CN114057982A

CN114057982A - Water-based polyurethane liquid dressing, preparation method thereof and antibacterial film layer

Info

Publication number: CN114057982A
Application number: CN202111486790.5A
Authority: CN
Inventors: 卢智慧; 侯志国
Original assignee: Huangpu Institute of Materials
Current assignee: Huangpu Institute of Materials
Priority date: 2021-12-07
Filing date: 2021-12-07
Publication date: 2022-02-18

Abstract

The invention relates to the technical field of medical materials, in particular to a water-based polyurethane liquid dressing, a preparation method thereof and an antibacterial film layer. In the invention, a certain amount of alcohol amine, hydroxymethyl carboxylic acid and sodium sulfonate are introduced as hydrophilic chain extenders in the process of preparing the polyurethane prepolymer, and the polyurethane prepolymer can be subjected to appropriate hydrophilic modification so as to be used as a film forming substance of a water-based liquid dressing; the antibacterial agent is introduced into the polymer chain segment in a chemical grafting mode by introducing a certain amount of antibacterial agent capable of chemically reacting with polyisocyanate, so that the antibacterial agent is not easy to run off to the environment to cause microbial drug resistance, and the long-term antibacterial effect of the dressing is realized.

Description

Water-based polyurethane liquid dressing, preparation method thereof and antibacterial film layer

Technical Field

The invention relates to the technical field of medical materials, in particular to a water-based polyurethane liquid dressing, a preparation method thereof and an antibacterial film layer.

Background

The medical dressing is used as a covering of a wound, can replace damaged skin to play a role of temporary barrier in the process of wound healing, avoids or controls wound infection, and provides an environment beneficial to wound healing. Traditional wound dressings, such as wound pads, have the functions of covering wounds, preventing infection and the like, but the traditional dressings have the defects of poor comfort, blood circulation obstruction, incomplete bacteria isolation, easy adhesion to wounds in the removal process and the like, so that the traditional dressings are limited in clinical application; the liquid wound dressing has the advantages of random spraying, film forming, transparency, water resistance, no influence on the appearance of a user and the like, so that the liquid wound dressing is more and more popular.

Depending on the materials used, medical dressings can be broadly divided into: natural materials, synthetic high molecular materials, inorganic materials and composite materials. There are many kinds of synthetic polymer materials that can be used as dressings, such as polyurethane, polyvinyl alcohol, polyethylene, polyacrylonitrile, silicone rubber, and the like. Animal experiments and clinical experiments prove that the polyurethane material has the advantages of safety, no toxicity, no stimulation, no sensitization, no foreign body reaction, quick wound healing, good biocompatibility and the like. However, most of the dressings on the market currently related to the use of polyurethane are solid dressings, only polyurethane is used as a foaming layer, polyurethane is rarely used as a film-forming substance of a liquid dressing, and even if polyurethane is used as a film-forming substance of a liquid dressing, the polyurethane is an oily liquid dressing rather than a warm and non-irritant aqueous liquid dressing in view of the hydrophobicity of the polyurethane. The traditional water-based dressing is mild and non-irritant, but the water resistance and the lasting antibacterial and antibacterial performance of the product are not enough, and the protective effect on the wound is weak.

In addition, in order to increase the active antibacterial performance of the liquid dressing, so that the liquid dressing is not limited to physical barrier to bacteria and viruses, some antibacterial components are often added into the dressing through physical mixing, but the antibacterial agent added through the physical mixing is easy to leak from a film-forming substance, so that the body surface environment is polluted, the bacterial resistance is caused, and even the generation of 'super bacteria' can be caused; and after the antibacterial agent is continuously leaked completely, the film-forming material of the liquid dressing has no antibacterial effect any more, so that the liquid dressing added with the antibacterial agent through physical blending hardly has a long-acting antibacterial effect.

Disclosure of Invention

Based on the above, there is a need for a water-based polyurethane liquid dressing and a preparation method thereof, wherein polyurethane is used as a film forming substance of the water-based liquid dressing, and the water-based polyurethane liquid dressing has the advantages of safety, no toxicity, no stimulation, no sensitization, no foreign body reaction, quick wound healing and good biocompatibility; the antibacterial agent is introduced by chemical grafting, has longer-acting antibacterial activity than physical blending, and is not easy to leak; and the film has waterproof function after being formed, so that the wound is more stably protected.

The invention provides a water-based polyurethane liquid dressing, which comprises the following raw material components in parts by mass:

the hydrophilic chain extender is one or more of alcohol amine, hydroxymethyl carboxylic acid and sodium sulfonate, and the antibacterial agent can chemically react with the polyisocyanate;

the hydrophilic chain extender is alcohol amine and/or hydroxymethyl carboxylic acid, and the raw material components further comprise 1-10 parts by mass of a neutralizing agent.

In some embodiments, the polyol has a number average molecular weight of 100Da to 10000 Da; and/or

The polyol is polyether polyol and/or polyester polyol; and/or

The polyisocyanate is non-aromatic polyisocyanate; and/or

The antibacterial agent is one or more of a quaternary ammonium salt antibacterial agent, a guanidine antibacterial agent and a natural antibacterial agent, and the natural antibacterial agent is one or more of chitosan, chitosan quaternary ammonium salt, chitin and antibacterial peptide.

In some embodiments, the polyether polyol is one or more of a polytetrahydrofuran polyol, a polypropylene glycol polyol, a polyethylene glycol polyol, a polypropylene glycol-ethylene glycol polyol, and a polytetrahydrofuran-butanediol polyol, and the polyester polyol is one or more of a poly (epsilon-caprolactone) polyol, a polycarbonate polyol, a polylactic acid, and a polyethylene-propylene-diene-polyol; and/or

The non-aromatic polyisocyanate is one or more of hexamethylene diisocyanate, 4-bis (isocyanate cyclohexyl) methane, methylcyclohexyl diisocyanate, 2, 4-trimethylhexamethylene diisocyanate, 2, 6-diisocyanate methylhexanoate and isophorone diisocyanate; and/or

The quaternary ammonium salt antibacterial agent is polyhydroxy quaternary ammonium salt or polyamino quaternary ammonium salt, and the guanidine antibacterial agent is one or more of polyhexamethylene guanidine, polyhexamethylene guanidine hydrochloride, polyhexamethylene biguanide hydrochloride, chitosan guanidine and chitosan guanidine hydrochloride.

In some embodiments, the hydrophilic chain extender is one or more of N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, t-butyldiethanolamine, N-ethyldiethanolamine, dimethylolpropionic acid, dimethylolbutyric acid, sodium 1, 2-propanediol-3-sulfonate, and sodium 1, 4-butanediol-2-sulfonate; and/or

The neutralizer is one or more of glacial acetic acid, lactic acid, glycolic acid, hydrochloric acid, sulfuric acid, malic acid, citric acid, arginine, lysine, histidine, triethylamine, triethanolamine, N-methyldiethanolamine, ammonia water, sodium hydroxide and potassium hydroxide.

