CN112904590B

CN112904590B - Natamycin nanoparticle-loaded contact lens and preparation method thereof

Info

Publication number: CN112904590B
Application number: CN202110093319.3A
Authority: CN
Inventors: 张维芬; 关秀文; 马金龙; 张竞竞; 崔晓明
Original assignee: Weifang Medical University
Current assignee: Weifang Medical University
Priority date: 2021-01-25
Filing date: 2021-01-25
Publication date: 2022-10-11
Anticipated expiration: 2041-01-25
Also published as: CN112904590A

Abstract

The invention relates to the technical field of natamycin new dosage forms (pharmaceutical preparations), and provides a natamycin nanoparticle loaded contact lens and a preparation method thereof. The novel natamycin dosage form provided by the invention is a natamycin nanoparticle loaded contact lens, and the natamycin nanoparticle is prepared by using chitosan as a carrier material through a uniaxial electrostatic spraying method; raw materials for preparing the nanoparticle-loaded contact lens comprise gamma- (methacryloyloxy) propyltrimethylsilane, hydroxyethyl methacrylate, polyvinyl alcohol, polyacrylamide, a cross-linking agent, an initiator and natamycin nanoparticles. The natamycin nano particles are loaded in the contact lens, when the symptom of fungal infection keratitis appears, the contact lens is worn for treatment, the defect that dosage forms such as eyedrops or eye ointments are used for non-continuous administration according to times can be overcome, the problem that frequent administration is needed is solved, the compliance of patients is improved, and the risk of eye vision loss is reduced.

Description

Natamycin nanoparticle-loaded contact lens and preparation method thereof

Technical Field

The invention relates to the technical field of natamycin new dosage forms (pharmaceutical preparations), in particular to a natamycin nanoparticle loaded contact lens and a preparation method thereof.

Background

Fungi do not normally infect the normal cornea, but excessive use of broad-spectrum antibiotics and steroids can cause imbalance in the microbial balance on the corneal surface, resulting in the invasion of pathogens into ocular tissues, in ocular trauma, in ocular surgery and in dry eye. In addition, in the field environment, particularly in temperate and tropical climates, soil and plant residues (often rich in fusarium) are susceptible to ocular damage and thus fungal infection. Fungal keratitis is a suppurative corneal ulcer, has slow onset and long course of disease, and can cause serious complications such as corneal perforation, blindness and the like if the fungal keratitis cannot be diagnosed and treated in time.

Natamycin is a polyene macrolide drug, has low toxicity and good effect on fungi, is considered as the first choice drug for treating the fungal keratitis, and is the only antifungal drug approved by the Food and Drug Administration (FDA) for treating the filamentous fungal keratitis. Its mechanism of action is to inhibit ergosterol biosynthesis by binding with ergosterol of the fungal cell wall, thereby distorting the cell membrane and eventually causing leakage, causing cell death and preventing fungal growth. However, the low solubility of the drug in water seriously hinders the application of the drug in antifungal field.

At present, the commercialized formulation of natamycin only contains suspension, the formulation and dosage scheme is to mix 5% (w/v) suspension, the suspension has short retention time in eyes, and needs to be infused into conjunctival sac every 1-2 h, the therapy can be completely relieved only by maintaining for 4-6 weeks, because the administration frequency is high, the treatment period is long, the compliance of patients is reduced, and the administration according to the advice can further cause the disease to be difficult to cure for a long time, even cause corneal perforation to cause blindness, and need surgical treatment.

Disclosure of Invention

In view of this, the invention provides a natamycin nanoparticle loaded contact lens and a preparation method thereof. The contact lens provided by the invention can stably maintain the stable release of natamycin nanoparticles, reduce the administration frequency, overcome the problem of non-continuous administration of dosage forms such as eye drops or eye ointments according to times, solve the problem of frequent administration, improve the compliance of patients and reduce the risk of eye vision loss.

In order to achieve the above object, the present invention provides the following technical solutions:

a natamycin nanoparticle-loaded contact lens is prepared from the following components in percentage by mass: 5 to 10 percent of gamma- (methacryloyloxy) propyltrimethylsilane, 60 to 80 percent of hydroxyethyl methacrylate, 6 to 20 percent of polyvinyl alcohol, 1 to 10 percent of polyacrylamide, 0.1 to 0.8 percent of cross-linking agent, 0.5 to 2 percent of initiator and 5 to 10 percent of natamycin nano-particles;

the natamycin nanoparticles are prepared by using chitosan as a carrier material through a uniaxial electrostatic spraying method.

