WO2020215800A1 - Polyurethane material, and preparing method therefor and application thereof, polymer material, and 3d stent - Google Patents

Abstract

A polyurethane material, and a preparing method therefor and an application thereof, a polymer material, and a 3D stent, relating to the technical field of new materials. The polyurethane material is mainly obtained by carrying out chain extension on a prepolymer A by means of a chain extender. The chain extender comprises a carbon material having a hydroxyl group on the surface, or similar materials of the carbon material. The prepolymer A has a structure shown in structural general formula 1, wherein X represents -(CH₂CH₂)- or (I); Y represents an optionally-substituted C₁-C₁₂ alkyl group, an optionally-substituted C₁-C₁₂ naphthenic group, an optionally-substituted C₆-C₁₂ aromatic group, an optionally-substituted C₆-C₁₂ heterocyclic group, or an optionally-substituted C₆-C₁₂ heteroaryl group; m and n represent respective polymerization degrees; the number-average molecular weight of the prepolymer A is 250-20000. The carbon material is prepared into amphiphilic polyurethane, the material can be modified and enhanced for various organic/inorganic material processing systems, and the mechanical performance and biocompatibility of the material can be remarkably improved.

Description

Polyurethane material, preparation method and application thereof, polymer material, 3D stent Technical field

The invention relates to the technical field of new materials, in particular to a polyurethane material, a preparation method and application thereof, a polymer material, and a 3D stent.

Background technique

With the introduction of the concept of additive manufacturing, 3D printing technology has developed rapidly in recent years, and has shown good application prospects in the field of biomedicine. It can personalize and customize complex tissues and organs and produce them in batches in a controlled and programmed manner. At present, the accuracy of 3D printing equipment on the market generally reaches the 100 micron level, and can even prepare tissue engineering materials accurately and programmed in the field of artificial blood vessels. However, it is relatively difficult to find bio-inks suitable for clinical application, because while maintaining good and suitable mechanical properties, it is also necessary to maintain biocompatibility, and to be able to introduce relevant biologically active substances, while chemically synthesized traditional materials It is difficult to satisfy all of the above characteristics.

At present, the development of bio-inks in the field of tissue engineering usually involves chemical modification of original materials or doping with inorganic-organic active materials, but these materials can basically only be targeted to improve mechanics, biological or cell adhesion value-added, etc. A certain aspect of performance limits the application of materials in a wider range.

At present, some bio-inks and biomedical materials containing graphene have appeared. Graphene is added as a doping material to biological materials, but due to the aggregation of graphene nanoparticles, it is not easy to disperse in most solvents, and It exhibits the characteristics of easy agglomeration, so the introduction of graphene for biomedical materials usually relies on chemical modification to improve the dispersion and biocompatibility of graphene. However, simple surface modification can only help graphene to disperse into the matrix material, and the performance improvement of the matrix material is very limited. In addition, for the processing system of each matrix material, graphene can only be surface modified in a targeted manner so that it can be dispersed in the processing system, and it is suitable for dispersible graphene oxide fresh in a variety of processing systems. There are reports. Moreover, the chemical modification process cannot avoid cumbersome reaction steps and various surface modification processes, and the use of toxic reagents is inevitable. Therefore, the introduction of graphene increases time, process and safety costs.

At present, there is no modified graphene additive that can be applied to a variety of processing systems, which can impart special properties to the material while uniformly introducing the graphene-enhanced material, and is convenient for processing and forming with the matrix material.

Therefore, it is desirable to provide a material reinforcing agent that can solve at least one of the above-mentioned problems.

In view of this, the present invention is proposed.

Summary of the invention

One of the objectives of the present invention is to provide a polyurethane material that has amphiphilic properties, can be stably dispersed in a variety of common organic/inorganic polymer material processing systems, and can significantly increase the mechanical properties and biocompatibility of the material.

The second object of the present invention is to provide a method for preparing polyurethane materials, which is prepared by prepolymerizing polyethylene glycol or polypropylene glycol and diisocyanate, and then chain extension using carbon materials with hydroxyl groups on the surface or the like. The reaction process is short.

The third object of the present invention is to provide an application of the aforementioned polyurethane material or the polyurethane material prepared by the aforementioned polyurethane material preparation method as a material enhancer in the processing and molding of organic and/or inorganic polymer materials.

The fourth object of the present invention is to provide a polymer material, including a matrix material and the above polyurethane material or the polyurethane material prepared by the above polyurethane material preparation method.

The fifth object of the present invention is to provide a 3D stent, which is mainly prepared from the above-mentioned polymer materials.

In order to achieve the above objectives of the present invention, the following technical solutions are specially adopted:

In a first aspect, a polyurethane material is provided, the polyurethane material is mainly obtained by chain extension of prepolymer A through a chain extender, and the chain extender includes a carbon material with hydroxyl groups on the surface or the like;

The general structural formula of prepolymer A is:

Where X is

Or; Y is an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted的C6-C12 heteroaryl;

m represents the degree of polymerization of polyurethane, m≥1, n>1;

The number average molecular weight of the prepolymer A is 250-20000.