In some embodiments, the composition further comprises an auxiliary agent, wherein the auxiliary agent comprises the following components in parts by mass:

0.01-1 part of a catalyst;

0.01-30 parts of a micromolecular chain extender; and

0.01-8 parts of a small-molecule cross-linking agent.

In some embodiments, the catalyst is stannous octoate and/or dibutyltin dilaurate; and/or

The micromolecule chain extender is one or more of ethylene glycol, 2-methyl-1, 3-propylene glycol, diethylene glycol, 1, 4-butanediol, 2, 3-butanediol, 1, 6-hexanediol, neopentyl glycol, diethylene glycol, ethylenediamine, hydrated ethylenediamine and ethylenediamine salt; and/or

The micromolecule cross-linking agent is one or more of triethanolamine, glycerol, sorbitol and glucose.

In some embodiments, the water is used in an amount of 200 to 1500 parts; the diluent is acetone or methyl ethyl ketone, and the using amount is 100-1000 parts.

In another aspect of the present invention, there is also provided a method for preparing a water-based polyurethane liquid dressing, which is selected from one of method a, method B or method C:

the method A comprises the following steps:

preparing raw material components of the water-based polyacrylate liquid dressing according to any one of the previous embodiments, wherein the antibacterial agent is divided into a first antibacterial agent and a second antibacterial agent, the diluent is divided into a first diluent and a second diluent, and the auxiliary agent is divided into a first auxiliary agent and a second auxiliary agent;

placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding the polyisocyanate and the first auxiliary agent, and reacting; adding the hydrophilic chain extender, the second auxiliary agent, the first antibacterial agent and the first diluent, and continuing to react; adding the neutralizing agent and the second diluent, and continuing to react to prepare a polyurethane prepolymer a; cooling the polyurethane prepolymer a to below 50 ℃ for later use;

dissolving the second antibacterial agent in the water to obtain an antibacterial agent aqueous solution; adding the antibacterial agent aqueous solution into the stirred polyurethane prepolymer a, and dispersing for 5-60 min to obtain aqueous polyurethane dispersion a containing a diluent; removing the diluent in the aqueous polyurethane dispersion liquid a containing the diluent to prepare the aqueous polyurethane liquid dressing;

the method B comprises the following steps:

preparing raw material components of the water-based polyacrylate liquid dressing according to any one of the previous embodiments, wherein the diluent is divided into a third diluent and a fourth diluent, and the auxiliary agents are divided into a third auxiliary agent, a fourth auxiliary agent and a fifth auxiliary agent;

placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding the polyisocyanate and the third auxiliary agent, and reacting; adding the hydrophilic chain extender, the fourth aid, the antibacterial agent and the third diluent, and continuing to react; adding the neutralizing agent and the fourth diluent, and continuing to react to prepare a polyurethane prepolymer b; cooling the polyurethane prepolymer b to below 50 ℃ for later use;

dissolving the fifth auxiliary agent in the water to obtain a fifth auxiliary agent water solution; adding the fifth auxiliary agent aqueous solution into the stirred polyurethane prepolymer b, and dispersing for 5-60 min to obtain aqueous polyurethane dispersion liquid b containing a diluent; removing the diluent in the aqueous polyurethane dispersion liquid b containing the diluent to prepare the aqueous polyurethane liquid dressing;

method C comprises the steps of:

preparing raw material components of the water-based polyacrylate liquid dressing according to any one of the previous embodiments, wherein the diluent is divided into a fifth diluent and a sixth diluent, and the auxiliary agent is divided into a sixth auxiliary agent and a seventh auxiliary agent;

placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding the polyisocyanate and the sixth auxiliary agent, and reacting; adding the hydrophilic chain extender, the seventh auxiliary agent and the fifth diluent, and continuing to react; adding the neutralizing agent and the sixth diluent, and continuing to react to prepare a polyurethane prepolymer c; cooling the polyurethane prepolymer c to below 50 ℃ for later use;

dissolving the antibacterial agent in the water to obtain an antibacterial agent aqueous solution; adding the antibacterial agent aqueous solution into the stirred polyurethane prepolymer c, and dispersing for 5-60 min to obtain aqueous polyurethane dispersion c containing a diluent; and removing the diluent in the aqueous polyurethane dispersion liquid c containing the diluent to prepare the aqueous polyurethane liquid dressing.

In some embodiments, the conditions for dehydration are: stirring and dehydrating for 1-4 hours at the temperature of 80-130 ℃ and the vacuum degree of less than-0.08 MPa; and/or

The first antibacterial agent is a quaternary ammonium salt antibacterial agent, the second antibacterial agent is a guanidine antibacterial agent and/or a natural antibacterial agent, and the natural antibacterial agent is one or more of chitosan, chitosan quaternary ammonium salt, chitin, antibacterial peptide, catechin and choline; and/or

The first auxiliary agent, the third auxiliary agent and the sixth auxiliary agent are catalysts, the second auxiliary agent, the fourth auxiliary agent and the seventh auxiliary agent are micromolecule chain extenders and/or micromolecule cross-linking agents, and the fifth auxiliary agent is micromolecule chain extender.

In another aspect of the present invention, there is also provided a polyurethane antibacterial film layer, which is formed by curing the water-based polyurethane liquid dressing according to any one of the foregoing embodiments or the water-based polyurethane liquid dressing prepared by the preparation method according to any one of the foregoing embodiments.

By introducing a certain amount of alcohol amine, hydroxymethyl carboxylic acid and sodium sulfonate as hydrophilic chain extenders in the process of preparing the polyurethane prepolymer, the polyurethane prepolymer can be subjected to appropriate hydrophilic modification, so that the polyurethane prepolymer can be used as a film forming substance of a water-based liquid dressing, has good film forming property, does not influence the flexibility, strength and biocompatibility of the water-based liquid dressing, and provides the water-based liquid dressing without stimulation and low sensitization; the antibacterial agent is introduced into the polymer chain segment in a chemical grafting mode by introducing a certain amount of antibacterial agent capable of chemically reacting with polyisocyanate, so that the antibacterial agent is not easy to run off to the environment to cause microbial drug resistance, and the long-term antibacterial effect of the dressing is realized.

Drawings

Fig. 1 is a water-based polyurethane liquid dressing prepared in example 1.

Detailed Description

To facilitate an understanding of the invention, the invention will now be described more fully with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.

Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the invention, "a plurality" means at least two, e.g., two, three, etc., unless explicitly specified otherwise; similarly, "polyhydroxyquaternary ammonium salt" means a quaternary ammonium salt containing at least two hydroxyl groups, such as bishydroxyquaternary ammonium salt, trihydroxyquaternary ammonium salt, and the like. In the description of the present invention, "a plurality" means at least one, e.g., one, two, etc., unless specifically limited otherwise.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

In the present invention, the technical features described in the open type include a closed technical solution composed of the listed features, and also include an open technical solution including the listed features.

In the present invention, the numerical intervals are regarded as continuous, and include the minimum and maximum values of the range and each value between the minimum and maximum values, unless otherwise specified. Further, when a range refers to an integer, each integer between the minimum and maximum values of the range is included. Further, when multiple range-describing features or characteristics are provided, the ranges may be combined. In other words, unless otherwise indicated, all ranges disclosed herein are to be understood to encompass any and all subranges subsumed therein.

