JP5368300B2 - Polymer beads and method for producing polymer beads - Google Patents

Abstract

Polymeric beads and methods of making the polymeric beads are described. The polymeric beads are crosslinked hydrogels or dried hydrogels. The polymeric beads are formed from droplets of a precursor composition that are exposed to radiation. The droplets are totally surrounded by a gas phase. The precursor composition contains a polar solvent and a polymerizable material miscible in the polar solvent. The polymerizable material has an average number of ethylenically unsaturated groups per monomer molecule equal to at least 1.2.

Description

(Claiming priority)
This application claims priority to US patent application Ser. No. 11/423048 (filed Jun. 8, 2006) and US Provisional Application No. 60/941148 (filed May 31, 2007).

(Field of Invention)
The present disclosure is directed to polymer beads and methods for producing polymer beads.

  There are many commercial applications for polymer beads, such as biological applications, medical applications, and industrial applications. Applications for polymer beads are increasing and continuing to expand. There is always a need for polymer beads with unique physical and chemical properties and added versatility. Various methods for producing polymer beads are known. In most of these methods, droplets of polymerizable material are reacted to form essentially spherical polymer beads.

  For example, an emulsion polymerization method is well known for producing polymer beads. Polymer beads are formed by reacting droplets in which a polymerizable material is present in an oil or water emulsion. Although these methods work well, the resulting polymer beads are often porous. In addition, the resulting polymer beads often need to be thoroughly cleaned to remove the remaining non-polymerizable materials, such as oils and emulsifiers. In many cases, this cleaning often removes only surface contaminants, but does not remove oils or other compounds that may be entrained within the polymer beads. The polymerizable material is often heated to initiate the polymerization reaction, but radiation can also be used.

  In another example, a drop of polymerizable material can be formed and dropped by gravity. The polymerization can be initiated by exposing the falling droplets to radiation. Polymerization occurs while the droplet falls, resulting in the formation of polymer beads. Alternatively, exposing the polymerizable material to radiation can occur before the droplets are formed. However, polymerization continues as the droplets fall, resulting in the formation of polymer beads.

  The polymer beads and the method for producing the polymer beads will be described. The polymer beads contain a cross-linked hydrogel that can optionally be dried. The polymer beads can contain an active agent in some embodiments. That is, the polymer beads can function as a carrier for various active agents.

  In a first aspect, a method for producing polymer beads is provided. The method includes a precursor composition comprising: (a) a polar solvent greater than 10 weight percent based on the total mass of the precursor composition; and (b) a polymerizable material that is miscible with the polar solvent. A step of forming a body composition is included. The polymerizable material has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. The method further includes forming a droplet of the precursor composition where the droplet is entirely surrounded by the gas phase. The droplet is exposed to radiation for a time sufficient for the polymerizable material to at least partially polymerize to form a first swollen polymer bead.

  In a second aspect, another method for producing polymer beads is provided. The method includes as precursor composition (a) a polar solvent of greater than 10 to 85 weight percent based on the total weight of the precursor composition, and (b) based on the total weight of the precursor composition. Forming a precursor composition containing from 15 weight percent to less than 90 weight percent polymerizable material. The polymerizable material is miscible with the polar solvent and has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. Polymerizable materials include poly (alkylene oxide (meth) acrylates) having at least two (meth) acryloyl groups and having at least five alkylene oxide units. The polymerizable material can also include 0 to less than 20 weight percent anionic monomer based on the total weight of the polymerizable material. In addition to the ethylenically unsaturated group, the anionic monomer contains an acidic group, a salt of an acidic group, or a mixture thereof. The method further includes forming a droplet of the precursor composition, where the droplet is entirely surrounded by the gas phase. The droplet is exposed to radiation for a time sufficient for the polymerizable material to at least partially polymerize to form a first swollen polymer bead.

  In a third aspect, an article comprising polymer beads is provided. The polymer beads have an aspect ratio of 3: 1 or less and are free radical polymerization reaction products of the precursor composition. The precursor composition includes (a) the total mass of the precursor composition as a reference. More than 10 to 85 weight percent polar solvent and (b) 15 to less than 90 weight percent polymerizable material based on the total weight of the precursor composition. The polymerizable material is miscible with the polar solvent and has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. Polymerizable materials include poly (alkylene oxide (meth) acrylates) having at least two (meth) acryloyl groups and having at least five alkylene oxide units. The polymerizable material can also include 0 to less than 20 weight percent anionic monomer based on the total weight of the polymerizable material. In addition to the ethylenically unsaturated group, the anionic monomer contains an acidic group, a salt of an acidic group, or a mixture thereof.

  In a fourth aspect, an article comprising polymer beads containing an active agent is provided. The polymer beads have an aspect ratio of 3: 1 or less and (a) a reaction product of a precursor composition containing a polymerizable material having an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2 And (b) an active agent. Polymerizable materials include poly (alkylene oxide (meth) acrylates) having at least two (meth) acryloyl groups and having at least five alkylene oxide units. The polymerizable material can also include 0 to less than 20 weight percent anionic monomer based on the total weight of the polymerizable material. In addition to the ethylenically unsaturated group, the anionic monomer contains an acidic group, a salt of an acidic group, or a mixture thereof.

  The above summary of the present invention is not intended to describe each disclosed embodiment or every implementation of the present invention. The following “Best Mode for Carrying Out the Invention” and examples illustrate these embodiments in more detail.

  The present invention may be more fully understood by considering the following "Best Mode for Carrying Out the Invention" of various embodiments of the invention in conjunction with the accompanying drawings.

  The polymer beads and the method for producing the polymer beads will be described. The polymer beads are a crosslinked hydrogel or a dried hydrogel. As used herein, the term “hydrogel” refers to a polymeric material that is hydrophilic and is swollen or swellable by a polar solvent. Polymeric materials usually swell but do not dissolve when contacted with a polar solvent. That is, the hydrogel does not dissolve in polar solvents. The swollen polymer beads can be dried to remove at least a portion of the polar solvent. In some embodiments, the polymer beads also contain an active agent.

  Polymer beads are formed from droplets of the precursor composition. As used herein, the term “precursor composition” refers to a reaction mixture to which radiation is exposed to form polymer beads. That is, the precursor composition describes a reaction mixture before polymerization. The precursor composition contains a polar solvent and a polymerizable material that is miscible with the polar solvent. The precursor composition can also include other optional additives such as processing agents, activators, or mixtures thereof. The droplets of the precursor composition are usually surrounded entirely by the gas phase. When exposed to radiation, the polymerizable material in the precursor composition undergoes a free radical polymerization reaction to form polymer beads. The reaction product is a hydrogel containing polymerized material, a polar solvent, and some optional additives.

  As used herein, the terms “bead” and “polymer bead” are used interchangeably and refer to particles such as: That is, particles that contain a polymeric material, have a smooth surface, and have an aspect ratio of 3: 1 or less, 2.5: 1 or less, 2: 1 or less, 1.5: 1 or less, or 1: 1 It is. That is, the aspect ratio is in the range of 3: 1 to 1: 1. Aspect ratio refers to the ratio of the longest dimension of a polymer bead to the dimension orthogonal to the longest dimension. The shape of the polymer beads is often spherical or elliptical. However, spherical or elliptical shapes can collapse when the polymer beads are dried. As used herein, the term “smooth” refers to a surface that is free of discontinuities and sharp portions. The shape of the polymer beads prepared from the droplets is not the same as the shape of the particles prepared by a process such as milling or grinding. These processes produce irregular surfaces.

  FIG. 1 is a schematic diagram of a polymer bead 10. The polymer bead 10 has an outer surface 12 and an inner composition 15. The polymer beads 10 are often homogeneous and even when an identifiable interface between the outer surface 12 and the inner composition 15 is observed using a microscope such as a scanning electron microscope or an optical microscope. Nothing exists. Dry polymer beads often remain homogeneous and do not contain internal pores or grooves such as macroscopic (ie, greater than 100 nm) pores or grooves. The homogeneity of the polymer beads and dried polymer beads refers to a polymer matrix containing polymerized material and a polar solvent. If an active agent is present, the active agent may or may not be homogeneously dispersed throughout the polymer beads. Furthermore, the active agent may be present in a phase separate from the polymer matrix.

