Polyurethane material for medical infusion apparatus and preparation method thereof

Abstract

The invention relates to the technical field of medical materials, in particular to a polyurethane material for a medical infusion apparatus and a preparation method of the polyurethane material, and the polyurethane material is prepared from the following raw materials in parts by weight: 30-40 parts of polyol, 10-16 parts of polyisocyanate, 2-6 parts of modified polylactic acid, 0.5-1 part of a chain extender, 0.01-0.05 part of a catalyst and 1-4 parts of a flexibilizer. The polyurethane material for the medical infusion apparatus, prepared by the invention, has good biocompatibility and mechanical properties.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a polyurethane material for a medical infusion set and a preparation method thereof. Background Art

[0002] With the development of materials science, some artificial synthetic polymer materials such as polyurethane, polyester fiber, polyvinyl pyrrolidone, polyetheretherketone, polymethyl methacrylate, polyvinyl alcohol, polylactic acid, polyethylene, as well as natural biopolymer materials cellulose, hyaluronic acid, collagen, gelatin and sodium alginate, have been used in the medical field to manufacture pharmaceutical preparations, medical devices, in vitro organs, artificial organs, etc. In most cases, the chemical composition and properties of existing materials cannot meet the requirements and need to be processed to have good mechanical properties and processability as well as good biocompatibility.

[0003] Patent CN108276556B discloses a medical polyurethane material, a preparation method thereof and a repair stent. The medical polyurethane material includes gastrodin and has good biocompatibility, blood compatibility and biostability. When used in the body, it can effectively avoid side effects such as rejection reactions and is more stable and safe. The repair stent prepared with the material has excellent mechanical properties, is not easy to damage, has a wide range of applicability, and can be used for the repair of bones, blood vessels or nerves. Although gastrodin can be used to treat neurological diseases such as vertigo and convulsions, people who do not have such diseases may experience side effects such as drowsiness and mental depression when using such materials.

[0004] Patent CN105418953B discloses a method for modifying phosphorylcholine on the surface of a medical polyurethane material. A clean and dry medical polyurethane material is pretreated by ozone activation to obtain active reaction sites on the surface, and then surface grafting is performed in a phosphorylcholine reaction solution to obtain a medical polyurethane material with phosphorylcholine modified on the surface. By using this bionic functionalized medical polyurethane material, the surface hydrophilicity is significantly improved, and it has good tissue compatibility and blood compatibility. However, phosphorylcholine has strong water absorption and the material is not easy to store.

[0005] Therefore, there is an urgent need in the market for a medical polyurethane material that has no side effects and is easy to store. Summary of the invention

[0006] In view of the problems existing in the prior art, the purpose of the present invention is to obtain a polyurethane material that can be used for medical infusion sets and has no side effects, is easy to store, and has good biocompatibility and mechanical properties.

[0007] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0008] On the one hand, the present invention provides a polyurethane material for a medical infusion set, which comprises the following raw materials, in parts by weight: 30-40 parts of polyol, 10-16 parts of polyisocyanate, 2-6 parts of modified polylactic acid, 0.5-1 parts of chain extender, 0.01-0.0.05 parts of catalyst, and 1-4 parts of toughening agent.

[0009] In some embodiments, the preparation method of the modified polylactic acid comprises the following steps: adding amino-terminated polylactic acid, vegetable oil, (S)-3-hydroxy-gamma-butyrolactone and sodium ethoxide to anhydrous ethanol, reacting at 70-80° C. for 5-6 hours, and rotary evaporating to obtain modified polylactic acid.

