Preparation and synthesis process of hydrophilic antibacterial polyurethane foam dressing

Abstract

The invention provides a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing, and relates to the technical field of preparation of polyurethane dressings. The invention relates to a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing. The preparation and synthesis process comprises the following steps: S1, synthesizing a brand-new polyurethane chain extender of which the side chain contains biquaternary ammonium salt; s2, a synthesis process of a hydrophilic antibacterial polyurethane prepolymer; s3, researching a synthesis process and a formula of the hydrophilic antibacterial polyurethane foam dressing; s4, studying the sterilization performance of the novel chain extender containing the biquaternary ammonium salt and the hydrophilic antibacterial polyurethane foam dressing; and S5, researching the biocompatibility of the hydrophilic antibacterial polyurethane foam dressing. Synthesis and application of the brand-new chain extender with the side chain containing the biquaternary ammonium salt are one of innovation points of the research, and the biquaternary ammonium salt chain extender not only has a very strong antibacterial property on gram-positive bacteria, but also has a very good antibacterial property on gram-negative bacteria.

Description

Technical Field

[0001] The invention relates to the technical field of polyurethane dressing preparation, in particular to a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing. Background Art

[0002] Polyurethane has good elasticity and has holes in its foam structure, which makes it highly absorbent. It can be used as a material that directly contacts wounds, or used to cover other dressings. When it comes into contact with moist wounds, pus, blood and other wound exudates are absorbed into the foam through the pores and transferred from the contact surface to the inside and back of the foam, thereby removing pus and blood from the wound surface. When it comes into contact with relatively dry wounds, the foam structure can prevent excessive evaporation of water from the wound to maintain a humid environment. Polyurethane has two types: hydrophilic and hydrophobic. The dressings commonly used on polyurethane are mostly quaternary ammonium salts.

[0003] However, due to the introduction of quaternary ammonium salts, the material has a high water absorption rate and is even soluble in water, which affects the performance of the material. Therefore, a new chain extender containing diquaternary ammonium salts in the side chain is used to prepare antibacterial polyurethane foam and waterproof and breathable antibacterial polyurethane film, so that the new material not only has good antibacterial effect, but also has the properties of being light, soft, skin-friendly, highly elastic, highly breathable, waterproof, antibacterial, non-cytotoxic, non-sensitizing, and non-irritating. Summary of the invention

[0004] 1. Technical issues to be resolved

[0005] In view of the deficiencies in the prior art, the present invention provides a preparation and synthesis process for a hydrophilic antibacterial polyurethane foam dressing, which solves the problem that the material has a high water absorption rate and is even soluble in water, which affects the performance of the material.

[0006] (II) Technical solution

[0007] To achieve the above objectives, the present invention is implemented by the following technical scheme: A preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing comprises the following steps:

[0008] S1. Synthesis of a novel polyurethane chain extender containing diquaternary ammonium salt in the side chain

[0009] Lysine is used as a raw material, and a lysine derivative containing dibromine on the side chain is obtained through several steps of reaction, and then quaternized with aliphatic tertiary amine and a tertiary amine containing a fluorinated carbon chain, respectively, to obtain aliphatic diquaternary ammonium salt chain extender and fluorinated diquaternary ammonium salt chain extender;

[0010] S2. Synthesis process of hydrophilic antibacterial polyurethane prepolymer

[0011] A prepolymer with an isocyanate terminal group is prepared by using a mixture of one or more hydrophilic polyethers, a diisocyanate, and a polyurethane chain extender having a diquaternary ammonium salt in the side chain to carry out a prepolymerization reaction;

[0012] S3. Study on the synthesis process and formulation of hydrophilic antibacterial polyurethane foam dressing

[0013] The hydrophilic antibacterial polyurethane prepolymer, polyether diol, water, foam stabilizer and catalyst were mixed in a certain proportion and foamed under certain conditions to prepare the hydrophilic antibacterial polyurethane foam dressing. The effects of the proportion of each component, the order of addition, the foaming conditions and other factors on the foam pore size, softness, hydrophilicity and mechanical strength were studied, and the process improvement of the scale-up experiment was studied.

[0014] S4. Study on the bactericidal properties of a new chain extender containing diquaternary ammonium salt and a hydrophilic antibacterial polyurethane foam dressing

[0015] The minimum inhibitory concentration (MIC) was used to test the antibacterial performance of the synthesized new chain extender. Gram-positive Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli) were selected as experimental strains. Fluorescence microscopy and plate counting methods were used to examine the bactericidal properties of hydrophilic antibacterial polyurethane foam dressings against Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli).