  In general, polymer beads (especially those with an active agent) have no distinguishable porosity or voids when viewed with a microscope. For example, when the polymer beads are observed using an environmentally controlled scanning electron microscope with magnification up to 50 times, there are no discernible holes (see the representative swollen polymer beads in FIG. 6A). In many cases, even when the polymer beads are observed using a field emission scanning electron microscope with the magnification increased to 50,000 times, no distinguishable holes are observed.

  The polymer beads are formed from a precursor composition containing (i) a polar solvent and (ii) a polymerizable material that is miscible with the polar solvent. The polymerizable material contains at least one monomer capable of free radical polymerization and having an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. In some embodiments, other optional additives such as treating agents, active agents, or mixtures thereof can be present in the precursor composition. If present, these optional additives can be dissolved or dispersed in the precursor composition.

  As used herein, the term “polar solvent” refers to water, a water-miscible organic solvent, or a mixture thereof. Although polar solvents do not react in the precursor composition (ie, polar solvents are not monomers), polar solvents usually swell the resulting polymer beads. That is, the polymerizable material is polymerized in the presence of a polar solvent where the resulting polymer beads are swollen by the polar solvent. The swollen polymer beads contain at least a part of the polar solvent contained in the precursor composition.

  Any water used in the precursor composition can be tap water, well water, deionized water, spring water, distilled water, sterilized water, or any other suitable type of water. A water-miscible organic solvent generally refers to an organic solvent capable of hydrogen bonding and forming a single phase solution when mixed with water. For example, a water-miscible organic solvent is present in a single phase solution when mixed with the following amounts of water: That is, at least 10 weight percent, at least 20 weight percent, at least 30 weight percent, at least 40 weight percent, or at least 50 weight percent, based on the total weight of the solution. Although ideally liquid at room temperature, the water-miscible organic solvent may be a solid having a melting temperature of less than about 50 ° C. Suitable water-miscible organic solvents often contain hydroxyl groups or oxy groups, but are alcohols, polyols having a weight average molecular weight of about 300 g / mol or less, ethers, and weight average molecular weights of about Examples include polyethers of 300 g / mol or less. Typical water miscible organic solvents include methanol, ethanol, isopropanol, n-propanol, ethylene glycol, triethylene glycol, glycerol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, ethylene oxide and propylene oxide random And block copolymers, dimethoxytetraglycol, butoxytriglycol, trimethylene glycol trimethyl ether, ethylene glycol dimethyl ether, ethylene glycol monobutyl ether, ethylene glycol monoethyl ether, and mixtures thereof, but are not limited thereto.

  The amount of polar solvent present is often greater than 10 weight percent based on the total weight of the precursor composition. In a typical precursor composition, the polar solvent is present in the following amounts. That is, at least 15 weight percent, at least 20 weight percent, at least 25 weight percent, at least 30 weight percent, at least 40 weight percent, or at least 50 weight percent, based on the total weight of the precursor composition. The polar solvent in the precursor composition can be present in the following amounts. That is, up to 85 weight percent, up to 80 weight percent, up to 75 weight percent, up to 70 weight percent, or up to 60 weight percent, based on the total weight of the precursor composition. In some precursor compositions, the polar solvent is present in the following amounts. That is, greater than 10 to 85 weight percent, greater than 10 to 80 weight percent, 20 to 80 weight percent, 30 to 80 weight percent, or 40 to 80 weight percent, based on the total weight of the precursor composition.

  The polymerizable material is miscible with the polar solvent and does not phase separate from the polar solvent. As used herein in connection with a polymerizable material, the term “miscible” means that the polymerizable material is predominantly soluble in or compatible with the polar solvent. . However, there may be a small amount of polymerizable material that does not dissolve in the polar solvent. For example, the polymerizable material may have impurities that do not dissolve in the polar solvent. Generally, at least 95 weight percent, at least 97 weight percent, at least 98 weight percent, at least 99 weight percent, at least 99.5 weight percent, at least 99.8 weight percent, or at least 99.9 weight percent polymerizable material Can be dissolved in a polar solvent.

  As used herein, the term “polymerizable material” can refer to a monomer or a mixture of monomers. The terms “monomer” and “monomer molecule” are used interchangeably to refer to a compound containing at least one polymerizable group capable of free radical polymerization. The polymerizable group is usually an ethylenically unsaturated group.

  In some embodiments, the polymerizable material includes a monomer of a single chemical structure. In other embodiments, the polymerizable material includes a plurality of different monomers (ie, there is a mixture of monomers having different chemical structures). Whether the polymerizable material includes a single monomer or a mixture of monomers, the average number of polymerizable groups (eg, ethylenically unsaturated groups) per monomer molecule of the polymerizable material is at least 1. 2. The polymerizable material can include, for example, a single type of monomer having two or more polymerizable groups. Alternatively, the polymerizable material can include a plurality of different types of monomers such that the average number of polymerizable groups per monomer molecule is equal to at least 1.2. In some embodiments, the average number of polymerizable groups per monomer molecule is the following value: That is, at least 1.3, at least 1.4, at least 1.5, at least 1.6, at least 1.7, at least 1.8, at least 1.9, at least 2.0, at least 2.1, at least 2. 2, at least 2.3, at least 2.4, at least 2.5, at least 2.6, at least 2.7, at least 2.8, at least 2.9, or at least 3.0.

  The average number of polymerizable groups per molecule is determined by determining the relative molar concentration of each monomer molecule and its functional group (number of polymerizable groups) and determining the number average functional group. For example, the polymerizable material may include X mole percent of a first monomer (having n polymerizable groups) and (100-X) mole percent of a second monomer (having m polymerizable groups). In this case, the average number of polymerizable groups per monomer molecule of the polymerizable material is [n (X) + m (100−X)] / 100. In another example, the polymerizable material includes a first monomer having n polymerizable groups as X mole percent, a second monomer having m polymerizable groups as Y mole percent, and q polymerizations. When the third monomer having a polymerizable group contains (100-XY) mole percent, the average number of polymerizable groups per molecule of the polymerizable material is [n (X) + m (Y) + q (100−X−Y)] / 100.

  The polymerizable material includes at least one monomer having two or more polymerizable groups. Similarly, a first monomer having three or more polymerizable groups has one polymerizable group provided that it contains a mixture having an average number of polymerizable groups per monomer molecule of at least 1.2. It can be mixed with a second monomer, a second monomer having two polymerizable groups, or a mixture thereof. In many cases, monomers having three or more polymerizable groups contain monomer impurities having two polymerizable groups, one polymerizable group, or a mixture thereof.

  The precursor composition generally contains 15 to 90 weight percent polymerizable material, based on the total weight of the precursor composition. For example, the precursor composition contains at least 15 weight percent, at least 20 weight percent, at least 25 weight percent, at least 30 weight percent, at least 40 weight percent, or at least 50 weight percent polymerizable material. The precursor composition can include up to 90 weight percent, up to 80 weight percent, up to 75 weight percent, up to 70 weight percent, or up to 60 weight percent polymerizable material. In some precursor compositions, the amount of polymerizable material is 20 to 90 weight percent, 30 to 90 weight percent, 40 to 90 weight percent, or 40 to 80 weight percent, based on the total weight of the precursor composition. Percentage range.

The polymerizable material often includes one or more (meth) acrylates. As used herein, the term “(meth) acrylate” refers to methacrylate, acrylate, or a mixture thereof. (Meth) acrylate contains a (meth) acryloyl group. The term “(meth) acryloyl” refers to a monovalent group of formula H ₂ C═CR ^b — (CO) —. Here, R ^b is hydrogen or methyl, and (CO) indicates that carbon is bonded to oxygen by a double bond. The (meth) acryloyl group is a polymerizable group (that is, an ethylenically unsaturated group) of (meth) acrylate capable of free radical polymerization. All polymerizable materials can be (meth) acrylates or the polymerizable material can include one or more (meth) acrylates in combination with other monomers having ethylenically unsaturated groups.