[0010] Polylactic acid has good degradability and biocompatibility. It can be added to polyurethane to improve the problem of poor biocompatibility of polyurethane. However, due to the poor compatibility of polylactic acid and polyurethane, the mechanical properties of the material prepared by direct blending are uneven. The present invention modifies polylactic acid by reacting terminal amino polylactic acid, vegetable oil and (S)-3-hydroxy-gamma-butyrolactone, and adds it to the chain segment of polyurethane to increase the mechanical properties and biocompatibility of polyurethane. The possible reason is that polylactic acid has good biocompatibility and the brittleness of the modified polylactic acid is reduced, so that the mechanical properties of the prepared polyurethane are increased and the comfort of contact with the human body is enhanced. In addition, the vegetable oil increases the lubrication effect and the processability, and the lactone ring further reduces the glass transition temperature of polylactic acid and increases the toughness.

[0011] In some embodiments, the mass ratio of the amino-terminated polylactic acid, the vegetable oil and the (S)-3-hydroxy-gamma-butyrolactone is 1:(2-3):(0.3-0.7).

[0012] The present invention improves the brittleness of polylactic acid and its compatibility with polyurethane by limiting the mass ratio of amino-terminated polylactic acid, vegetable oil and (S)-3-hydroxy-gamma-butyrolactone, while increasing the processability, thereby avoiding the problem of easy adhesion of catheters obtained from polyurethane materials prepared by excessive vegetable oil.

[0013] In some embodiments, the vegetable oil is one or more of linseed oil, olive oil, and camellia oil.

[0014] In some embodiments, the toughening agent is modified silica and chitosan, and the mass ratio of the two is 1:(2-4).

[0015] In some embodiments, the method for preparing the modified silicon dioxide comprises the following steps:

[0016] (1) adding silica and silane coupling agent KH560 into ethanol and reacting at 70-80° C. for 5-6 hours to obtain silane-modified silica;

[0017] (2) Add the silane-modified silica, hyaluronic acid and phosphoric acid obtained in step (1) into DMF and react at 70-80° C. for 5-6 hours to obtain modified silica.

[0018] In some embodiments, the mass ratio of the silane-modified silica to hyaluronic acid is 1:(0.4-0.8).

[0019] In order to further increase the mechanical properties of polyurethane, the applicant added modified silica and chitin in a specific ratio to polyurethane as toughening agents, but the dispersibility of silica was poor and the toughening effect was not good. The present invention modified silica with a specific silane coupling agent and then reacted it with hyaluronic acid, thereby increasing the dispersibility of silica, stabilizing the mechanical properties of the prepared polyurethane material and further increasing the biocompatibility. The possible reason is that the addition of hyaluronic acid makes the surface of silica have a large number of groups that can react with polyurethane, increasing the degree of cross-linking, further improving the mechanical properties of polyurethane while increasing biocompatibility, and being non-toxic and harmless to the human body.

[0020] In some embodiments, the chain extender is 1,6-hexanediol or 1,8-octanediol.

[0021] In some embodiments, the polyisocyanate is 4,4'-phenylmethane diisocyanate or L-lysine diisocyanate.

[0022] The second aspect of the present invention provides a method for preparing a polyurethane material for a medical infusion set, comprising the following steps: reacting a polyol, a polyisocyanate, and a catalyst at 70-80°C for 3-4 hours, then adding modified polylactic acid, a chain extender, and a toughening agent to react at 50-60°C for 1-2 hours, and drying to obtain the obtained material.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] (1) The polyurethane material prepared by the present invention has good compatibility with humans and is not easily repelled. It also has good mechanical properties and a high sense of use.

[0025] (2) The present invention modifies polylactic acid by reacting terminal amino polylactic acid, vegetable oil and (S)-3-hydroxy-gamma-butyrolactone. The brittleness of the modified polylactic acid is reduced, the mechanical properties of the prepared polyurethane are improved, and the comfort of contact with the human body is enhanced. In addition, the vegetable oil increases the lubrication effect and the processability, and the lactone ring further reduces the glass transition temperature of the polylactic acid and increases the toughness.

