CN112646082B

CN112646082B - Acrylate polymer microsphere aggregate and preparation method thereof

Info

Publication number: CN112646082B
Application number: CN201910959498.7A
Authority: CN
Inventors: 陈忠; 项炜
Original assignee: Individual
Current assignee: Individual
Priority date: 2019-10-10
Filing date: 2019-10-10
Publication date: 2023-06-23
Anticipated expiration: 2039-10-10
Also published as: CN112646082A

Abstract

The invention provides an acrylic polymer microsphere with capillary action, which has a core-shell structure, and the hydrophilicity of a core layer is stronger than that of a shell layer. The invention also provides a method for preparing the acrylic polymer microsphere, which ensures that the acrylic polymer microsphere has different hydrophilic properties by adjusting the monomer composition and the proportion of a core layer and a shell layer; the pH value is regulated to ensure that the linear polymer of the core layer is spread and forms an interpenetrating network structure with the crosslinked polymer of the shell layer; adding a cross-linking agent to react with the core layer linear polymer to form a stable polymer interpenetrating network structure; upon drying, the microporous channels left by the loss of water from the interior of the microspheres are stabilized by the presence of the crosslinked network. The acrylate polymer microsphere aggregates of the present invention may be used as dressings.

Description

Acrylate polymer microsphere aggregate and preparation method thereof

Technical Field

The invention belongs to the field of medical materials, and particularly relates to an acrylate polymer microsphere aggregate powder dressing with capillary action.

Background

Medical dressings are medical materials used to cover sores, wounds, or other lesions. Along with the deep research on pathophysiology of the wound healing process, people understand the wound healing process more and more deeply, so that the medical wound dressing is continuously improved and developed.

Natural gauze is the earliest and most widely used dressing type. But has too high permeability, and is easy to dehydrate the wound surface; sticking to the wound surface, and causing mechanical damage again during replacement; the microorganisms in the external environment are easy to pass through, and the probability of cross infection is high; the dosage is large, the replacement is frequent and time-consuming, and the patients are painful.

Synthetic fiber dressings have the same advantages as gauze, such as economy, good absorption properties, etc., and some products also have self-adhesiveness, making them very convenient to use. However, such products also have the same disadvantages as gauze, such as high permeability, no barrier to particulate contaminants of the external environment, etc.

The dressing is an advanced dressing, and has the characteristics that gases such as oxygen, water vapor and the like can freely permeate, and particulate foreign matters such as dust, microorganisms and the like in the environment cannot pass through. However, the dressing has the defects of poor liquid seepage absorbing capacity, relatively high cost, large opportunity for impregnating skin around the wound surface and the like, so the dressing is mainly applied to the wound surface which is not much exuded after operation or used as an auxiliary dressing of other dressings.

The foaming polymer dressing is a dressing formed by foaming a high polymer material (PU), and the surface of the dressing is often covered with a layer of polymeric semipermeable membrane, and some of the dressing also has self-adhesion. However, the wound surface has stronger absorption performance, and the wound surface with low exudation can influence the debridement process; the cost is relatively high; the defects of opaque and inconvenient observation of wound surface and the like are overcome.

The main component of the hydrocolloid dressing is a hydrocolloid-sodium carboxymethyl cellulose (CMC) with very strong hydrophilic capacity, and the hydrocolloid-sodium carboxymethyl cellulose and the low-allergic medical adhesive are added with an elastomer, a plasticizer and the like to form a dressing main body. The surface of the hydrocolloid dressing is a layer of semi-permeable polymeric membrane structure. After the dressing is contacted with wound exudate, the dressing can absorb the exudate and form gel, so that the adhesion of the dressing and the wound is avoided; at the same time, the semi-permeable membrane structure on the surface can allow oxygen and water vapor to exchange, but has barrier property to external particulate foreign matters such as dust and bacteria. However, it has a less strong absorption capacity, so for a highly exudative wound, it is often necessary to use other auxiliary dressings to enhance the absorption capacity; the product cost is high; individual patients may suffer from allergic to the ingredients, etc.

Alginate dressing is one of the most advanced medical dressings at present. The main component of alginate dressing is alginate, which is natural polysaccharide carbohydrate extracted from seaweed and is a natural cellulose. An alginate medical dressing is a functional wound dressing with high absorption performance, which consists of alginate. After the medical film is contacted with wound exudates, soft gel can be formed, an ideal moist environment is provided for wound healing, the wound healing is promoted, and the wound pain is relieved.

The various natural or synthetic dressings described above have some unavoidable drawbacks. Thus, there remains a need in the art for a medical dressing that has a combination of superior properties.

Disclosure of Invention

Aiming at the defects of the existing dressing, the invention adopts the molecular design and the principle of molecular engineering to design a synthetic path, so that the final product has stronger absorption performance, can form soft gel, provides ideal moist environment for wound healing, promotes wound healing, relieves wound pain, is not adhered to a wound surface, is permeable and breathable, and can well block external environment particulate pollutants.

Specifically, the invention provides an acrylic polymer microsphere which has a core-shell structure, and the polymer contained in the core layer of the acrylic polymer microsphere has stronger hydrophilicity than the polymer contained in the shell layer.

In one or more embodiments, the polymer contained in the core layer and the polymer contained in the shell layer of the acrylate polymer microsphere are intertwined to form an interpenetrating network structure.

In one or more embodiments, the polymer contained in the core layer and the polymer contained in the shell layer of the acrylate polymer microsphere each have a crosslinked structure.

In one or more embodiments, the mass ratio of polymer contained in the core layer to polymer contained in the shell layer of the acrylate polymer microsphere is in the range of 1.5:1 to 1:1.5, preferably in the range of 1.2:1 to 1:1.2, more preferably in the range of 1.1:1 to 1:1.1.

In one or more embodiments, the acrylate polymer microspheres are optionally adsorbed with an adjuvant.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer copolymerized from a first crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylate monomers, and acrylate monomers.

In one or more embodiments, the first crosslinkable monomer is diacetone acrylamide.

In one or more embodiments, the methacrylate-based monomer is selected from the group consisting of hydroxyethyl methacrylate, hydroxypropyl methacrylate, and methyl methacrylate.

In one or more embodiments, the acrylic monomer is selected from the group consisting of hydroxyethyl acrylate, hydroxypropyl acrylate, and methyl acrylate.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or any plurality of monomers selected from methacrylate monomers and acrylate monomers.

In one or more embodiments, the first crosslinkable monomer comprises from 0.5% to 5%, preferably from 0.5% to 3%, of the total weight of the polymer contained in the acrylate polymer microsphere core layer.

In one or more embodiments, the core layer of the acrylate polymer microsphere contains a polymer that is crosslinked via a crosslinking agent.

In one or more embodiments, the crosslinker is adipoyl hydrazine.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylate monomers and acrylate monomers.

In one or more embodiments, the second crosslinkable monomer is ethylene glycol dimethacrylate.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer and one or more monomers selected from the group consisting of methacrylate monomers and acrylate monomers.

In one or more embodiments, the second crosslinkable monomer comprises from 0.5% to 5%, preferably from 1% to 5%, of the total weight of the polymer contained in the acrylate polymer microsphere shell layer.

In one or more embodiments, the total content of methacrylic acid and acrylic acid in the polymer contained in the core layer of the acrylate polymer microsphere is higher than the total content of methacrylic acid and acrylic acid in the polymer contained in the shell layer.

In one or more embodiments, the polymer contained in the core layer of the acrylate polymer microsphere contains methacrylic acid and/or acrylic acid, and the polymer contained in the shell layer of the acrylate polymer microsphere does not contain methacrylic acid and acrylic acid.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methyl methacrylate and methyl acrylate.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer copolymerized from a first crosslinkable monomer, methacrylic acid, and one or two monomers selected from hydroxyethyl methacrylate and hydroxypropyl methacrylate.

In one or more embodiments, the core layer of the acrylate polymer microsphere comprises a polymer derived from the copolymerization of a first crosslinkable monomer, methacrylic acid, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

In one or more embodiments, the total content of methacrylic acid and acrylic acid is 2% to 15%, preferably 4% to 10% of the total weight of the polymer contained in the acrylate polymer microsphere core layer.

In one or more embodiments, the shell layer of the acrylate polymer microsphere contains a polymer obtained by copolymerizing a second crosslinkable monomer, one or two monomers selected from the group consisting of methyl methacrylate and methyl acrylate, and one or more monomers selected from the group consisting of methacrylate monomers other than methyl methacrylate and acrylate monomers other than methyl acrylate.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer, one or two monomers selected from methyl methacrylate and methyl acrylate, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid and acrylic acid.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer, one or two selected from methyl methacrylate and methyl acrylate, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer copolymerized from a second crosslinkable monomer, methyl methacrylate, and one or two monomers selected from hydroxyethyl methacrylate and hydroxypropyl methacrylate.