  In many embodiments, the polymerizable material includes poly (alkylene oxide (meth) acrylate). The terms poly (alkylene oxide (meth) acrylate), poly (alkylene glycol (meth) acrylate), alkoxylated (meth) acrylate, and alkoxylated poly (meth) acrylate can be used interchangeably, and two or more A (meth) acrylate having at least one group containing a constituent unit of an alkylene oxide residue (sometimes referred to as an alkylene oxide unit). In many cases, there are at least five alkylene oxide residue building blocks. The alkylene oxide unit is a divalent group of formula -OR-. Wherein R is an alkylene having up to 10 carbon atoms, up to 8 carbon atoms, up to 6 carbon atoms, or up to 4 carbon atoms. The alkylene oxide units are often selected from ethylene oxide units, propylene oxide units, butylene oxide units, or mixtures thereof.

  As long as the average number of ethylenically unsaturated groups (eg, (meth) acryloyl groups) per monomer molecule is at least 1.2, the polymerizable material includes a single (meth) acrylate or a mixture of (meth) acrylates Can be included. In order for the average number of (meth) acryloyl groups per monomer molecule to be at least 1.2, at least a portion of the (meth) acrylate present in the polymerizable material is more than one (meth) per monomer molecule. Has an acryloyl group. For example, the polymerizable material can contain (meth) acrylates having two (meth) acryloyl groups per monomer molecule, and as a mixture (meth) acrylates having two (meth) acryloyl groups per monomer molecule; A combination of one or more (meth) acrylates having one (meth) acryloyl group per monomer molecule can be contained. In another example, the polymerizable material can contain (meth) acrylates having 3 (meth) acryloyl groups per monomer molecule, or as a mixture (meth) having 3 (meth) acryloyl groups per monomer molecule. Combinations of acrylates and one or more (meth) acrylates having one (meth) acryloyl group per monomer molecule, two (meth) acryloyl groups per monomer molecule, or mixtures thereof can be included.

  Specific examples of suitable polymerizable materials having one ethylenically unsaturated group per monomer molecule include, but are not limited to: That is, 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, (meth) acrylonitrile, (meth) acrylamide, caprolactone ( (Meth) acrylates, poly (alkylene oxide (meth) acrylates) (eg, poly (ethylene oxide (meth) acrylate), poly (propylene oxide (meth) acrylate), and poly (ethylene oxide-co-propylene oxide (meth) acrylate))) , Alkoxy poly (alkylene oxide (meth) acrylate), (meth) acrylic acid, β-carboxyethyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, N Vinylpyrrolidone, N-vinylcaprolactam, N-alkyl (meth) acrylamide (eg, N-methyl (meth) acrylamide), and N, N-dialkyl (meth) acrylamide (eg, N, N-dimethyl (meth) acrylamide) It is.

  Suitable polymerizable materials having two ethylenically unsaturated groups per monomer molecule include, for example, alkoxy di (meth) acrylates. Examples of alkoxy di (meth) acrylates include, but are not limited to: Poly (alkylene oxide di (meth) acrylate) such as poly (ethylene oxide di (meth) acrylate) and poly (propylene oxide di (meth) acrylate); alkoxydiol di (meth) acrylate such as ethoxylated butanediol di (meth) Acrylate, propoxylated butanediol di (meth) acrylate, and ethoxylated hexanediol di (meth) acrylate; alkoxytrimethylolpropane di (meth) acrylate, such as ethoxylated trimethylolpropane di (meth) acrylate and propoxylated trimethylolpropane di (Meth) acrylates; and alkoxypentaerythritol di (meth) acrylates such as ethoxylated pentaerythritol di (meth) acrylates And a propoxylated pentaerythritol di (meth) acrylate.

  Examples of suitable polymerizable materials having three ethylenically unsaturated groups per monomer molecule include, for example, alkoxylated tri (meth) acrylates. Examples of alkoxylated tri (meth) acrylates include, but are not limited to: That is, alkoxylated trimethylolpropane tri (meth) acrylate such as ethoxylated trimethylolpropane tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, and ethylene oxide / propylene oxide copolymer trimethylolpropane tri (meth) Acrylates; and alkoxylated pentaerythritol tri (meth) acrylates such as ethoxylated pentaerythritol tri (meth) acrylates.

  Suitable polymerizable materials having at least 4 ethylenically unsaturated groups per monomer include, for example, alkoxylated tetra (meth) acrylate and alkoxylated penta (meth) acrylate. Examples of alkoxylated tetra (meth) acrylates include alkoxylated pentaerythritol tetra (meth) acrylates such as ethoxylated pentaerythritol tetra (meth) acrylate.

  In some embodiments, the polymerizable material includes a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups per monomer molecule. In order to obtain an average of at least 1.2 ethylenically unsaturated groups per monomer molecule, the poly (alkylene oxide (meth) acrylate) can be used alone or in combination with other monomers. Alkoxy moieties (ie, poly (alkylene oxide) moieties) often have at least 5 alkylene oxide units selected from ethylene oxide units, propylene oxide units, butylene oxide units, or combinations thereof. That is, each mole of poly (alkylene oxide (meth) acrylate) contains at least 5 moles of alkylene oxide units. The presence of multiple alkylene oxide units facilitates dissolution of poly (alkylene oxide (meth) acrylate) in polar solvents. Some representative poly (alkylene oxide (meth) acrylates) include at least 6 alkylene oxide units, at least 8 alkylene oxide units, at least 10 alkylene oxide units, at least 12 alkylene oxide units, at least 15 Contains at least 20 alkylene oxide units, at least 20 alkylene oxide units, or at least 30 alkylene oxide units. The poly (alkylene oxide (meth) acrylate) can contain poly (alkylene oxide) chains, the poly (alkylene oxide) chains being homopolymer chains, block copolymer chains, random copolymer chains, or mixtures thereof. is there. In some embodiments, the poly (alkylene oxide) chain is a poly (ethylene oxide) chain.

  It is possible to use any molecular weight of this poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups, as long as the polymer beads can be formed from the precursor composition. The weight average molecular weight of the poly (alkylene oxide (meth) acrylate) is often 2000 g / mole or less, 1800 g / mole or less, 1600 g / mole or less, 1400 g / mole or less, 1200 g / mole or less, or 1000 g / mole or less. It is. However, in other applications, it is desirable to include poly (alkylene oxide (meth) acrylate) having a weight average molecular weight greater than 2000 g / mol in the polymerizable material.

  The preparation of some representative poly (alkylene oxide (meth) acrylates) having multiple (meth) acryloyl groups is described in the following references. US Pat. No. 7,005,143 (Abuelyaman et al.), In addition to US Patent Application Publication No. 2005/0215752 A1 (Popp et al.), 2006/0212011 A1 (Pop et al.), And No. 2006/0235141 A1 (Riegel et al.). Suitable poly (alkylene oxide (meth) acrylates) having an average (meth) acryloyl functionality per monomer molecule of at least 2 and having at least 5 alkylene oxide units include, for example, Sartomer (Exton, Pa.) (Exton)), trade names "SR9035" (ethoxylated (15) trimethylolpropane triacrylate), "SR499" (ethoxylated (6) trimethylolpropane triacrylate), "SR502" (ethoxylated (9) triacrylate). Methylolpropane triacrylate), "SR415" (ethoxylated (20) trimethylolpropane triacrylate), and "CD501" (propoxylated (6) trimethylolpropane triacrylate) and "CD9038" (Ethoxylated (30) bis-phenol A diacrylate). The number in parentheses refers to the average number of alkylene oxide units per monomer molecule. Other suitable poly (alkylene oxide (meth) acrylates) include polyalkoxytrimethylolpropane triacrylate. This is, for example, commercially available from BASF (Ludwigshafen, Germany) under the trade name “LAROMER” and has at least 30 alkylene oxide units.