[0026] (3) The present invention improves the dispersibility of silica by modifying silica with a specific silane coupling agent and then reacting it with hyaluronic acid. The addition of hyaluronic acid makes the surface of silica have a large number of groups that can react with polyurethane, which increases the degree of cross-linking, further improves the mechanical properties of polyurethane and increases biocompatibility, making it non-toxic and harmless to the human body. DETAILED DESCRIPTION

[0027] The present invention will be described below in conjunction with specific embodiments. It should be noted that the following embodiments are examples of the present invention and are only used to illustrate the present invention, but not to limit the present invention. Other combinations and various modifications within the concept of the present invention may be performed without departing from the spirit or scope of the present invention.

[0028] In the following examples and comparative examples, the compounds and related reagents used can be purchased from the market, among which camellia oil was purchased from Hubei Xinghengye Technology Co., Ltd.; amino-terminated polylactic acid was purchased from Shaanxi Xingbei Aike Biotechnology Co., Ltd., model xb-18; polycaprolactone diol was purchased from Shandong Hui'an Chemical Co., Ltd., with a number average molecular weight of 3000; silicon dioxide was purchased from Hubei Huifu Nanomaterials Co., Ltd., model HB-132.

[0029] Preparation Example 1

[0030] The preparation method of modified polylactic acid-1 comprises the following steps: adding 40g amino-terminated polylactic acid, 100g vegetable oil, 20g (S)-3-hydroxy-gamma-butyrolactone and 0.5g sodium ethoxide into 200ml anhydrous ethanol, reacting at 65°C for 5.5h, and rotary evaporating to obtain modified polylactic acid-1.

[0031] Preparation Example 2

[0032] The preparation method of modified polylactic acid-2 is the same as that of Preparation Example 1, except that the amount of vegetable oil added is 160 g.

[0033] Preparation Example 3

[0034] The preparation method of modified polylactic acid-3 is the same as that of Preparation Example 1, except that the added amount of (S)-3-hydroxy-gamma-butyrolactone is 36 g.

[0035] Preparation Example 4

[0036] The preparation method of modified silicon dioxide-1 comprises the following steps:

[0037] (1) Add 10 g of silica and 5 g of silane coupling agent KH560 into 50 ml of anhydrous ethanol and react at 75° C. for 5.5 h to obtain silane-modified silica;

[0038] (2) 10 g of the silane-modified silica obtained in step (1), 6 g of hyaluronic acid and 5 ml of 75 wt % phosphoric acid solution were added to 100 ml of DMF and reacted at 75° C. for 5.5 h to obtain modified silica-1.

[0039] Preparation Example 5

[0040] The preparation method of modified silica-2 is the same as that of Preparation Example 4, except that the amount of hyaluronic acid added is 10 g.

[0041] Example 1

[0042] A polyurethane material for a medical infusion set comprises the following raw materials, measured in parts by weight: 35 parts of polycaprolactone polyol, 12 parts of L-lysine diisocyanate, 5 parts of modified polylactic acid-1, 0.7 parts of 1,6-hexanediol, 0.02 parts of dibutyltin dilaurate, and 2 parts of a toughening agent.

[0043] Among them, the toughening agents are modified silica-1 and chitin, and the mass ratio of the two is 1:3.

[0044] The preparation method of the polyurethane material for medical infusion sets in this embodiment comprises the following steps: reacting polycaprolactone polyol, L-lysine diisocyanate and dibutyltin dilaurate at 75°C for 3.5 hours, adding modified polylactic acid-1,1,6-hexanediol and toughening agent, reacting at 55°C for 1.5 hours, and drying to obtain the product.

[0045] Example 2

[0046] A polyurethane material for a medical infusion set comprises the following raw materials, measured in parts by weight: 30 parts of polycaprolactone polyol, 10 parts of L-lysine diisocyanate, 2 parts of modified polylactic acid-1, 0.5 parts of 1,6-hexanediol, 0.01 parts of dibutyltin dilaurate, and 1 part of a toughening agent.

[0047] Among them, the toughening agent is modified silica-1 and chitin, and the mass ratio of the two is 1:2.