Preferably, the crosslinking agent is one or more of N, N' -methylene bisacrylamide, divinylbenzene, diisocyanate, ethylene glycol diacrylate and vinyl acetate; the initiator is one or more of azobisisobutyronitrile, azobisisoheptonitrile and dimethyl azobisisobutyrate.

Preferably, the natamycin nanoparticles are prepared from the following components in percentage by mass: 76 to 98 percent of chitosan and 2 to 24 percent of natamycin.

Preferably, the chitosan has a number average molecular weight of 12 to 120 ten thousand.

Preferably, the preparation method of the natamycin nanoparticle comprises the following steps:

mixing a chitosan solution and a natamycin solution, carrying out uniaxial electrostatic spraying on the obtained mixed solution, and freeze-drying the obtained product liquid to obtain natamycin nanoparticles; wherein the solvent of the chitosan solution is 0.5 to 1 weight percent of acetic acid solution, and the solvent of the natamycin solution is 0.5 to 5 weight percent of acetic acid solution

Preferably, the concentration of chitosan in the chitosan solution is 1-20 mg/mL, and the pH value of the chitosan solution is 5.5-6.5; the concentration of the natamycin solution is 1-5.7 mg/mL.

Preferably, the parameters of the uniaxial electrostatic spraying include: the voltage is 6.5-12.5 kV, the receiving distance is 6-10 cm, and the injection speed is 0.1-1 mm/min.

The invention also provides a preparation method of the natamycin nanoparticle loaded contact lens, which comprises the following steps:

(1) Mixing gamma- (methacryloyloxy) propyltrimethylsilane, hydroxyethyl methacrylate, polyvinyl alcohol, polyacrylamide, a cross-linking agent and an initiator to obtain a mixed solution;

(2) Dispersing natamycin nanoparticles in water, mixing the obtained natamycin nanoparticle dispersion liquid with the mixed solution, and then carrying out a crosslinking reaction to obtain the natamycin nanoparticle loaded contact lens.

Preferably, the temperature of the crosslinking reaction is 60-150 ℃ and the time is 20-60 min.

Has the advantages that:

(1) According to the invention, natamycin nanoparticles are prepared by a uniaxial electrostatic spraying technology, the electrostatic spraying technology is a nanoparticle preparation technology which gradually approaches to maturity, the preparation steps are simple, the accuracy is high, the production can be scaled, and the difference between batches is small, so that the method is very suitable for industrial processing; the chitosan natamycin-loaded nanoparticles prepared by the uniaxial electrostatic spraying method are respectively subjected to data determination such as potential, transmission electron microscope, fourier infrared analysis, in-vitro release and bacteriostasis, and feasible basis is provided for the form, slow release characteristic and antifungal characteristic of the nanoparticles.

(2) According to the invention, chitosan is used as a carrier material to carry out coating and loading on natamycin, and the chitosan which is a natural material carries positive charge characteristics, so that natamycin nanoparticles are more easily combined with cell membranes carrying negative charges, the binding force between cells is enhanced, the killing effect of medicines on fungal cells is enhanced, the bioavailability of the medicines is improved, and the waste of the medicines is reduced.

(3) The natamycin nano particles are loaded in the contact lens, the contact lens is used as a carrier of the nano particles, and the nano particles are loaded in the contact lens, so that the method has the following two advantages: firstly, nanoparticles are fixed, and the effect of the nanoparticles for slowly releasing the medicine is stably maintained; the daily medication frequency is reduced, a treatment mode of taking the medicine once in 1-2 h in the traditional treatment method is not required, the burden and the pressure of medication of a patient are reduced, and the patient can completely work and live normally; when the symptom of fungal keratitis appears, the defect that the dosage forms such as eye drops or eye ointments must be applied non-continuously according to times when the contact lenses are worn for treatment can be overcome, the problem that normal work and life are influenced due to frequent application of medicines can be solved by directly wearing the tacrolimus nanoparticle contact lenses, the compliance of patients is improved, and the risk of visual loss of the eyes is reduced.

