阅读说明：本技术 一种抗菌聚氨酯泡沫材料及其制备方法和应用 (Antibacterial polyurethane foam material and preparation method and application thereof ) 是由 丁雪佳 丛文龙 宋长统 徐福建 姚振勇 徐乐 于 2021-08-26 设计创作，主要内容包括：本发明涉及一种抗菌聚氨酯泡沫材料及其制备方法和应用,其解决了现有鼻腔止血材料存在的成本较高、效果不理想的技术问题,本发明提供一种抗菌聚氨酯泡沫材料,所述抗菌聚氨酯泡沫材料中抗菌有效成分为侧链具有12个碳的长侧链季铵化壳聚糖。本发明同时提供了其制备方法和应用。本发明可用于抗菌材料领域。(The invention relates to an antibacterial polyurethane foam material, and a preparation method and application thereof, and solves the technical problems of high cost and unsatisfactory effect of the existing nasal cavity hemostatic material. The invention also provides a preparation method and application thereof. The invention can be used in the field of antibacterial materials.)

1. An antibacterial polyurethane foam material, characterized in that the antibacterial polyurethane foam material is prepared by using long-side-chain quaternized chitosan with 12 carbons in the side chain as a crosslinking agent for foaming reaction.

2. The method of preparing an antibacterial polyurethane foam material as set forth in claim 1, comprising the steps of:

(1) preparing quaternized chitosan: weighing chitosan, adding epoxypropyl dimethyl dodecyl ammonium chloride solution, heating for reaction, washing and drying to obtain quaternized chitosan;

(2) carrying out water removal treatment on polyether polyol and polyester polyol; mixing polyether polyol and polyester polyol with the quaternized chitosan, water, a foam stabilizer and a catalyst, and stirring to obtain a material;

(3) and (3) adding the material obtained in the step (2) into aliphatic isocyanate, stirring, pouring into a mold, foaming, and curing to obtain the antibacterial polyurethane foam material.

3. The method of claim 2, wherein the solution of glycidyl dimethyldodecyl ammonium chloride is 10-40 wt%.

4. The method of claim 2, wherein the molar ratio of amino groups in the chitosan to the epoxypropyldimethyldodecylammonium chloride is 1: (1-9).

5. The method of claim 2, wherein the polyester polyol is one or a combination of two of polylactic acid and polycaprolactone diol.

6. The method of claim 2, wherein the aliphatic diisocyanate is one of hexamethylene diisocyanate, isophorone diisocyanate, or a combination of at least two thereof.

7. The preparation method of the antibacterial polyurethane foam material as claimed in claim 2, wherein the molar ratio of the polyester polyol to the polyether polyol is 1 (0.6-4), and the molar ratio of the hydroxyl groups in the polyester polyol and the polyether polyol to the isocyanate groups in the aliphatic isocyanate is 1: (1.5-5).

8. The method for preparing the antibacterial polyurethane foam material as claimed in claim 2, wherein in the step (2), the mass fractions of the components in the total material are polyether polyol: 37.5-80%; polyester polyol: 20 to 62.5 percent; water: 5-15%; quaternization of chitosan: 0.5-2%; foam stabilizer: 0.5-2%, catalyst: 0.3 to 1.5 percent.

9. The method for preparing an antibacterial polyurethane foam material according to claim 2, wherein in the step (2), the catalyst is a composite catalyst of triethylene diamine and dibutyltin dilaurate, and the mass ratio of the triethylene diamine to the dibutyltin dilaurate is (0.25-1): 1.

10. use of the antibacterial polyurethane foam material as claimed in claim 1 for preparing a hemostatic material for nasal cavity filling.

Technical Field

The invention relates to a polyurethane foam material, a preparation method and application thereof, in particular to an antibacterial polyurethane foam material, a preparation method and application thereof.

Background

Nasal cavity diseases such as chronic sinusitis, nasal polyps, nasal septum and the like are common diseases in the ear-nose-throat department, and about 50 ten thousand cases of nasal endoscope operations are required to treat the diseases in the United states each year. With the economic growth and the improvement of living standard in China, more and more people adopt the nasal endoscope operation to treat the nasal diseases. Since hemostasis by nasal packing after operation is the key point of successful nasal endoscope operation, the problems of effectiveness of hemostasis by nasal hemostatic materials, comfort of use, postoperative infection and postoperative removal are often the focus of attention.