  Some exemplary precursor compositions are poly (alkylene oxide (meth) acrylates) having at least 2 (meth) acryloyl groups per monomer molecule, having at least 5 ethylene oxide units, And those having a weight average molecular weight of less than 2000 g / mol. This polymerizable material can be the only polymerizable material in the precursor composition, or it can be combined with other monomers that are miscible in the polar solvent. Whether the poly (alkylene oxide (meth) acrylate) is the only monomer in the precursor composition or in combination with other monomers, the average number of functional groups per monomer molecule of the polymerizable material is at least 1.2. is there.

  A more specific representative precursor composition is poly (ethylene oxide) (meth) acrylate having at least 2 (meth) acryloyl groups per monomer molecule and having at least 5 alkylene oxide units. And those having a weight average molecular weight of 2000 g / mol or less. An even more specific representative precursor composition may contain ethoxylated trimethylolpropane triacrylate having a weight average molecular weight of 2000 g / mol or less. In many cases, ethoxylated trimethylolpropane triacrylate contains impurities having one (meth) acryloyl group, two (meth) acryloyl groups, or mixtures thereof. For example, commercially available “SR415” (ethoxylated (20) trimethylolpropane triacrylate) often has an average number of functional groups per monomer molecule of less than 3 (when analyzed, the average number of functional groups per monomer molecule is about 2.5). Even if impurities are present, the average number of functional groups per monomer molecule in the precursor composition is at least 1.2.

In addition to poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups per monomer molecule, other monomers added to the precursor composition to impart specific properties to the polymer beads Can be included. Optionally, the precursor composition can contain an anionic monomer. As used herein, the term “anionic monomer” refers to a monomer containing the following acidic group in addition to an ethylenically unsaturated group. That is, a carboxylic acid (that is, carboxy) group (—COOH) or a salt thereof, a sulfonic acid group (—SO ₃ H) or a salt thereof, a sulfate group (—SO ₄ H) or a salt thereof, a phosphonic acid group (—PO ₃₎ H ₂ ) or a salt thereof, a phosphate group (—OPO ₃ H) or a salt thereof, or a mixture thereof. Depending on the pH of the precursor composition, the anionic monomer can be in a neutral state (acidic type) or in the form of a salt (anionic type). Anionic counterions are often selected from: That is, alkali metals, alkaline earth metals, ammonium ions, or ammonium ions having various alkyl groups such as tetraalkylammonium.

  Suitable anionic monomers having a carboxy group include, but are not limited to: That is, acrylic acid, methacrylic acid, and various carboxyalkyl (meth) acrylates such as 2-carboxyethyl acrylate, 2-carboxyethyl methacrylate, 3-carboxypropyl acrylate, and 3-carboxypropyl methacrylate. Other suitable anionic monomers having a carboxy group include, for example, (meth) acryloyl amino acids such as those described in US Pat. No. 4,157,418 (Heilmann. Representative (meth). Acrylyl amino acids include, but are not limited to, N-acryloylglycine, N-acryloylaspartic acid, N-acryloyl-β-alanine and 2-acrylamidoglycolic acid Suitable anionic monomers having a β sulfonic acid group Include, but are not limited to, various (meth) acrylamide sulfonic acids such as N-acrylamide methanesulfonic acid, 2-acrylamidoethanesulfonic acid, 2-acrylamido-2-methylpropanesulfone. Acid, and Such as 2-methacrylamide-2-methylpropane sulfonic acid, etc. Suitable anionic monomers having a phosphonic acid group include, but are not limited to, the following: (meth) acrylamide alkylphosphonic acid For example, 2-acrylamidoethylphosphonic acid, 3-methacrylamidopropylphosphonic acid, etc. Suitable anionic monomers having a phosphoric acid group include: an alkylene glycol (meth) acrylate Phosphate, for example, ethylene glycol (meth) acrylate phosphate, propylene glycol (meth) acrylate phosphate, etc. Salts of any of these acid monomers can also be used.

  Anionic monomers, if present, can increase the degree of swelling of the polymer beads. That is, the degree of swelling can often be changed by changing the amount of anionic monomer as well as the amount of other hydrophilic monomers in the precursor composition. The degree of swelling is usually proportional to the total amount of polar solvent that the polymer beads can sorb. The amount of anionic monomer is controlled so that the average number of ethylenically unsaturated groups per monomer molecule of the polymerizable material is at least 1.2. The amount of anionic monomer present is often in the range of 0 to less than 20 weight percent (based on the total weight of the polymerizable material). For example, the precursor composition includes less than 20 weight percent anionic monomer, less than 15 weight percent anionic monomer, less than 10 weight percent anionic monomer, less than 5 weight percent anionic monomer, less than 3 weight percent. Anionic monomer, less than 2 weight percent anionic monomer, less than 1 weight percent anionic monomer, less than 0.5 weight percent anionic monomer, less than 0.2 weight percent anionic monomer, or 0.1 weight percent Less than anionic monomer. Some precursor compositions do not contain anionic monomers. A low level or no anionic monomer may be preferred in compositions with certain biologically active agents. For example, a specific anionic antibacterial agent may be restrained more firmly than necessary in the beads so as not to elute as necessary.

  In other embodiments, the precursor composition can contain a cationic monomer. As used herein, the term “cationic monomer” refers to a monomer having an amino group, a salt of an amino group, or a mixture thereof in addition to an ethylenically unsaturated group. For example, the cationic monomer can be amino (meth) acrylate or amino (meth) acrylamide. The amino group can be a primary amino group or a salt thereof, a secondary amino group or a salt thereof, a tertiary amino group or a salt thereof, or a quaternary salt. Cationic monomers often include a tertiary amino group or salt thereof, or a quaternary amino salt. Depending on the pH of the precursor composition, some cationic monomers can be in a neutral state (basic form) or in a salt form (cationic form). Cationic counterions are often selected from: That is, not only the various carboxylate anions (eg acetate), but also halides (eg bromide or chloride), sulfates, alkyl sulfates (eg methosulfate or ethosulphate).

  Typical amino (meth) acrylates include the following. That is, N, N-dialkylaminoalkyl (meth) acrylate and N-alkylaminoalkyl (meth) acrylate, such as N, N-dimethylaminoethyl methacrylate, N, N-acrylic acid dimethylaminoethyl acrylate, N, N- Diethylaminoethyl methacrylate, N, N-diethylaminoethyl acrylate, N, N-dimethylaminopropyl methacrylate, N, N-dimethylaminopropyl acrylate, N-tert-butylaminopropyl methacrylate, N-tert-butylaminopropyl acrylate, etc. is there.

  Typical amino (meth) acrylamides include the following, for example. That is, N- (3-aminopropyl) methacrylamide, N- (3-aminopropyl) acrylamide, N- [3- (dimethylamino) propyl] methacrylamide, N- (3-imidazolylpropyl) methacrylamide, N- (3-imidazolylpropyl) acrylamide, N- (2-imidazolylethyl) methacrylamide, N- (1,1-dimethyl-3imidazolylpropyl) methacrylamide, N- (1,1-dimethyl-3imidazolylpropyl) acrylamide, N- (3-benzimidazolylpropyl) acrylamide and N- (3-benzimidazolylpropyl) methacrylamide.

  Representative monomer quaternary salts include, but are not limited to: (Meth) acrylamide alkyltrimethylammonium salts (eg, 3-methacrylamidopropyltrimethylammonium chloride and 3-acrylamidopropyltrimethylammonium chloride) and (meth) acryloxyalkyltrimethylammonium salts (eg, 2-acryloxyethyltrimethylammonium chloride) Chloride, 2-methacryloxyethyltrimethylammonium chloride, 3-methacryloxy-2hydroxypropyltrimethylammonium chloride, 3-acryloxy-2hydroxypropyltrimethylammonium chloride, and 2-acryloxyethyltrimethylammonium methylsulfate).