The percentage contents referred to in the present invention are, unless otherwise specified, all percentages by mass.

The percentage concentrations referred to in the present invention refer to the final concentrations unless otherwise specified. The final concentration refers to the ratio of the additive component in the system to which the component is added.

The temperature parameter in the present invention is not particularly limited, and may be a constant temperature treatment or a treatment within a certain temperature range. The constant temperature process allows the temperature to fluctuate within the accuracy of the instrument control.

The neutralizer is used for neutralizing with the hydrophilic chain extender, so that hydrophilic modification of polyurethane is realized. The neutralizing agent may be, for example, one or more of an organic acid, an inorganic acid, an organic base, and an inorganic base.

wherein the hydrophilic chain extender is one or more of alcohol amine, hydroxymethyl carboxylic acid and sodium sulfonate, and the antibacterial agent can chemically react with polyisocyanate;

when the hydrophilic chain extender is alcohol amine and/or hydroxymethyl carboxylic acid, the raw material components also comprise 1-10 parts by mass of a neutralizing agent.

Compared with high molecular materials such as polyvinyl alcohol, polyethylene, polyacrylonitrile, silicon rubber and the like, when the polyurethane is used in the field of medical dressings, the polyurethane has better comprehensive performance, and animal experiments and clinical experiments prove that the polyurethane is safer, nontoxic, non-irritant, non-allergenic, free of foreign body reaction, capable of enabling a wound to heal faster and good in biocompatibility. However, because of the hydrophobicity of polyurethane, polyurethane can only be used for a foaming layer of a solid dressing, and of course, few studies exist at present to use polyurethane as a film-forming substance of an oily liquid dressing, and the polyurethane has not been applied to the field of non-irritant and non-allergenic water-based liquid dressings. The invention introduces a certain amount of alcohol amine, hydroxymethyl carboxylic acid and sodium sulfonate as hydrophilic chain extender in the process of preparing polyurethane prepolymer, and can carry out appropriate hydrophilic modification on the polyurethane prepolymer, so that the polyurethane prepolymer can be used as a film forming substance of the water-based liquid dressing, has better film forming property, does not influence the flexibility, strength and biocompatibility, and provides the water-based liquid dressing without stimulation and low sensitization; the antibacterial agent is introduced into the polymer chain segment in a chemical grafting mode by introducing a certain amount of antibacterial agent capable of chemically reacting with polyisocyanate, so that the antibacterial agent is not easy to run off to the environment to cause microbial drug resistance, and the long-term antibacterial effect of the dressing is realized.

Preferably, the water-based polyurethane liquid dressing comprises the following raw material components in parts by mass:

if a neutralizing agent is required to be added, the amount of the neutralizing agent is preferably 1 to 10 parts.

Further preferably, the water-based polyurethane liquid dressing comprises the following raw material components in parts by mass:

if a neutralizing agent is required to be added, the using amount of the neutralizing agent is preferably 1 to 6 parts.

The dosage of the polyalcohol and the polyisocyanate is controlled within a reasonable range, so that the generated polyurethane has proper elasticity and strength, and is more suitable for being used as a film forming agent of a liquid dressing.

When the hydrophilic chain extender is a hydrophilic salt such as sodium sulfonate, an additional neutralizing agent for neutralizing the acidic or basic hydrophilic chain extender to form a salt to modify the hydrophilicity of the polyurethane is not required. The amount of the hydrophilic chain extender is controlled within a reasonable range, the polyurethane can be controlled to have a proper polymerization degree, after a proper neutralizer is added, the polyurethane has certain hydrophilicity and is easy to emulsify, and meanwhile, certain water resistance can be still kept after film forming.

The dosage of the antibacterial agent is maintained in a reasonable range, so that the dressing has sufficient antibacterial activity, and meanwhile, the formed film is softer and the use feeling is more comfortable.

In some embodiments, the polyol has a molecular weight of 100Da to 10000 Da. Alternatively, the molecular weight of the polyol may be, for example, from 500Da to 2000Da, as well as, for example, from 200Da, 600Da, 1000Da, 1400Da, 1800Da, 2200Da, 3000Da, 4000Da, 5000Da, 6000Da, 7000Da, 8000Da or 9000 Da. The molecular weight of the polyhydric alcohol is controlled within a proper range, so that the liquid dressing has strength and flexibility after being filmed.

In some embodiments, the polyol is a polyether polyol and/or a polyester polyol.

In some embodiments, the polyisocyanate is a non-aromatic polyisocyanate. The aromatic polyisocyanate contains benzene rings, has carcinogenic effect and is harmful to human bodies.

In some embodiments, the antimicrobial agent is one or more of a quaternary ammonium salt antimicrobial agent, a guanidine antimicrobial agent, and a natural antimicrobial agent, and the natural antimicrobial agent is one or more of chitosan, quaternary ammonium salt of chitosan, chitin, and antimicrobial peptide. Preferably, the antimicrobial agent includes at least a quaternary ammonium salt-based antimicrobial agent.

In some embodiments, the polyether polyol is one or more of a polytetrahydrofuran polyol, a polypropylene glycol polyol, a polyethylene glycol polyol, a polypropylene glycol-ethylene glycol polyol, and a polytetrahydrofuran-butanediol polyol.

In some embodiments, the polyester polyol is one or more of a poly (epsilon-caprolactone) polyol, a polycarbonate polyol, a polylactic acid, and an epdm polyol. Preferably, medical grade polyethylene glycol polyols and/or medical grade poly (epsilon-caprolactone) polyols are used.

In some embodiments, the non-aromatic polyisocyanate is one or more of hexamethylene diisocyanate, 4-bis (isocyanatocyclohexyl) methane, methylcyclohexyl diisocyanate, 2, 4-trimethylhexamethylene diisocyanate, 2, 6-diisocyanate methylhexanoate, and isophorone diisocyanate.

In some embodiments, the quaternary ammonium salt-based antimicrobial agent is a polyhydroxy quaternary ammonium salt or a polyamino quaternary ammonium salt. Preferably, the quaternary ammonium salt antibacterial agent is bihydroxy quaternary ammonium salt, compared with amino quaternary ammonium salt, hydroxy quaternary ammonium salt is milder in polymerization reaction, and the reaction speed is controllable; the bishydroxy quaternary ammonium salt can be grafted to the polyurethane backbone without being excessively crosslinked as easily as a quaternary ammonium salt containing 3 or more hydroxyl groups, as compared to a monohydroxy quaternary ammonium salt which can only be grafted to the terminal of the polyurethane molecular chain.

In some embodiments, the guanidine antimicrobial agent is one or more of polyhexamethylene guanidine, polyhexamethylene guanidine hydrochloride, polyhexamethylene biguanide hydrochloride, chitosan guanidine, and chitosan guanidine hydrochloride.

