CN113683804A

CN113683804A - Double-crosslinked chitosan poly (ester-urethane) modified oxidized starch and preparation method thereof

Info

Publication number: CN113683804A
Application number: CN202111191870.8A
Authority: CN
Inventors: 张�浩; 候昭升; 孙晨; 朱玉正; 邵帅帅; 秦建丽
Original assignee: Shandong Tianming Medical Technology Co ltd
Current assignee: Shandong Tianming Medical Technology Co ltd
Priority date: 2021-10-13
Filing date: 2021-10-13
Publication date: 2021-11-23
Anticipated expiration: 2041-10-13
Also published as: CN113683804B

Abstract

The invention discloses a double-crosslinked chitosan poly (ester-urethane) modified oxidized starch and a preparation method thereof. The modified starch material is prepared by using degradable raw materials of NCO-terminated polyester, chitosan and oxidized starch through a chemical double-crosslinking method, has excellent mechanical properties (the breaking strength is more than 6MPa and the elongation at break is more than 150%), has few components, is easy to regulate and control, has full degradability and antibacterial performance, can be used for manufacturing various tableware and packaging materials directly contacting with food, and can be used in the medical field as a medical material because the degradation product is nontoxic and absorbable to human bodies and has good biocompatibility.

Description

Double-crosslinked chitosan poly (ester-urethane) modified oxidized starch and preparation method thereof

Technical Field

The invention belongs to the technical field of natural high polymer materials, and particularly relates to double-crosslinked chitosan poly (ester-urethane) modified oxidized starch and a preparation method thereof.

Background

Polyurethane (PU) materials are a class of polymer materials with excellent performance, are widely applied to various fields of light industry, textile, medical use and the like, and become one of six synthetic polymer materials in the world. However, the use of polyurethane in a large amount is also attracting high attention to improve the life of people, and simultaneously, the depletion of petroleum resources and the negative influence of waste on the environment are caused. With the growing awareness of environmental protection, research and development of environmentally degradable polyurethane materials from renewable natural resources have been one of the issues that have been receiving considerable attention in recent years.

The addition reaction of isocyanate and polyol is the basic reaction for synthesizing polyurethane, and most of plant raw materials are natural compounds rich in hydroxyl group, which is regarded as important conditions for synthesizing polyurethane. The environmental-friendly polyurethane is researched at present, and starch is an inexhaustible, biodegradable and environment-friendly natural renewable resource, wherein the oxidized starch is modified starch obtained by oxidizing starch under the action of an oxidant in acid, alkali and neutral media. The oxidized starch reduces the gelatinization temperature of the starch, reduces the viscosity of hot paste, increases the thermal stability, has white color, transparent paste, good film forming property and good freeze-thaw resistance, and is a thickening agent with low viscosity and high concentration. However, little work has been done to crosslink polyurethanes with oxidized starches to form modified materials. In addition, the reactivity of polyurethane and oxidized starch in the traditional modified material is not high, and the water resistance and the anti-mold property of the material are bottlenecks which influence the large-scale production of starch materials at present.

Patent CN93109978.1 discloses a biodegradable starch-containing composition, a method for producing the same and use thereof. The preparation of the composition comprises the following steps: starch, polyethylene, ethylene-acrylic acid copolymer (EAA), polyalcohol, polyvinyl alcohol, ethylene-vinyl acetate copolymer (EVA), calcium stearate, urea, alkali, surfactant, etc. are continuously mixed and processed by a double-screw extruder to obtain the plastic product. Although the material has simple processing technology and good mechanical property and certain biodegradability, the degradation is only partial degradation, the components such as polyethylene and the like in the material cannot be degraded, and the material has no biocompatibility and cannot be used in the medical field.

Patent CN03117398.5 discloses a fully biodegradable thermoplastic starch resin, which is mainly made of starch, thermoplastic resin, cellulose (or polyvinyl alcohol or polyester), chemical initiator, plasticizer, coating agent and antioxidant. The material has good degradability in nature, can be used as tableware, cup and dish, packaging material and the like, and can be degraded after being discarded, thereby avoiding white pollution. However, the technical components are more, the compounding difficulty is higher, and the plasticizer is used, so that the tableware has potential pollution. Meanwhile, the material has no biocompatibility, so that the material cannot be used as a medical material.