[0016] S5. Study on the biocompatibility of hydrophilic antibacterial polyurethane foam dressing

[0017] To determine the cytotoxicity of hydrophilic antimicrobial polyurethane foam dressings; allergy and irritation tests.

[0018] Preferably, in step S1:

[0019] The two amine groups of lysine have good reactivity and can be used as a raw material for synthesizing polyamides or as a chain extender for polyurethanes.

[0020] Preferably, in step S2:

[0021] The diisocyanate may be TDI or HDI.

[0022] Preferably, in step S5:

[0023] A. Determination of cytotoxicity of hydrophilic antibacterial polyurethane foam dressing: It needs to be determined in accordance with the provisions of the "direct contact test" in GB / T 16886.5-1997;

[0024] B. Allergy test and irritation test: It needs to be carried out according to the methods of "skin irritation test" and "closed sensitization test" in GB / T 16886.10-2000.

[0025] Optimally, the main technical indicators of polyurethane foam dressings are:

[0026] No odor, no slag, uniform pore size, soft; tensile strength is not less than 5MPa, elongation at break is not less than 300%; moisture vapor permeability is 600-800g / m2 / day; has good bactericidal effect; no cytotoxicity.

[0027] (III) Beneficial effects

[0028] The present invention provides a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing, which has the following beneficial effects:

[0029] 1. The synthesis and application of the new side chain containing diquaternary ammonium salt chain extender in the present invention is one of the innovative points of this study. This diquaternary ammonium salt chain extender not only has strong antibacterial properties against Gram-positive bacteria, but also has good antibacterial properties against Gram-negative bacteria.

[0030] 2. The invention adopts a new polyurethane chain extender containing diquaternary ammonium salt in the side chain to synthesize the hydrophilic antibacterial polyurethane foam dressing, which is an innovative research work.

[0031] 3. The present invention solves the molecular design and synthesis problems of a brand-new polyurethane chain extender containing a diquaternary ammonium salt in the side chain, ensures that the polyurethane foam dressing has good biocompatibility, maintains the characteristics of the foam dressing being soft, hydrophilic, having good resilience and good mechanical strength, while also having a small pore size, uniform texture, no slag falling, low scrap rate, and still having excellent performance in an enlarged experiment. DETAILED DESCRIPTION

[0032] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0033] Embodiment 1:

[0034] The embodiment of the present invention provides a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing, comprising the following steps:

[0035] S1. Synthesis of a novel polyurethane chain extender containing diquaternary ammonium salt in the side chain

[0036] Lysine is used as a raw material, and a lysine derivative containing dibromine on the side chain is obtained through several steps of reaction, and then quaternized with aliphatic tertiary amine and a tertiary amine containing a fluorinated carbon chain, respectively, to obtain aliphatic diquaternary ammonium salt chain extender and fluorinated diquaternary ammonium salt chain extender;

[0037] S2. Synthesis process of hydrophilic antibacterial polyurethane prepolymer

[0038] A prepolymer with an isocyanate terminal group is prepared by using a mixture of one or more hydrophilic polyethers, a diisocyanate, and a polyurethane chain extender having a diquaternary ammonium salt in the side chain to carry out a prepolymerization reaction;

[0039] S3. Study on the synthesis process and formulation of hydrophilic antibacterial polyurethane foam dressing

[0040] The hydrophilic antibacterial polyurethane prepolymer, polyether diol, water, foam stabilizer and catalyst were mixed in a certain proportion and foamed under certain conditions to prepare the hydrophilic antibacterial polyurethane foam dressing. The effects of the proportion of each component, the order of addition, the foaming conditions and other factors on the foam pore size, softness, hydrophilicity and mechanical strength were studied, and the process improvement of the scale-up experiment was studied.

[0041] S4. Study on the bactericidal properties of a new chain extender containing diquaternary ammonium salt and a hydrophilic antibacterial polyurethane foam dressing

[0042] The minimum inhibitory concentration (MIC) was used to test the antibacterial performance of the synthesized new chain extender. Gram-positive Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli) were selected as experimental strains. Fluorescence microscopy and plate counting methods were used to examine the bactericidal properties of hydrophilic antibacterial polyurethane foam dressings against Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli).

[0043] S5. Study on the biocompatibility of hydrophilic antibacterial polyurethane foam dressing

[0044] To determine the cytotoxicity of hydrophilic antimicrobial polyurethane foam dressings; allergy and irritation tests.