In some embodiments, the bis-hydroxy quaternary ammonium salt is one or more of alkyl bis-hydroxyethyl methylammonium halides, alkyl bis-hydroxyethyl ethylammonium halides, alkyl bis-hydroxyethyl propylammonium halides, alkyl bis-hydroxyethyl butylammonium halides, aliphatic bis-hydroxyethyl methylammonium halides, aliphatic bis-hydroxyethyl ethylammonium halides, aliphatic bis-hydroxyethyl propylammonium halides, and aliphatic bis-hydroxyethyl butylammonium halides. The alkyl group is an alkyl group with any carbon chain length, such as methyl bis hydroxyethyl methyl ammonium chloride, ethyl bis hydroxyethyl methyl ammonium chloride, dodecyl bis hydroxyethyl methyl ammonium chloride or tetradecyl bis hydroxyethyl methyl ammonium chloride, hexadecyl bis hydroxyethyl methyl ammonium chloride, octadecyl bis hydroxyethyl methyl ammonium chloride and the like, and preferably, the alkyl group is an alkyl group with a carbon chain length of 12-18; the lipid group is any carbon chain length, such as tallow-based bis-hydroxyethyl methyl ammonium chloride, stearyl-based bis-hydroxyethyl methyl ammonium chloride or coco-based bis-hydroxyethyl methyl ammonium chloride.

In some embodiments, the hydrophilic chain extender is one or more of N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, t-butyldiethanolamine, N-ethyldiethanolamine, dimethylolpropionic acid, dimethylolbutyric acid, sodium 1, 2-propanediol-3-sulfonate, and sodium 1, 4-butanediol-2-sulfonate.

In some embodiments, the neutralizing agent is one or more of glacial acetic acid, lactic acid, glycolic acid, hydrochloric acid, sulfuric acid, malic acid, citric acid, arginine, lysine, histidine, triethylamine, triethanolamine, N-methyldiethanolamine, ammonia, sodium hydroxide, and potassium hydroxide.

It is understood that the hydrophilic chain extender and the neutralizing agent can perform a neutralization reaction, and therefore, when the hydrophilic chain extender is an anionic hydrophilic chain extender, a cationic neutralizing agent should be selected; when the hydrophilic chain extender is a cationic hydrophilic chain extender, an anionic neutralizing agent should be selected.

The hydrophilic chain extender can extend the chain of polyurethane and increase the film forming property of the polyurethane on one hand, and can form a salt with a neutralizer on the other hand, so that the hydrophilic property of the polyurethane is increased.

In some embodiments, the composition further comprises an auxiliary agent, and the auxiliary agent comprises the following components in parts by mass:

0.01-1 part of a catalyst;

0.01-30 parts of a micromolecular chain extender; and

0.01-8 parts of a small-molecule cross-linking agent.

Preferably, the auxiliary agent comprises the following components in parts by mass:

0.01-1 part of a catalyst;

0.01-15 parts of a micromolecular chain extender; and

0.01-8 parts of a small-molecule cross-linking agent.

Further preferably, the auxiliary agent comprises the following components in parts by mass:

0.05-0.3 part of catalyst;

1-8 parts of a micromolecular chain extender; and

0.5-5 parts of a small molecular crosslinking agent.

The catalyst is used for catalyzing polymerization reaction, and the reaction speed can be effectively improved by proper addition amount without implosion; the small-molecular chain extender is a chain extender with the relative molecular weight of less than 200, preferably a chain extender with the molecular weight of 60-200, and is used for further improving the film forming property of polyurethane, and the proper addition amount can enable the polyurethane to be fully chain extended and has better flexibility so as not to become brittle and hard after film forming; the relative molecular mass of the small molecular cross-linking agent is less than or equal to 300, and the small molecular cross-linking agent is used for controlling the strength, the water resistance and the flexibility of a formed film, wherein the strength is weaker and the water resistance is poor when the small molecular cross-linking agent is used in a small amount, and the flexibility of the formed film is poor when the small molecular cross-linking agent is used in an excessive amount.

In some embodiments, the catalyst is stannous octoate and/or dibutyltin dilaurate.

In some embodiments, the small molecule chain extender is one or more of ethylene glycol, 2-methyl-1, 3-propanediol, diethylene glycol, 1, 4-butanediol, 2, 3-butanediol, 1, 6-hexanediol, neopentyl glycol, diethylene glycol, ethylenediamine hydrate, ethylenediamine salts.

In some embodiments, the small molecule cross-linking agent is one or more of triethanolamine, glycerol, sorbitol, glucose.

In some embodiments, the amount of water is 200 to 1500 parts; the diluent is acetone or methyl ethyl ketone, and the using amount is 100-1000 parts. Preferably, the amount of water is 240-300 parts; the diluent is acetone, and the using amount is 150-400 parts. The amount of water is controlled within a reasonable range, so that the polyurethane film forming agent can be better dispersed to help film formation, and meanwhile, the film forming thickness is appropriate, and the film forming agent is not easy to crack and too long in surface drying time. The amount of diluent is controlled within a reasonable range, which enables easier control of the polymerization reaction, better dispersion of the components, and no time-consuming removal of the components from the system.

the method A comprises the following steps:

placing polyol in a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding polyisocyanate and a first auxiliary agent, and reacting; adding a hydrophilic chain extender, a second auxiliary agent, a first antibacterial agent and a first diluent, and continuing to react; adding a neutralizing agent and a second diluent, and continuing to react to prepare a polyurethane prepolymer a; cooling the polyurethane prepolymer a to below 50 ℃ for later use; preferably, placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, and adding the polyisocyanate and the first auxiliary agent; adding a hydrophilic chain extender, a second auxiliary agent, a first antibacterial agent and a first diluent, and continuously reacting for 2-12 hours; adding a neutralizing agent and a second diluent, and continuously reacting for 0.5-3 hours to obtain a polyurethane prepolymer; cooling the polyurethane prepolymer to below 50 ℃ for later use;

dissolving a second antibacterial agent in water to obtain an antibacterial agent aqueous solution; adding an antibacterial agent aqueous solution into the stirred polyurethane prepolymer a, and dispersing for 5-60 min to prepare aqueous polyurethane dispersion liquid a containing a diluent; removing the diluent in the aqueous polyurethane dispersion liquid a containing the diluent to prepare the aqueous polyurethane liquid dressing;

the method B comprises the following steps:

preparing raw material components of the water-based polyacrylate liquid dressing according to any one of the previous embodiments, wherein the diluent is divided into a third diluent and a fourth diluent, and the auxiliary agent is divided into a third auxiliary agent, a fourth auxiliary agent and a fifth auxiliary agent;

placing polyol in a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding polyisocyanate and a third auxiliary agent, and reacting; adding a hydrophilic chain extender, a fourth aid, an antibacterial agent and a third diluent, and continuing to react; adding a neutralizing agent and a fourth diluent, and continuing to react to prepare a polyurethane prepolymer b; cooling the polyurethane prepolymer b to below 50 ℃ for later use; preferably, placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding the polyisocyanate and the third auxiliary agent, and reacting to a set R value; adding a hydrophilic chain extender, a fourth aid, an antibacterial agent and a third diluent, and continuously reacting for 2-12 hours; adding a neutralizing agent and a fourth diluent, and continuously reacting for 0.5-3 hours to obtain a polyurethane prepolymer; cooling the polyurethane prepolymer to below 50 ℃ for later use;