Patent cn201010602122.x discloses a high-strength biodegradable thermoplastic starch resin. Mainly prepared by physically mixing food-grade starch, sorbitol, diethylene glycol, stearic acid, calcium stearate, monoglyceride, ethylene acrylic acid copolymer, ethylene-vinyl acetate copolymer, linear low-density polyethylene, ultralow-density polyethylene and high-density polyethylene. The prepared film material has higher tensile strength, elongation at break, tearing strength and heat seal strength, but the biodegradation rate is only about 40 percent and can not be completely degraded, so the film material is mainly used for producing various high-strength films, is particularly suitable for producing industrial packaging films, bags, commercial gift bags, garbage bags and the like, can not be used in the medical field, and has no antibacterial property.

Patent application CN202110640623.5 discloses a biocompatible antibacterial film and a preparation method thereof, the antibacterial film takes polyvinyl alcohol as a substrate, chitosan is modified by starch to obtain a modified chitosan/polyvinyl alcohol/starch composite film, and capsaicin with antibacterial property is added, so that the prepared film has excellent mechanical property, oxidation resistance, barrier property, antibacterial property and biocompatibility. However, the material is mainly formed by physical compounding, and the main raw material is the polyethanol, so that the biodegradation absorption performance is poor.

As can be seen from the above patent documents: the modified starch technology disclosed at present is mainly used for preparing degradable (or partially degradable) plastics, which can only be used in nature to avoid white pollution in nature and cannot be used in the medical field although the modified starch technology has mechanical properties; and mainly adopts the physical composition of starch, the components are complex, and the performance is not easy to adjust.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a double-crosslinked chitosan poly (ester-urethane) modified oxidized starch and a preparation method thereof. The modified starch material is prepared by using degradable raw materials of NCO-terminated polyester, chitosan and oxidized starch through a chemical double-crosslinking method, has excellent mechanical properties, few components, easy regulation and control, complete degradability, water resistance and antibacterial performance, can be used for manufacturing various tableware and packaging materials of direct contact food, and can be used as a medical material in the medical field because degradation products are nontoxic and absorbable to human bodies and have good biocompatibility.

The technical scheme of the invention is as follows: a preparation method of double-crosslinked chitosan poly (ester-urethane) modified oxidized starch is characterized by comprising the following steps:

1) dissolving-NCO end-capped polyester and chitosan in an organic solvent, and stirring for reaction until the reaction is complete;

2) adding oxidized starch dispersion, reacting while stirring until the solution becomes viscous (can be smoothly poured into a mold), stopping stirring, and removing dissolved gas under pressure;

3) slowly pouring the chitosan poly (ester-urethane) modified starch oxide film material into a mold, standing to volatilize the organic solvent into a film, and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified starch oxide film material.

Further, the organic solvent is N, N-Dimethylformamide (DMF), tetrahydrofuran, dimethyl sulfoxide, etc., preferably N, N-Dimethylformamide (DMF).

The preferred technical scheme is as follows:

1) dissolving-NCO end-capped polyester and chitosan in N, N-Dimethylformamide (DMF) at 5 ℃, heating to 18-25 ℃ under stirring, and reacting completely;

2) adding DMF dispersion of oxidized starch, reacting at normal temperature while stirring until the solution becomes viscous, stopping stirring, and removing dissolved gas under pressure;

3) slowly pouring the mixture into a mold, standing at 40 ℃ to volatilize the solvent into a film, and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified oxidized starch film material.

preferred-NCO-terminated polyesters are according to the literature

2017,69, 1600071. Wherein the polyester diol is homopolyester, preferably poly (epsilon-caprolactone), poly (L-lactide) and polydioxanone, and the number average molecular weight is 1500-4500 g/mol; the diisocyanate is preferably L-Lysine Diisocyanate (LDI). The molar ratio of diisocyanate to polyester diol was 2: 1.

Preferably, the molecular weight of the chitosan is 2000-3000 g/mol, the deacetylation degree is more than 90%, and the ignition residue is less than 0.3%.

Preferably, the oxidized starch is prepared according to the method disclosed in patent CN201210092939.6, wherein the content of aldehyde groups in the oxidized starch is 0.9-1.5 mmol/g.

Preferably, the total dosage of the NCO end-capping polyester and the chitosan is 0.5 to 1.0g/mL in DMF.