(4) The natamycin new dosage form is natamycin nanoparticle-loaded contact lenses, compared with the original medicine, the natamycin nanoparticle antibacterial activity is obviously improved, the treatment effect can be enhanced, the natamycin nanoparticle preparation is not only suitable for treating fungal keratitis, but also provides a new medicine application idea for treating other eye diseases; the traditional natamycin suspension has the defects of high medication frequency, low bioavailability of the medicine, influence on the medicine effect exertion of the medicine due to indissolvable medicine, long treatment period and the like; the new formulation of natamycin according to the invention solves the disadvantages mentioned for the suspension.

(5) The invention also provides a preparation method of the natamycin nanoparticle loaded contact lens, which has the advantages of simple steps, easy operation and easy large-scale production.

Drawings

FIG. 1 is a transmission electron microscope photograph of natamycin nanoparticles prepared in example 1;

FIG. 2 is Zeta potential of natamycin nanoparticles (NAT @ CTS NPs) prepared in example 1;

FIG. 3 is a spectrum of infrared characteristic peaks of Chitosan (CTS), natamycin (NAT) and natamycin nanoparticles (NAT @ CTS NPs) prepared in example 1;

FIG. 4 shows the results of the antibiotic activity test of natamycin nanoparticles, nanoparticles and natamycin prepared in example 1 against Candida albicans;

FIG. 5 is an in vitro release profile of natamycin nanoparticles (NAT @ CTS NPs) prepared in example 1 and free Natamycin (NAT).

Detailed Description

The invention provides a natamycin nanoparticle loaded contact lens, which is prepared from the following components in percentage by mass: 5-10% of gamma- (methacryloyloxy) propyltrimethylsilane, 60-80% of hydroxyethyl methacrylate, 6-20% of polyvinyl alcohol, 1-10% of polyacrylamide, 0.1-0.8% of cross-linking agent, 0.5-2% of initiator and 5-10% of natamycin nanoparticles, and the nano-particles are preferably prepared from the following components in percentage by mass: 5% of gamma- (methacryloyloxy) propyltrimethylsilane, 65% of hydroxyethyl methacrylate, 15% of polyvinyl alcohol, 5% of polyacrylamide, 0.5% of a cross-linking agent, 0.5% of an initiator and 9% of natamycin nanoparticles.

In the present invention, the γ - (methacryloyloxy) propyltrimethylsilane can improve the mechanical and light transmission properties of the contact lens; the hydroxyethyl methacrylate has water absorption and gel property, and is a main material for forming the contact lens with optical transparency and stable structure; the polyvinyl alcohol and the polyacrylamide have the effects of hydrophilicity, oxygen permeability and precipitation resistance, and can improve the hydrophilicity of the lens.

In the invention, the crosslinking agent is preferably one or more of N, N' -methylene bisacrylamide, divinylbenzene, diisocyanate, glycol diacrylate and vinyl acetate; the initiator is preferably one or more of azobisisobutyronitrile, azobisisoheptonitrile and dimethyl azobisisobutyrate.

In the invention, the natamycin nanoparticles are prepared by taking Chitosan (CTS) as a carrier material and Natamycin (NAT) as a model drug through a single-axis electrostatic spraying technology.

In the invention, the natamycin nanoparticles are preferably prepared from the following components in percentage by mass: 76-98% of chitosan and 2-24% of natamycin, and the natamycin is more preferably prepared from the following components in percentage by mass: 82% of chitosan and 18% of natamycin. In the present invention, the number average molecular weight of the chitosan is preferably 12 to 120 ten thousand, and preferably 20 to 40 ten thousand. In the invention, the mass fraction of natamycin in the natamycin nanoparticles prepared by feeding the natamycin according to the mass percentage is preferably 4.02-10%.

In the invention, the preparation method of the natamycin nanoparticles comprises the following steps:

mixing the chitosan solution and the natamycin solution, carrying out uniaxial electrostatic spraying on the obtained mixed solution, and freeze-drying the obtained product liquid to obtain the natamycin nanoparticles.