dissolving the fifth additive in water to obtain a fifth additive aqueous solution; adding a fifth auxiliary agent aqueous solution into the stirred polyurethane prepolymer b, and dispersing for 5-60 min to prepare a waterborne polyurethane dispersion liquid b containing a diluent; removing the diluent in the aqueous polyurethane dispersion liquid b containing the diluent to prepare the aqueous polyurethane liquid dressing;

method C comprises the steps of:

preparing raw material components of the water-based polyurethane liquid dressing according to any one of the previous embodiments, wherein the diluent is divided into a fifth diluent and a sixth diluent, and the auxiliary agent is divided into a sixth auxiliary agent and a seventh auxiliary agent;

placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding polyisocyanate and a sixth auxiliary agent, and reacting; adding a hydrophilic chain extender, a seventh additive and a fifth diluent, and continuing to react; adding a neutralizing agent and a sixth diluent, and continuing to react to prepare a polyurethane prepolymer c; cooling the polyurethane prepolymer c to below 50 ℃ for later use; preferably, placing the polyol into a container for dehydration, introducing nitrogen or argon, adjusting the temperature to 50-90 ℃, adding the polyisocyanate and the sixth auxiliary agent, and reacting to a set R value; adding a hydrophilic chain extender, a seventh auxiliary agent and a fifth diluent, and continuously reacting for 2-12 hours; adding a neutralizing agent and a sixth diluent, and continuing to react for 0.5-3 hours to obtain a polyurethane prepolymer; cooling the polyurethane prepolymer to below 50 ℃ for later use;

dissolving an antibacterial agent in water to obtain an antibacterial agent aqueous solution; adding an antibacterial agent aqueous solution into the stirred polyurethane prepolymer c, and dispersing for 5-60 min to prepare aqueous polyurethane dispersion c containing a diluent; and removing the diluent in the aqueous polyurethane dispersion liquid c containing the diluent to prepare the aqueous polyurethane liquid dressing.

In some embodiments, the method of removing the diluent is distillation under reduced pressure.

Preferably, after the diluent is removed, the method further comprises the step of radiation sterilizing the dressing.

In some embodiments, the conditions for dehydration are: the temperature is 80-130 ℃, the vacuum degree is less than-0.08 MPa, and the stirring dehydration is carried out for 1-4 hours.

Preferably, the preparation method is selected from method a.

In some embodiments, the first antimicrobial agent is a quaternary ammonium salt antimicrobial agent, the second antimicrobial agent is a guanidine antimicrobial agent and/or a natural antimicrobial agent, and the natural antimicrobial agent is one or more of chitosan, chitosan quaternary ammonium salt, chitin and antimicrobial peptide. Quaternary ammonium salt antibacterial agents are introduced to a polyurethane prepolymer molecular chain in a prepolymerization stage, so that the polyurethane molecular chain has stronger antibacterial performance on the whole, microbes such as bacteria and the like are prevented from breeding locally, and the waterborne polyurethane antibacterial dressing has omnibearing antibacterial performance after being filmed; in the water dispersion stage of the polyurethane prepolymer, the polyurethane prepolymer is dispersed in water and reacts with the guanidine antibacterial agent or the natural antibacterial agent at the same time, the guanidine antibacterial agent or the natural antibacterial agent is grafted at the tail end of a polyurethane macromolecular chain, and the quaternary ammonium salt antibacterial agent uniformly dispersed on the polyurethane chain and the guanidine antibacterial agent or the natural antibacterial agent at the tail end of the polyurethane macromolecular chain are used for synergistically sterilizing, so that the antibacterial performance of the polyurethane dressing is stronger and more durable. In addition, the guanidine antibacterial agent or the natural antibacterial agent has more amino groups, and the crosslinking degree of polyurethane can be further improved by the reaction with prepolymer in water dispersion, so that the water resistance and water resistance of the dressing after film formation are better.

In some embodiments, the first, third, and sixth additives are catalysts, the second, fourth, and seventh additives are small molecule chain extenders and/or small molecule cross-linkers, and the fifth additive is a small molecule chain extender.

In some embodiments, the amount of the first diluent and/or the third diluent is 65% to 86% of the total amount of the diluent, preferably 70% to 80% of the total amount of the diluent, and more preferably 75% of the total amount of the diluent.

In yet another aspect of the present invention, there is also provided a polyurethane antibacterial film layer, which is formed by curing the water-based polyurethane liquid dressing of any one of the foregoing embodiments or the water-based polyurethane liquid dressing prepared by the preparation method of any one of the foregoing embodiments.

The present invention will be described in further detail with reference to specific examples and comparative examples. Experimental parameters not described in the following specific examples are preferably referred to the guidelines given in the present application, and may be referred to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by the manufacturer. It is understood that the following examples are more specific to the apparatus and materials used, and in other embodiments, are not limited thereto.

Example 1

The formula is as follows: 60 parts of polytetrahydrofuran polyol (with the molecular weight of 1000), 39 parts of 4, 4-bis (isocyanate cyclohexyl) methane, 6 parts of hydrophilic chain extender tert-butyl diethanolamine, 2.5 parts of micromolecular chain extender 1, 4-butanediol, 0.5 part of micromolecular cross-linking agent triethanolamine, 3 parts of dodecyl bis-hydroxyethyl methyl ammonium chloride, 0.3 part of polyhexamethylene biguanide, 0.3 part of antibacterial peptide, 240 parts of water, 400 parts of acetone, 0.3 part of stannous octoate and 2.3 parts of glacial acetic acid;

according to the formula, adding polytetrahydrofuran polyalcohol into a container, and stirring and dehydrating for 2 hours at the temperature of 100 ℃ and the vacuum degree of-0.098 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polytetrahydrofuran polyol to 70 ℃, adding 4, 4-bis (isocyanate cyclohexyl) methane and stannous octoate, and stirring for reaction for 1 hour under the protection of nitrogen; adding tert-butyl diethanolamine, 1, 4-butanediol, triethanolamine and dodecyl bis-hydroxyethyl methyl ammonium chloride, stirring and reacting for 4 hours under the protection of nitrogen, and adding 300 parts of acetone in the reaction process; adding glacial acetic acid and 100 parts of acetone, and reacting for 0.5 hour to obtain a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 30 ℃ for later use;

dissolving polyhexamethylene biguanide and antibacterial peptide in water to obtain an aqueous solution in which the polyhexamethylene biguanide and the antibacterial peptide are dissolved; slowly adding an aqueous solution in which the hexamethylbiguanide and the antibacterial peptide are dissolved while stirring the polyurethane prepolymer, and dispersing for 30min to obtain an acetone-containing polyurethane dispersion liquid; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Example 2

Substantially the same as in example 1 except that 0.6 parts of small-molecule chain extender ethylenediamine was used in place of the polyhexamethylene biguanide and the antimicrobial peptide in example 1.