Preferably, the feeding ratio of the-NCO end capping polyester to the chitosan is-NCO to-NH₂The molar ratio of the groups is 1: 4-1: 6.

Preferably, the reaction end point of the-NCO end-capped polyester and the chitosan is infrared detection, and the disappearance of an NCO characteristic absorption peak requires about 1.5-2 hours.

Preferably, the oxidized starch is added in such an amount that aldehyde groups in the oxidized starch are the end of the reaction of step 1)remaining-NH at point₂45-55%, preferably 50% of the number of moles of groups. More preferably, the oxidized starch is present in an amount of 40% to 55% by weight of the final product.

Preferably, the DMF dispersion liquid of the oxidized starch is prepared by ultrasonically dispersing the oxidized starch in DMF, and the concentration is 1-2.5 g/10 mL.

The film material of the chitosan poly (ester-urethane) modified oxidized starch prepared by the invention has a double cross-linking structure, so the film material has good mechanical property, the breaking strength is more than 6MPa, the breaking elongation is more than 150%, the film material can be completely degraded (the degradation time is less than or equal to 9 days), and the film material has certain antibacterial property, so the film material can be used for manufacturing various tableware and packaging materials directly contacting with food. The material has good biocompatibility, the cytotoxicity is 0 grade to 1 grade, the requirement of the material implanted in vivo is met, and the material can be used as a medical material to be applied to the inside of a living body.

The invention has the following beneficial effects:

1. can be degraded completely

The modified starch material is prepared by using degradable raw materials of NCO-terminated polyester, chitosan and oxidized starch through a chemical double-crosslinking method, has excellent mechanical properties, has full degradability and antibacterial performance, and can be used for manufacturing various tableware and packaging materials directly contacting with food.

2. Can be applied to the medical field of in-vivo implanted materials and the like

The main components of the polymer provided by the invention are polyester, chitosan and starch, and the polymer has good biocompatibility, does not harm organisms and has degradable and absorbable performance. The cytotoxicity is 0 grade to 1 grade, meets the requirements of in vivo implanted materials, and can be applied to organisms as medical materials.

3. Simple process and can realize large-scale production of starch materials

The starch has large stock in nature, but the application in the aspect of materials is greatly limited due to no mechanical property, the invention provides a simple and easy-to-operate (few components and easy to regulate and control) starch modification method, and the starch after double crosslinking has good mechanical property, so that the large-scale production of starch materials can be realized.

4. Antibacterial property

The polymers provided by the present invention have unreacted-NH₂Can be further modified as an active group and simultaneously has certain antibacterial property.

5. Water resistance

Due to the addition of ester bonds, the polymer provided by the invention has a stronger hydrophobic effect than unmodified starch, and the water resistance of the polymer is enhanced.

Drawings

FIG. 1 is a picture of M1 of a film prepared in example 1;

FIG. 2 is a graph showing the experimental inhibition zone of the membrane M1 prepared in example 1 for Escherichia coli, the diameter of the inhibition zone being 36.04mm (approximately 36 mm).

Detailed Description

The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.

The invention will be further explained and illustrated with reference to the following specific examples.

Example 1

10g of an-NCO-terminated poly (. epsilon. -caprolactone) (number-average molecular weight 2000g/mol) were mixed with 7.04g of chitosan (molecular weight 2000g/mol, degree of deacetylation 92%) (-NCO and-NH)₂Dissolving in 25mL of N, N-Dimethylformamide (DMF) at 5 ℃, heating to 20 ℃, reacting under stirring until an infrared detection-NCO characteristic absorption peak disappears (about 1.6h), adding DMF dispersion (12.5g of oxidized starch (with aldehyde group content of 1.2mmol/g) dispersed in 60mL of DMF, reacting under stirring until the solution becomes viscous (about 15min), stopping stirring, and reducingAnd (3) after removing dissolved gas by pressure, slowly pouring the mixture into a mold, standing the mixture at 40 ℃ to volatilize the solvent into a film (about 60 hours), and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified oxidized starch film M1.

The picture of the sample M1 prepared in example 1 is shown in FIG. 1, because chitosan is light yellow, the prepared sample is light yellow, and in addition, oxidized starch has poor solubility in DMF, so the film sample has poor transparency.

