A polyurethane porous material, its preparation method and application

Abstract

A polyurethane porous material, its preparation method and application relate to the technical field of medical materials, and solve the problems of biocompatibility and degradability caused by the foaming process of existing polyurethane hemostatic materials. First, an amphiphilic copolymer is obtained by reacting polyethylene glycol and an aliphatic cyclic ester monomer; then, the amphiphilic copolymer is dehydrated and added to a diisocyanate for reaction to generate a prepolymer; a chain extender is added to the prepolymer emulsion for chain extension reaction to obtain a polyurethane emulsion; it is diluted to a solid content of 5% - 10%, pre-frozen and then freeze-dried under vacuum conditions to obtain the polyurethane porous material. The present invention can be used as a hemostatic material, a tissue engineering scaffold and a drug sustained-release carrier in the field of medical materials.

Description

Technical Field

[0001] The present invention relates to the technical field of medical materials, and particularly relates to a polyurethane porous material, a preparation method thereof, and an application thereof. Background Art

[0002] Traditional hemostatic materials such as gauze, cotton balls, etc. have limited hemostatic effects, and long-term use may cause foreign body reactions and residue problems. In recent years, synthetic polymer materials have been widely used in the field of hemostatic materials due to their excellent properties.

[0003] Biodegradable polyurethane hemostatic sponges are a new type of hemostatic material that combines the excellent properties of polyurethane and biodegradable characteristics, and have attracted much attention due to their good hemostatic effects and degradation properties. However, in the existing preparation processes of polyurethane hemostatic sponges, a foaming reaction is required. Although this process can endow the material with a porous structure and enhance its liquid absorption capacity, it also brings many problems. During the foaming process, the reaction temperature and time need to be strictly controlled to ensure the uniformity and stability of the foam body. The heat and gas generated during the reaction may cause defects or uneven bubbles inside the foam body. To this end, in order to ensure uniform and fine foam, a suitable emulsifier is generally required to reduce the interfacial tension between the oil and water phases and improve the uniformity and stability of the foam. However, although this method can prepare materials with good water absorption and hemostatic properties, an inappropriate emulsifier may affect the biocompatibility and degradation properties of the product. In addition, the presence of the emulsifier may also cause environmental pollution problems. Summary of the Invention

[0004] In order to solve the problems of biocompatibility and degradability caused by the foaming process of existing polyurethane hemostatic materials, the present invention provides a polyurethane porous material, a preparation method thereof, and an application thereof.

[0005] The technical solution of the present invention is as follows:

[0006] A preparation method of a polyurethane porous material, comprising the following steps:

[0007] S1. Under nitrogen protection, polyethylene glycol, an aliphatic cyclic ester monomer, and a toluene solution of stannous octoate are heated to 120°C - 140°C and reacted for 8h - 12h. After the reaction ends, it is dissolved in dichloromethane and then precipitated with ether to obtain an amphiphilic copolymer including a polyethylene glycol chain segment and an aliphatic polyester chain segment;

[0008] S2. Subsequently, the amphiphilic copolymer is heated to 100°C - 140°C and vacuum dehydrated for 2h. After dehydration, the temperature is lowered to 80°C, and then a diisocyanate is added and reacted at 80°C - 90°C for 2h - 3h to generate a prepolymer;

[0009] S3. Disperse the prepolymer in water, heat it up to 40°C - 50°C, and stir at high speed to form a stable prepolymer emulsion. Add a chain extender to the emulsion for a chain extension reaction for 3h - 4h to obtain a polyurethane emulsion.

[0010] S4. Dilute the prepared polyurethane emulsion to a solid content of 5% - 10%, first pour it into a mold for pre-freezing, and then perform freeze-drying under vacuum conditions to obtain a polyurethane porous material.

[0011] Preferably, in step S1, the aliphatic polyester is a polymer prepared by ring-opening polymerization of aliphatic cyclic ester monomers; the aliphatic cyclic ester monomers are selected from at least one of lactide (LA), glycolide (GA), p-dioxanone (PDO), and caprolactone (CL).

[0012] Preferably, in step S1, the molecular weight of the polyethylene glycol is 500 - 5000; the mass ratio of the polyethylene glycol to the aliphatic cyclic ester monomer is 1:(0.1 - 2.5); the mass of stannous octoate is 0.1‰ - 1‰ of the sum of the masses of the polyethylene glycol and the aliphatic cyclic ester monomer.