In one or more embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer derived from the copolymerization of a second crosslinkable monomer, methyl methacrylate, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

In one or more embodiments, the total content of methyl methacrylate and methyl acrylate is from 4% to 30%, preferably from 8% to 20%, of the total weight of polymer contained in the acrylate polymer microsphere core layer.

The present invention also provides an aggregate or aqueous dispersion of acrylate polymer microspheres comprising the acrylate polymer microspheres described in any one of the embodiments of the invention.

In one or more embodiments, the aggregate of acrylate polymer microspheres is obtained from an aqueous dispersion of acrylate microspheres by drying.

In one or more embodiments, the drying is freeze drying.

The invention also provides a method for preparing the acrylic polymer microsphere, which is characterized by comprising the following steps:

(A) Preparing an acrylate polymer microsphere core layer through a first emulsion polymerization step to obtain a core emulsion, wherein the polymer contained in the acrylate polymer microsphere core layer prepared through the first emulsion polymerization step is a linear polymer and contains a crosslinkable group;

Preferably, the monomers used in the first emulsion polymerization include a first crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, preferably include a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from methacrylic acid ester monomers and acrylic acid ester monomers, more preferably include a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl methacrylate, methyl methacrylate and methyl acrylate, and more preferably include a first crosslinkable monomer, methacrylic acid, hydroxyethyl methacrylate and hydroxypropyl methacrylate; preferably, the first crosslinkable monomer is diacetone acrylamide; preferably, the total amount of methacrylic acid and acrylic acid is 2% to 15%, preferably 4% to 10% of the total weight of the monomers used in the first emulsion polymerization step;

(B) Preparing an acrylic polymer microsphere shell layer on the surface of the acrylic polymer microsphere core layer prepared by the emulsion polymerization in the first step through the emulsion polymerization in the second step to obtain core-shell emulsion, wherein the polymer contained in the acrylic polymer microsphere shell layer has a cross-linked structure;

preferably, the monomers used in the second emulsion polymerization include a second crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, preferably include a second crosslinkable monomer and one or more monomers selected from methacrylic acid ester monomers and acrylic acid ester monomers, more preferably include a second crosslinkable monomer, one or two monomers selected from methyl methacrylate and methyl acrylate, and one or more monomers selected from methacrylic acid ester monomers other than methyl methacrylate and acrylic acid ester monomers other than methyl acrylate, more preferably include a second crosslinkable monomer, methyl methacrylate, hydroxyethyl methacrylate and hydroxypropyl methacrylate; preferably, the second crosslinkable monomer is ethylene glycol dimethacrylate; preferably, the total content of methyl methacrylate and methyl acrylate is from 4% to 30%, preferably from 8% to 20%, of the total weight of monomers used in the second emulsion polymerization step; and

(C) The pH value of the core-shell emulsion prepared by the emulsion polymerization in the second step is adjusted to be more than 7, preferably 7-9, and then a cross-linking agent is added for reaction, so that the acrylic ester polymer microsphere is obtained; preferably, the cross-linking agent is adipoyl hydrazine;

preferably, the total amount of methacrylic acid and acrylic acid used in the first emulsion polymerization is higher than the total amount of methacrylic acid and acrylic acid used in the second emulsion polymerization.

In one or more embodiments, the method further comprises: after step (B), before step (C), or after step (C), adding an auxiliary agent to the core-shell emulsion or the aqueous dispersion of acrylate polymer microspheres, such that the auxiliary agent is adsorbed by the acrylate polymer microspheres.

In one or more embodiments, the method has one or more of the following features:

(1) The reaction temperature of the first emulsion polymerization is 50-90 ℃, preferably 65-75 ℃;

(2) The first crosslinkable monomer is used in an amount of from 0.5% to 5%, preferably from 0.5% to 3%, based on the total weight of the monomers used in the first emulsion polymerization stage;

(3) The first emulsion polymerization step uses sodium dodecyl sulfate as an emulsifier and potassium persulfate as an initiator;

(4) The reaction temperature of the second emulsion polymerization is 50-90 ℃, preferably 65-75 ℃;

(5) The second crosslinkable monomer is used in an amount of 0.5% to 5%, preferably 1% to 5%, based on the total weight of monomers used in the second emulsion polymerization step;

(6) The second emulsion polymerization step uses potassium persulfate as an initiator; and

(7) The mass ratio of the monomer used in the first emulsion polymerization to the monomer used in the second emulsion polymerization is in the range of 1.5:1 to 1:1.5, preferably in the range of 1.2:1 to 1:1.2, more preferably in the range of 1.1:1 to 1:1.1.

In one or more embodiments, the acrylate polymer microspheres produced by the method are acrylate polymer microspheres described in any one of the embodiments of the invention.

The invention also provides acrylate polymer microspheres, aqueous dispersions or aggregates thereof prepared by the method described in any one of the embodiments of the invention.

In one or more embodiments, the aggregate of acrylate polymer microspheres is obtained from an aqueous dispersion of acrylate polymer microspheres by drying; preferably, the drying is freeze-drying.

The invention also provides a dressing comprising an aggregate of acrylate polymer microspheres as described in any one of the embodiments of the invention.

Drawings

Fig. 1 to 6 are electron microscopic views of the acrylate polymer microsphere aggregate prepared in example 1, wherein the magnification of fig. 1 and 2 is x 50, the magnification of the method of fig. 3 and 4 is x 100, and the magnification of fig. 5 and 6 is x 500.

FIG. 7 is a graph showing the relationship between the weight loss ratio of water in the film and time after the acrylate polymer microsphere aggregate prepared in example 1 absorbs water to form a film.

FIG. 8 is an infrared spectrum of an acrylic polymer microsphere aggregate prepared in example 1.

FIG. 9 is a graph showing the heat flow curve of the acrylate polymer microsphere aggregate prepared in example 1.

FIG. 10 is a graph showing the particle size distribution of the polymer microsphere aggregates of acrylic acid ester prepared in example 1.

Detailed Description

So that those skilled in the art can appreciate the features and effects of the present invention, a general description and definition of the terms and expressions set forth in the specification and claims follows. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs, and in the event of a conflict, the present specification shall control.

The theory or mechanism described and disclosed herein, whether right or wrong, is not meant to limit the scope of the invention in any way, i.e., the present disclosure may be practiced without limitation to any particular theory or mechanism.

All features such as values, amounts, and concentrations that are defined herein in the numerical or percent ranges are for brevity and convenience only. Accordingly, the description of a numerical range or percentage range should be considered to cover and specifically disclose all possible sub-ranges and individual values (including integers and fractions) within the range.

Herein, unless otherwise specified, the ratio means mass ratio, and the percentage means mass percentage.

In this context, not all possible combinations of the individual technical features in the individual embodiments or examples are described in order to simplify the description. Accordingly, as long as there is no contradiction between the combinations of these technical features, any combination of the technical features in the respective embodiments or examples is possible, and all possible combinations should be considered as being within the scope of the present specification.

According to the invention, a new technical means is introduced in the preparation process of the acrylic polymer microsphere, so that a micropore channel is formed in the synthesized polymer microsphere, a new capillary channel is formed when the polymer microsphere is aggregated in the drying process, and the interaction of the two channels enables acrylic polymer powder to be quickly fused together to form a polymer film with good water permeability and air permeability when encountering substances containing moisture, so that the wet healing of wounds can be promoted.

The invention adopts a core-shell emulsion polymerization method to prepare microphase separated polymer microspheres, firstly synthesizes polymer cores containing more hydrophilic monomers, then adopts a continuous drop processing technology to prepare polymer shells containing more lipophilic monomers, and controls the crosslinking density and ionization degree of the cores and the shells, thereby causing microphase migration of the polymers of the cores and the shells in the post-treatment process to form an interpenetrating network structure. Due to the existence of the hydrophilic monomer, the particles contain a large amount of bound water, and in the later drying process, the support of the interpenetrating network crosslinked structure enables the space occupied by the original water to form a micropore channel. Also during the drying process, the particles are fused together to form a certain capillary channel, and the interaction of the particles and the capillary channel enables the acrylate polymer microsphere aggregate to be fused together quickly when contacting with substances containing moisture to form a polymer film with microscopic channels. The core-shell structure of the polymer microsphere enables the microsphere aggregate to have a microphase separation structure. Therefore, the acrylate polymer microsphere aggregate has an interpenetrating network crosslinking structure and a microphase separation structure, so that a polymer film formed after meeting water has high strength and high elasticity.