Quaternary amino salts of other representative monomers include those in which the alkyl group has 2 to 22 carbon atoms or 2 to 20 carbon atoms as a dimethylalkylammonium group. That is, the monomer includes a group of formula —N (CH ₃ ) ₂ (C _n H _{2 + 1} ) ⁺ . Here, n is an integer and the value is 2-22. Representative monomers include, but are not limited to, monomers of the following formula:

  Here, n is an integer and the range is 2-22. The synthesis of these monomers is described in US Pat. No. 5,437,932 (Ali et al.). These monomers can be prepared, for example, by combining dimethylaminoethyl methacrylate salt, acetone, 1-bromoalkane having 2 to 22 carbon atoms, and optionally an antioxidant. The resulting mixture may be stirred for about 16 hours at about 35 ° C. and then cooled to room temperature. The resulting white solid precipitate may then be separated by filtration, washed with cold ethyl acetate, and dried at 40 ° C. under vacuum.

  Some cationic monomers (eg, those having quaternary amino groups) can impart antimicrobial properties to the polymer beads. The amount of cationic monomer present is often in the range of 0 to 50 weight percent based on the total weight of the polymerizable material. For example, the precursor composition can contain up to 40 weight percent, up to 30 weight percent, up to 20 weight percent, up to 15 weight percent, or up to 10 weight percent. The precursor composition in some examples contains at least 0.5 weight percent, at least 1 weight percent, at least 2 weight percent, or at least 5 weight percent cationic monomer. Some precursor compositions do not contain a cationic monomer.

  Some representative polymerizable materials contain only nonionic monomers. That is, the polymerizable material is substantially free of both anionic and cationic monomers. As used herein in connection with anionic or cationic monomers, “substantially free” means that the polymerizable material includes less than 1 weight percent, less than 0.5 weight percent, based on the weight of the polymerizable material. This means that less than 0.2 mass percent, less than 0.2 mass percent, or less than 0.1 mass percent of anionic monomer or cationic monomer is contained.

  In some embodiments, the precursor composition includes (a) greater than 10 weight percent to 85 weight percent polar solvent, based on the total weight of the precursor composition, and (b) the precursor composition. 15 weight percent to less than 90 weight percent polymerizable material based on the total weight. The polymerizable material is miscible in the polar solvent and has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. The polymerizable material includes (i) a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups and having at least five alkylene oxide units, and (ii) polymerization in the precursor composition. An anionic monomer having 0 to less than 20 mass percent based on the total mass of the conductive material and having an acidic group, a salt of an acidic group, or a mixture thereof in addition to the ethylenically unsaturated group It is done.

  In addition to the polar solvent and the polymerizable material, the precursor composition can include one or more optional additives such as processing agents, activators, or mixtures thereof. Any of these optional additives can be dissolved in the precursor composition or dispersed in the precursor composition.

  As used herein, the term “treatment agent” refers to a compound or mixture of compounds that is added primarily to alter the physical or chemical properties of either the precursor composition or the polymeric material. That is, the purpose of adding the treating agent is to change the precursor composition or to facilitate the formation of the polymeric material. When added, the treating agent is usually added to the precursor composition. These treatment agents are not normally considered to be active agents.

  Suitable treatment agents include, but are not limited to: That is, rheology modifiers such as polymer thickeners (eg rubber, cellulose, pectin etc.) or inorganic thickeners (eg clay, silica gel etc.), surfactants that change the surface tension, emulsifiers that stabilize the precursor composition , Solubilizers that increase the solubility of monomers in polar solvents, initiators that accelerate the polymerization reaction of polymerizable materials, chain transfer or retarders, binders, dispersants, fixing agents, foaming agents, flow aids, bubble stabilization Agents, foaming agents, gelling agents, polishes, propellants, waxes, compounds for lowering the freezing point and / or raising the boiling point of precursor compositions, and plasticizers.

  The amount of any optional treating agent present is typically 20 weight percent or less, 15 weight percent or less, 10 weight percent or less, 8 weight percent or less, 6 weight percent or less, based on the total weight of the precursor composition. The mass percent or less, 2 mass percent or less, 1 mass percent or less, or 0.5 mass percent or less.

  One representative treating agent is an initiator. Most precursor compositions include an initiator for causing a free radical polymerization reaction. The initiator can be a photoinitiator, a thermal initiator, or a redox couple. The initiator can be soluble in the precursor composition or can be dispersed in the precursor composition.

  An example of a suitable soluble photoinitiator is 2-hydroxy-1- [4- (2-hydroxyethoxy) phenyl] -2methyl-1-propanone. This is commercially available from Ciba Specialty Chemicals (Taritown, NY) under the trade designation “IRGACURE 2959”. An example of a suitable dispersed photoinitiator is alpha, alpha-dimethoxy-alphaphenylacetophenone. This is commercially available from Ciba Specialty Chemicals under the trade name “Irgacure 651”. Another suitable photoinitiator is the acrylamide acetyl photoinitiator described in US Pat. No. 5,506,279. This photoinitiator contains not only a group capable of functioning as an initiator but also a polymerizable group. Initiators are typically not redox initiators as known in the art and used in some polymerizable compositions. Such redox initiators will react with the bioactive agent, if present.

  Suitable thermal initiators include, for example, azo compounds, peroxides or hydroperoxides, persulfates and the like. Representative azo compounds include 2,2 "-azobis [2- (2-imidazolin-2-yl) propane] dihydrochloride, 2,2" -azobis (2-amidinopropane) dihydrochloride and 4,4 '. -Azobis- (4-cyanopentanoic acid). Examples of commercially available thermal azo compound polymerization initiators include DuPont Specialty Chemical (DuPont) under the trade name “VAZO” such as “VAZO” 44, “VAZO” 56 and “VAZO” 68. Materials available from Specialty Chemical (Wilmington, Del.). Suitable peroxides and hydroperoxides include acetyl peroxide, t-butyl hydroperoxide, cumene hydroperoxide and peroxyacetic acid. Suitable persulfates include, for example, sodium persulfate and ammonium persulfate.

  In other examples, the free radical polymerization initiator is a redox couple, such as ammonium persulfate or sodium persulfate and N, N, N ′, N′-tetramethyl-1,2-diaminoethane, ammonium persulfate or persulfate. Examples thereof include sodium and ammonium ferrous sulfate, hydrogen peroxide and ammonium ferrous sulfate, cumene hydroperoxide and N, N-dimethylaniline.

  In some embodiments, the precursor composition includes only a polymerizable material, a polar solvent, and an initiator (eg, a photoinitiator). In most embodiments, the amount of initiator present is no more than 4 weight percent, no more than 3 weight percent, no more than 2 weight percent, no more than 1 weight percent, or no more than 0.5 weight percent, based on the total weight of the precursor composition. It is.

  The precursor composition can include one or more optional active agents. The activator imparts some added functionality to the polymer beads. The polymer beads function as a carrier for the active agent. When present, the active agent abundance is typically 30 weight percent or less, 25 weight percent or less, 20 weight percent or less, 15 weight percent or less, 10 weight percent or less, or 5 weight percent, based on the total weight of the precursor composition. Less than a percent.

  In some embodiments, the active agent can migrate into and out of the polymer beads. In other embodiments, the active agent tends to remain stationary within the polymer beads. For example, the active agent molecular size may prevent the active agent from eluting or diffusing out of the bead. In another example, the active agent may be bound to the beads by covalent or ionic bonds. The activator optionally reacts with other ethylenically unsaturated groups to become part of the polymeric material or can be bound to the polymeric material in the beads. It can have a system unsaturated group.