[0013] Preferably, in step S2, the diisocyanate is any one of hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), 4,4'-diphenylmethane diisocyanate (MDI), 1,4-diisocyanatobutane (BDI), and 4,4'-dicyclohexylmethane diisocyanate (HMDI).

[0014] Preferably, in step S2, the molar ratio of the amphiphilic copolymer to the diisocyanate is 1:(2.0 - 3.0).

[0015] Preferably, in step S3, the chain extender is a small molecule diol.

[0016] Preferably, the chain extender is any one of 1,4-butanediol, hydroquinone bis(2-hydroxyethyl) ether, and ethylene glycol.

[0017] Preferably, in step S3, the molar ratio of the prepolymer to the small molecule diol is 1:(1.0 - 2.0).

[0018] The present invention also provides a polyurethane porous material prepared by using the above preparation method.

[0019] The present invention also provides an application of the above polyurethane porous material, which is used as a hemostatic material, a tissue engineering scaffold, or a drug sustained-release carrier in the field of medical materials.

[0020] Compared with the prior art, the specific beneficial effects of the present invention are:

[0021] The present invention makes use of the characteristic that the reaction rate of isocyanate group (-NCO) and hydroxyl group (-OH) in the polyurethane synthesis reaction is much higher than that with water, and innovatively proposes a method for preparing biodegradable polyurethane porous materials in an aqueous system without the use of foaming agents and emulsifiers, and without involving the foaming process. Therefore, the problems of biocompatibility and degradability caused by the foaming process are avoided. The obtained materials not only have excellent hemostatic effects in terms of performance, but also have good mechanical properties and biocompatibility. This method has a simple process, is environmentally friendly, and the prepared materials have broad application prospects in the medical field.

[0022] The materials provided by the present invention can not only be applied to hemostatic materials, but also be used in tissue engineering scaffolds and drug delivery carriers, and have broad application potential, meeting the requirements of modern medicine for environmental protection and sustainable development. Specific embodiments

[0023] To make the technical solutions of the present invention clearer, the technical solutions in the embodiments of the present invention will be described clearly and completely below. It should be noted that the following embodiments are only used to better understand the technical solutions of the present invention and should not be construed as a limitation of the present invention.

[0024] Example 1.

[0025] Under nitrogen protection, 10.0 g of PEG with a molecular weight of 1000, 3.0 g of LA, and 2.5 mL of 0.1 wt% stannous octoate toluene solution were heated to 140 °C and reacted for 12 h. After the reaction, the amphiphilic copolymer PEG-PLA was obtained by dissolving in dichloromethane and precipitating with ether.

[0026] 5.0 g of PEG-PLA was heated to 120 °C and vacuum dehydrated for 2 h. Subsequently, the temperature was lowered to 80 °C, 1.3 g of HDI was added, and the reaction was carried out at 90 °C for 2 h to generate a prepolymer.

[0027] The prepolymer was dispersed in 15.0 mL of water, the temperature was raised to 50 °C, and a stable prepolymer emulsion was formed by high-speed stirring. 0.4 g of BDO was added to the emulsion for chain extension reaction, and a polyurethane emulsion was obtained after reacting for 4 h.

[0028] The prepared polyurethane emulsion was diluted to a solid content of 10%, poured into a mold, pre-frozen, and then freeze-dried under vacuum conditions to obtain a polyurethane porous material.

[0029] Example 2.

[0030] Under nitrogen protection, 10.0 g of PEG with a molecular weight of 1000, 3.0 g of LA, and 2.5 mL of a 0.1 wt% stannous octoate toluene solution were heated to 140 °C and reacted for 12 h. After the reaction, the amphiphilic copolymer PEG-PLA was obtained by dissolving in dichloromethane and precipitating with ether.

[0031] 5.0 g of PEG-PLA was heated to 120 °C and vacuum dehydrated for 2 h. Subsequently, the temperature was lowered to 80 °C, 1.3 g of HDI was added, and the reaction was carried out at 90 °C for 2 h to form a prepolymer.

[0032] The prepolymer was dispersed in 15.0 mL of water, the temperature was raised to 50 °C, and a stable prepolymer emulsion was formed by high-speed stirring. 0.4 g of BDO was added to the emulsion for chain extension reaction, and a polyurethane emulsion was obtained after 4 h of reaction.

[0033] The prepared polyurethane emulsion was diluted to a solid content of 5%, poured into a mold, pre-frozen, and then freeze-dried under vacuum conditions to obtain a polyurethane porous material.

[0034] Example 3.