Example 3

Substantially the same as in example 1 except that dodecylbis hydroxyethyl methyl ammonium chloride was not added, 1,4 parts of butanediol were adjusted to 3.3 parts.

Example 4

Substantially the same as in example 1 except that the amount of 4, 4-bis (isocyanatocyclohexyl) methane was adjusted to 63 parts and that 1, 4-butanediol was adjusted to 10 parts.

Example 5

The same as example 1 except that the amount of the hydrophilic chain extender t-butyldiethanolamine was 10 parts, the amount of the neutralizer glacial acetic acid was adjusted to 3.72 parts, and 1, 4-butanediol was adjusted to 0.2 part.

Example 6

Substantially the same as in example 1 except that dodecylbis hydroxyethyl methylammonium chloride was replaced with 2-hydroxy-1, 3-bis [ di- (2-hydroxyethyl) dodecylammonium bromide ], and 1, 4-butanediol was adjusted to 1.2 parts.

Example 7

The formula is as follows: 60 parts of polycaprolactone diol (with the molecular weight of 1000), 27.1 parts of 2, 6-diisocyanate methyl caproate, 4 parts of hydrophilic chain extender dimethylolpropionic acid, 1 part of micromolecular chain extender 1, 4-butanediol, 0.1 part of micromolecular cross-linking agent triethanolamine, 3 parts of dodecyl bis-hydroxyethyl methyl ammonium chloride, 0.3 part of polyhexamethylene biguanide, 240 parts of water, 300 parts of acetone, 0.3 part of stannous octoate and 3 parts of triethylamine;

according to the formula, polycaprolactone diol is added into a container, and stirring and dehydration are carried out for 2 hours under the conditions that the temperature is 110 ℃ and the vacuum degree is-0.095 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polycaprolactone diol to 70 ℃, adding 2, 6-diisocyanate methyl caproate and stannous octoate, and stirring for reaction for 2 hours under the protection of nitrogen; then adding dimethylolpropionic acid, 1, 4-butanediol, triethanolamine and octadecyl bis-hydroxyethyl methyl ammonium chloride, stirring and reacting for 3 hours under the protection of nitrogen, and adding 200 parts of acetone in the reaction process; adding 100 parts of lysine and acetone, and reacting for 0.5 hour to obtain a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 30 ℃ for later use;

dissolving polyhexamethylene biguanide in water to obtain an aqueous solution in which the polyhexamethylene biguanide is dissolved; slowly adding the aqueous solution in which the polyhexamethylene biguanide is dissolved while stirring the polyurethane prepolymer, and dispersing for 15min to obtain polyurethane dispersion containing acetone; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Example 8

The formula is as follows: 50 parts of polyethylene glycol (with the molecular weight of 500), 89 parts of isophorone diisocyanate, 10 parts of hydrophilic chain extender N-ethyldiethanolamine, 10 parts of micromolecule chain extender ethylene glycol, 1.5 parts of micromolecule cross-linking agent triethanolamine, 10 parts of dodecyl bis hydroxyethyl methyl ammonium chloride, 0.5 part of polyhexamethylene guanidine hydrochloride, 450 parts of water, 500 parts of acetone, 0.5 part of stannous octoate and 3.5 parts of glacial acetic acid;

adding polyethylene glycol into a container according to the formula, and stirring and dehydrating for 3 hours at the temperature of 90 ℃ and the vacuum degree of-0.098 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polyethylene glycol to 70 ℃, adding isophorone diisocyanate and stannous octoate, and stirring for reaction for 1 hour under the protection of nitrogen; then adding N-ethyldiethanolamine, ethylene glycol, triethanolamine and dodecyl bis-hydroxyethyl methyl ammonium chloride, stirring and reacting for 4 hours under the protection of nitrogen, and adding 400 parts of acetone in the reaction process; then adding 100 parts of glacial acetic acid and acetone, and reacting for 1 hour to obtain a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 50 ℃ for later use;

dissolving polyhexamethylene biguanide hydrochloride in water to obtain an aqueous solution in which the polyhexamethylene biguanide hydrochloride is dissolved; slowly adding the aqueous solution in which the hexamethyl biguanide hydrochloride is dissolved while stirring the polyurethane prepolymer, and dispersing for 30min to obtain polyurethane dispersion containing acetone; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Example 9

The formula is as follows: 100 parts of polypropylene oxide polyalcohol (molecular weight is 2000), 30 parts of 2,2, 4-trimethyl hexamethylene diisocyanate, 11.25 parts of hydrophilic chain extender 1, 2-propylene glycol-3-sodium sulfonate, 0.25 part of micromolecular chain extender 1, 6-hexanediol, 0.25 part of micromolecular cross-linking agent sorbitol, 3 parts of dodecyl bis hydroxyethyl methyl ammonium chloride, 0.25 part of chitosan, 300 parts of water, 600 parts of acetone and 0.25 part of dibutyltin dilaurate;

according to the formula, the polyoxypropylene polyol is added into a container, and stirred and dehydrated for 1 hour under the conditions that the temperature is 120 ℃ and the vacuum degree is-0.098 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polyoxypropylene polyol to 60 ℃, adding 2,2, 4-trimethylhexamethylene diisocyanate and dibutyltin dilaurate, and stirring for reaction for 3 hours under the protection of nitrogen; then adding 1, 2-propylene glycol-3-sodium sulfonate, 1, 6-hexanediol, sorbitol and dodecyl bis-hydroxyethyl methyl ammonium chloride, stirring and reacting for 4 hours under the protection of nitrogen, and adding 600 parts of acetone in the reaction process to obtain a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 40 ℃ for later use;

dissolving chitosan in water to obtain a water solution in which the chitosan is dissolved; slowly adding the aqueous solution dissolved with the chitosan while stirring the polyurethane prepolymer, and dispersing for 40min to obtain polyurethane dispersion liquid containing acetone; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Example 10

The formula is as follows: 300 parts of polyethylene glycol (PEG) (with the molecular weight of 10000), 14 parts of isophorone diisocyanate, 4 parts of hydrophilic chain extender dimethylolpropionic acid, 0.5 part of octadecyl bis-hydroxyethyl methyl ammonium chloride, 0.1 part of chitosan quaternary ammonium salt, 1000 parts of water, 1000 parts of acetone and 2.26 parts of triethylamine;

according to the formula, the following components are prepared: adding polyethylene glycol into a container, and stirring and dehydrating for 1 hour at the temperature of 120 ℃ and the vacuum degree of-0.098 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polyethylene glycol (PEG) to 90 ℃, adding isophorone diisocyanate, and stirring for reaction for 3 hours under the protection of nitrogen; then dimethylolpropionic acid and octadecyl bis-hydroxyethyl methyl ammonium chloride are added, stirred and reacted for 12 hours under the protection of nitrogen, and 800 parts of acetone is added in the reaction process; adding 200 parts of triethylamine and 200 parts of acetone, and reacting for hours to obtain a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 30 ℃ for later use;

dissolving chitosan quaternary ammonium salt in water to obtain an aqueous solution in which the chitosan quaternary ammonium salt is dissolved; slowly adding the aqueous solution dissolved with the chitosan while stirring the polyurethane prepolymer, and dispersing for 40min to obtain polyurethane dispersion liquid containing acetone; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Example 11