  Some active agents are biologically active agents. As used herein, the terms “biologically active agent” and “bioactive agent” are used interchangeably and refer to biological systems (eg, bacteria or other microorganisms, plants, fish, insects, or mammals). Refers to a compound or mixture of compounds having some known effect on animals, etc.). The bioactive agent is added to affect the biological system, for example, to affect the metabolism of the biological system. Examples of bioactive agents include, but are not limited to: That is, pharmaceutical agents, herbicides, insecticides, antibacterial agents, disinfectants and preservatives, local anesthetics, astringents, antifungal agents, antibacterial substances, growth factors, vitamins, herbal extracts, antioxidants, steroids or others Anti-inflammatory agents, compounds that aid in wound treatment, vasodilators, exfoliants such as alpha hydroxy acids or beta hydroxy acids, enzymes, nutrients, proteins, and carbohydrates. Still other bioactive agents include the following. Artificial tanning agents, tanning accelerators, skin soothing agents, skin tightening agents, anti-wrinkle agents, skin repair agents, sebum suppressors, sebum stimulating substances, protease inhibitors, anti-itch ingredients, hair growth inhibitors, Hair accelerant, skin sensation agent, anti-acne treatment, hair remover, hair remover, fish eye remover, octopus remover, wart remover, sunscreen preparation, insect repellent, deodorant and antiperspirant, hair coloring Agents, bleaches, and antidandruff agents. Any other suitable bioactive agent known in the art can also be used.

  Other active agents are not biologically active. These active agents are added to impart some non-biological functionality to the polymer beads. That is, the addition of these active agents is not for affecting the biological system, for example, for affecting the metabolism of the biological system. For example, a suitable active agent can be selected to alter the odor, charge, color, density, pH, osmolarity, water activity, ionic strength, or refractive index of the polymer beads. Activators can also be selected to provide reactive groups or compounds. Examples of drugs that are not biologically active include the following: Emulsifiers or surfactants (including anionic surfactants, cationic surfactants, zwitterionic surfactants, nonionic surfactants, and combinations thereof), pigments, inorganic oxides (eg silicon dioxide) , Titania, alumina, and zirconia), fragrance ingredients such as fragrance therapeutics and fragrances, odor absorbers, wetting agents, lubricants, dyes, bleaches or colorants, seasonings, decorative agents such as brighteners, emollients, Acids, bases, buffers, indicators, soluble salts, chelating agents and the like. Some wetting agents (eg, glycols and other polyols) that are included in the amount used and that are liquid at room temperature and miscible with water can be used in calculating the composition percentage of swollen or dried polymer beads. It is considered part of the polar solvent.

  In some embodiments, the active agent is an indicator. Any suitable chemistry can be used for the indicator. For example, an indicator can be used to detect the presence of a specific pH range or a specific type of compound. The presence of several specific types of compounds can cause a color change. For example, ninhydrin can be used to detect the presence of a protein or amino group. Alternatively, the indicator can be a typical pH indicator such as methyl blue or phenolphthalein.

  Inorganic oxide nanoparticles can be added to the polymer beads to increase the refractive index of the beads. For example, polymer beads can be loaded with zirconia nanoparticles or titania nanoparticles. Preparation of zirconia nanoparticles can be performed using, for example, the methods described in US Pat. No. 6,376,590 (Kolb et al.) And US Patent Publication No. 2006 / 0148950A1 (Davidson et al.). it can.

  Any of the activators may have a polymerizable group. Using a polymerizable group on the activator can be used to prevent the activator from moving out of the polymer beads. Cationic monomers can be included in the polymerizable material of the precursor composition if they have not only quaternary amino groups that may function as antimicrobial agents, but also ethylenically unsaturated groups. The cationic monomer is often a (meth) acrylate having a quaternary amino group.

  Since polymer beads usually have unreacted polymerizable groups, the polymer beads can be reacted with an activator having a polymerizable group by post-molding. For example, if the cationic monomer has an ethylenically unsaturated group and a quaternary amino group, it can be reacted with polymer beads having unreacted ethylenically unsaturated groups. Exposing the mixture containing polymer beads, cationic monomer, and photoinitiator to actinic radiation to react the ethylenically unsaturated group of the cationic monomer with the unreacted ethylenically unsaturated group of the polymer bead. it can. The reaction product is a polymer bead having a quaternary amino group added thereto.

  The method of producing polymer beads includes the steps of providing a precursor composition and forming droplets of the precursor composition that are entirely surrounded by the gas phase. The method further includes exposing the droplet to radiation for a time sufficient to at least partially polymerize the polymerizable material in the precursor composition to form a first swollen polymer bead. The droplet can be dropped by gravity so as to pass through the radiation source, or it can be blown upward as a spray.

  Any of the precursor compositions described above can be used in a method for producing polymer beads. The polymerizable material included in the precursor composition has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. In some embodiments, the polymerizable material includes a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups and having at least five alkylene oxide units. The polymerizable material can optionally include 0 to 20 weight percent anionic monomer, based on the total weight of the polymerizable material in the precursor composition.

  Upon exposure to radiation, the polymerizable material in the precursor composition undergoes a free radical polymerization reaction. As used herein, the term “radiation” refers to actinic radiation (eg, radiation whose wavelength is in the ultraviolet or visible region of the spectrum), accelerated particles (eg, electron beam irradiation), hot rays (eg, heat or infrared). Radiation). Often the radiation is actinic radiation or accelerated particles. This is because these energy sources tend to provide good control over the initiation and rate of polymerization. In addition, actinic radiation and accelerated particles can be used to effect curing at relatively low temperatures. As a result, deterioration of components that are sensitive to relatively high temperatures that may be required to initiate the polymerization reaction by thermal radiation is avoided. Any suitable source of actinic radiation that can generate the energy of the desired region of the electromagnetic spectrum can be used. Typical sources of actinic radiation include mercury lamps, xenon lamps, carbon arc lamps, tungsten filament lamps, lasers and sunlight.

  FIG. 2 is a schematic diagram illustrating one exemplary process for making polymer beads. Process 20 includes a feed system 30 and a polymerization system 40. A precursor composition 50 containing a polymerizable material and a polar solvent is provided to the delivery system 30. Feed system 30 delivers precursor composition 50 to polymerization system 40. Within the polymerization system 40, the polymerizable material in the precursor composition 50 is exposed to radiation to cause a free radical polymerization reaction to form a polymeric material. Each of the feed system 30 and the polymerization system 40 of the process 20 can include various elements.

  The supply system 30 includes a receiving portion 32 having an outlet 34. Receiving portion 32 is a pot, container, hopper, hose, funnel, or other element that can pour or otherwise add an amount of precursor composition 50 therein. obtain. The receiving portion 32 may be metal, plastic, glass, or any other suitable material. Preferably, the precursor composition 50 can be easily removed from the receiving portion 32 without adhering to the receiving portion 32 or reacting with the receiving portion 32. The outlet 34 may be as simple as an opening or hole in the receiving portion 32, or may be another element, such as an ultrasonic atomizer. In the embodiment shown in FIG. 2, the outlet 34 is simply an opening in the receiving portion 32. Through the outlet 34, droplets of the precursor composition 50 can be easily formed.

  The polymerization system 40 includes a radiation source 42 and a shield device 44. The presence of the shield device 44 is often to direct radiation emanating from the source 42 to the desired location to shield people or equipment that may be in close proximity. In this embodiment, the polymerization system 40 also includes a management element 46. The management element 46 protects or isolates the precursor composition 50 (eg, a droplet of the precursor composition 50) from any high velocity airflow that may arise from the radiation source 42. Management element 46 can control the local environment in which polymerization occurs. That is, the management element 46 can be used to control the gas phase composition that generally surrounds the droplets of the precursor composition 50 when the droplets are exposed to the radiation source 42.