Microsphere, as used herein, refers to microspheroidal particles having a particle size in the nano-and microscale range; the polymer microsphere is a microsphere whose main component is a polymer. The acrylate polymer microsphere disclosed by the invention is a polymer microsphere of which the monomer forming the polymer is mainly one or more monomers selected from acrylic acid, acrylic ester monomers, methacrylic acid and methacrylic ester monomers. Herein, the acrylate polymer refers to a polymer in which the monomer is mainly (for example, 90% or more, preferably 95% or more) one or more monomers selected from the group consisting of acrylic acid, acrylic acid ester-based monomers, methacrylic acid and methacrylic acid ester-based monomers.

Herein, the acrylic monomer may be various acrylic monomers known in the art, preferably one or more selected from the group consisting of hydroxyethyl acrylate, hydroxypropyl acrylate and methyl acrylate; the methacrylate monomer may be various methacrylate monomers known in the art, preferably one or more selected from the group consisting of hydroxyethyl methacrylate, hydroxypropyl methacrylate and methyl methacrylate.

Herein, when one or both of acrylic acid and methacrylic acid is mentioned, methacrylic acid is preferably contained or included and acrylic acid is optionally contained or included because methacrylic acid has better polymerization stability in the present invention, whereas when acrylic acid is used alone, in some cases, the polymerization process may be unstable to cause reaction failure.

Herein, when one or more of the acrylic monomer and the methacrylic monomer is mentioned, it is preferable to include one or more of the methacrylic monomer and optionally the acrylic monomer because the glass transition temperature of the polymer obtained by polymerizing the acrylic monomer is low, and in some cases, water absorption is too soft after plasticization, and the alpha hydrogen of the acrylic monomer is easily attacked by radicals during polymerization to cause the degree of crosslinking of the final polymer to be inconsistent with expectations.

The aqueous dispersion of the acrylate polymer microspheres herein refers to a material obtained by dispersing the acrylate polymer microspheres in water, and may be, for example, an emulsion.

The acrylate polymer microsphere aggregate refers to tiny particles formed by aggregating a small amount of acrylate polymer microspheres, and is in a powder shape, so that the acrylate polymer microsphere aggregate is also called acrylate polymer powder, acrylate polymer microsphere powder and acrylate polymer microsphere aggregate powder, and can be obtained by drying an aqueous dispersion of acrylate polymer microspheres.

Herein, the core-shell structure refers to a structure in which one material is coated with another material having different physical or chemical properties through chemical bonds or other acting forces. The core layer (core) material and the shell layer material of the core-shell structure can be different in chemical composition or same in chemical composition, but different in physical structure (such as density, pore diameter, microphase structure and the like). The core layer material and the shell layer material of the core-shell structure can be partially mutually penetrated, namely a transition layer can exist between the core layer and the shell layer of the core-shell structure. Thus, for a polymeric microsphere, if there are inner and outer two-layer structures that differ in physical or chemical properties as a whole, the polymeric microsphere is considered to have a core-shell structure even if some of the polymers between the two-layer structures are entangled with each other to form an interpenetrating network structure.

Herein, the polymer contained in the core layer of the acrylate polymer microsphere (core layer polymer) is a polymer obtained by polymerizing a monomer used in the preparation of the core layer of the microsphere, and the polymer contained in the shell layer of the acrylate polymer microsphere (shell layer polymer) is a polymer obtained by polymerizing a monomer used in the preparation of the shell layer of the microsphere. Herein, even if the core layer polymer undergoes microphase migration in the subsequent preparation process to be entangled with the shell layer polymer to form an interpenetrating network structure, the polymer obtained by polymerization of the monomer used in the preparation of the microsphere core layer and the polymer obtained by polymerization of the monomer used in the preparation of the microsphere shell layer in the interpenetrating network structure are regarded as the core layer polymer and the shell layer polymer, respectively.

Herein, the polymer contained in the core layer (or shell layer) of the acrylate polymer microsphere contains a certain monomer (for example, hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, acrylic acid, methyl acrylate, methyl methacrylate, ethylene glycol dimethacrylate, diacetone acrylamide, etc.) means that the polymer contained in the core layer (or shell layer) is polymerized from a monomer composition including the monomer.

The acrylate polymer microsphere has a core-shell structure, and the core layer and the shell layer of the acrylate polymer microsphere contain or consist of acrylate polymers.

In certain embodiments, the mass ratio of polymer contained in the core layer to polymer contained in the shell layer of the acrylate polymer microspheres of the invention is in the range of 1.5:1 to 1:1.5, preferably in the range of 1.2:1 to 1:1.2, more preferably in the range of 1.1:1 to 1:1.1.

In a preferred embodiment, the core layer and/or the shell layer of the polyacrylate polymer microsphere of the present invention has a crosslinked structure, i.e. the core layer and/or the shell layer of the polyacrylate polymer microsphere of the present invention contains or consists of a crosslinked acrylate polymer.

In certain embodiments, the core and/or shell layers of the acrylate polymer microspheres of the present invention comprise a polymer (hereinafter, referred to as a crosslinkable monomer-containing acrylate polymer) polymerized from one or more monomers selected from methacrylic acid, acrylic acid, methacrylate-based monomers (e.g., hydroxyethyl methacrylate, hydroxypropyl methacrylate, and methyl methacrylate) and acrylate-based monomers (e.g., hydroxyethyl acrylate, hydroxypropyl acrylate, and methyl acrylate). In the present invention, the crosslinkable monomer means a monomer having two or more functional groups which can be used for polymerization or crosslinking, and examples thereof include Ethylene Glycol Dimethacrylate (EGDMA), diacetone acrylamide (DAAM) and the like. The crosslinkable monomer may be present in an amount conventional in the art for crosslinking acrylate polymers, typically from 0.5% to 5% by weight of the total acrylate polymer.

In certain embodiments, the core layer of the polyacrylate polymer microsphere of the present invention contains a first crosslinkable monomer. In this context, the first crosslinkable monomer contained in the core layer is preferably a monomer containing one carbon-carbon double bond available for polymerization and containing one or more functional groups (for example, ketocarbonyl groups) available for crosslinking other than carbon-carbon double bonds, and may be diacetone acrylamide or the like, for example. In certain embodiments, the core layer of the acrylate polymer microspheres of the present invention comprises a polymer derived from the copolymerization of a first crosslinkable monomer (e.g., diacetone acrylamide) and one or more monomers selected from the group consisting of methacrylic acid, acrylic acid ester monomers, and methacrylic acid ester monomers. In certain embodiments, the core layer polymer is crosslinked via a crosslinking agent. The crosslinking agent suitable for the core layer polymer is not particularly limited as long as it matches the first crosslinkable monomer contained in the core layer, that is, the crosslinking agent of the core layer polymer contains two or more functional groups (for example, hydrazino groups) capable of reacting with a functional group available for crosslinking other than a carbon-carbon double bond contained in the first crosslinkable monomer contained in the core layer, for example, in an embodiment in which the first crosslinkable monomer contained in the core layer is diacetone acrylamide, the crosslinking agent is preferably adipic acid dihydrazide (adipoyl hydrazide, ADH). The amount of crosslinking agent may be conventionally determined based on the amount of the corresponding first crosslinkable monomer, for example adipoyl hydrazine is typically used in an amount of half the diacetone acrylamide content.

In certain embodiments, the polymer contained in the core layer of the polyacrylate polymer microsphere of the present invention is a polymer obtained from crosslinking a linear acrylate polymer containing a first crosslinkable monomer via a crosslinking agent; the first crosslinkable monomer is preferably diacetone acrylamide and the crosslinking agent is preferably adipic acid dihydrazide (adipoyl hydrazide, ADH). In certain embodiments, the first crosslinkable monomer (e.g., diacetone acrylamide) comprises from 0.5% to 5%, preferably from 0.5% to 3%, of the total weight of the polymer contained in the acrylate polymer microsphere core layer. In certain embodiments, the crosslinker (e.g., adipoyl hydrazide) comprises from 0.25% to 2.5%, preferably from 0.25% to 1.5% of the total weight of polymer contained in the acrylate polymer microsphere core layer.