The formula is as follows: 50 parts of polyethylene glycol (PEG) (molecular weight 200), 200 parts of isophorone diisocyanate, 20 parts of hydrophilic chain extender N-ethyldiethanolamine, 22 parts of micromolecule chain extender 1, 4-butanediol, 9 parts of glacial acetic acid, 50 parts of tetradecyl bis-hydroxyethyl methyl ammonium chloride, 3 parts of antibacterial peptide, 1200 parts of water, 700 parts of acetone and 0.3 part of stannous octoate;

adding polyethylene glycol into a container according to the formula, and stirring and dehydrating for 1 hour at the temperature of 120 ℃ and the vacuum degree of-0.098 MPa; after dehydration, introducing nitrogen for protection, adjusting the temperature of the dehydrated polyethylene glycol to 80 ℃, adding isophorone diisocyanate, and stirring for reaction for 3 hours under the protection of nitrogen; then adding N-ethyldiethanolamine, 1, 4-butanediol and tetradecyl bis-hydroxyethyl methyl ammonium chloride, stirring and reacting for 4 hours under the protection of nitrogen, and adding 600 parts of acetone in the reaction process; then adding 100 parts of glacial acetic acid and acetone, and reacting for 1 hour to obtain a polyurethane prepolymer; obtaining a polyurethane prepolymer; reducing the temperature of the polyurethane prepolymer to 40 ℃ for later use;

dissolving antibacterial peptide in water to obtain an aqueous solution in which the antibacterial peptide is dissolved; slowly adding the aqueous solution dissolved with the antibacterial peptide while stirring the polyurethane prepolymer, and dispersing for 40min to obtain polyurethane dispersion containing acetone; and (3) evaporating acetone in the polyurethane dispersion liquid containing acetone to obtain the aqueous polyurethane liquid dressing, and then performing radiation sterilization to obtain the sterile aqueous polyurethane liquid dressing.

Comparative example 1

The water-based dressing containing the antibacterial agent is prepared by adopting neutralized medical polyacrylic resin PA-IV as a film forming agent, and comprises the following specific steps:

adding 25 parts of commercially available pharmaceutical grade polyacrylic resin PA-IV, 0.4 part of Tween 80, 5 parts of citric acid and 70 parts of purified water into a container, heating to 60 ℃, stirring for 0.5h, adding 0.5 part of dodecyl trimethyl ammonium bromide, continuously stirring for 0.5h, and filtering to obtain the polyacrylic resin.

Comparative example 2

The water-based dressing containing the antibacterial agent is prepared by adopting commercially available medical polyvinyl alcohol as a film forming agent, and comprises the following specific steps:

adding 15 parts of commercially available pharmaceutical grade polyvinyl alcohol (medium viscosity, 1788 type), 85 parts of water and 0.5 part of dodecyl trimethyl ammonium bromide into a container, heating to 60 ℃, stirring for 3 hours, and filtering to obtain the product.

Comparative example 3

In substantial agreement with example 2, except that dodecylbis hydroxyethyl methylammonium chloride did not participate in the prepolymer preparation process, and was physically blended with the liquid dressing after the preparation thereof, the amount of 1, 4-butanediol was adjusted to 3.2 parts.

Comparative example 4

Essentially identical to example 1, except that the hydrophilic chain extender t-butyldiethanolamine and the neutralizing agent glacial acetic acid were not added.

Because the polyurethane is not subjected to hydrophilic modification, the system cannot be emulsified in a water dispersion stage, and polymers are separated out and agglomerated and cannot be normally used.

Characterization test:

the liquid dressings or films formed by the liquid dressings prepared in the examples and the comparative examples are subjected to characterization tests, and mainly comprise two parts, wherein the first part is used for basic performance, and the second part is used for related tests of bacterium resistance, sterilization and bacteriostasis.

A first part:

(1) appearance of the antibacterial liquid wound dressing: and observing the physical states of the sample such as color, properties and the like by naked eyes, and observing whether the sample is deposited after being placed for 180 days. All examples and comparative examples produced dressings that were clear or milky bluish, with no precipitation after 180 days of standing except comparative example 4.

(2) The pH range is as follows: the center value was identified as. + -. 0.5 as measured by pH meter at standard temperature and pressure. The pH values of all the examples and the comparative examples are between 6 and 8.

(3) Water resistance test:

the test method comprises the following steps: YY/T0471.3-2004 contact wound dressing Experimental method part 3: water-blocking property

The detection means is as follows: putting a polytetrafluoroethylene drying dish on a flat table, taking 8mL of a sample by using a 10mL measuring cylinder, slowly pouring the sample into the polytetrafluoroethylene drying dish, and after the moisture is completely volatilized, uncovering the film for testing to obtain the sample. The test is carried out according to the water resistance test method specified by the YY/T0471.3-2004 standard, and the result meets 2.2 requirements: the capacity of bearing 500mm hydrostatic pressure for 300 s.

(4) Surface dry time test: the test procedure was to plot a 4.5cm target area in the center of the base film, apply the liquid dressings prepared in examples and comparative examples to the target area, wet film thickness 150-.

(5) Air permeability: the water vapor transmission rate was measured and tested according to YY/T0471.2-2004.

(6) Wound liquid dressing samples per se bacterial assay: the method was carried out according to the method specified in GB 15980-2009, and the results of the determination were determined in that the samples prepared in all the examples and comparative examples were themselves sterile.

(7) Wound liquid dressing samples skin irritation index (PII) determination: the method is carried out according to the method specified in GB/T16886.10-2000, and the indexes are not more than 0.5 when the acute contact is required for 24 hours. All examples and comparative examples were prepared with a sample index of 0.

(8) Skin sensitization reaction of wound liquid dressing samples: all samples prepared in examples and comparative examples were free from skin sensitization by the closed sensitization test method specified in GB/T16886.10-2000.

TABLE 1

TABLE 2

A second part:

(1) resistance to bacteria test

The test method comprises the following steps: GB/T19633.1-2015 terminally sterilized medical device packaging part 1: materials, sterile barrier systems; YY/T0471.5-2017 contact wound dressing test method part 5 antibacterial Properties

Adding an antibacterial liquid wound dressing solution into a 96-well plate paved with agar gel to form a film (the 96-well plate is made of solvent-resistant polypropylene); inoculating a loop of staphylococcus aureus strain into a trypticase soytone liquid medium, culturing at 30-35 ℃ for 24h, and diluting the cultured bacterial liquid to 5 multiplied by 10⁷cfu/ml. Taking the processed film forming sample and putting the film forming sample in a clean workbench. To be free ofBacteria operation the sample membrane is placed on the surface of the nutrient agar gel, and is completely contacted, then 0.5ml of bacteria liquid (containing 5X 10 of bacteria) is respectively taken by a sterile pipette⁷cfu/ml), dropping on a sample membrane, culturing at 30-35 ℃ for 3 days and 7 days, observing the growth of bacteria on the agar gel, and obtaining the results shown in table 3, wherein, + represents that the bacteria can not be counted, and-represents that the bacteria grow aseptically.