  The radiation source 42 may be a single radiation source, or may be the same or different types of radiation sources. The radiation source 42 provides energy such as infrared radiation, visible radiation, ultraviolet radiation, electron beam radiation, microwave radiation, or radio frequency radiation. The particular energy source used will depend on the particular precursor composition 50. Suitable non-ionizing radiation sources include continuous and pulsed sources and may be a broadband source, for example a narrow band source of a monochromatic light source. Representative non-ionizing radiation sources include, but are not limited to: That is, mercury lamps (low pressure type, medium pressure type, high pressure type, and additive type or dope type thereof), fluorescent lamps, germicidal lamps, metal halide lamps, halogen lamps, light emitting diodes, lasers, excimer lamps, Pulsed xenon lamps, tungsten lamps, and incandescent lamps. In addition to ionizing radiation sources such as electron beams, infrared radiation sources and microwave radiation sources may be used. A combination of radiation sources may also be used.

  Some exemplary methods can use electromagnetic radiation having a wavelength in the range of 100-1000 nanometers, 100-800 nanometers, or 100-700 nanometers. In some methods, ultraviolet radiation having a wavelength in the range of 100-400 nanometers or 200-400 nanometers can be used. For example, ultraviolet radiation with a wavelength of less than 200 nm from an excimer source can be used. In many embodiments, radiation source 42 is a high emission UV source, such as a medium pressure mercury lamp (at least 40 W / cm (100 W / inch)). A low-emission lamp, such as a low-pressure mercury lamp including a germicidal lamp, can also be used.

  The shield device 44 can be any suitable shape and material that prevents radiation from the source 42 from coming into contact with a person or device in close proximity. The shield device 44 is well known in the radiation art.

  The management element 46 can be any suitable shape and material that, if present, isolates or protects the fall or flow of the precursor composition 50 past the radiation source 42. In most processes, the management element 46 is transparent or at least partially transparent to radiation from the source 42. An example of element 46 is a quartz tube through which droplets of precursor composition 50 are sent.

  During production of the beads 10, the precursor composition 50 is carried (eg, poured) into the receiving portion 32, for example through an open top, and discharged through the outlet 34 to form droplets. Due to the dynamic properties of natural fluids, the precursor composition 50 specifically forms droplets, either before falling or when falling through the polymerization system 40 (eg, free-falling). As it passes through the management element 46 and past the radiation source 42.

  The droplet size is often controlled to have a diameter in the range of 500 to 3000 micrometers. The droplet size can be adjusted by changing the outlet 34, the viscosity of the precursor composition 50, or both. The passage of the precursor composition 50 through the polymerization system 40 is generally affected only by natural forces such as gravity, and possibly air flow, thermal convection, surface tension, and the like. In some embodiments, an upward gas flow may be used to slow down the fall of the precursor composition 50 that occurs through the polymerization system 40. The duration that the precursor composition 50 is in the polymerization system 40 or the time that the precursor composition 50 is exposed to radiation is typically 10 seconds or less, 5 seconds or less, 3 seconds or less, 2.5 seconds or less, 2 1 second or less, 1 second or less, or 0.5 second or less.

  The droplets of the precursor composition 50 are entirely surrounded by the gas phase. Usually, the atmosphere in which the precursor composition 50 falls is ambient air, but other gas atmospheres such as an inert atmosphere can be used. Suitable inert atmospheres can include, for example, argon, helium, nitrogen, or mixtures thereof. From the polymerization system 40, swollen polymer beads 10 are obtained. If the composition relies on surface tension to form droplets from the falling liquid stream, there is a minimum distance required from the outlet 34 to the radiation source 42. This flow instability is well known in the art.

  FIG. 3 is a schematic diagram illustrating another exemplary method of producing polymer beads. In its most basic form, process 120 includes a feed system 130 and a polymerization system 140. As described above, the precursor composition 50 is provided to the delivery system 130. Feed system 130 delivers precursor composition 50 to polymerization system 140. After the droplets of precursor composition 50 have passed through the polymerization system 140, homogeneous swollen polymer beads are obtained. The feed system 130 and the polymerization system 140 of the process 120 each include various elements.

  Supply system 130 can be similar to supply system 30 and includes a receiving portion 132 having an outlet 134. A spray head, for example, an ultrasonic atomizer 136 is connected to the outlet 134. The ultrasonic atomizer 136 is to form small droplets (eg, a diameter of about 10-500 micrometers) of the precursor composition 50. The droplet size depends on the atomizer used, the viscosity of the precursor composition, and other factors. An optional pump 135 is shown. Pump 135 facilitates movement of precursor composition 50 to atomizer 136.

  The polymerization system 140 can be similar to the system 40 described above and includes a radiation source 142 and a shield device 144. In this illustrated example, the shield device 144 also functions as a management element that directs the composition 50 to pass through the polymerization system 140.

  During production of the beads 10, the precursor composition 50 is provided from the receiver 132 via the outlet 134 and pressurized by the pump 135. The composition 50 is released by mechanical means, such as an atomizer 136. The atomizer 136 creates a spray of droplets that fall through the polymerization system 140 and into the ambient atmosphere. The droplets usually range in diameter from 10 micrometers to 500 micrometers. The polymer beads are formed from droplets of the precursor composition 50.

  Any other means of forming droplets can be used. Examples of other suitable droplet forming means include the following. That is, spray sprayers and many types of spray nozzles with atomizers, atomizers, large volume low pressure sprays, ultrasonic atomizers and piezoelectric droplet generators.

  The process described above illustrates the precursor composition 50 falling vertically from the receiver through the polymerization system. In another alternative process configuration, the precursor composition 50 may be discharged from the receiver, for example in a horizontal direction, so that the precursor composition 50 is in front of and / or passes through the polymerization system. The path contains a horizontal vector.

  For a specific droplet formation method, the particle size distribution may be broad or narrow. The narrow particle size distribution can be monodisperse or nearly monodisperse. As an example, when droplets are generated using ultrasonic atomization, an average diameter of approximately 50 micrometers may be obtained, but the bead size distribution ranges from about 1 micrometer to about 100 micrometers. There is. Other drop formation techniques achieve different bead size distributions. For applications that require beads with a narrow particle size distribution, a more controlled drop formation method may be used, or additional post-screening can be performed to narrow the particle size distribution. This is known to those skilled in the art.

  Formation of the polymer beads is performed by subjecting the droplets of the precursor composition to radiation to cause free radical polymerization of the polymerizable material. Since the precursor composition contains not only a polymerizable material but also a polar solvent, the polymer beads are swollen by the polar solvent. Polymer beads can be described as swollen beads, hydrogel beads, polymer beads swollen by a solvent, or swollen polymer beads. All of these terms may be used interchangeably herein.

  The polymeric material in the swollen polymer beads is crosslinked but may contain unreacted polymerizable or reactive groups. The unreacted polymerizable group usually contains an ethylenically unsaturated group capable of further free radical reaction. There may be other types of polymerizable groups capable of condensation or nucleophilic substitution reactions such as hydroxyl groups or amino groups.

  The swollen polymer beads generally include 15 to 90 weight percent polymeric material, based on the weight of the swollen polymer beads. If less than 15 weight percent of the swollen polymer beads are polymeric material, there may not be enough polymeric material to form a well-shaped bead. If more than 90 weight percent of the swollen polymer beads are polymeric material, the ability to sorb the dried polymer bead sorbate may be inadequately low.

  In some exemplary swollen polymer beads, at least 15 weight percent, at least 20 weight percent, at least 25 weight percent, at least 30 weight percent, at least 40 weight percent, or at least 50 weight percent of the swollen polymer bead is high. It is a molecular material. Up to 85 weight percent, up to 80 weight percent, or up to 70 weight percent of the swollen polymer beads are polymeric material. For example, the swollen polymer beads can contain 15 to 85 weight percent, 20 to 80 weight percent, 30 to 80 weight percent, or 40 to 80 weight percent polymeric material.