Example 2

10g of-NCO-terminated poly (L-lactide) (number average molecular weight 2000g/mol) and 7.04g of chitosan (molecular weight 2800g/mol, degree of deacetylation 92%) (-NCO and-NH)₂Dissolving the materials in 25mL of N, N-Dimethylformamide (DMF) at 5 ℃, heating to 20 ℃, reacting under stirring until an infrared detection-NCO characteristic absorption peak disappears, adding a DMF dispersion (12.5g of oxidized starch (with the aldehyde group content of 1.2mmol/g) to disperse in 60mL of DMF, reacting under stirring until the solution becomes viscous (about 15min), stopping stirring, removing dissolved gas under reduced pressure, slowly pouring the solution into a mold, standing at 40 ℃ to volatilize the solvent to form a film (about 60h), and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified starch oxide film M2.

Example 3

7.5g of an-NCO-terminated poly (. epsilon. -caprolactone) (number-average molecular weight 1500g/mol) and 7.04g of chitosan (molecular weight 2800g/mol, degree of deacetylation 92%) (-NCO and-NH)₂The molar ratio is 1:4), dissolving in 20mL of N, N-Dimethylformamide (DMF) at 5 ℃, heating to 20 ℃, reacting under stirring until an infrared detection-NCO characteristic absorption peak disappears (about 1.5h), adding a DMF dispersion (13.6g of oxidized starch (with the aldehyde group content of 1.1mmol/g) and dispersing in 65mL of DMF, reacting under stirring until the solution becomes viscous (about 18min), stopping stirring, slowly pouring into a mold after removing the dissolved gas under reduced pressure, standing at 40 ℃ to volatilize the solvent to form a film (about 60h), and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified oxidized starch film M3.

Example 4

10g of an-NCO-terminated poly (. epsilon. -caprolactone) (number-average molecular weight 2000g/mol) were reacted with 10.6g of chitosan (E)Molecular weight 2800g/mol, degree of deacetylation 92%) (-NCO and-NH₂The molar ratio is 1:6) is dissolved in 20mL of N, N-Dimethylformamide (DMF) at 5 ℃, the temperature is raised to 20 ℃, the reaction is carried out under stirring until an infrared detection-NCO characteristic absorption peak disappears (about 1.5h), 20.8g of DMF dispersion liquid of oxidized starch (with the aldehyde group content of 1.2mmol/g) is added and dispersed in 100mL of DMF, the reaction is carried out under stirring until the solution becomes viscous (about 13min), the stirring is stopped, the dissolved gas is removed under reduced pressure, the mixture is slowly poured into a mold, the mixture is kept stand at 40 ℃ to volatilize the solvent to form a film (about 78h), and finally, the film material is dried under reduced pressure to constant weight, thus obtaining the chitosan poly (ester-urethane) modified oxidized starch film M4.

Test example:

mechanical properties: the breaking strength and breaking elongation of the film were measured using HY939C model computer type single column tensile tester from Steady apparatus, Inc., of Dongguan, Guangdong, with a tensile rate of 10 mm/min.

Antibacterial property: the film samples were cut into 5mm by 5mm sections and sterilized by irradiation. An overnight culture obtained from a single colony of E.coli was used and cultured in agar medium. Each culture solution (1mL) was inoculated into 9mL of PBS to give a concentration of 3X 10⁵～5×10⁵Colony forming units (CFUs/mL). With a concentration of 3X 10⁵～5×10⁵The bacteriostatic tests were carried out on bacterial solutions of CFUs/mL in a 10cm diameter petri dish.

Degradation performance: the degradation performance of the material is evaluated by testing the tensile strength of the material at different stages. The membrane material was immersed in physiological saline at 37 ℃ and measured for 1 day as a cycle, and when the tensile strength was zero, the degradation was considered complete.

Cytotoxicity: the determination is carried out according to the national standard GB/T-16886 by the MTT method.