In a second aspect, a method for preparing the above polyurethane material is provided, including the following steps:

(a) Provide prepolymer A: prepolymerize reactant A and diisocyanate to obtain prepolymer A, reactant A includes polyethylene glycol or polypropylene glycol; the molar ratio of reactant A to diisocyanate is 1: 1-1:2;

(b) Adding a chain extender to the prepolymer A to extend the chain. The chain extender includes a carbon material with hydroxyl groups on the surface or the like to obtain a polyurethane material.

Preferably, on the basis of the technical solution of the present invention, the diisocyanate includes one or more of aliphatic diisocyanate, aromatic diisocyanate, and alicyclic diisocyanate, preferably including 1,6-hexamethylene diisocyanate , Lysine diisocyanate, isophorone diisocyanate, 4,4-dicyclohexylmethane diisocyanate, 4,4-diphenylmethane diisocyanate, toluene diisocyanate or xylylene diisocyanate One or more.

Preferably, on the basis of the technical solution of the present invention, the carbon material or the like with hydroxyl groups on the surface includes two-dimensional carbon material, three-dimensional carbon material or black scale, preferably including graphene, graphene oxide, reduced graphene oxide, carbon One or more of nanotubes, fullerenes, or black phosphorous, and more preferably graphene oxide.

In a third aspect, the application of the above-mentioned polyurethane material or the polyurethane material prepared by the above-mentioned polyurethane material preparation method as a material enhancer in the processing and molding of organic and/or inorganic polymer materials is provided.

In a fourth aspect, a polymer material is provided, including a matrix material and the above-mentioned polyurethane material or the above-mentioned polyurethane material prepared by the method for preparing the above-mentioned polyurethane material;

Preferably, the matrix material is an organic and/or inorganic polymer material, preferably polylactic acid-glycolic acid copolymer or polyethylene glycol diacrylate;

Preferably, the polyurethane material accounts for 2.5-7.5% by mass of the base material.

In a fifth aspect, a 3D stent is provided, which is mainly prepared from the above-mentioned polymer materials.

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

(1) The polyurethane material of the present invention is mainly obtained by chain extension of prepolymer A through a carbon material with hydroxyl groups on the surface or the like. Because prepolymer A has hydrophilic and hydrophobic segments, it has amphiphilic properties. The polymer dispersible polyurethane system prepared by connecting multiple prepolymer A segments as a chain extender makes the carbon material or its analogue have the amphiphilic property of being stably dispersed in organic/inorganic solvents. It can be uniformly dispersed in a sol state. The polyurethane material can be uniformly dispersed in various polar and non-polar solvents for at least 24 hours without coagulation, indicating that it can be applied in most polymer processing systems and has a broad and universal application prospect.

(2) The polyurethane material of the present invention can be directly added as an additive to other polymer matrix materials for molding, does not involve chemical reactions, and has the advantages of safety, energy saving and convenient use. At the same time, it will not affect the inherent and unique properties of the polymer matrix, as well as processability and formability. The material can be added to the matrix material for industrialized large-scale printing production, and has potential industrial application capabilities.

(3) After the matrix material of the polyurethane material of the present invention is added, the mechanical properties and biocompatibility of the material are significantly enhanced, and it can possess the unique conductivity, adsorption, photothermal performance, drug release, and shape memory of carbon materials. performance.

Description of the drawings

Fig. 1 is a schematic diagram of a synthesis process of a polyurethane material according to an embodiment of the present invention;

Figure 2 is the infrared spectrum of the polyurethane obtained in Examples 1-3 and Comparative Example 1 of the present invention (the left is the infrared full-wavelength spectrum, and the right is the enlarged spectrum of the wavelength of the middle A section on the left);

3 is a 1H NMR chart of polyurethane obtained in Example 1 and Comparative Example 1 of the present invention;

Figure 4 is a graph showing the mechanical properties of the PEGDA material and PLGA material without adding and adding the polyurethane of Example 1 with different contents after molding (where (a) is the PEGDA material without adding and adding the polyurethane of Example 1 with different contents after molding The graph of compressive stress vs. strain, (b) is the fracture stress graph of the PEGDA material without adding and adding the polyurethane of Example 1 with different content, (c) is the PEGDA material without adding and adding the polyurethane of Example 1 with different content The graph of elongation at break after molding, (d) is the graph of compressive stress versus strain after molding of the PLGA material without adding and adding the polyurethane of Example 1 with different content, (e) is the graph of the change of compression stress with strain without adding and adding different content of Example 1 (F) is the graph of breaking stress after molding of the polyurethane PLGA material of, (f) is the graph of breaking elongation after molding of the PLGA material without and with different content of polyurethane of Example 1);

Figure 5 is a graph showing the relationship between the viscosity and the shear rate of the PEGDA material and the PLGA material without adding and adding the polyurethane of Example 1 (where (a) is the relationship between the viscosity of the PEGDA material without adding and adding the polyurethane of Example 1 and the shear rate , (B) is the relationship between viscosity and shear rate of PLGA material without and with the polyurethane of Example 1);