TABLE 3

(2) Liquid wound dressing bacteriostatic ability test

The obtained polyurethane antibacterial dressing is prepared into a sheet after being filmed, the obtained sheet is placed in a constant temperature and humidity box, the antibacterial performance of the sheet is tested when the placing days are 1 day according to national standard QB/T2591-2003, and the calculation method of the antibacterial rate is as follows:

R＝(B-C)/B*100

wherein, R is the antibacterial rate (%); b is the average recovery bacteria count (cfu/plate) of the blank control sample; c is the average number of recovered bacteria (cfu/piece) of the antibacterial sample.

The results of the antibacterial ratio (%) of each example and comparative example are shown in Table 4.

TABLE 4

The results of the antibacterial ratio (%) against Staphylococcus aureus when the samples obtained in each example and comparative example were left for 1 day, 7 days, and 30 days are shown in Table 5.

TABLE 5

As can be seen from the above characterization, examples 1 to 11 can all form stable emulsions, and in comparative example 4, because the polyurethane is not subjected to hydrophilic modification, the system is difficult to emulsify in the water dispersion stage, and the prepared liquid dressing cannot exist stably and uniformly, and cannot be normally used for film formation. Compared with the optimal example 1, the small-molecular chain extender is adopted to replace the hexamethyl biguanide and the antibacterial peptide in the example 2, the quaternary ammonium salt antibacterial agent is not introduced in the water dispersion stage in the example 3, and in order to ensure that the reaction is not influenced, the dosage of the small-molecular chain extender is correspondingly increased, but the crosslinking density of the small-molecular chain extender and the quaternary ammonium salt antibacterial agent is increased, so that the water vapor permeability is reduced, and the antibacterial performance is also reduced; in example 4, the amount of polyisocyanate used was large, the hardness after film formation was slightly high, the hydrophobicity was enhanced but the air permeability was also reduced; the hydrophilic chain extender in the embodiment 5 is used in a large amount, so that the film forming surface drying time is prolonged; example 6 the water vapor transmission rate was lower than that of example 1 because the reaction control was slightly difficult due to the introduction of the polyfunctional quaternary ammonium salt antibacterial agent, the degree of crosslinking was increased, and the water vapor transmission rate was reduced; however, in general, the dressing prepared by the embodiments of the present invention has balanced performance, and has excellent antibacterial property, antibacterial long-lasting property and use feeling (film forming speed and air permeability), and can completely meet daily use requirements.

As can be seen from comparative examples 1 and 2, the water-blocking performance of the waterborne polyurethane dressing is better than that of common waterborne dressings such as acrylic resin waterborne dressings and polyvinyl alcohol waterborne dressings after film forming, and the common waterborne dressings are difficult to play a water-blocking role; in addition, the film forming speed of the polyurethane is obviously superior to that of acrylic resin and polyvinyl alcohol. As can be seen from comparative example 3, the physical blending of the antimicrobial agent results in the effect of long-term antimicrobial activity, and the antimicrobial agent gradually runs off during use, so that the dressing eventually loses active antimicrobial activity.

The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.

The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the patent of the present invention should be subject to the appended claims, and the description and the drawings can be used for explaining the contents of the claims.

Claims

1. The water-based polyurethane liquid dressing is characterized by comprising the following raw material components in parts by mass:

2. The water-based polyurethane liquid dressing of claim 1, wherein the polyol has a number average molecular weight of 100Da to 10000 Da; and/or

The polyol is polyether polyol and/or polyester polyol; and/or

The polyisocyanate is non-aromatic polyisocyanate; and/or

The antibacterial agent is one or more of quaternary ammonium salt antibacterial agent, guanidine antibacterial agent and natural antibacterial agent, and the natural antibacterial agent is one or more of chitosan, chitosan quaternary ammonium salt, chitin and antibacterial peptide.

3. The water-based polyurethane liquid dressing of claim 2, wherein the polyether polyol is one or more of polytetrahydrofuran polyol, polypropylene glycol polyol, polyethylene glycol polyol, polypropylene glycol-ethylene glycol polyol, and polytetrahydrofuran-butanediol polyol, and the polyester polyol is one or more of poly (epsilon-caprolactone) polyol, polycarbonate polyol, polylactic acid, and polyethylene-propylene-diene-terpolymer polyol; and/or

4. The water-based polyurethane liquid dressing of claim 1, wherein the hydrophilic chain extender is one or more of N-methyldiethanolamine, N-ethyldiethanolamine, N-propyldiethanolamine, t-butyldiethanolamine, N-ethyldiethanolamine, dimethylolpropionic acid, dimethylolbutyric acid, sodium 1, 2-propanediol-3-sulfonate and sodium 1, 4-butanediol-2-sulfonate; and/or

5. The water-based polyurethane liquid dressing according to any one of claims 1 to 4, further comprising an auxiliary agent, wherein the auxiliary agent comprises the following components in parts by mass:

0.01-1 part of a catalyst;

0.01-30 parts of a micromolecular chain extender; and

0.01-8 parts of a small-molecule cross-linking agent.

6. The water-based polyurethane liquid dressing according to claim 5, wherein the catalyst is stannous octoate and/or dibutyltin dilaurate; and/or

7. The water-based polyurethane liquid dressing according to any one of claims 1 to 4, wherein the amount of the water is 200 to 1500 parts; the diluent is acetone or methyl ethyl ketone, and the using amount is 100-1000 parts.

8. A preparation method of the water-based polyurethane liquid dressing is characterized in that one of the method A, the method B or the method C is selected:

the method A comprises the following steps:

the raw material component preparation of the water-based polyacrylate liquid dressing according to any one of claims 1 to 7, wherein the antibacterial agent is divided into a first antibacterial agent and a second antibacterial agent, the diluent is divided into a first diluent and a second diluent, and the auxiliary agent is divided into a first auxiliary agent and a second auxiliary agent;

the method B comprises the following steps:

the raw material component preparation of the water-based polyurethane liquid dressing according to any one of claims 1 to 7, wherein the diluent is divided into a third diluent and a fourth diluent, and the auxiliary agents are divided into a third auxiliary agent, a fourth auxiliary agent and a fifth auxiliary agent;

method C comprises the steps of:

the raw material component preparation of the water-based polyacrylate liquid dressing according to any one of claims 1 to 7, wherein the diluent is divided into a fifth diluent and a sixth diluent, and the auxiliary agent is divided into a sixth auxiliary agent and a seventh auxiliary agent;

9. The method according to claim 8, wherein the dehydration is performed under the following conditions: stirring and dehydrating for 1-4 hours at the temperature of 80-130 ℃ and the vacuum degree of less than-0.08 MPa; and/or

10. An antibacterial polyurethane film layer, which is formed by curing the water-based polyurethane liquid dressing according to any one of claims 1 to 7 or the water-based polyurethane liquid dressing prepared by the preparation method according to any one of claims 8 to 9.