claim 1, which is characterized by comprising the following raw materials in parts by weight:

4. the medical water-resistant gel according to claim 1, 2 or 3, characterized in that: the xanthan gum is a powdery raw material with the molecular weight of more than 100 ten thousand and the purity of more than 95 percent.

5. The medical water-resistant gel according to claim 1, 2 or 3, characterized in that: the sericin is water-soluble sericin powder with the purity of more than 99 percent.

6. The medical water-resistant gel according to claim 1, 2 or 3, characterized in that: the Aristoflex AVC is prepared from powdery raw materials with the purity of more than 92 percent.

7. The medical water-resistant gel according to claim 1, 2 or 3, characterized in that: the citric acid is a citric acid aqueous solution with the mass fraction of 10%.

8. The medical water-resistant gel according to claim 1, 2 or 3, characterized in that: the triethyl citrate is a food-grade liquid raw material with the purity of more than 99 percent.

9. A preparation method of medical water-resistant gel sequentially comprises the following steps:

(1) taking xanthan gum, sericin and Aristoflex AVC according to a formula proportion, sequentially adding the xanthan gum, sericin and Aristoflex AVC into deionized water for dissolving, and stirring while adding to obtain a mixed solution A;

(5) adjusting the pH of the gel coarse body to 4.5-6.0 by using a sodium hydroxide solution with the mass fraction of 5% under stirring, naturally cooling to room temperature, standing for defoaming, filling, and performing irradiation sterilization to obtain the gel coarse body;

in the preparation process, the value ranges of the raw materials in parts by weight are as follows: 0.1-5 parts of xanthan gum; 0.1-1 parts of sericin; aristoflex AVC 0.1-1; 0.01-1 parts of citric acid; 0.01-1 parts of triethyl citrate; 3-8 parts of glycerol; and 85-98 parts of deionized water.