Figure 6 shows the biocompatibility test results of the PLGA material and the PEGDA material scaffold without and adding the polyurethane of Example 1 (where (a) is the PLGA material scaffold without the polyurethane added and the osteoblasts are grown and stained after 7 days of culture Figure, (b) is a stained image of living dead after 7 days of cultured osteoblasts on the PLGA material scaffold added with polyurethane of Example 1, (c) is a stained image of living dead after 7 days of cultured osteoblasts on the PEGDA material scaffold without polyurethane added , (D) is a stained image of alive and dead cells grown on the PEGDA material scaffold with the polyurethane of Example 1 after 7 days of culture, and (e) is the PLGA material and PEGDA material scaffold without and without the polyurethane of Example 1 being planted into bone Figure of cell count results after cell culture for 7 days);

Figure 7 is a temperature measurement diagram of the PLGA material and PEGDA material stent without and without adding the polyurethane of Example 1 after infrared irradiation;

Figure 8 is a graph showing the drug release performance of the PLGA material and PEGDA material stent without and adding the polyurethane of Example 1 (where (a) is the drug release performance graph of the PEGDA material stent without adding and adding the polyurethane of Example 1 , (B) is the drug release performance graph of the PLGA material stent without and without adding the polyurethane of Example 1).

Detailed ways

The embodiments of the present invention will be described in detail below in conjunction with examples, but those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. If specific conditions are not indicated in the examples, it shall be carried out in accordance with the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used without the manufacturer's indication are all conventional products that can be purchased commercially.

According to the first aspect of the present invention, a polyurethane material is provided, which is mainly obtained by chain extension of prepolymer A through a chain extender, and the chain extender includes a carbon material with hydroxyl groups on the surface or the like;

The general structural formula of prepolymer A is:

Among them, X is—(CH ₂ CH ₂ )—or

Y is an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted C6 -C12 heteroaryl; m represents the degree of polymerization of polyurethane, m≥1, n>1; the number average molecular weight of prepolymer A is 250-20000.

Polyurethane (PU) is a type of multi-block polymer that is rich in urethane bonds (–NHCOO–) and consists of a soft segment with a lower softening temperature and a hard segment with a higher softening temperature. Its molecular structure has good designability. Choose different soft segments, hard segments and different proportions of soft and hard segments to design and synthesize polyurethane materials with different properties, thus having good processability.

Carbon materials are widely used in polymer materials due to their good mechanical properties and other special properties. For example, graphene is a two-dimensional sheet-like nano-carbon material composed of a single layer of carbon atoms, which improves the mechanical and electrical properties of polymers. And thermal performance has shown great potential. The uniformity and quality of graphene as a nano additive dispersed into the polymer body is directly related to its effectiveness in improving performance. However, due to the intermolecular interaction force of graphene, the strong tendency of graphene stacking makes the dispersion of graphene in most organic/inorganic media very poor. In order to improve this problem, the usual method is to modify the surface of graphene to reduce surface interactions, so that it can be dispersed in a solvent. However, simple surface modification can only help graphene to disperse into the matrix material, and the performance improvement of the matrix material is very limited, and this method can only be enhanced for a specific material or processing system, and the chemical modification process cannot avoid cumbersome The reaction steps and various surface modification processes are cumbersome and unsuitable for wide application. At present, there is no modified graphene additive that can be applied to a variety of processing systems. It can improve the mechanical properties, optical properties, electrical properties and biocompatibility of a variety of matrix materials while introducing graphene uniformly, and hardly affect the matrix. The characteristics of the material itself.

Therefore, it is necessary to design a carbon-based reinforcing agent that can be applied to a variety of organic/inorganic systems. On the one hand, this will greatly reduce the cost of personalized modification. Due to the universality of the application, the coating materials, Building materials, industrial damping materials, optoelectronic materials, and biomedical materials all have potential application prospects. On the other hand, many materials that are originally limited due to their own performance defects will find further applications after being modified by the addition of enhancers. Possible.

The polyurethane material of the present invention is mainly obtained by chain extension of a prepolymer A through a carbon material or the like with a hydroxyl group on the surface, and a plurality of chain segments of the prepolymer A are connected by a carbon material or the like with a hydroxyl group on the surface Here, carbon materials with hydroxyl groups on the surface or the like are used as chain extenders.

Prepolymer A

The general structural formula of prepolymer A is:

Among them, X means—(CH ₂ CH ₂ )—or

Y represents an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted C6 -C12 heteroaryl; m represents the degree of polymerization of polyurethane, m≥1, n>1.

The source of polymer A is not limited, and the typical source is polymerized by polymerized glycol (polyethylene glycol or polypropylene glycol) and diisocyanate.

The typical reaction process is as follows:

Among them, m represents the degree of polymerization of polyurethane, m≥1, the minimum is 1 time, and the maximum is finite times; n>1, the maximum is finite times.

X means—(CH ₂ CH ₂ )—or

Polymerized diol

Polyethylene glycol

Or polypropylene glycol

Preferably, the number average molecular weight of the polymeric glycol is 200-20000.

Preferably, the range of n is 4-460, and n can be 4, 5, 6, 7, 8, 10, 12, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 110, 120, 130, 150, 160, 180, 200, 250, 300, 350, 400, 450 or 460.