In the invention, the solvent of the chitosan solution is preferably 0.5-1 wt% acetic acid solution, the invention uses acetic acid to promote the dissolution of chitosan, and the invention preferably adds chitosan into 0.5-1 wt% acetic acid solution, and then magnetically stirs for 4h at room temperature to obtain the chitosan solution. In the present invention, the concentration of the chitosan solution is preferably 1 to 20mg/mL, more preferably 5 to 15mg/mL; the pH value of the chitosan solution is preferably 5.5-6.5, and more preferably 5.5-6; according to the invention, preferably, after the chitosan is completely dissolved, the pH value of the solution is adjusted to 5.5-6.5 by using ammonia water; the invention controls the pH value of the chitosan solution to be 5.5-6.5, can fully dissolve the chitosan and the natamycin, does not destroy the drug effect of the drug, and is beneficial to forming the nanoparticles which exist stably and have uniform particle size distribution.

In the present invention, the solvent of the natamycin solution is preferably 0.5 to 5wt% acetic acid solution; the concentration of the natamycin solution is preferably 1 to 5.7mg/mL, more preferably 2 to 4mg/mL.

In the present invention, the parameters of the uniaxial electrostatic spraying preferably include: the voltage is 6.5-12.5 kV, preferably 7-12 kV, the receiving distance is 6-10 cm, preferably 7-9 cm, and the injection speed is 0.1-1 mm/min, preferably 0.3-0.6 mm/min.

Preferably, chitosan solution and natamycin solution are mixed, then the obtained mixed solution is filled into a disposable sterile injector and is connected with a single-shaft electrostatic spraying needle, electrostatic spraying is carried out after parameters are set, and freeze drying is carried out after the obtained product liquid is dialyzed, so that natamycin nano-particles are obtained; in the present invention, the temperature of the reaction is preferably room temperature.

In the present invention, the temperature of the freeze-drying is preferably-40 ℃ and the time is preferably 24 hours.

Mixing gamma- (methacryloyloxy) propyltrimethylsilane, hydroxyethyl methacrylate, polyvinyl alcohol, polyacrylamide, a cross-linking agent and an initiator to obtain a mixed solution; in the invention, the gamma- (methacryloyloxy) propyltrimethylsilane, hydroxyethyl methacrylate, polyvinyl alcohol, polyacrylamide, a cross-linking agent and an initiator are preferably mixed and then stirred magnetically for 30min to obtain a mixed solution.

After the mixed solution is obtained, the natamycin nano-particles are dispersed in water, and the natamycin nano-particle dispersion liquid and the mixed solution are mixed and then subjected to a crosslinking reaction to obtain the natamycin nano-particle loaded contact lens. The natamycin nanoparticle dispersion liquid has no special requirement on the concentration of the natamycin nanoparticle dispersion liquid, natamycin nanoparticles can be completely dispersed, and the using amount of the natamycin nanoparticles meets the mass fraction in the scheme.

The natamycin nanoparticle dispersion liquid and the mixed liquid are preferably mixed and then stirred for 30min at room temperature, and then the stirred liquid is poured into a mould for crosslinking reaction; the temperature of the crosslinking reaction is preferably 60-150 ℃, more preferably 80 ℃, and the time is preferably 20-60 min, more preferably 50min; the crosslinking reaction is preferably carried out under the condition of constant-temperature water bath; the present invention has no particular requirements for the mold, and may be used with molds commonly used in the art for making contact lenses.

The natamycin-loaded contact lens provided by the invention can be used for treating fungal keratitis, and is preferably worn when fungal infection symptoms of cornea appear, the wearing time of each lens is preferably 20h, and the lens is worn until the symptoms are completely relieved. The natamycin-loaded contact lens for treating fungal keratitis can overcome the non-continuity of using natamycin suspension for eye administration, eye drops or eye ointments are dropped into eyes for several times, and the natamycin-loaded contact lens can be directly worn, so that the problem that the traditional dosage form needs frequent administration in the daytime can be solved, the compliance of patients is improved, and the risk of eye vision loss is reduced.