Early nasal hemostatic materials were based on petrolatum gauze, which has the advantage that a cheap and easily cut gauze can effectively support the injured nasal cavity and provide hemostasis by mechanical compression. The polyvinyl acetal sponge which can be produced at home at present is mainly polyvinyl acetal sponge which has better liquid absorption capacity, but is not degradable like vaseline sliver, and generally needs to be taken out within one to two days after operation. Therefore, the nondegradable materials have the problems that the nasal mucosa is easily damaged when the nondegradable materials are taken out, and the secondary bleeding of tissues is caused. Most of the degradable nasal hemostatic materials used clinically today are based on Naspere, which is a biologically inert foam material synthesized from polyurethane and can be degraded into fragments in the nasal environment. However, in practical application, the material itself has no antibacterial ability, but when the nasal cavity hemostatic material is used, the material is slowly degraded in the nasal cavity, which often requires a long packing time (for example, packing for 3 to 4 days or even longer), and thus the hemostatic material after absorbing blood may go bad and foul. The method for solving the problem of postoperative infection caused by the phenomenon and the stuffing hemostasis is generally implemented by adding antibiotics, but the problems of difficult control of dosage and time and bacterial resistance caused by the abuse of the antibiotics exist.

The Chinese patent application with the application number of 201610597337.4 discloses an efficacy type nasal cavity hemostatic material and a preparation method thereof, wherein a chitosan coating with an antibacterial effect is sprayed on the surface of a polyvinyl alcohol substrate by adopting a high-pressure atomization spraying process. However, most of the nasal cavity hemostatic materials need to be cut to adapt to practical clinical use, and the nasal cavity hemostatic material only has the surface with an antibacterial function and is inconvenient to cut, so that the practical application is greatly limited.

At present, the antibacterial modification in practical application is mainly dip coating, spray coating or blending with materials of the antibacterial agent, and the methods have the defects of poor stability, easy leaching and incapability of long-acting antibacterial of the antibacterial agent in the materials.

The nasal cavity hemostatic material taken out after the operation can bring a plurality of problems of pain, secondary injury and the like to patients, so the degradable and absorbable nasal cavity hemostatic material has attracted people's interest. The degradable nasal cavity hemostatic material produced in China at present mainly comprises polysaccharide materials, the mechanical property loss of the materials is large in the degradation process of the materials, the effect is poor in practical use, and the recurrence is easy to cause.

In addition, the degradation performance of the clinically used Naspere material is good, but the freeze-drying foaming mode is adopted, so the cost is high and the price is high.

Disclosure of Invention

The invention aims to solve the technical problems of high cost and unsatisfactory effect of the existing nasal cavity hemostatic material, and provides an antibacterial polyurethane foam material which not only has basic performances of a nasal cavity hemostatic sponge such as good mechanical property and liquid absorption capacity, but also has controllable degradation performance and stable antibacterial effect, and a preparation method and application thereof.

To this end, the present invention provides an antibacterial polyurethane foam material prepared by using long side chain quaternized chitosan having 12 carbons in the side chain as a crosslinking agent for foaming reaction

The invention also provides a preparation method of the antibacterial polyurethane foam material, which comprises the following steps:

(1) preparing quaternized chitosan: weighing a certain amount of chitosan, adding 10-40% epoxypropyl dimethyl dodecyl ammonium chloride solution, heating to 60-80 ℃, reacting for 12-48 h at a constant temperature, washing, and drying to obtain powdery quaternized chitosan (QCS-12).

(2) Firstly, preparing a 2-10% QCS-12 aqueous solution by using deionized water, and carrying out water removal treatment on polyether polyol and polyester polyol in advance. And then stirring the polyether polyol, the polyester polyol, the QCS-12 solution, the foam stabilizer and the catalyst for 1-2 min at 500-1000 r/min, and keeping the temperature of the materials to 50-80 ℃.

(3) And (3) adding aliphatic isocyanate into the stirred material obtained in the step (2) under the high-speed stirring of 2000-5000 r/min, continuously stirring for 10-60 s, pouring into a mold, foaming at normal temperature, curing at 80 ℃ for 1h after the foam is debonded, and finally curing at normal temperature for 3-7 days to obtain the polyurethane foam.

Preferably, in step (1), the concentration of the solution of epoxypropyldimethyldodecylammonium chloride is 20%.

In the step (1), the molar ratio of the amino group in the chitosan to two kinds of ammonium chloride with epoxy groups is 1: 1-9, preferably 1: 6.

in the step (1), the number average molecular weight of the chitosan is 3 to 15 ten thousand, preferably 8 to 12 ten thousand.