[0048] The preparation method of the polyurethane material for medical infusion sets in this embodiment comprises the following steps: reacting polycaprolactone polyol, L-lysine diisocyanate and dibutyltin dilaurate at 70°C for 4 hours, adding modified polylactic acid-1,1,6-hexanediol and toughening agent and reacting at 50°C for 2 hours, and drying to obtain the product.

[0049] Example 3

[0050] A polyurethane material for a medical infusion set, comprising the following raw materials, in parts by weight: 40 parts of polycaprolactone polyol, 16 parts of L-lysine diisocyanate, 6 parts of modified polylactic acid-1, 1 part of 1,6-hexanediol, 0.05 parts of dibutyltin dilaurate, and 4 parts of a toughening agent;

[0051] Among them, the toughening agents are modified silica-1 and chitin, and the mass ratio of the two is 1:4.

[0052] The preparation method of the polyurethane material for medical infusion sets in this embodiment comprises the following steps: reacting polycaprolactone polyol, L-lysine diisocyanate and dibutyltin dilaurate at 80°C for 3h, adding modified polylactic acid-1,1,6-hexanediol and toughening agent and reacting at 60°C for 1h, and drying to obtain the obtained product.

[0053] Example 4

[0054] A polyurethane material for a medical infusion set and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of modified polylactic acid-1 is replaced by modified polylactic acid-2.

[0055] Example 5

[0056] A polyurethane material for a medical infusion set and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of modified polylactic acid-1 is replaced by modified polylactic acid-3.

[0057] Example 6

[0058] A polyurethane material for a medical infusion set and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of modified silica-1 is replaced by modified silica-2.

[0059] Example 7

[0060] A polyurethane material for a medical infusion set and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of modified silica-1 is replaced by silica.

[0061] Comparative Example 1

[0062] A polyurethane material for a medical infusion set and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of modified polylactic acid-1 is replaced by amino-terminated polylactic acid.

[0063] Performance Testing

[0064] The polyurethane materials for medical infusion sets obtained in the above embodiments and comparative examples were subjected to the following tests:

[0065] 1. Mechanical properties

[0066] The polyurethane materials prepared in the above embodiments and comparative examples were rolled into film samples of 2.0 cm×0.5 cm×1 mm (length×width×thickness). The films were cut into dumbbell-shaped film strips according to GB1040-92 and tested using a universal testing machine. The tensile rate at room temperature was 200 mm / min.

[0067] 2. Hemolysis test

[0068] Take 20 mL of human blood, add 1 mL of 2 wt% K2C2O4 solution to prepare fresh anticoagulated blood, take 10 mL of anticoagulated blood and add 10 mL of 0.9 wt% NaCl solution to dilute to obtain diluted human blood; weigh 5 g of the polyurethane material obtained in each embodiment and comparative example, add 10 ml of normal saline, place in a 37°C constant temperature water bath for 30 min, add 0.5 mL of diluted human blood and continue to keep warm for 60 min, then centrifuge at 1000 r / min for 5 min, remove the supernatant and measure the absorbance at 545 nm, and measure 3 times in parallel for each group;

[0069] Positive control: no polyurethane material was added, and 10 ml of normal saline was replaced with 10 ml of distilled water;

[0070] Negative control: no polyurethane material was added, and 10 ml of normal saline was replaced with 10 ml of 0.9 wt% NaCl solution;

[0071] Hemolysis rate % = (sample absorbance - negative absorbance) / (positive absorbance - negative absorbance) × 100%.

[0072] 3. Cytocompatibility test

[0073] 5 g of the polyurethane material obtained in each embodiment and comparative example was added to 50 ml of CH2Cl2 and smeared on sterile glass. The coating thickness was 0.1 mm. After CH2Cl2 was completely volatilized, it was torn off and cut into 0.1 cm × 0.1 cm pieces. The coating was cleaned and disinfected with medical alcohol and then placed in a 96-well culture plate. The ultraviolet light was continued to be used for 10 min. The spleen cells of the growing mice were digested and counted. 100 μl of cell suspension (1×10 6 / ml) and 20μl MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), continue incubation at 37°C for 4h, remove the supernatant in the wells, continue to add 150μl DMSO, gently shake for 20min, centrifuge and measure the light absorption value (OD value) of the cell culture with an enzyme label reader at a wavelength of 570nm.