The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. It should be apparent that the described embodiments are only some embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

(1) Preparation of natamycin nanoparticles:

the natamycin nanoparticles are prepared from the following components in percentage by mass: 82% of chitosan (with the molecular weight of 12-120 ten thousand) and 18% of natamycin; the preparation steps are as follows:

adding chitosan into 1% acetic acid solution, and stirring the solution overnight at room temperature by using a magnetic stirrer to obtain chitosan solution with the concentration of 10 mg/mL; dissolving natamycin in 1% acetic acid water solution to obtain natamycin solution with the concentration of 1 mg/mL;

adjusting the pH value of a chitosan solution to 5.5, adding a natamycin solution into the chitosan solution with the pH value adjusted, then filling the obtained mixed solution into a disposable sterile injector at room temperature, connecting a single-shaft electrostatic spraying needle head, carrying out electrostatic spraying after setting parameters, dialyzing the obtained product liquid, and carrying out freeze drying to obtain natamycin nanoparticles, which are marked as NAT @ CTS NPs; wherein the parameters of the uniaxial electrostatic spraying are voltage of 7.8kV, receiving distance of 8cm and pushing speed of 0.5mm/min.

(2) Preparation of natamycin nanoparticle loaded contact lenses:

the natamycin nanoparticle-loaded contact lens is prepared from the following components in percentage by mass: 5% of gamma- (methacryloyloxy) propyltrimethylsilane, 65% of hydroxyethyl methacrylate, 15% of polyvinyl alcohol, 5% of polyacrylamide, 0.5% of N, N' -methylene bisacrylamide, 0.5% of azobisisobutyronitrile and 9% of natamycin nano-particles prepared in the step (1). The preparation steps are as follows: mixing gamma- (methacryloyloxy) propyltrimethylsilane, hydroxyethyl methacrylate, polyvinyl alcohol, polyacrylamide, N' -methylenebisacrylamide and azobisisobutyronitrile to obtain a mixed solution; dispersing natamycin nanoparticles in water, mixing the obtained natamycin nanoparticle solution with the mixed solution, and carrying out crosslinking reaction for 50min at the temperature of 80 ℃ to obtain the natamycin nanoparticle-loaded contact lens.

FIG. 1 is a transmission electron microscope photograph of the resulting natamycin nanoparticles. As can be seen from FIG. 1, the natamycin nanoparticles prepared by this example have uniform particle size and good dispersibility, the particle size being 90-100 nm.

Fig. 2 shows the Zeta potential of natamycin nanoparticles (nat @ cts NPs), and the positive potential of +26.2mV indicates that the nanoparticles have excellent stability, and since the cell surface carries negative charges, the positively charged nanoparticles are more easily adsorbed on the cells to kill and kill fungi, thereby improving the bioavailability of the drug, and enhancing the curative effect of the preparation and the toxic and side effects of the drug on the whole body.

FIG. 3 is an infrared characteristic peak spectrum of Chitosan (CTS), natamycin (NAT) and natamycin nanoparticles (NAT @ CTS NPs); as can be seen from FIG. 3, the infrared characteristic peaks of chitosan and natamycin appeared simultaneously in the infrared characteristic curve of the natamycin nanoparticles, indicating that natamycin was successfully loaded into the nanoparticles.

And (3) testing antibacterial activity:

preparing blank nanoparticles: the other conditions were the same as in example 1, step (1), except that no natamycin was added, to obtain Blank nanoparticles, which were designated Blank-NPs.

The natamycin nanoparticles, the blank nanoparticles and the natamycin are respectively dissolved in PBS solution with pH =7.4 to prepare natamycin nanoparticle solution and blank nanoparticle solution with the nanoparticle concentration of 1mg/mL, wherein the concentration of the natamycin in the natamycin nanoparticle solution is 71 mug/mL, and the concentration of the natamycin in the natamycin solution is 71 mug/mL.

Co-culturing Candida albicans and sterilized liquid Sabouraud's medium at 37 deg.C for 24 hr, and diluting with fresh medium to 10% ⁶ CFU/mL. Pouring the sterilized solid Sabouraud's medium into a disposable culture dish, solidifying the medium at room temperature, uniformly coating 0.5mL of diluted Candida albicans, and placing sterilized filter paper with diameter of 6mmPlaced in the center of a culture plate containing Candida albicans, and then 8. Mu.L of the sample (i.e., natamycin nanoparticle solution, blank nanoparticle solution and natamycin solution) was added to the filter paper. In order to guarantee the growth of the fungi and the diffusion time of the preparation, all the culture dishes are placed in a constant temperature incubator at 37 ℃ for 24 hours, and the growth condition of the candida albicans is observed.