Preferably, in the step (1), the reaction time is 30-36 h, and the reaction temperature is 80 ℃.

Preferably, in step (2), the polyether polyol is one or a combination of at least two of polyethylene glycol, polypropylene glycol and polytetrahydrofuran glycol, preferably one or a combination of two of polyethylene glycol and polypropylene glycol. The polyester polyol is one or the combination of at least two of polylactic acid, polycaprolactone or polycarbonate diol, and preferably one or the combination of two of polylactic acid and polycaprolactone diol.

Preferably, in the step (2), the aliphatic diisocyanate is selected from one or a combination of at least two of hexamethylene diisocyanate, isophorone diisocyanate, cyclohexyl diisocyanate, cyclohexane dimethylene diisocyanate or dicyclohexylmethane diisocyanate. Preferred is one or a combination of at least two of hexamethylene diisocyanate, isophorone diisocyanate.

Preferably, in step (2), the polyether polyol and the polyester polyol have a number average molecular weight of 1000 to 4000, preferably 1500 to 3000, for example 1500, 1800, 2000, 2200, 2500, 2800, 3000 or the like.

In the step (2), the molar ratio of the polyester polyol to the polyether polyol is 1 (0.6-4), preferably 1 (3-4).

In step (2), the molar ratio of hydroxyl groups in the polyether polyol and the polyester polyol to isocyanate groups in the aliphatic isocyanate is 1: (1.5-5), preferably 1: (2-3).

In the step (2), the water removal treatment is to vacuumize the raw materials for more than 3 hours under the vacuum degree of-0.9 to-0.95 MPa.

Preferably, in the step (2), the mass fractions of the water and the QCS-12 in the total material are respectively 5-15% and 0.5-2%; the mass fractions of the foam stabilizer and the catalyst are 0.5-2% and 0.3-1.5%.

Preferably, in the step (2), the catalyst is a composite catalyst of triethylene diamine and dibutyltin dilaurate, and the mass ratio of the triethylene diamine to the dibutyltin dilaurate is (0.25-1): 1, the preferable mass ratio is (0.5-0.75): 1.

the invention also provides application of the antibacterial polyurethane foam material in preparation of the nasal cavity filling hemostatic material.

The invention has the following beneficial effects:

(1) according to the invention, macromolecular quaternized chitosan QCS-12 is used as an antibacterial effective component, and the foam material with the addition of 0.5% can simultaneously achieve 99.99% of sterilization rate on escherichia coli and staphylococcus aureus, and has excellent antibacterial performance. Most importantly, the antibacterial active component is not simply combined with the material in a physical mode, but is used as a cross-linking agent to react with isocyanate groups in a foaming process to form a cross-linked network, namely, the antibacterial agent is bonded to a polyurethane molecular chain in a chemical bond mode, so that the product has a long-acting and stable antibacterial effect.

(2) The degradation rate of the polyurethane foam material can be regulated and controlled by regulating the amounts of the foaming agent water and the cross-linking agent QCS-12, so that the purpose of controlling the degradation time of the material in the nasal cavity can be achieved.

(3) The invention uses polyether glycol with good hydrophilicity and aliphatic isocyanate with low toxicity, so the sponge also has the characteristics of good mechanical property, strong imbibition capability, low biological toxicity and good biological compatibility. The tensile strength is 300-800 kPa, the elongation at break is 300-500%, the tensile strength after water absorption is 100-200 kPa, and the elongation at break is 150-250%. The water absorption rate can reach 15-25 times, and the water absorption capacity is enough. The density, mechanical property and degradation rate of the product can be obviously changed by adjusting the water adding amount, the degradation rate can be regulated, 3-35% of the total mass can be degraded in an in-vitro simulation environment for two weeks, and the product meeting the requirements of different mechanical properties and degradation rates can be obtained.

(4) The antibacterial agent is only added in the foaming process, and the method is simple and has high practical value.

(5) The invention adopts one-step foaming, and has lower cost.

Drawings

FIG. 1 is a reaction equation for preparing quaternized chitosan according to step 2 of the present invention;

FIG. 2 is a graph showing the degradation rate of examples 1, 2 and 3 of the present invention in comparison with that of a control example;

FIG. 3 is a graph comparing the degradation rates of examples 1, 5, 6, and 7 of the present invention.

Detailed Description

The present invention will be further described with reference to the following examples.