In certain embodiments, the shell layer of the polyacrylate polymer microsphere of the present invention contains a second crosslinkable monomer. The second crosslinkable monomer contained in the shell layer is preferably an acrylic or methacrylic monomer containing two or more carbon-carbon double bonds which can be used for polymerization, and may be, for example, ethylene glycol dimethacrylate. In certain embodiments, the shell layer of the acrylate polymer microspheres of the invention comprises a crosslinked polymer derived from the copolymerization of a second crosslinkable monomer (e.g., ethylene glycol dimethacrylate) and one or more monomers selected from the group consisting of methacrylic acid, acrylic acid ester monomers, and methacrylic acid ester monomers. In certain embodiments, the second crosslinkable monomer (e.g., ethylene glycol dimethacrylate) comprises from 0.5% to 5%, preferably from 1% to 5%, of the total weight of the polymer contained in the shell layer of the acrylate polymer microsphere.

In certain embodiments, the shell layer of the polyacrylate polymer microsphere of the present invention comprises a second crosslinkable monomer (e.g., ethylene glycol dimethacrylate) comprising two or more carbon-carbon double bonds available for polymerization, wherein no crosslinking agent is added, and the polymer formed by copolymerizing the second crosslinkable monomer with other monomers has a crosslinked structure.

The hydrophilicity of the core layer of the acrylate polymer microsphere is stronger than that of the shell layer.

Herein, the hydrophilic monomer refers to a monomer containing a hydrophilic group (e.g., carboxyl group, hydroxyl group, etc.), such as hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methacrylic acid, acrylic acid, etc. In general, hydrophilic monomers (e.g., methacrylic acid and acrylic acid) whose hydrophilic group is a carboxyl group are more hydrophilic than hydrophilic monomers (hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate) whose hydrophilic group is a hydroxyl group, because carboxylate is formed after the carboxyl group is neutralized by hydroxyl groups, the hydrophilicity and water absorption thereof will be greatly enhanced.

The manner of realizing the core layer of the acrylate polymer microsphere having hydrophilicity stronger than that of the shell layer is not particularly limited, and for example, the core layer polymer may contain more hydrophilic monomer than the shell layer polymer, or the core layer polymer may contain hydrophilic monomer having hydrophilicity stronger, and the shell layer polymer may contain hydrophilic monomer having hydrophilicity weaker. In certain embodiments, the present invention provides for the core layer of the acrylate polymer microsphere to be more hydrophilic than the shell layer by providing the core layer of the acrylate polymer microsphere with a total content of methacrylic acid and acrylic acid that is greater than the total content of methacrylic acid and acrylic acid in the polymer comprising the shell layer. In certain embodiments, the acrylate polymer microsphere core layer contains 2% to 15%, preferably 4% to 10%, methacrylic acid and/or acrylic acid (preferably methacrylic acid) based on the total weight of the polymer it contains. In certain embodiments, the acrylate polymer microsphere shell layer is free of methacrylic acid and acrylic acid.

In certain embodiments, the core layer of the acrylate polymer microsphere comprises a polymer derived from the copolymerization of a first crosslinkable monomer (e.g., diacetone acrylamide), one or both selected from methacrylic acid and acrylic acid (preferably methacrylic acid), and one or more monomers selected from methacrylate monomers and acrylate monomers (preferably methacrylate monomers).

In certain embodiments, the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer (e.g., diacetone acrylamide), one or two monomers selected from methacrylic acid and acrylic acid (preferably methacrylic acid), and one or more monomers selected from other methacrylate monomers and acrylate monomers other than methyl methacrylate and methyl acrylate (e.g., hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate, preferably hydroxyethyl methacrylate and hydroxypropyl methacrylate).

In certain embodiments, the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing diacetone acrylamide, methacrylic acid, hydroxyethyl methacrylate and hydroxypropyl methacrylate; preferably, the polymer contained in the core layer of the acrylate polymer microsphere is crosslinked via adipoyl hydrazine.

In embodiments where the microsphere core layer comprises methacrylic acid and/or acrylic acid, the acrylate polymer microsphere core layer preferably comprises 2% to 15%, preferably 4% to 10%, methacrylic acid and/or acrylic acid (preferably methacrylic acid) based on the total weight of the polymer it comprises.

In embodiments in which the microsphere core layer contains a plurality of methacrylate monomers and/or acrylate monomers, the content ratio of the various methacrylate monomers and/or acrylate monomers is not particularly limited, for example, when the microsphere core layer contains hydroxyethyl methacrylate and hydroxypropyl methacrylate, the mass ratio of hydroxyethyl methacrylate and hydroxypropyl methacrylate may be 10:1 to 1:10, for example, 6:4, 8:2, 9:1, etc.

In certain embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer (e.g., ethylene glycol dimethacrylate) and one or more monomers selected from the group consisting of methacrylate monomers and acrylate monomers (preferably methacrylate monomers).

In certain embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer (e.g., ethylene glycol dimethacrylate), one or two monomers selected from the group consisting of methyl methacrylate and methyl acrylate (preferably methyl methacrylate), and one or more monomers selected from the group consisting of methacrylic acid, acrylic acid, methacrylate monomers other than methyl methacrylate and methyl acrylate, and acrylate monomers (e.g., hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate and hydroxypropyl acrylate, preferably hydroxyethyl methacrylate and hydroxypropyl methacrylate).

In certain embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer (e.g., ethylene glycol dimethacrylate), one or two monomers selected from the group consisting of methyl methacrylate and methyl acrylate (preferably methyl methacrylate), and one or more monomers selected from the group consisting of methacrylate monomers other than methyl methacrylate and methyl acrylate (e.g., hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, and hydroxypropyl acrylate, preferably hydroxyethyl methacrylate and hydroxypropyl methacrylate).

In certain embodiments, the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing ethylene glycol dimethacrylate, methyl methacrylate, hydroxyethyl methacrylate and hydroxypropyl methacrylate.

In the embodiment in which the microsphere shell layer contains a plurality of monomers selected from the group consisting of acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, the content ratio of the monomers selected from the group consisting of acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers in the shell layer is not particularly limited, as long as the total content of methacrylic acid and acrylic acid in the polymer contained in the shell layer is lower than the total content of methacrylic acid and acrylic acid in the polymer contained in the shell layer (for example, the shell layer polymer may not contain methacrylic acid and acrylic acid).

In embodiments where the microsphere shell layer comprises methyl methacrylate and/or methyl acrylate, the acrylate polymer microsphere core layer preferably comprises from 4% to 30%, preferably from 8% to 20%, methyl methacrylate and/or methyl acrylate (preferably methyl methacrylate) based on the total weight of the polymer it comprises; in such embodiments, the content ratio of the other methacrylate-based monomers and acrylate-based monomers other than methyl methacrylate and methyl acrylate is not particularly limited, for example, when the microsphere shell layer contains hydroxyethyl methacrylate and hydroxypropyl methacrylate, the mass ratio of hydroxyethyl methacrylate to hydroxypropyl methacrylate may be 10:1 to 1:10, for example, 5:4, 4:5, 3:6, and the like.

In certain embodiments, the core polymer and shell polymer of the acrylate polymer microspheres of the invention are intertwined to form an interpenetrating network structure.

The acrylate polymer microspheres of the invention contain microporous channels.

The acrylate polymer microspheres of the present invention may be adsorbed with adjuvants such as including, but not limited to, sodium deoxycholate, growth factors, and the like.

The invention provides a method for preparing acrylate polymer microspheres, which comprises the following steps:

(A) Preparing an acrylate polymer microsphere core layer through emulsion polymerization in the first step to obtain a core emulsion;

(B) The core layer of the acrylate polymer microsphere prepared by the emulsion polymerization in the first step is taken as a core, and the shell layer of the acrylate polymer microsphere is prepared by the emulsion polymerization in the second step to obtain core-shell emulsion; and

(C) And (3) regulating the pH value of the core-shell emulsion prepared by the emulsion polymerization in the second step to be more than 7, preferably 7-9, more preferably 7.5-9, and adding a cross-linking agent for reaction to obtain the acrylic ester polymer microsphere.

In the present invention, the monomer used in the first emulsion polymerization may be the monomer contained in the acrylate polymer microsphere core polymer described in any of the embodiments herein, the monomer used in the second emulsion polymerization may be the monomer contained in the acrylate polymer microsphere shell polymer described in any of the embodiments herein, and the amount and ratio of the monomer may be as described in any of the embodiments herein.

In certain embodiments, the acrylate polymer microsphere core layer prepared in step (a) comprises a linear polymer and comprises crosslinkable groups.

In certain embodiments, the acrylate polymer microsphere shell layer prepared in step (B) has a crosslinked structure.