Y is an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted C6 -C12 heteroaryl.

"Optionally substituted" means substituted or unsubstituted. The optionally substituted C1-C12 alkyl means C1-C12 alkyl or substituted C1-C12 alkyl. The substituents are not limited and may include halogen, amino, and amino. Alkyl group, ester group or acyl group, etc., others are the same.

In some embodiments, Y can be methylene, ethylene, propylene, isopropylene, butylene, pentylene, hexylene, heptylene, octylene, nonylidene, naphthalene Group, decylene, 1,2-cyclohexylene, 1,3-cyclohexylene, 1,4-cyclohexylene, phenyl, 1,2-phenylene, 1,3-phenylene, 1 , 4-phenylene, tolyl or xylyl, in some preferred embodiments, Y is C1-C12 alkyl or C6-C12 aromatic group, for example, Y may preferably be hexylene, phenyl, or tolyl Or xylyl.

It is understood that the diisocyanate may include aliphatic diisocyanate, aromatic diisocyanate or ester ring diisocyanate. Exemplary aliphatic diisocyanates include, but are not limited to, 1,6-hexamethylene diisocyanate, lysine diisocyanate, isophorone diisocyanate or 4,4-dicyclohexylmethane diisocyanate, etc.; exemplary Aromatic diisocyanates include, but are not limited to, 4,4-diphenylmethane diisocyanate, toluene diisocyanate, or xylylene diisocyanate.

In some embodiments, an exemplary prepolymer A structure is as follows:

That is, X is —(CH ₂ CH ₂ )—, Y is hexylene, m is 1; or,

That is, X is —(CH2CH2) —, Y is hexylene, and m is 2.

Chain extender

The polyurethane material of the present invention is a product obtained by chain-extending the prepolymer A with a chain extender.

The chain extender includes a carbon material with hydroxyl groups on the surface or the like. "Carbon material with hydroxyl groups on the surface or its analogues" refers to carbon materials with hydroxyl active groups on the surface or carbon material analogs with hydroxyl active groups on the surface. The hydroxyl active groups are derived from hydroxyl or carboxyl groups; those with hydroxyl groups on the surface Carbon materials include two-dimensional or three-dimensional carbon materials. Typical examples of two-dimensional carbon materials are graphene (the surface of graphene also has hydroxyl groups, but the number is small), graphene oxide or reduced graphene oxide. Three-dimensional carbon materials are typical For example, carbon nanotubes or fullerenes, and carbon material analogs with hydroxyl groups on the surface are typically black phosphorus. Preferably, the exemplary chain extender is graphene oxide, that is, an exemplary polyurethane material is obtained by chain extension of the prepolymer A through graphene oxide.

In some embodiments, the general structural formula of the polyurethane material is:

among them,

And its end-capping group is:

R ₃ ＝H, or,

x>1, n>1.

In some embodiments, an exemplary polyurethane material structure is as follows:

among them,

And its end-capping group is:

R ₃ ＝H, or,

x>1, n>1. That is, X is —(CH ₂ CH ₂ ) — and Y is hexylene.

In the long molecular chains R _2, R ₂ -1 has a number of ordered repetitive structure, R _2-2 is an end portion (i.e. terminated _2-2 R), wherein R ₂ -1 is:

R ₂ -2 is

The polyurethane material of the present invention is mainly obtained by chain extension of prepolymer A through a carbon material or the like with hydroxyl groups on the surface. Because prepolymer A has hydrophilic and hydrophobic segments, it has amphiphilic properties, carbon materials or the like As a chain extender, the polymer dispersible polyurethane system prepared by connecting multiple prepolymer A segments makes the carbon material or the like have the amphiphilic property of being stably dispersed in organic/inorganic solvents, and can be used as a sol The state is evenly dispersed. The polyurethane material can be uniformly dispersed in various polar and non-polar solvents for at least 24 hours without coagulation, indicating that it can be applied in most polymer processing systems and has a broad and universal application prospect.

The polyurethane material of the present invention can be directly added as an additive to other polymer matrix materials for molding, does not involve chemical reactions, and has the advantages of safety, energy saving and convenient use. At the same time, it will not affect the inherent and unique properties of the polymer matrix, as well as processability and formability. The material can be added to the matrix material for industrialized large-scale printing production, and has potential industrial application capabilities.

After the base material of the polyurethane material of the present invention is formed, it can not only improve the mechanical properties and biocompatibility of the base material, but also promote the adhesion and proliferation of cells to a certain extent. It has broad application prospects in biomedical materials and can Endow the material with the unique properties of carbon materials such as photothermal performance, drug delivery, conductivity, adsorption and shape memory.

According to the second aspect of the present invention, there is provided a method for preparing the above-mentioned polyurethane material, including the following steps:

(a) Provide prepolymer A: prepolymerize reactant A and diisocyanate to obtain prepolymer A, reactant A includes polyethylene glycol or polypropylene glycol; the molar ratio of reactant A to diisocyanate is 1: 1-1:2;

(b) Adding a chain extender to the prepolymer A to extend the chain. The chain extender includes a carbon material with hydroxyl groups on the surface or the like to obtain a polyurethane material.