[0045] In step S1:

[0046] The two amine groups of lysine have good reactivity and can be used as a raw material for synthesizing polyamides or as a chain extender for polyurethanes.

[0047] In step S2:

[0048] The diisocyanate may be TDI or HDI.

[0049] In step S5:

[0050] A. Determination of cytotoxicity of hydrophilic antibacterial polyurethane foam dressing: It needs to be determined in accordance with the provisions of the "direct contact test" in GB / T16886.5-1997;

[0051] B. Allergy test and irritation test: It needs to be carried out according to the methods of "skin irritation test" and "closed sensitization test" in GB / T 16886.10-2000.

[0052] Main technical indicators of polyurethane foam dressings:

[0053] No odor, no slag, uniform pore size, soft; tensile strength is not less than 5MPa, elongation at break is not less than 300%; moisture vapor permeability is 600g / m2 / day; has good bactericidal effect; non-cytotoxic, non-sensitizing, non-irritating.

[0054] Embodiment 2:

[0055] The embodiment of the present invention provides a preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing, comprising the following steps:

[0056] S1. Synthesis of a novel polyurethane chain extender containing diquaternary ammonium salt in the side chain

[0057] Lysine is used as a raw material, and a lysine derivative containing dibromine on the side chain is obtained through several steps of reaction, and then quaternized with aliphatic tertiary amine and a tertiary amine containing a fluorinated carbon chain, respectively, to obtain aliphatic diquaternary ammonium salt chain extender and fluorinated diquaternary ammonium salt chain extender;

[0058] S2. Synthesis process of hydrophilic antibacterial polyurethane prepolymer

[0059] A prepolymer with an isocyanate terminal group is prepared by using a mixture of one or more hydrophilic polyethers, a diisocyanate, and a polyurethane chain extender having a diquaternary ammonium salt in the side chain to carry out a prepolymerization reaction;

[0060] S3. Study on the synthesis process and formulation of hydrophilic antibacterial polyurethane foam dressing

[0061] The hydrophilic antibacterial polyurethane prepolymer, polyether diol, water, foam stabilizer and catalyst were mixed in a certain proportion and foamed under certain conditions to prepare the hydrophilic antibacterial polyurethane foam dressing. The effects of the proportion of each component, the order of addition, the foaming conditions and other factors on the foam pore size, softness, hydrophilicity and mechanical strength were studied, and the process improvement of the scale-up experiment was studied.

[0062] S4. Study on the bactericidal properties of a new chain extender containing diquaternary ammonium salt and a hydrophilic antibacterial polyurethane foam dressing

[0063] The minimum inhibitory concentration (MIC) was used to test the antibacterial performance of the synthesized new chain extender. Gram-positive Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli) were selected as experimental strains. Fluorescence microscopy and plate counting methods were used to examine the bactericidal properties of hydrophilic antibacterial polyurethane foam dressings against Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli).

[0064] S5. Study on the biocompatibility of hydrophilic antibacterial polyurethane foam dressing

[0065] To determine the cytotoxicity of hydrophilic antimicrobial polyurethane foam dressings; allergy and irritation tests.

[0066] In step S1:

[0067] The two amine groups of lysine have good reactivity and can be used as a raw material for synthesizing polyamides or as a chain extender for polyurethanes.

[0068] In step S2:

[0069] The diisocyanate may be TDI or HDI.

[0070] In step S5:

[0071] A. Determination of cytotoxicity of hydrophilic antibacterial polyurethane foam dressing: It needs to be determined in accordance with the provisions of the "direct contact test" in GB / T16886.5-1997;

[0072] B. Allergy test and irritation test: It needs to be carried out according to the methods of "skin irritation test" and "closed sensitization test" in GB / T 16886.10-2000.

[0073] Main technical indicators of polyurethane foam dressings:

[0074] No odor, no dregs, uniform pore size, soft; tensile strength is not less than 5MPa, elongation at break is not less than 300%; moisture vapor permeability is 800g / m2 / day; has good bactericidal effect; non-cytotoxic, non-sensitizing, non-irritating.

[0075] Animal experiments and clinical trials of new hydrophilic antibacterial wound dressings:

[0076] The hydrophilic antibacterial polyurethane foam dressing and the transparent sealing film were used in combination and carried out together with the negative pressure wound treatment system animal test and clinical experiment.