The first stage emulsion polymerization and the second stage emulsion polymerization of the present invention can be carried out using emulsion polymerization conditions conventional in the art. In certain embodiments, the reaction system of the first emulsion polymerization step comprises a solvent (water), an emulsifier (e.g., sodium lauryl sulfate), a monomer, and an initiator (e.g., potassium persulfate), and the reaction temperature may be 50 ℃ -90 ℃ (preferably 65 ℃ -75 ℃), and the reaction may be conducted under a nitrogen atmosphere, typically by adding a pre-dissolved initiator to the reaction after the monomer and emulsifier are uniformly mixed in the solvent, and the reaction time may be 3-12 hours (e.g., 6 hours). In certain embodiments, the reaction system of the second emulsion polymerization comprises the core emulsion prepared in the first emulsion polymerization, the monomer, and the initiator (e.g., potassium persulfate), the reaction temperature may be 50 ℃ -90 ℃ (preferably 65 ℃ -75 ℃), the reaction may be conducted under a nitrogen atmosphere, the pre-dissolved initiator may generally be added to the core emulsion, and the monomer may be slowly (e.g., at a rate of 2.5 g/h) added dropwise to conduct the reaction, and the reaction time may be 1-4h (e.g., 2 h).

In step (C), the pH of the core-shell emulsion may be adjusted by means conventional in the art, for example, an alkaline substance such as sodium hydroxide may be added to the core-shell emulsion.

The core layer and the shell layer of the acrylate polymer microsphere have obviously different hydrophilic properties, especially when the pH value of the core-shell emulsion is regulated to be more than 7 by using an alkaline substance, carboxyl contained in the core layer polymer is neutralized into carboxylate, the molecular chain of the carboxylate stretches out to penetrate through the polymer layer of the shell layer, and a large amount of bound water can be contained in the polymer microsphere while an interpenetrating network structure is formed, so that a basis for forming capillary micropores is provided for dried polymer powder.

The conditions of the crosslinking reaction in step (C) may be conventional crosslinking reaction conditions. In certain embodiments, the crosslinking agent used in step (C) is adipoyl hydrazine and the crosslinking reaction time may be 24 hours. The amount of cross-linking agent may be as described in any of the embodiments herein.

The microsphere treated by alkaline substances forms an interpenetrating network structure with a core layer and a shell layer, at the moment, the polymer of the core layer does not form a cross-linked network through chemical bonding, and a cross-linking agent is required to be introduced to form chemical bonding, so that the interpenetrating network structure through chemical bonding is obtained, and capillary micropore channels formed in the drying process are stabilized.

In certain embodiments, the method of preparing acrylate polymer microspheres of the present invention further comprises: and adding an auxiliary agent to the core-shell emulsion or the aqueous dispersion of the acrylate polymer microsphere to enable the auxiliary agent to be adsorbed by the acrylate polymer microsphere. The timing of adding the auxiliary agent is not particularly limited, and may be performed after step (B), before step (C), or after step (C), for example.

The invention also includes an aqueous dispersion of the acrylate polymer microspheres of the invention.

The invention also provides an aggregate of the acrylate polymer microspheres of the invention, namely acrylate polymer microsphere powder. The acrylate polymer microsphere aggregates of the present invention may be obtained from the aqueous dispersion of acrylate polymer microspheres described in any one of the embodiments of the present invention by drying.

The acrylate polymer microsphere aggregate of the invention contains microporous channels and capillary channels. The specific gravity of the acrylate microsphere aggregates of the present invention is typically 0.05g/cm ³ -0.06g/cm ³ 。

In a preferred embodiment, the drying means is freeze drying; the conditions for lyophilization may be conventional in the art, and may be, for example, the following conditions:

the vacuum degree is lower than 10Pa;

The freezing procedure was: -50 ℃ for 3 hours; -40 ℃,2 hours; -30 ℃,1 hour; -20 ℃,1 hour; -10 ℃,1 hour; 0 ℃ for 3 hours; 10 ℃ for 1 hour; 20℃for 2 hours.

Before drying, some auxiliary agent can be added into the acrylate polymer microsphere water dispersion so that the auxiliary agent can be adsorbed by the polymer microsphere, and thus, after drying, the auxiliary agent can be uniformly dispersed in the acrylate polymer powder.

The preparation method comprises the steps of preparing acrylate polymer microspheres with core-shell structures by emulsion polymerization, wherein the cores of the polymer microspheres contain linear polymers with potential crosslinking capability, crosslinkable groups are contained on the linear polymers, and the shells of the polymer microspheres contain space network crosslinked polymers and have crosslinked structures; the monomer composition and proportion of the core layer and the shell layer are adjusted to enable the core layer and the shell layer to have different hydrophilic properties; the pH value of the core-shell emulsion is regulated by alkaline substances, so that the linear polymer of the core layer is spread and forms an interpenetrating network structure with the crosslinked polymer of the shell layer; crosslinking agent is added to react with the linear polymer of the core layer to form a stable polymer interpenetrating network structure of the core layer and the shell layer, so that the capability of forming capillary micropore channels in the drying process is obtained; by drying, the microporous channels left by the water loss inside the polymer microspheres are stabilized by the presence of a crosslinked network, thereby obtaining acrylate polymer microsphere aggregate powder, which can be used as a dressing.

The present invention therefore also provides the use of the acrylate polymer microspheres, the aqueous dispersion thereof or the aggregates thereof according to the invention in the preparation of a dressing. The invention also includes dressings, particularly medical dressings, comprising the acrylate polymer microsphere aggregates of the invention.

The dressing of the present invention may be the acrylate polymer microsphere aggregates of the present invention themselves, optionally further comprising various additives, adjuvants, pharmaceutical ingredients and active ingredients known in the art as suitable for dressing, including for example but not limited to antibacterial agents, hemostatic agents, anti-inflammatory agents, pH adjusting agents, nutritional agents, etc. When the dressing of the invention is used, the dressing can be shaken off on skin or wound uniformly, a small amount of physiological saline is sprayed on the dressing, and the dressing can form a high water absorption film with high elasticity and high strength after contacting with moisture.

The dressing containing the acrylate polymer microsphere aggregate has the following advantages: after contacting moisture, the film forming speed is high (film forming can be carried out in five minutes generally), the formed film has good air permeability, transparency, water absorption and adhesiveness, has enough strength and elasticity, is convenient for observing wound healing conditions, can absorb wound exudates, is tightly and firmly attached to a wound in the initial use stage, is not easy to damage under the action of external force, is prolonged along with time or heals of the wound, reduces tissue fluid exudation, gradually dries the super absorbent film, gradually separates from the skin or healed wound, can not adhere to the skin or the wound, can not damage the wound when removing the dressing, is easy to tear off, and brings lighter pain to a patient.

The present invention will be described in detail with reference to examples. The embodiments described in the present specification are only for illustrating the present invention, and do not limit the scope of the present invention. The scope of the present invention is defined only by the claims, and any omission, substitution or modification made by those skilled in the art based on the embodiments disclosed herein will fall within the scope of the present invention.

The following examples use instrumentation conventional in the art. The experimental methods, in which specific conditions are not noted in the following examples, are generally conducted under conventional conditions or under conditions recommended by the manufacturer. The following examples use various starting materials, and unless otherwise indicated, conventional commercial products were used.

Example 1

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the core comprises the following steps: into a 500mL four-necked flask, 1.0g of Sodium Dodecyl Sulfate (SDS) and 380g of deionized water were weighed respectively, then a stirrer, a nitrogen pipe, a thermometer and a condenser were installed, the temperature of the water bath was maintained at 73℃and the stirring was continuously turned on, when the emulsifier was completely dissolved and the internal temperature reached 70.+ -. 1 ℃, a pre-weighed monomer mixture containing 12g of hydroxyethyl methacrylate (HEMA), 8g of hydroxypropyl methacrylate (HPMA), 1g of methacrylic acid (MAA) and 0.4g of diacetone acrylamide (DAAM) was added, and after the temperature was stabilized, a pre-dissolved potassium persulfate (KPS) solution containing 0.1g of KPS and 20g of deionized water was added, and the time counting was started. After about 5 minutes, the reactants were blue light and the monomers began to polymerize to form polymer particles, and after about 6 hours the core preparation reaction was completed, producing a core emulsion.

(2) The preparation process of the shell comprises the following steps: 210g of nuclear emulsion and 180g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, after the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.1g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer is dropwise added at the rate of 2.5g/h, wherein the acrylate mixed monomer contains 5g HEMA, 4g HPMA, 1g Methyl Methacrylate (MMA) and 0.2g Ethylene Glycol Dimethacrylate (EGDMA), and the reaction is continued for 2h after the monomer dropwise addition is completed, so that the acrylate nuclear shell emulsion is prepared.