[0074] The test results are shown in Table 1:

[0075] Table 1

[0076]

[0077] By comparing the experimental data of Examples 1-3 in Table 1, it can be seen that the polyurethane material has good mechanical properties and biocompatibility; by comparing Examples 4 and 5 with Example 1, it can be seen that the ratio of amino-terminated polylactic acid, vegetable oil and (S)-3-hydroxy-gamma-butyrolactone is changed, and the mechanical properties and biocompatibility of the polyurethane material are both reduced; by comparing Example 6 with Example 1, it can be seen that the ratio of silane-modified silica and hyaluronic acid is changed, resulting in excessive crosslinking and reduced mechanical properties of the polyurethane material; by comparing Example 7 with Example 1, it can be seen that the direct use of silica has poor dispersibility, and the mechanical properties and biocompatibility of the polyurethane material are both reduced; by comparing Comparative Example 1 with Example 1, it can be seen that the direct use of amino-terminated polylactic acid reduces various properties.

[0078] The above implementation modes are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with this technology to understand the content of the present invention and implement it, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A polyurethane material for a medical infusion set, characterized in that: The invention comprises the following raw materials in parts by weight: 30-40 parts of polyol, 10-16 parts of polyisocyanate, 2-6 parts of modified polylactic acid, 0.5-1 parts of chain extender, 0.01-0.05 parts of catalyst and 1-4 parts of toughening agent.

2. The polyurethane material for medical infusion set according to claim 1, characterized in that: The preparation method of the modified polylactic acid comprises the following steps: adding amino-terminated polylactic acid, vegetable oil, (S)-3-hydroxy-gamma-butyrolactone and sodium ethoxide into anhydrous ethanol, reacting at 70-80° C. for 5-6 hours, and rotary evaporating to obtain the modified polylactic acid.

3. The polyurethane material for medical infusion set according to claim 2, characterized in that: The mass ratio of the amino-terminated polylactic acid, the vegetable oil and the (S)-3-hydroxy-gamma-butyrolactone is 1:(2-3):(0.3-0.7).

4. The polyurethane material for medical infusion set according to claim 2, characterized in that: The vegetable oil is one or more of linseed oil, olive oil and camellia oil.

5. The polyurethane material for medical infusion set according to claim 1, characterized in that: The toughening agent is modified silicon dioxide and chitosan, and the mass ratio of the two is 1: (2-4).

6. The polyurethane material for medical infusion set according to claim 5, characterized in that: The preparation method of the modified silicon dioxide comprises the following steps: (1) adding silica and silane coupling agent KH560 into ethanol and reacting at 70-80° C. for 5-6 hours to obtain silane-modified silica; (2) Add the silane-modified silica, hyaluronic acid and phosphoric acid obtained in step (1) into DMF and react at 70-80° C. for 5-6 hours to obtain modified silica.

7. The polyurethane material for medical infusion set according to claim 6, characterized in that: The mass ratio of the silane-modified silica to the hyaluronic acid is 1:(0.4-0.8).

8. The polyurethane material for medical infusion set according to claim 1, characterized in that: The chain extender is 1,6-hexanediol or 1,8-octanediol.

9. The polyurethane material for medical infusion set according to claim 1, characterized in that: The polyisocyanate is 4,4'-phenylmethane diisocyanate or L-lysine diisocyanate.

10. A method for preparing the polyurethane material for medical infusion set according to claims 1-9, characterized in that: The method comprises the following steps: reacting polyol, polyisocyanate and catalyst at 70-80°C for 3-4h, adding modified polylactic acid, chain extender and toughening agent and reacting at 50-60°C for 1-2h, and drying to obtain the product.

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