[0077] Experimental methods:

[0078] A. Experimental subjects: 30 tender-skinned white piglets, 50 kg;

[0079] B. Injury site: back, symmetrical, 30*15CM*2 pieces;

[0080] C. Traumatic method: Two water tanks with the same contact area of ​​30*15CM and equal volume are made of identical metal sheets. After filling with water, they are boiled in the pot for a sufficient time. The temperature of both water tanks is exactly the same and reaches 100℃. The pig is placed on a special experimental rack (which can fix the four legs of the pig and let it lie prone on it). After anesthesia, the skin is prepared symmetrically on the left and right sides of the pig's back. Then two hot water boxes are taken and applied to the left and right skin preparations with equal pressure and equal time to cause local scald wounds.

[0081] D. Group experiment: 30 pigs were randomly divided into 2 groups, with the scalding time of each group being 5 seconds and 30 seconds respectively. They are called: 5-second group and 30-second group respectively.

[0082] 5-second group: 1 hour after the scald, the left wound was the treatment group, which was locally debrided and closed with a new antibacterial breathable polyurethane foam dressing; the right wound was the control group, which was locally debrided and closed with a traditional dressing, and the dressing was changed at the same time every day until it was healed;

[0083] 30-second group: The left wound surface of 10 pigs was used as the treatment group, and the right wound surface was used as the control group. After scalding, both groups were only given anti-shock and supportive treatment. After tissue necrosis and wound infection, they began to be divided into groups for treatment. The wound treatment was the same as the 5-second group. Both groups used negative pressure wound treatment, changed the dressing regularly for observation, and statistical processing and analysis were performed after the experiment, and an experimental report was written.

[0084] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing, characterized in that: The following steps are involved: S1. Synthesis of a novel polyurethane chain extender containing diquaternary ammonium salt in the side chain Lysine is used as a raw material, and a lysine derivative containing dibromine on the side chain is obtained through several steps of reaction, and then quaternized with aliphatic tertiary amine and a tertiary amine containing a fluorinated carbon chain, respectively, to obtain aliphatic diquaternary ammonium salt chain extender and fluorinated diquaternary ammonium salt chain extender; S2. Synthesis process of hydrophilic antibacterial polyurethane prepolymer A prepolymer with an isocyanate terminal group is prepared by using a mixture of one or more hydrophilic polyethers, a diisocyanate, and a polyurethane chain extender having a diquaternary ammonium salt in the side chain to carry out a prepolymerization reaction; S3. Study on the synthesis process and formulation of hydrophilic antibacterial polyurethane foam dressing The hydrophilic antibacterial polyurethane prepolymer, polyether diol, water, foam stabilizer and catalyst were mixed in a certain proportion and foamed under certain conditions to prepare the hydrophilic antibacterial polyurethane foam dressing. The effects of the proportion of each component, the order of addition, the foaming conditions and other factors on the foam pore size, softness, hydrophilicity and mechanical strength were studied, and the process improvement of the scale-up experiment was studied. S4. Study on the bactericidal properties of a new chain extender containing diquaternary ammonium salt and a hydrophilic antibacterial polyurethane foam dressing The minimum inhibitory concentration (MIC) was used to test the antibacterial performance of the synthesized new chain extender. Gram-positive Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli) were selected as experimental strains. Fluorescence microscopy and plate counting methods were used to examine the bactericidal properties of hydrophilic antibacterial polyurethane foam dressings against Staphylococcus aureus (S. aureu) and Gram-negative bacteria Escherichia coli (E. coli). S5. Study on the biocompatibility of hydrophilic antibacterial polyurethane foam dressing To determine the cytotoxicity of hydrophilic antimicrobial polyurethane foam dressings; allergy and irritation tests.

2. The preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing according to claim 1, characterized in that: In step S1: The two amine groups of lysine have good reactivity and can be used as a raw material for synthesizing polyamides or as a chain extender for polyurethanes.

3. The preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing according to claim 1, characterized in that: In step S2: The diisocyanate may be TDI or HDI.

4. The preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing according to claim 1, characterized in that: In step S5: A. Determination of cytotoxicity of hydrophilic antibacterial polyurethane foam dressing: It needs to be determined in accordance with the provisions of "direct contact test" in GB / T16886.5-1997; B. Allergy test and irritation test: It needs to be carried out according to the methods of "skin irritation test" and "closed sensitization test" in GB / T16886.10-2000.

5. The preparation and synthesis process of a hydrophilic antibacterial polyurethane foam dressing according to claim 1, characterized in that: Main technical indicators of polyurethane foam dressings: No odor, no slag, uniform pore size, soft; tensile strength is not less than 5MPa, elongation at break is not less than 300%; moisture vapor permeability is 600-800g / m2 / day; has good bactericidal effect; non-cytotoxic, non-sensitizing, non-irritating.