(3) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylic ester core-shell emulsion prepared in the step (2) to enable the pH value to reach 7.5, then adding 0.1g of adipoyl hydrazide (ADH), reacting for 24 hours to obtain an aqueous dispersion of the core-crosslinked acrylic ester polymer microsphere, and then performing freeze drying to obtain the acrylic ester polymer microsphere aggregate.

The polymer particles prepared by the core-shell emulsion polymerization method have the advantages that the core contains a large amount of hydrophilic monomers, crosslinking is realized in the shell due to the existence of EGDMA, when sodium hydroxide is adopted to neutralize the polymer emulsion, carboxyl in the core is converted into sodium carboxylate, the hydrophilicity is greatly improved, the core substance and the shell substance are mutually entangled to form an interpenetrating network structure due to the large difference of the hydrophilicity between the core and the shell, and after neutralization, ADH equivalent to DAAM is added into the system, and the ADH equivalent to DAAM reacts with the core substance and the shell substance to form a stable interpenetrating network structure, and the polymer particles contain a large amount of moisture due to the existence of hydrophilic substances such as sodium carboxylate. In the subsequent drying process, the micropore channels left by the water loss are reserved due to the support of the cross-linked structure, so that the acrylate polymer microsphere aggregate containing a large amount of micropore structures is finally formed.

FIGS. 1 to 6 show electron microscopic images of the acrylate polymer microsphere aggregates prepared in example 1. As can be seen from the figure, after drying, the acrylate polymer microspheres are aggregated and fused, the surfaces of the microspheres are provided with micropore channels, capillary channels are formed between the microspheres, and the interaction of the two microspheres enables the acrylate polymer microsphere aggregate to quickly form a super-absorbent film after contacting with a substance containing moisture.

The acrylate polymer microsphere aggregate prepared in example 1 was allowed to absorb water to form a film, and then the weight loss ratio of water in the film was measured as a function of time, and the results are shown in fig. 7. The specific experimental method for measuring the weight reduction ratio comprises the following steps: 200mg of acrylic ester polymer powder is weighed, placed in a circular ring with the diameter of 2cm, evenly spread, placed on qualitative filter paper, sprayed with water by a small spraying device to enable the powder to be wet to saturation, and after about 2-3 minutes, the powder forms a complete elastic film under the action of water, the qualitative filter paper is used for absorbing the water on the surface, and the water absorption rate is calculated by weighing. The film fully absorbing water is placed on a clean plastic film, naturally dried, the ambient temperature is controlled to be about 25 ℃, the air humidity is controlled to be between 30 and 50 percent, and the weight reduction rate of the film is calculated by weighing periodically.

The infrared spectrum of the acrylate polymer microsphere aggregate prepared in example 1 was measured using a Thermo Scientific Nicolet iS infrared spectrometer, and the result is shown in fig. 8, and the infrared spectrum shows typical polymethacrylate.

Differential scanning calorimetric testing was performed on the acrylate polymer microsphere aggregates prepared in example 1 using a PerkinElmer DSC 8000. Test conditions: -20 ℃ for 2min, heating from-20 ℃ to 150 ℃ at a rate of 20 ℃/min, heating at 150 ℃ for 2min, cooling from 150 ℃ to-20 ℃ at a rate of 50 ℃/min, heating at-20 ℃ for 3min, and heating from-20 ℃ to 150 ℃ at a rate of 20 ℃/min. The data processing was performed on the two warming scan process, and the result is shown in fig. 9. The first heating scan process has a distinct endothermic peak, which is caused by the vaporization of the moisture in the air absorbed by the acrylate polymer powder during the heating process, the vaporization enthalpy becomes 113J/g, and the second heating scan process can see a distinct glass transition temperature of the acrylate polymer, tg is 110.7 ℃.

The particle size distribution and average particle size of the acrylic polymer microspheres in the aqueous dispersion of step (3) of example 1 were measured using a Malvern Nano ZS ZEN 3600 particle size analyzer, the particle size distribution curve is shown in fig. 10, and the average particle size of the acrylic polymer microspheres was measured to be 93nm.

Example 2

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the core comprises the following steps: into a 500mL four-neck flask, 1.5g of emulsifier SDS and 380g of deionized water are respectively weighed, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the temperature of a water bath is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the emulsifier is completely dissolved and the internal temperature reaches 70+/-1 ℃, a pre-weighed monomer mixture containing 16g of HEMA, 4g of HPMA, 1.5g of MAA and 0.2g of DAAM is added, after the temperature is stable, a pre-dissolved KPS solution containing 0.15g of KPS and 20g of deionized water is added, and timing begins. After about 5 minutes, the reactants exhibited blue light and the monomers began to polymerize to form polymer particles, after about 6 hours the core preparation reaction was complete.

(2) 200g of nuclear emulsion and 190g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.15g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer containing 4g HEMA, 5g HPMA, 1.5g MMA and 0.4g EGDMA is dropwise added at a rate of 2g/h, and the reaction is continued for 2h after the monomer is dropwise added, so that the acrylate nuclear shell emulsion is prepared.

(3) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylic ester core-shell emulsion prepared in the step (2) to enable the pH value to reach 8, then adding 0.05g of ADH, reacting for 24 hours to obtain an aqueous dispersion of the core-crosslinked acrylic ester polymer microsphere, and then performing freeze drying to obtain the acrylic ester polymer microsphere aggregate.

Example 3

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the core comprises the following steps: into a 500mL four-neck flask, 0.5g of emulsifier SDS and 380g of deionized water are respectively weighed, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the temperature of a water bath is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the emulsifier is completely dissolved and the internal temperature reaches 70+/-1 ℃, a pre-weighed monomer mixture containing 18g of HEMA, 2g of HPMA, 2.0g of MAA and 0.6g of DAAM is added, after the temperature is stable, a pre-dissolved KPS solution containing 0.2g of KPS and 20g of deionized water is added, and timing begins. After about 5 minutes, the reactants exhibited blue light and the monomers began to polymerize to form polymer particles, after about 6 hours the core preparation reaction was complete.

(2) The preparation process of the shell comprises the following steps: 180g of nuclear emulsion and 210g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.2g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer is dropwise added at a rate of 1.5g/h, 3g of HEMA, 6g of HPMA, 2g of MMA and 0.3g of EGDMA are contained, and the reaction is continued for 2h after the monomer dropwise addition is completed, so that the acrylate nuclear shell emulsion is prepared.

(3) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylic ester core-shell emulsion prepared in the step (2) to enable the pH value to reach 8.5, then adding 0.15g of ADH, reacting for 12 hours to obtain an aqueous dispersion of the core-crosslinked acrylic ester polymer microsphere, and then performing freeze drying to obtain the acrylic ester polymer microsphere aggregate.

The polymer particles prepared by the core-shell emulsion polymerization means of examples 1-3, the core contains a large amount of hydrophilic monomers, crosslinking is realized in the shell due to the existence of EGDMA, when sodium hydroxide is used for neutralizing the polymer emulsion, carboxyl in the core is converted into sodium carboxylate, the hydrophilicity is greatly improved, the core substance and the shell substance are intertwined to form an interpenetrating network structure due to the large difference of the hydrophilicity between the core substance and the shell substance, after neutralization is finished, ADH equivalent to DAAM is added into the system, and the ADH equivalent to DAAM is reacted with the core substance and the shell substance to form a stable interpenetrating network structure, and the polymer particles contain a large amount of moisture due to the existence of hydrophilic substances such as sodium carboxylate. In the subsequent drying process, the micropore channels left by the water loss are reserved due to the support of the cross-linked structure, so that the acrylate polymer microsphere aggregate containing a large amount of micropore structures is finally formed.

Comparative example 1

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the core comprises the following steps: into 500mL four-neck flask, 1.0g of emulsifier SDS and 380g of deionized water are respectively weighed, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the emulsifier is completely dissolved and the internal temperature reaches 70+/-1 ℃, a pre-weighed monomer mixture containing 12g of HEMA, 8g of HPMA and 1g of MAA is added, after the temperature is stable, a pre-dissolved KPS solution containing 0.1g of KPS and 20g of deionized water is added, and timing begins. After about 5 minutes, the reactants exhibited blue light and the monomers began to polymerize to form polymer particles, after about 6 hours the core preparation reaction was complete.

(2) The preparation process of the shell comprises the following steps: 210g of nuclear emulsion and 180g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.1g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer is dropwise added at the rate of 2.5g/h, 5g of HEMA, 4g of HPMA and 1g of MMA are contained, and the reaction is continued for 2h after the monomer dropwise addition is completed, so that the acrylate nuclear shell emulsion is prepared.