For the description of the diisocyanate and the carbon material with a hydroxyl group on the surface or the like, please refer to the corresponding description in the first aspect of the present invention, which will not be repeated here.

The molar ratio of reactant A to diisocyanate is, for example, 1:1, 2:3, or 1:2.

When 1:1, the corresponding m is very large, when 2:3, the corresponding m is 2, and when 1:2, the corresponding m is 1.

If the molar ratio is less than 1:1, it cannot further react with the hydroxyl group. If the molar ratio is greater than 1:2, part of the diisocyanate does not participate in the reaction.

In the present invention, prepolymer A is obtained by prepolymerizing polyethylene glycol or polypropylene glycol as the soft segment and diisocyanate as the hard segment, and then the carbon material with hydroxyl on the surface or the like is used as the chain extender to extend the chain. A plurality of prepolymerized chain segments are connected by carbon materials or the like. The preparation method is simple, the reaction process is short, the conditions are not harsh, the cost is low, and the energy saving and environmental protection are achieved. The polyurethane material prepared by the method has the same advantages as the polyurethane material of the first aspect.

In some embodiments, in step (a), the pre-polymerization reaction temperature is 50-80°C, for example, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, or 80°C, and the pre-polymerization reaction time is 1 -4h, such as 1h, 2h, 3h or 4h.

Preferably, a catalyst is added in the pre-polymerization reaction, the catalyst is stannous octoate, and the molar ratio of stannous octoate to reactant A is 0.001:1 to 0.01:1, for example, 0.001:1, 0.002:1, 0.005:1, 0.008: 1 or 0.01:1.

By optimizing the pre-polymerization reaction conditions and optimizing the degree of polymerization, polymer A obtains better amphiphilicity.

In some embodiments, in step (b), the chain extension reaction temperature is 35-55°C, such as 35°C, 40°C, 45°C, 50°C or 55°C, and the chain extension reaction time is 8-24h, such as 8h, 9h, 10h, 11h, 12h, 14h, 16h, 18h, 20h, 22h or 24h.

Preferably, the mass ratio of the carbon material or its analogue with hydroxyl groups on the surface to the reactant A is 0.1:100-1:100, such as 0.1:100, 0.2:100, 0.5:100, 0.8:100 or 1:100.

In some embodiments, a typical polyurethane material preparation method uses polyethylene glycol (PEG) (number average molecular weight is 200-20000, such as PEG 200, PEG 400, PEG 1000, etc.) as the soft segment, using 1, 6-Hexamethylene diisocyanate (HDI) is used as the hard segment. After prepolymerization, graphene oxide is added for chain extension, and multiple prepolymerized segments are connected by graphene oxide. The synthesis process is shown in Figure 1, including the following steps:

(1) Pre-polymerize according to the molar ratio of PEG:HDI=1:1-1:2, the pre-polymerization temperature is 50-80℃, with stannous octoate as a catalyst, the molar ratio of stannous octoate to PEG is 0.001 :1-0.01:1, prepolymerization time is 1-4h;

(2) After the prepolymerization is completed, add graphene oxide. The mass ratio of graphene oxide to polyethylene glycol is 0.1:100-1:100. After reacting at 35-55°C for 8-24 hours, wash off with absolute ethanol. Unreacted graphene oxide can produce amphiphilic polyurethane containing graphene blocks.

The polyurethane can be dispersed in a variety of organic and inorganic systems. It can be added to enhance modification before other organic materials are formed. It can evenly introduce graphene into the matrix material while improving the mechanical properties and biocompatibility of the material, and endow the matrix material with the original It does not possess the unique properties of graphene such as photothermal performance and drug release.

According to the third aspect of the present invention, there is provided an application of the aforementioned polyurethane material or the polyurethane material prepared by the aforementioned polyurethane material preparation method as a material enhancer in the processing and molding of organic and/or inorganic polymer materials.

Since the present invention uses carbon materials such as graphene or the like to make amphiphilic polyurethane, the polyurethane can be dispersed in a variety of organic and inorganic systems, and can be used as a material enhancer to enhance polymer materials, without the need for specific The polymer matrix that needs to be modified is further modified and only needs to be directly added before other materials are processed and shaped, which is simple and convenient, has universal application, and improves production efficiency. The amphiphilic polyurethane has potential application prospects in the processing and molding of coating materials, building materials, industrial damping materials, optoelectronic materials, and biomedical materials.

According to a fourth aspect of the present invention, there is provided a polymer material, including a matrix material and the above-mentioned polyurethane material or the polyurethane material prepared by the above-mentioned polyurethane material preparation method.

The polymer materials can be various functional materials, including but not limited to coating materials, building materials, industrial damping materials, optoelectronic materials, or biomedical materials.

The matrix material is not limited, and includes various organic and/or inorganic polymer materials, such as polylactic acid-glycolic acid copolymer or polyethylene glycol diacrylate.

The polymer material after adding the polyurethane material of the present invention has better mechanical properties and biocompatibility, and will have photothermal properties, electrical properties, and drug-loading and drug-releasing properties that may not have been originally available, and the original characteristics of the matrix material Not affected.