[0035] Under nitrogen protection, 10.0 g of PEG with a molecular weight of 2000, 1.5 g of LA, and 2.5 mL of a 0.1 wt% stannous octoate toluene solution were heated to 140 °C and reacted for 12 h. After the reaction, the amphiphilic copolymer PEG-PLA was obtained by dissolving in dichloromethane and precipitating with ether.

[0036] 5.0 g of PEG-PLA was heated to 120 °C and vacuum dehydrated for 2 h. Subsequently, the temperature was lowered to 80 °C, 0.7 g of HDI was added, and the reaction was carried out at 90 °C for 2 h to form a prepolymer.

[0037] The prepolymer was dispersed in 15.0 mL of water, the temperature was raised to 50 °C, and a stable prepolymer emulsion was formed by high-speed stirring. 0.2 g of BDO was added to the emulsion for chain extension reaction, and a polyurethane emulsion was obtained after 4 h of reaction.

[0038] The prepared polyurethane emulsion was diluted to a solid content of 10%, poured into a mold, pre-frozen, and then freeze-dried under vacuum conditions to obtain a polyurethane porous material.

[0039] Example 4.

[0040] Under nitrogen protection, 10.0 g of PEG with a molecular weight of 1000, 2.0 g of PDO, and 2.5 mL of a 0.1 wt% stannous octoate toluene solution were heated to 140 °C and reacted for 12 h. After the reaction, the amphiphilic copolymer PEG-PPDO was obtained by dissolving in dichloromethane and precipitating with ether.

[0041] Heat 5.0 g of PEG-PPDO to 120 °C and conduct vacuum dehydration for 2 h. Then cool down to 80 °C, add 1.4 g of HDI, and react at 90 °C for 2 h to form a prepolymer.

[0042] Disperse the prepolymer in 15.0 mL of water, heat up to 50 °C, and form a stable prepolymer emulsion by high-speed stirring. Add 0.4 g of BDO to the emulsion for chain extension reaction. After reacting for 4 h, a polyurethane emulsion is obtained.

[0043] Dilute the prepared polyurethane emulsion to a solid content of 10%, pour it into a mold, conduct pre-freezing, and then perform freeze-drying under vacuum conditions to obtain a polyurethane porous material.

[0044] Example 5.

[0045] Under nitrogen protection, heat 10.0 g of PEG with a molecular weight of 1000, 1.4 g of LA, 1.2 g of GA, and 2.5 mL of 0.1 wt% stannous octoate toluene solution to 140 °C and react for 12 h. After the reaction, dissolve it in dichloromethane and precipitate with ether to obtain the amphiphilic copolymer PEG-PLGA.

[0046] Heat 5.0 g of PEG-PLGA to 120 °C and conduct vacuum dehydration for 2 h. Then cool down to 80 °C, add 1.1 g of BDI, and react at 90 °C for 2 h to form a prepolymer.

[0047] Disperse the prepolymer in 15.0 mL of water, heat up to 50 °C, and form a stable prepolymer emulsion by high-speed stirring. Add 0.4 g of BDO to the emulsion for chain extension reaction. After reacting for 4 h, a polyurethane emulsion is obtained.

[0048] Dilute the prepared polyurethane emulsion to a solid content of 10%, pour it into a mold, conduct pre-freezing, and then perform freeze-drying under vacuum conditions to obtain a polyurethane porous material.

[0049] Effect example.

[0050] Test the various properties of the materials in Examples 1-5 above:

[0051] (1) Tensile properties:

[0052] According to GB / T 6344-2008, prepare the polyurethane porous materials prepared in Examples 1-5 into dumbbell-shaped samples and test the tensile properties under a testing machine at a tensile speed of 50 mm / min.

[0053] (2) Water absorption rate:

[0054] According to the national standard GB / T 1034-2008, the polyurethane porous materials prepared in Examples 1-5 were cut into specimens with dimensions of approximately 20×20×2 mm, dried to a constant weight and recorded as m1, and then completely immersed in deionized water for 1 h and taken out and weighed and recorded as m2. Then the water absorption rate = (m2 - m1) / m1 * 100%.

[0055] (3)Degradation time:

[0056] The polyurethane porous materials prepared in Examples 1-5 were cut into a size of 2×1×1 cm, placed in a sealed container containing PBS solution, and placed in a constant temperature shaker at 37±1°C. Observe and record the changes of the samples. When the polyurethane porous material breaks, it is the degradation time.

[0057] The above test results are shown in Table 1.