(3) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylic ester core-shell emulsion prepared in the step (2) to enable the pH value to reach 7.5, obtaining an aqueous dispersion of acrylic ester polymer microspheres, and obtaining an acrylic ester polymer microsphere aggregate through freeze drying.

The polymer particles prepared by the core-shell emulsion polymerization method have the advantages that the core contains a large amount of hydrophilic monomers, when sodium hydroxide is adopted to neutralize the polymer emulsion, carboxyl in the core is converted into sodium carboxylate, the hydrophilicity is greatly improved, and core substances and shell substances are mutually entangled to form an interpenetrating network structure due to the large difference of the hydrophilicity between the core and the shell, but the cross-linked structure cannot be formed due to the fact that the core layer and the shell layer of the polymer do not contain cross-linked monomers, and in the subsequent drying process, micropore channels left by water loss collapse due to the fact that the support of the cross-linked structure is not obtained, and finally acrylate polymer microsphere aggregates containing the micropore structure cannot be formed.

Comparative example 2

An acrylate polymer microsphere aggregate is prepared by the steps of:

(2) The preparation process of the shell comprises the following steps: 200g of nuclear emulsion and 180g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.1g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer is dropwise added at the rate of 2.5g/h, 5g of HEMA, 4g of HPMA and 1g of MMA are contained, and the reaction is continued for 2h after the monomer dropwise addition is completed, so that the acrylate nuclear shell emulsion is prepared.

The polymer particles prepared by the core-shell emulsion polymerization method have the advantages that the core contains a large amount of hydrophilic monomers, when sodium hydroxide is adopted to neutralize the polymer emulsion, carboxyl groups in the core are converted into sodium carboxylate, the hydrophilicity is greatly improved, and as the core-shell hydrophilicity is greatly different, the core material and the shell material are intertwined to form an interpenetrating network structure, and after neutralization, ADH with the same amount as that in the embodiment 2 is added into the system. DAAM and ADH react to form a space network structure, but as the shell layer does not form a cross-linked structure, in the subsequent drying process, a micropore channel left by water loss collapses due to the fact that the effective support of the cross-linked structure of the shell layer is not obtained, and finally, an acrylate polymer microsphere aggregate containing the micropore structure cannot be formed.

Comparative example 3

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the core comprises the following steps: into 500mL four-neck flask, 1.5g of emulsifier SDS and 380g of deionized water are respectively weighed, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the emulsifier is completely dissolved and the internal temperature reaches 70+/-1 ℃, a pre-weighed monomer mixture containing 16g of HEMA, 4g of HPMA and 1.5g of MAA is added, after the temperature is stable, a pre-dissolved KPS solution containing 0.15g of KPS and 20g of deionized water is added, and timing begins. After about 5 minutes, the reactants exhibited blue light and the monomers began to polymerize to form polymer particles, after about 6 hours the core preparation reaction was complete.

(2) The preparation process of the shell comprises the following steps: 200g of nuclear emulsion and 180g of deionized water are respectively weighed into a 500mL four-neck flask, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the water bath temperature is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the internal temperature reaches 70+/-1 ℃, a pre-dissolved KPS solution containing 0.2g KPS and 20g of deionized water is added, meanwhile, the acrylate mixed monomer is dropwise added at a rate of 1.5g/h, 5g HEMA, 4g HPMA, 1g MMA and 0.2g EGDMA are contained, and the reaction is continued for 2h after the monomer dropwise addition is completed, so that the acrylate nuclear shell emulsion is prepared.

(3) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylic ester core-shell emulsion prepared in the step (2) to enable the pH value to reach 8.5, obtaining an aqueous dispersion of acrylic ester polymer microspheres, and obtaining an acrylic ester polymer microsphere aggregate through freeze drying.

The polymer particles prepared by the core-shell emulsion polymerization method have the advantages that the core contains a large amount of hydrophilic monomers, when sodium hydroxide is adopted to neutralize the polymer emulsion, carboxyl in the core is converted into sodium carboxylate, the hydrophilicity is greatly improved, core substances and shell substances are mutually entangled to form an interpenetrating network structure due to large difference of the hydrophilicity between the core and the shell, and after neutralization, the polymer macromolecules of the core layer slowly migrate outwards under the help of water phase because the core layer is not crosslinked, and finally macroscopic phase separation is generated between the core layer and the shell layer, so that an elastic high-water-absorption film cannot be formed in the final application process.

Comparative example 4

An acrylate polymer microsphere aggregate is prepared by the steps of:

(1) The preparation process of the emulsion comprises the following steps: into a 500mL four-neck flask, 1.5g of emulsifier SDS and 380g of deionized water are weighed respectively, then a stirrer, a nitrogen guide pipe, a thermometer and a condenser are arranged, the temperature of a water bath is maintained at 73 ℃, nitrogen is continuously introduced and stirring is started, when the emulsifier is completely dissolved and the internal temperature reaches 70+/-1 ℃, a pre-weighed monomer mixture containing 15g of HEMA, 4.5g of HPMA, 1.3g of MAA, 0.2g of DAAM and 0.2g of EGDMA is added, after the temperature is stabilized, a pre-dissolved KPS solution containing 0.15g of KPS and 20g of deionized water is added, and timing begins. After about 5 minutes, the reactants exhibited blue light and the monomers began to polymerize to form polymer particles, after about 6 hours the reaction was complete.

(2) The preparation process of the microporous structure comprises the following steps: and (3) adding sodium hydroxide into the acrylate emulsion prepared in the step (1) to enable the pH value to reach 8.0, then adding 0.1g of ADH, reacting for 12 hours to obtain an acrylate polymer microsphere dispersion, and then performing freeze drying to obtain an acrylate polymer microsphere aggregate.

The polymer microsphere aggregate prepared by the steps has a good cross-linking structure, but does not have a microphase separation structure, so that the water-absorbing film formed after meeting water has insufficient elasticity.

Application examples

The acrylate polymer microsphere powder prepared in examples 1-3 was uniformly shaken off on skin or wound, and a small amount of physiological saline was sprayed thereon, so that a super absorbent film having high elasticity and high strength was formed within about five minutes, and the super absorbent film was gradually dried and gradually separated from the skin or healed wound without sticking to the skin or wound as time was prolonged or wound healing was reduced in exudation of tissue fluid.

The acrylate polymer microsphere powder prepared in comparative examples 1 to 4 was uniformly shaken off on the skin or wound, and a small amount of physiological saline was sprayed thereon, so that a highly water-absorbing film having sufficient elasticity and strength could not be formed, and the formed film was easily broken under the action of external force.

Claims

1. The acrylate polymer microsphere is characterized by having a core-shell structure, wherein the polymer contained in the core layer of the acrylate polymer microsphere has stronger hydrophilicity than the polymer contained in the shell layer, and the polymer contained in the core layer of the acrylate polymer microsphere and the polymer contained in the shell layer of the acrylate polymer microsphere have cross-linked structures respectively; the polymer contained in the core layer of the acrylic polymer microsphere and the polymer contained in the shell layer are intertwined to form an interpenetrating network structure; the mass ratio of the polymer contained in the core layer to the polymer contained in the shell layer of the acrylate polymer microsphere is in the range of 1.5:1-1:1.5;

the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, wherein the polymer contained in the core layer of the acrylate polymer microsphere is crosslinked by a crosslinking agent, the first crosslinkable monomer is diacetone acrylamide, and the crosslinking agent is adipoyl hydrazide;

the shell layer of the acrylic polymer microsphere contains a polymer obtained by copolymerizing a second crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, wherein the second crosslinkable monomer is ethylene glycol dimethacrylate.

2. The acrylate polymer microsphere of claim 1, wherein the mass ratio of polymer contained in the core layer to polymer contained in the shell layer of the acrylate polymer microsphere is in the range of 1.2:1 to 1:1.2.

3. The acrylate polymer microsphere of claim 1, wherein the mass ratio of polymer contained in the core layer to polymer contained in the shell layer of the acrylate polymer microsphere is in the range of 1.1:1 to 1:1.1.

4. The acrylate polymer microsphere of claim 1, wherein the acrylate polymer microsphere is adsorbed with an adjuvant.

5. The acrylate polymer microsphere according to claim 1, wherein the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a first crosslinkable monomer, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from methacrylate monomers and acrylate monomers.

6. The acrylate polymer microsphere of claim 1, wherein the first crosslinkable monomer comprises from 0.5% to 5% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

7. The acrylate polymer microsphere of claim 1, wherein the first crosslinkable monomer comprises from 0.5% to 3% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

8. The acrylate polymer microsphere according to claim 1, wherein the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing a second crosslinkable monomer and one or more monomers selected from the group consisting of methacrylate monomers and acrylate monomers.