In some embodiments, the amount of polyurethane material added is 2.5-7.5%, that is, the mass percentage of the polyurethane material in the matrix material can be 2.5%, 3%, 4%, 5%, 6% or 7.5%.

Only a small amount of polyurethane material needs to be added before polymer molding to play a good role in reinforcement, and the mechanical properties and biocompatibility after molding are improved to varying degrees.

According to the fifth aspect of the present invention, a 3D stent is provided, which is mainly prepared from the above-mentioned polymer material.

After the polymer material is added to the polyurethane material of the present invention, the rheological properties of the polymer material are not affected. The reinforced matrix material can still be three-dimensionally printed to prepare a complete biomedical scaffold, which has a positive effect on cell proliferation and adhesion, and makes the scaffold It has photothermal performance and drug release performance.

The present invention will be further illustrated by specific examples and comparative examples below. However, it should be understood that these examples are only used for more detailed description, and should not be understood as limiting the present invention in any form. All raw materials involved in the present invention can be obtained commercially.

Example 1 Preparation of amphiphilic polyurethane containing graphene oxide blocks

An amphiphilic polyurethane containing graphene oxide blocks, using polyethylene glycol (PEG) 10000 as the soft segment, 1,6-hexamethylene diisocyanate (HDI) as the hard segment, and graphene oxide (GO) as the Chain extender, synthetic polyurethane material.

The preparation method of amphiphilic polyurethane containing graphene oxide blocks includes the following steps:

(1) Add toluene and PEG to the reactor, stir to dissolve PEG in toluene, then add HDI according to the molar ratio of PEG: HDI=1:1, and add stannous octoate according to the molar ratio of stannous octoate: PEG=0.001:1. Prepolymerize at 60°C under nitrogen for 4 hours to obtain prepolymer A;

(2) Add 0.1 wt% of PEG GO to prepolymer A, and after reacting at 55°C for 16 hours, wash off the unreacted GO with absolute ethanol to obtain an amphiphilic polyurethane containing graphene blocks.

Example 2

The difference between this embodiment and embodiment 1 is that in step (2), 0.2 wt% of PEG is added with GO, and the rest remains unchanged.

Example 3

The difference between this embodiment and embodiment 1 is that in step (2), GO accounting for 1 wt% of PEG is added, and the rest remains unchanged.

Example 4

The difference between this embodiment and Embodiment 1 is that PEG 10000 is replaced with polypropylene glycol 2000.

Example 5

The difference between this embodiment and Embodiment 1 is that HDI is replaced with TDI (toluene diisocyanate).

Example 6

The difference between this embodiment and embodiment 1 is that in step (1), the molar ratio of PEG:HDI is 1:2.

Example 7

The difference between this embodiment and embodiment 1 is that in step (1), the molar ratio of PEG:HDI is 2:3.

The more HDI, the harder the material and the higher the molecular weight. Example 1 has a higher molecular weight than Example 6 and a higher yield.

Example 8 Preparation of amphiphilic polyurethane containing fullerene block

An amphiphilic polyurethane containing fullerene blocks, using polyethylene glycol (PEG) 10000 as the soft segment, 1,6-hexamethylene diisocyanate (HDI) as the hard segment, and fullerene as the chain extender , Synthetic polyurethane material.

The preparation method of amphiphilic polyurethane containing fullerene block includes the following steps:

(1) Add toluene and PEG to the reactor, stir to dissolve PEG in toluene, then add HDI according to the molar ratio of PEG: HDI = 1:1, and add stannous octoate according to the molar ratio of stannous octoate: PEG = 0.002:1. Prepolymerize at 75°C under nitrogen for 3 hours to obtain prepolymer A;

(2) Add 0.1wt% fullerene of PEG to prepolymer A, and after reacting at 45°C for 24h, wash away the unreacted fullerene with absolute ethanol to obtain the amphiphile containing the fullerene block性polyurethane.

Comparative example 1

The difference between this comparative example and Example 1 is that the GO in step (2) is replaced with ethylene glycol, and the rest remains unchanged to obtain polyurethane.

Test Example 1 Structure Characterization of Amphiphilic Polyurethane Containing Graphene Oxide Blocks

The polyurethane material was characterized by 1H NMR and ATR-IR (Attenuated Total Reflection Infrared Spectroscopy), and the results are shown in Figures 2 and 3.

As shown in Figure 2, graphene oxide is a two-dimensional material of carbon. There are C=C double bonds between the carbons. The amphiphilic polyurethane containing graphene oxide blocks (Example 1-3) contains 1645 cm-1 The characteristic absorption peak of the graphene C=C double bond appears at the place, and the characteristic peak is not seen in the PPU material without graphene for chain extension (Comparative Example 1), while the graphene control group also has the characteristic at 1645 cm-1 peak.

As shown in Figure 3, after graphene oxide enters the polyurethane segment, it brings a lot of active hydrogen and presents a sharp single peak (arrow), while PPU without graphene oxide (comparative example 1) is at the same 1.5ppm Active hydrogen is obviously less and the peak is not obvious. The active hydrogen of PPU mixed with graphene oxide (Comparative Example 1 Physically Mixed GO) at a chemical shift of 1.7 ppm showed a blunt peak. This shows that the graphene oxide in Example 1 was successfully inserted into the polyurethane molecular segment.