FIG. 4 shows the results of the antibiotic activity test of natamycin nanoparticles against Candida albicans, wherein NAT-NPs indicate natamycin nanoparticles. According to fig. 4, it can be seen that the diameter of the zone of inhibition of the natamycin nanoparticle group is significantly increased compared to natamycin and the blank nanoparticle group, and it can be considered that the natamycin-loaded nanoparticle has a good inhibitory effect on the activity of pathogenic fungi.

And (3) testing the slow release property:

NAT @ CTS NPs prepared in example 1 and free NAT were subjected to in vitro release test in dissolution medium PBS buffer (pH 7.4) at 37 deg.C, specifically: NAT @ CTS NPs and free NAT were dissolved in PBS and dialysis was performed for 48 h. Then 2mL of NAT @ CTS NPs and NAT were immersed in 48mL of PBS buffer dialysis tube at 37 ℃ and 100rpm, respectively, and 1mL of the solution was taken out at a predetermined time point and an equal amount of PBS buffer was immediately added. The cumulative released dose of natamycin was determined by HPLC method.

FIG. 5 is an in vitro release profile of NAT @ CTS NPs and free NAT prepared in example 1. As can be seen from FIG. 5, the natamycin nanoparticles prepared by the invention have excellent sustained release property compared with free natamycin, and can be released for 20h continuously.

Example 2

The other conditions were identical to those of example 1, except that the amounts of the components of the natamycin nanoparticles were changed to: 90 percent of chitosan (with the molecular weight of 12-120 ten thousand) and 10 percent of natamycin.

The usage of the components of the natamycin nanoparticle-loaded contact lens is changed into that: 6% of gamma- (methacryloyloxy) propyltrimethylsilane, 70% of hydroxyethyl methacrylate, 12% of polyvinyl alcohol, 5% of polyacrylic acid, 0.5% of N, N' -methylene bisacrylamide, 0.5% of azobisisobutyronitrile and 6% of natamycin nanoparticles.

The natamycin nanoparticles prepared were tested for antibacterial activity and in vitro release according to the method of example 1, and the results were similar to example 1.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. A preparation method of a natamycin nanoparticle-loaded contact lens is characterized by comprising the following components in percentage by mass: 5 to 10 percent of gamma- (methacryloyloxy) propyl trimethyl silane, 60 to 80 percent of hydroxyethyl methacrylate, 6 to 20 percent of polyvinyl alcohol, 1 to 10 percent of polyacrylamide, 0.1 to 0.8 percent of cross-linking agent, 0.5 to 2 percent of initiator and 5 to 10 percent of natamycin nano-particles;

the natamycin nanoparticles are prepared by using chitosan as a carrier material through a uniaxial electrostatic spraying method;

the preparation method of the natamycin nanoparticles comprises the following steps:

mixing a chitosan solution and a natamycin solution, carrying out uniaxial electrostatic spraying on the obtained mixed solution, and freeze-drying the obtained product liquid to obtain natamycin nanoparticles; wherein the solvent of the chitosan solution is 0.5 to 1wt% of acetic acid solution, and the solvent of the natamycin solution is 0.5 to 5wt% of acetic acid solution; the concentration of chitosan in the chitosan solution is 1-20mg/mL, and the pH value of the chitosan solution is 5.5-6.5; the concentration of the natamycin solution is 1 to 5.7mg/mL;

the preparation method of the natamycin nanoparticle-loaded contact lens comprises the following steps:

2. The preparation method according to claim 1, wherein the crosslinking agent is one or more of N, N' -methylenebisacrylamide, divinylbenzene, diisocyanate, ethylene glycol diacrylate and vinyl acetate; the initiator is one or more of azobisisobutyronitrile, azobisisoheptonitrile and dimethyl azobisisobutyrate.

3. The preparation method according to claim 1, characterized in that the natamycin nanoparticles are prepared from the following components in percentage by mass: 76 to 98 percent of chitosan and 2 to 24 percent of natamycin.

4. The production method according to claim 1 or 3, wherein the chitosan has a number average molecular weight of 12 to 120 ten thousand.

5. The method of claim 1, wherein the parameters of the uniaxial electrostatic spraying include: the voltage is 6.5 to 12.5kV, the receiving distance is 6 to 10cm, and the pushing speed is 0.1 to 1mm/min.

6. The method for preparing the polyurethane foam material according to claim 1, wherein the temperature of the crosslinking reaction is 60 to 150 ℃ and the time is 20 to 60min.