[0058] Table 1

[0059]

[0060] It can be proved that the tensile strength of the polyurethane porous material provided by the present invention is between 0.35 MPa and 0.95 MPa, which can better maintain the shape and structural integrity and is not easily torn during actual use; the elongation at break is between 129% and 207%, indicating that the material has good flexibility. When used as a hemostatic cotton, it can better fit the wound during contact and operation and is not likely to cause secondary damage to the wound due to rigidity; the water absorption rate of the hemostatic cotton is one of the key performance indicators. A higher water absorption rate can quickly absorb blood to achieve the purpose of hemostasis. The water absorption rates of each example are between 810% and 1020%, and the water absorption rate is relatively high, which can quickly and effectively absorb blood. As a medical material, the hemostatic cotton should be able to degrade within a reasonable time after completing the hemostasis mission to avoid residual adverse effects on the human body. The degradation time is between 28 h and 52 h, which can not only ensure the stability of the material during hemostasis but also not remain in the body for a long time. Therefore, generally speaking, the polyurethane porous material provided by the present invention has the potential to become a hemostatic cotton with excellent performance.

[0061] This material can also be used in tissue engineering scaffolds. The mechanical properties of the material can provide basic support, and its high flexibility can better adapt to the physiological activities of tissues, avoiding damage to surrounding tissues due to excessive rigidity. A high water absorption rate indicates that the material has good hydrophilicity, and thus good biocompatibility, which is beneficial to cell adhesion, growth, and proliferation. The degradation time of the material is suitable for some tissues with a relatively fast repair rate. In addition, it can also be used as a drug sustained-release carrier. A high water absorption rate means that the material has a large porosity and a high liquid capacity, which is conducive to drug loading. More drugs can be loaded by adsorption or encapsulation. The drug release rate can be coordinated with the material degradation rate to achieve slow and continuous drug release, achieving a sustained-release effect. The material has a certain mechanical stability, which can ensure the integrity of the carrier structure to a certain extent during the drug sustained-release process.

[0062] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention. Each component not clearly defined in this embodiment can be implemented by existing technologies.

Claims

1. A method for preparing a polyurethane porous material, characterized in that, It includes the following steps: S1. Under nitrogen protection, heat a toluene solution of polyethylene glycol, aliphatic cyclic ester monomer and stannous octoate to 120°C - 140°C and react for 8h - 12h. After the reaction, dissolve it in dichloromethane and then precipitate it with ether to obtain an amphiphilic copolymer including a polyethylene glycol segment and an aliphatic polyester segment; S2. Subsequently, heat the amphiphilic copolymer to 100°C - 140°C, carry out vacuum dehydration for 2h, then cool it to 80°C - 90°C, and then add diisocyanate and react at 80°C - 90°C for 2h - 3h to generate a prepolymer; wherein the molar ratio of the amphiphilic copolymer to the diisocyanate is 1:(2.0 - 3.0); S3. Disperse the prepolymer in water, heat it to 40°C - 50°C, stir to form a stable prepolymer emulsion, add chain extender 1,4 - butanediol to the emulsion for chain extension reaction for 3h - 4h to obtain a polyurethane emulsion; S4. Dilute the prepared polyurethane emulsion to a solid content of 5% - 10%, first pour it into a mold for pre - freezing, and then carry out freeze - drying under vacuum conditions to obtain a polyurethane porous material; Wherein, in step S1, the aliphatic cyclic ester monomer is selected from at least one of lactide, glycolide, dioxanone, and caprolactone; The mass ratio of the polyethylene glycol to the aliphatic cyclic ester monomer is 1:(0.1 - 2.5).

2. The preparation method of the polyurethane porous material according to claim 1, wherein, In step S1, the molecular weight of the polyethylene glycol is 500 - 5000; the mass of the stannous octoate is 0.1‰ - 1‰ of the sum of the masses of the polyethylene glycol and the aliphatic cyclic ester monomer.

3. The preparation method of the polyurethane porous material according to claim 1, characterized in that, In step S2, the diisocyanate is any one of hexamethylene diisocyanate, toluene diisocyanate, 4,4'-diphenylmethane diisocyanate, 1,4 - diisocyanatobutane, and 4,4'-dicyclohexylmethane diisocyanate.

4. The preparation method of the polyurethane porous material according to claim 1, wherein, In step S3, the molar ratio of the prepolymer to 1,4 - butanediol is 1:(1.0 - 2.0).

5. A polyurethane porous material, characterized in that, It is prepared by using the preparation method described in any one of claims 1 - 4.

6. Use of the polyurethane porous material according to claim 5, characterized in that, It is applied to the preparation of hemostatic materials, tissue engineering scaffolds or drug - controlled release carriers.

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