It was detected by 1H NMR and ATR-IR that the amphiphilic polyurethane material containing graphene oxide blocks of the present invention was successfully synthesized.

Test Example 2 Test of the mechanical properties of the matrix material after adding the material of the present invention

Polylactic acid-glycolic acid copolymer (PLGA) is selected as the matrix material of the organic processing system, and polyethylene glycol diacrylate (PEGDA) is selected as the matrix material of the inorganic processing system, which proves the material enhancement performance of the present invention.

Before molding the PLGA material, 2.5 wt%, 5 wt%, and 7.5 wt% of the polyurethane material of Example 1 were added, and the mechanical properties of the material were tested after molding. Before molding the PEGDA material, add 2.5wt%, 5wt% and 7.5wt% of the polyurethane material of Example 1, and test the mechanical properties of the material after molding. The test method is: PLGA material: After laying the film with tetrafluoroethylene board, use dynamic Mechanical analyzer measures tensile strength and elongation at break;

PEGDA material: Use a tetrafluoroethylene mold to form a column, and measure the fracture stress and compressibility during fracture.

The result is shown in Figure 4. It can be seen from Figure 4 that the mechanical properties of the PLGA material and the PEGDA material added with 2.5%, 5% and 7.5% of the polyurethane material of the present invention have different improvements after molding. Among them, a, b, and c indicate that the amphiphilic polyurethane of the present invention and the PEGDA material are formed together to increase the compression modulus. d, e, and f show that the amphiphilic polyurethane of the present invention and the PLGA material are co-molded, and the breaking stress and breaking elongation are significantly improved.

Test Example 3 Three-dimensional printing of the matrix material after adding the material of the present invention

The PLGA material and PEGDA material added with 5wt% of the polyurethane material of Example 1 were processed for three-dimensional printing stents under the same parameter conditions. The viscosity and shear rate of the PLGA material and PEGDA material before and after the addition were tested. The test method is: configure equal concentrations PLGA ink, one group is added with 5% PGUC, the other group is not added, use a rheometer for ink rheology test, PEGDA is the same as the above method. The result is shown in Figure 5.

It can be seen from Figure 5 that the rheological properties of the polymer matrix materials PEGDA and PLGA after adding the polyurethane material of the present invention are not affected, which means that the machinability of the matrix material is not affected, and the enhanced matrix material can still be prepared by three-dimensional printing. By processing a complete biomedical stent, the shear thinning performance is improved, so that a finer stent can be prepared.

Use Adobe Acrobat pro software to analyze the printed SEM image of the stent, and calculate the aperture. The results are shown in Table 1.

Table 1

PEGDA	PEGDA (5% Example 1)	PLGA	PLGA (5% Example 1)
0.136±0.006	0.189±0.014	0.086±0.014	0.105±0.034

It can be seen from Table 1 that the PEGDA and PLGA materials added with the polyurethane of the present invention can print products with larger and more uniform pore sizes.

Test Example 4 Biocompatibility test of the scaffold

The PLGA material and PEGDA material without the polyurethane material of Example 1 and the stent printed by the PLGA material and PEGDA material with 5wt% of the polyurethane material of Example 1 were tested for biocompatibility. The test method was to plant 10,000 stents respectively. The osteoblasts were cultured for 7 days and then stained for live death, and the cells on the scaffold were counted with CCK-8. The result is shown in Figure 6.

The biocompatibility test shows that the addition of 5% of the PLGA material and PEGDA material of the present invention has a positive effect on the proliferation and adhesion of osteoblasts.

Test Example 5 Other performance tests of the bracket

The stent printed with PLGA material and PEGDA material without the polyurethane material of Example 1 and PLGA material and PEGDA material with the polyurethane material of Example 1 added 5wt% was irradiated with 808nm near infrared for 1 min, and then the temperature was measured. The test method is : Use an infrared thermometer to measure the real-time infrared temperature of the bracket. The result is shown in Figure 7.

The results show that the temperature of the material containing the polyurethane of the present invention is significantly increased after being irradiated by 808 nm infrared for one minute, which proves that the stent processed and molded with the polyurethane of the present invention has photothermal properties.

Using minocycline as the prototype drug to explore the drug release performance of the processed stent:

The stent printed out of the PLGA material and PEGDA material without the polyurethane material of Example 1 and the PLGA material and PEGDA material of the polyurethane material of Example 1 added by 5 wt% was immersed in a 0.25 wt% minocycline hydrochloride (NIR) solution statically. Leave it for 1 hour to load the drug, then wash it with PBS three times and then immerse it in an equal amount of PBS. The amount of minocycline released is measured at 1, 2, 3, and 4 hours. The results are shown in Figure 8.

As a result, it was found that the PLGA stent that does not contain the polyurethane of the present invention can hardly be loaded with drugs, and because PEGDA is a water-absorbing gel, it can load a certain amount of drugs. However, after 808nm infrared radiation was administered at the second hour, the stent containing the polyurethane of the present invention produced a burst of drug release, indicating that the stent has good drug loading and controlled release effects after adding the polyurethane material of the present invention.