Example 1

The preparation method of the antibacterial polyurethane nasal cavity hemostatic material comprises the following steps:

s1, preparation of quaternized chitosan: weighing 10g of chitosan, adding 150ml of 20% epoxypropyl dimethyl dodecyl ammonium chloride solution, heating to 80 ℃, reacting for 12h at constant temperature, washing and drying to obtain powdery quaternized chitosan QCS-12.

S2, dehydrating 70g of polyethylene glycol (molecular weight 1000) and 30g of polycaprolactone diol (molecular weight 1000), uniformly mixing, adding a water solution of QCS-12, a catalyst (stannous octoate and triethylene diamine) and a foam stabilizer L-580, stirring at 500r/min for 1-2 min, and keeping the temperature of the material at 50 ℃.

And S3, adding 15g of isophorone diisocyanate into the mixture under stirring at 3000r/min, stirring for 10-60S, pouring into a mold, foaming at normal temperature, curing at 80 ℃ for 1h after foam debonding, and finally curing at normal temperature for 7 days to obtain the antibacterial polyurethane foam.

Examples 1-7 and comparative examples were carried out according to the above procedure and the dosage ratios of the components listed in Table 1.

In the above examples 1 to 7 and comparative examples, the mechanical properties, antibacterial effect, degradation and other properties of the foam were adjusted by changing the concentration of QCS-12 solution, the amount of water used and the amount of catalyst.

And carrying out mechanical test, water absorption, apparent density and antibacterial performance on the sample and the comparative sample. The test method is as follows:

the tensile strength test was carried out by cutting the sponge into 50X 12.5X 0.5mm, measuring the tensile strength with a material testing machine having a moving speed of 10mm/min and a holding interval of 20mm, and recording the tensile strength and elongation at break. Compressive Strength test A sponge was cut into 3X 3cm at a moving speed of 10mm/min and the compressive strength at 25% strain was recorded.

Each foam (2X 0.2 cm)³) Dried overnight at 55 ℃ and accurately weighed before testing (m 1). After the foam had been left in 10ml of water for 4 hours, the foam was removed and weighed (M2). Then, the water absorption of each sample was calculated by the equation of (M2-M1)/M1X 100%.

Staphylococcus aureus and Escherichia coli were used as the antibacterial activity of the test materials. To 1mL of the bacterial suspension (about 1X 105CFU/mL) was added 0.5g of the sterilized foam sample (1X 2)m³) And incubated at 37 ℃ in an environment with a relative humidity of more than 90%, in order to measure the antibacterial activity of each foam sample, 10. mu.L of the bacterial suspension after incubation for 4 hours was spread on LB agar plates to be measured at least three times independently in Colony Forming Units (CFU) counting.

In vitro degradation assays were performed under simulated physiological conditions. Weighing 1X 1cm³Sponge samples (W0) were then immersed in 15ml of PBS solution, respectively, and then incubated at 37 ℃ for two weeks. The samples were transferred every two days to a vacuum oven at 37 ℃ after vacuum drying for 72h and weighed (Wd). The degradation rate is Wd/W0 multiplied by 100%

Apparent Density was measured using a foam (3X 3 cm)³) After drying, M was accurately weighed and the apparent density of each sample was calculated by M/27.

The cytotoxicity test was carried out according to GB/T16886.5-2017, part 5 of the biological evaluation of medical instruments, in vitro cytotoxicity test, appendix C.

TABLE 1

Animal experiments

Taking 36 healthy rabbits with the weight of 2.5-3.0 kg. The groups were randomized into 9 groups of 4. After the domestic rabbits are anesthetized by 30mg/kg ear edge intravenous injection of 1% sodium pentobarbital, the ear artery is cut off at a position 8cm away from the ear tip, the wound surface is wiped after 3 seconds, and the corresponding test object is covered on the wound surface. And observing the bleeding condition of the wound every 5 seconds, slightly dipping and sucking the wound by using a filter paper strip until the blood does not seep out, namely the blood does not adhere to the filter paper strip any more, and recording the required time, namely the effective hemostasis time. The antibacterial test is that before the foam material is filled, 10 drops are added on the foam⁵CFU/mL Staphylococcus aureus, then sacrificed on days 1,3,5, and the tissue homogenized at the wound site for characterization according to the antimicrobial experiment above.

TABLE 2

However, the above description is only exemplary of the present invention, and the scope of the present invention should not be limited thereby, and the replacement of the equivalent components or the equivalent changes and modifications made according to the protection scope of the present invention should be covered by the claims of the present invention.