9. The acrylate polymer microsphere according to claim 1, wherein the second crosslinkable monomer comprises from 0.5% to 5% of the total weight of the polymer contained in the shell layer of the acrylate polymer microsphere.

10. The acrylate polymer microsphere according to claim 1, wherein the second crosslinkable monomer comprises 1% to 5% of the total weight of the polymer contained in the shell layer of the acrylate polymer microsphere.

11. The acrylate polymer microsphere according to claim 1, wherein the total content of methacrylic acid and acrylic acid in the polymer contained in the core layer of the acrylate polymer microsphere is higher than the total content of methacrylic acid and acrylic acid in the polymer contained in the shell layer.

12. The acrylate polymer microsphere according to claim 1, wherein the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing diacetone acrylamide, one or two monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methyl methacrylate and methyl acrylate.

13. The acrylate polymer microsphere of claim 1, wherein the core layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing diacetone acrylamide, methacrylic acid, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

14. The acrylate polymer microsphere according to claim 5, wherein the total content of methacrylic acid and acrylic acid is 2% -15% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

15. The acrylate polymer microsphere according to claim 5, wherein the total content of methacrylic acid and acrylic acid is 4% to 10% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

16. The acrylic acid ester polymer microsphere according to claim 1, wherein the shell layer of the acrylic acid ester polymer microsphere contains a polymer obtained by copolymerizing ethylene glycol dimethacrylate, one or two monomers selected from methyl methacrylate and methyl acrylate and one or more monomers selected from methacrylate monomers other than methyl methacrylate and acrylic acid ester monomers other than methyl acrylate.

17. The acrylate polymer microsphere according to claim 1, wherein the shell layer of the acrylate polymer microsphere comprises a polymer obtained by copolymerizing ethylene glycol dimethacrylate, methyl methacrylate, hydroxyethyl methacrylate and hydroxypropyl methacrylate.

18. The acrylate polymer microsphere of claim 16, wherein the total content of methyl methacrylate and methyl acrylate is from 4% to 30% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

19. The acrylate polymer microsphere of claim 16, wherein the total content of methyl methacrylate and methyl acrylate is 8% to 20% of the total weight of the polymer contained in the core layer of the acrylate polymer microsphere.

20. An aqueous dispersion or aggregate of acrylate polymer microspheres comprising the acrylate polymer microspheres of any one of claims 1-19.

21. The aggregate of acrylate polymer microspheres according to claim 20, wherein the aggregate of acrylate polymer microspheres is obtained from an aqueous dispersion of acrylate polymer microspheres by drying.

22. The aggregate of acrylate polymer microspheres according to claim 21, wherein the drying is freeze drying.

23. A method of preparing acrylate polymer microspheres, the method comprising:

(A) Preparing an acrylate polymer microsphere core layer through a first emulsion polymerization, wherein the polymer contained in the acrylate polymer microsphere core layer prepared through the first emulsion polymerization is a linear polymer and contains a crosslinkable group;

the monomer used in the first emulsion polymerization step comprises a first crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, wherein the first crosslinkable monomer is diacetone acrylamide;

the monomers used in the second-step emulsion polymerization comprise a second crosslinkable monomer and one or more monomers selected from methacrylic acid, acrylic acid, methacrylic acid ester monomers and acrylic acid ester monomers, wherein the second crosslinkable monomer is ethylene glycol dimethacrylate; and

(C) And (3) regulating the pH value of the core-shell emulsion prepared by the emulsion polymerization in the second step to be more than 7, and then adding a cross-linking agent to react to obtain the acrylic ester polymer microsphere, wherein the cross-linking agent is adipoyl hydrazine.

24. The method of claim 23, wherein the monomers used in the first emulsion polymerization step comprise a first crosslinkable monomer, one or both monomers selected from methacrylic acid and acrylic acid, and one or any plurality of monomers selected from methacrylate monomers and acrylate monomers.

25. The method of claim 23, wherein the monomers used in the first emulsion polymerization step comprise a first crosslinkable monomer, one or both monomers selected from methacrylic acid and acrylic acid, and one or more monomers selected from hydroxyethyl methacrylate, hydroxypropyl methacrylate, hydroxyethyl acrylate, hydroxypropyl acrylate, methyl methacrylate and methyl acrylate.

26. The method of claim 23, wherein the monomers used in the first emulsion polymerization step comprise a first crosslinkable monomer, methacrylic acid, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

27. The method of claim 24, wherein the total amount of methacrylic acid and acrylic acid is from 2% to 15% of the total weight of monomers used in the first emulsion polymerization step.

28. The method of claim 24, wherein the total amount of methacrylic acid and acrylic acid is from 4% to 10% of the total weight of monomers used in the first emulsion polymerization step.

29. The method of claim 23, wherein the monomers used in the second emulsion polymerization step comprise a second crosslinkable monomer and one or more monomers selected from the group consisting of methacrylate monomers and acrylate monomers.

30. The method of claim 23, wherein the monomers used in the second emulsion polymerization step comprise a second crosslinkable monomer, one or two monomers selected from the group consisting of methyl methacrylate and methyl acrylate, and one or more monomers selected from the group consisting of methacrylate monomers other than methyl methacrylate and acrylate monomers other than methyl acrylate.

31. The method of claim 23, wherein the monomers used in the second emulsion polymerization step comprise a second crosslinkable monomer, methyl methacrylate, hydroxyethyl methacrylate, and hydroxypropyl methacrylate.

32. The method of claim 30, wherein the total content of methyl methacrylate and methyl acrylate is from 4% to 30% of the total weight of monomers used in the second emulsion polymerization step.

33. The method of claim 30, wherein the total content of methyl methacrylate and methyl acrylate is from 8% to 20% of the total weight of monomers used in the second emulsion polymerization step.

34. The method of claim 23, wherein in step (C), the pH of the core-shell emulsion obtained by the second emulsion polymerization is adjusted to 7 to 9, and a crosslinking agent is added to perform the reaction.

35. The method of claim 23, wherein the total amount of methacrylic acid and acrylic acid in the first emulsion polymerization step is greater than the total amount of methacrylic acid and acrylic acid in the second emulsion polymerization step.

36. The method of claim 23, wherein the method further comprises: after step (B), before step (C), or after step (C), adding an auxiliary agent to the core-shell emulsion or the aqueous dispersion of acrylate polymer microspheres, such that the auxiliary agent is adsorbed by the acrylate polymer microspheres.

37. The method of claim 23, wherein the method has one or more of the following features:

(1) The reaction temperature of the emulsion polymerization in the first step is 50-90 ℃;

(2) The first crosslinkable monomer is used in an amount of from 0.5% to 5% by weight based on the total weight of the monomers used in the first emulsion polymerization step;

(4) The reaction temperature of the emulsion polymerization in the second step is 50-90 ℃;

(5) The second crosslinkable monomer is used in an amount of 0.5% to 5% by weight based on the total weight of the monomers used in the second emulsion polymerization step;

(7) The mass ratio of the monomer used in the first-step emulsion polymerization to the monomer used in the second-step emulsion polymerization is in the range of 1.5:1-1:1.5.

38. The method of claim 23, wherein the method has one or more of the following features:

the reaction temperature of the emulsion polymerization in the first step is 65-75 ℃;

the first crosslinkable monomer is used in an amount of 0.5% to 3% by weight based on the total weight of the monomers used in the first emulsion polymerization step;

the reaction temperature of the second emulsion polymerization is 65-75 ℃;

The amount of the second crosslinkable monomer is 1% -5% of the total weight of the monomers used in the second emulsion polymerization step;

the mass ratio of the monomer used in the first-step emulsion polymerization to the monomer used in the second-step emulsion polymerization is in the range of 1.2:1-1:1.2.

39. The method of claim 23, wherein the mass ratio of the monomer used in the first emulsion polymerization to the monomer used in the second emulsion polymerization is in the range of 1.1:1 to 1:1.1.

40. An acrylic polymer microsphere, an aqueous dispersion or an aggregate thereof produced by the method of any one of claims 23 to 39.

41. The aggregate of acrylate polymer microspheres according to claim 40, wherein the aggregate of acrylate polymer microspheres is obtained from an aqueous dispersion of acrylate microspheres by drying.

42. The aggregate of acrylate polymer microspheres according to claim 41, wherein the drying is freeze-drying.

43. A dressing comprising the acrylate polymer microsphere aggregate of claim 20 or 40.