It can be seen that the polymer material using the polyurethane of the present invention has better mechanical properties, and can further possess drug release performance, photothermal performance, etc., and the rheological properties, formability, and biocompatibility of the raw materials are also It has not been negatively affected, and even slightly improved. In addition, the present invention is convenient to use, only a small amount of direct addition is performed before the matrix is formed, which further reduces complex modification steps and modification steps, does not involve complex chemical reactions, and improves the complex design in the traditional material modification process , Modification process. This means that the material has a wide range of potential applications in the processing and molding of various materials such as coating materials, building materials, industrial damping materials and biomedical materials.

Although specific embodiments have been used to illustrate and describe the present invention, it should be appreciated that many other changes and modifications can be made without departing from the spirit and scope of the present invention. Therefore, this means that all these changes and modifications that fall within the scope of the present invention are included in the appended claims.

Claims (13)

1. A polyurethane material, characterized in that the polyurethane material is mainly obtained by chain extension of prepolymer A through a chain extender, and the chain extender includes a carbon material with hydroxyl groups on the surface or the like;

   The general structural formula of prepolymer A is:

   

   Among them, X is—(CH ₂ CH ₂ )—or

   

   Y is an optionally substituted C1-C12 alkyl group, an optionally substituted C1-C12 cycloalkyl group, an optionally substituted C6-C12 aromatic group, an optionally substituted C6-C12 heterocyclic group or an optionally substituted C6 -C12 heteroaryl;

   m represents the degree of polymerization of polyurethane, m≥1, n>1;

   The number average molecular weight of the prepolymer A is 250-20000.
2. The polyurethane material according to claim 1, wherein the carbon material or the like with hydroxyl groups on the surface comprises a two-dimensional carbon material, a three-dimensional carbon material or black scale.
3. The polyurethane material according to claim 2, wherein the carbon material or the like with hydroxyl groups on the surface includes graphene, graphene oxide, reduced graphene oxide, carbon nanotubes, fullerene or black phosphorus. One or more of them.
4. The polyurethane material according to claim 3, wherein the carbon material or the like with hydroxyl groups on the surface is graphene oxide.
5. The polyurethane material according to claim 1, wherein the polyurethane material is mainly obtained by chain extension of prepolymer A through graphene oxide;

   The general structural formula of the polyurethane material is:

   

   among them,

   

   

   And its end-capping group is:

   

   R ₃ ＝H, or,

   

   x>1, n>1.
6. The polyurethane material according to any one of claims 1 to 5, wherein X is -(CH ₂ CH ₂ )-; the range of n is 4-460.
7. The polyurethane material according to any one of claims 1-5, wherein Y is methylene, ethylene, propylene, isopropylidene, butylene, pentylene, hexylene, heptylene Group, octylene, nonylidene, naphthylene, decylene, 1,2-cyclohexylene, 1,3-cyclohexylene, 1,4-cyclohexylene, phenyl, 1,2-ylidene Phenyl, 1,3-phenylene, 1,4-phenylene, tolyl or xylyl; m is 1 or 2.
8. A method for preparing polyurethane material according to any one of claims 1-7, characterized in that it comprises the following steps:

   (a) Provide prepolymer A: prepolymerize reactant A and diisocyanate to obtain prepolymer A, reactant A includes polyethylene glycol or polypropylene glycol; the molar ratio of reactant A to diisocyanate is 1: 1-1:2;

   (b) Adding a chain extender to the prepolymer A to extend the chain. The chain extender includes a carbon material with hydroxyl groups on the surface or the like to obtain a polyurethane material;

   The diisocyanate includes one or more of aliphatic diisocyanate, aromatic diisocyanate, and ester ring diisocyanate.
9. The method for preparing a polyurethane material according to claim 8, wherein in step (a), the pre-polymerization temperature is 50-80°C, and the pre-polymerization time is 1-4 h;

   The pre-polymerized catalyst is stannous octoate, and the molar ratio of stannous octoate to reactant A is 0.001:1-0.01:1;

   In step (b), the chain extension reaction temperature is 35-55°C, and the chain extension reaction time is 8-24h;

   The mass ratio of the carbon material or its analogue with hydroxyl groups on the surface to the reactant A is 0.1:100-1:100.
10. A polyurethane material according to any one of claims 1-7 or a polyurethane material prepared by the preparation method of the polyurethane material according to claim 8 or 9 is used as a material reinforcing agent in the processing and molding of organic and/or inorganic polymer materials Applications.
11. A polymer material, characterized by comprising a matrix material and the polyurethane material according to any one of claims 1-7 or the polyurethane material obtained by the preparation method of the polyurethane material according to any one of claims 8 or 9;

    The matrix material is an organic and/or inorganic polymer material;

    The polyurethane material accounts for 2.5-7.5% by mass of the base material.
12. The polymer material according to claim 11, wherein the matrix material is polylactic acid-glycolic acid copolymer or polyethylene glycol diacrylate.
13. A 3D stent, characterized in that it is mainly prepared from the polymer material according to claim 11 or 12.

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