TABLE 1 Properties of samples prepared in examples 1-4

Film sample	Breaking strength/MPa	Elongation at break/%	Degradation time/day	Diameter/mm of bacteriostatic circle	Level of cytotoxicity
						M1	7.8	180	8.2	36	Level 1
M2	7.9	185	8	37	Level 1
						M3	8.4	170	6.5	42	Level 0
M4	6.5	268	4.5	53	Level 0

The test results are shown in table 1. As can be seen from the properties of the film samples in table 1, since the material has a double cross-linked structure, the film material has good breaking strength and elongation at break, and M1 is compared with M4, as the degree of cross-linking (the greater the NCO content, the greater the degree of cross-linking) in the material increases, the breaking strength of the film material increases, and the elongation at break decreases. The polyester segment, the starch segment and the chitosan segment in the material have biodegradability, so that the material has degradability, and degradation products are nontoxic and absorbable, wherein the larger the crosslinking degree of M1 is compared with that of M4, the smaller the degradation rate (the longer the degradation time) is, and the larger the ester bond content of M1 is, the lower the degradation rate (the longer the degradation time) is compared with that of M1 and M3.

As the material has unreacted primary amino group, the material has certain broad-spectrum antibacterial performance, and escherichia coli inhibition zone experiments show (as shown in figure 2) that the antibacterial capacity of the material is enhanced along with the increase of the content of the primary amino group in the material.

The cytotoxicity experiment shows that the cytotoxicity of the membrane material prepared in the embodiment 1-4 is 0-1 grade, the requirement of the material implanted in vivo is met, and the material contains polysaccharide structures such as starch and chitosan, so that the material can provide nutrition for cell proliferation, and has excellent cell compatibility.

Claims

1. A preparation method of double-crosslinked chitosan poly (ester-urethane) modified oxidized starch is characterized by comprising the following steps:

2) adding oxidized starch dispersion, reacting while stirring until the solution becomes viscous, stopping stirring, and removing dissolved gas under pressure;

2. The method according to claim 1, wherein the organic solvent is N, N-dimethylformamide.

3. The method of claim 2, comprising the steps of:

1) dissolving-NCO end-capped polyester and chitosan in N, N-dimethylformamide, heating to 18-25 ℃ under stirring, and reacting until the reaction is complete;

2) adding N, N-dimethylformamide dispersion of oxidized starch, reacting at normal temperature under stirring until the solution becomes viscous, stopping stirring, and removing dissolved gas under pressure;

3) slowly pouring the chitosan poly (ester-urethane) modified starch film material into a mold, standing to volatilize the solvent into a film, and finally drying the film material under reduced pressure to constant weight to obtain the chitosan poly (ester-urethane) modified starch oxide film material.

4. The process according to claim 3, wherein the-NCO-terminated polyester is prepared from a polyester diol and a diisocyanate; the polyester diol is poly (epsilon-caprolactone), poly (L-lactide) or polydioxanone, and the number average molecular weight is 1500-4500 g/mol; the diisocyanate is L-lysine diisocyanate.

5. The method according to claim 3, wherein the reaction mixture,

the molecular weight of the chitosan is 2000-3000 g/mol, the deacetylation degree is more than 90%, and the ignition residue is less than 0.3%;

the content of aldehyde groups in the oxidized starch is 0.9-1.5 mmol/g.

6. The method according to claim 3, wherein the reaction mixture,

the concentration of the total dosage of the-NCO end-capped polyester and the chitosan in DMF is 0.5-1.0 g/mL;

the feeding ratio of the-NCO end capping polyester to the chitosan is-NCO and-NH₂The molar ratio of the groups is 1: 4-1: 6;

the reaction end point of the-NCO end-capped polyester and the chitosan is infrared detection, and an NCO characteristic absorption peak disappears.

7. The method according to claim 3, wherein the reaction mixture,

the addition amount of the oxidized starch is that aldehyde groups in the oxidized starch are-NH remained at the end point of the reaction in the step 1)₂45-55% of the mole number of the groups;

the mass content of the oxidized starch in the final product is 40-55%;

the N, N-dimethylformamide dispersion liquid of the oxidized starch is obtained by ultrasonically dispersing the oxidized starch in N, N-dimethylformamide, wherein the concentration of the N, N-dimethylformamide dispersion liquid is 1-2.5 g/10 mL.

8. A chitosan poly (ester-urethane) modified oxidized starch prepared by the preparation method of any one of claims 1 to 7.

9. Use of the chitosan poly (ester-urethane) modified oxidized starch of claim 8 in the manufacture of packaging materials for various tableware, direct contact food.

10. Use of the chitosan poly (ester-urethane) modified oxidized starch of claim 8 in the manufacture of an in vivo implantable medical material.