  The amount of polar solvent within the swollen polymer beads often ranges from greater than 10 weight percent to 85 weight percent of the swollen polymer beads. If the amount of polar solvent is greater than 85 weight percent, there may not be enough polymeric material to form well-shaped beads. If the amount of polar solvent is less than or equal to 10 weight percent of the swollen polymer beads, the ability of the dried polymer beads to sorb additional liquid may be inadequately low. Any polar solvent contained in the swollen polymer beads is usually not covalently bound to the matrix. In some representative swollen polymer beads, at least 15 weight percent, at least 20 weight percent, at least 25 weight percent, at least 30 weight percent, or at least 40 weight percent of the swollen polymer beads are polar solvents. Up to 85 weight percent, up to 80 weight percent, up to 70 weight percent, up to 60 weight percent, or up to 50 weight percent of the swollen polymer beads are polar solvents.

  In some embodiments, the swollen polymer beads can also contain an active agent. These active agents may be present in the precursor composition used to prepare the swollen polymer beads. Alternatively, a second drying and swelling of the swollen polymer beads can be performed using sorbate. That is, the dried polymer beads can sorb the sorbate to form a second swollen polymer bead. The sorbate often contains an active agent. The active agent can be a biologically active agent, a non-biologically active agent, or a mixture thereof. Suitable activators are described above.

  When included in the precursor composition, the activator is preferably stable and / or resistant to the radiation used to polymerize the material. Even if the active agent is neither stable nor resistant to radiation, it may develop better if added after the polymer beads are formed (ie, the sorbate containing the active agent after the polymer beads are dried) Can be exposed to). Unlike the active agent, which can often be added to the precursor composition or can be added after formation of the polymer beads, the treating agent is typically included only in the precursor composition.

  The amount of active agent can range from 0 to 30 weight percent (based on the weight of swollen polymer beads). In some exemplary swollen polymer beads, the amount of active agent is no more than 20 weight percent, no more than 15 weight percent, no more than 10 weight percent, no more than 5 weight percent, no more than 3 weight percent of the swollen polymer beads, or 1 mass percent or less.

  Some exemplary swollen polymer beads include 15 to less than 90 weight percent polymeric material, 10 to 85 weight percent polar solvent, and 0 to 30 weight percent active agent (swelled (Based on the total mass of the polymer beads).

  Swelled polymer beads are usually homogeneous and do not contain distinguishable internal pores or internal grooves. A matrix of polymer comprising a polar solvent and a polymeric material usually exists as a single phase within the swollen polymer beads and there is no discernable boundary between the solvent and the polymeric material. However, if an active agent is present, the active agent may or may not be uniformly dispersed throughout the polymer beads. Furthermore, the active agent may be present in a phase separate from the polymer matrix.

  In general, polymer beads (especially those without an active agent) have a porosity and void that can be discerned even when viewed under a microscope, for example, using an environmentally controlled scanning electron microscope with magnification up to 50 times. None (see FIG. 6A). In many cases, polymer beads have no discernable porosity or voids when observed using a field radiation scanning electron microscope with magnification up to 50,000 times.

  When the swollen polymer beads are prepared without an opaque component that can scatter light, it can be clear or transparent with little or no opacity or haze. In some embodiments, the swollen polymer beads are preferably clear. In other embodiments, transparency is not necessary and various components can be added that can affect the appearance of the polymer beads.

  When used in connection with polymer beads, the term “transparent” means that no visible light scattering by the beads occurs in a visually detectable amount. In some embodiments, air can be entrained within the polymer beads, which can result in the formation of opaque portions at the phase boundary. However, this is not a phase separation of the polymer material in a polar solvent. A composition is considered transparent if at least 85 percent of light having a wavelength of 550 nanometers is transmitted through a film of the cured precursor composition having a thickness of 1 millimeter. These films can be cast on glass or other incoherent substrates. In some embodiments, at least 88 percent, at least 90 percent, at least 95 percent of light having a wavelength of 550 nanometers is transmitted through the membrane.

  Haze or opacity characterization can be performed using a haze meter, such as a BYK-Gardner Hazegard Plus haze meter (with a broadband light source). The permeability through this same membrane prepared from the precursor composition is at least 85 percent, at least 88 percent, at least 90 percent, or at least 95 percent, and the haze is less than 10 percent, less than 8 percent, 5 percent Less than or less than 3 percent. In many embodiments, the haze component exhibits phase separation.

  The beads may be stiff or rubber elastic, may be easily crushed (eg, friable) or not. When the content of the polymer material increases, the elastic modulus and crushing strength of the swollen polymer beads tend to increase. By using a precursor composition having a higher average number of functional groups, the modulus and crush strength of the polymer beads tend to increase even when higher amounts of crosslinking are achieved. The average number of functional groups refers to the average number of polymerizable groups (ethylenically unsaturated groups) per monomer molecule.

  The polymer beads can have a wide range of sizes. The bead diameter depends on the exact method used to produce the precursor composition droplets prior to radiation curing, and the range can be from less than 1 micrometer to several thousand micrometers. Particularly suitable bead diameters are in the range of 1 to about 5000 micrometers, in the range of 1 to 1000 micrometers, in the range of 10 to 1000 micrometers, or in the range of 100 to 1000 micrometers.

  In some embodiments of the polymer beads and polymer beads manufacturing method, at least a portion of the polar solvent can be removed from the first swollen polymer beads to form dried beads. The terms “dry beads” and “dry polymer beads” are used interchangeably herein. The dried beads can then be contacted with the sorbate for a time sufficient for the dried beads to sorb at least a portion of the sorbate. That is, the first swollen polymer beads can be dried to form dry polymer beads. The dried polymer beads can then be contacted with a sorbate to form a second swollen polymer bead. The sorbate can contain at least one active agent. In addition to the active agent, the sorbate can include a fluid, such as a liquid or a supercritical fluid. Some representative sorbates include a polar solvent in addition to the active agent.

  As used herein, the term “sorbs” refers to adsorbing, absorbing, or a combination thereof. Similarly, the term “sorption” refers to adsorption, absorption, or a combination thereof. Sorption can be a chemical process (ie, a chemical reaction takes place), a physical process (ie, no chemical reaction takes place), or both. The term “sorbate” refers to a composition that can be sorbed by polymer beads, such as dried polymer beads.

  More specifically, a method for producing polymer beads comprising an active agent is provided. The method includes a step of forming a precursor composition containing (a) a polar solvent and (b) a polymerizable material that is miscible with the polar solvent as the precursor composition. The polymerizable material is capable of free radical polymerization and has an average number of ethylenically unsaturated groups per monomer molecule greater than 1.2. The method further includes forming a droplet of the precursor composition, forming a droplet that is entirely surrounded by the gas phase. Exposing the droplets to radiation is performed for a time sufficient for the polymerizable material to at least partially polymerize to form first swollen polymer beads. The method further includes removing at least a portion of the polar solvent from the first swollen polymer bead to form a dried bead. The dried beads are then contacted with the sorbate for a time sufficient for the dried beads to sorb at least a portion of the sorbate and form a second swollen polymer bead. The sorbate usually contains an active agent. The active agent can be a biologically active agent, a non-biologically active agent, or a mixture thereof.

  This method often includes as precursor composition (a) a polar solvent of greater than 10 to 85 weight percent based on the total weight of the precursor composition, and (b) the total weight of the precursor composition. Forming a precursor composition containing from 15 weight percent to less than 90 weight percent polymerizable material based on weight. The polymerizable material is miscible with the polar solvent. The polymerizable material is capable of free radical polymerization and has an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2. Polymerizable materials include poly (alkylene oxide (meth) acrylates) having at least two (meth) acryloyl groups and having at least five alkylene oxide units. The polymerizable material can also include 0 to less than 20 weight percent anionic monomer. In addition to the ethylenically unsaturated group, the anionic monomer contains an acidic group, a salt of an acidic group, or a mixture thereof. Exposing the droplet to the radiation is performed for a time sufficient to at least partially polymerize the polymerizable material to form the first swollen polymer bead. The method further includes removing at least a portion of the polar solvent from the first swollen beads to form dry beads. The dried beads are contacted with the sorbate for a time sufficient for the dried beads to sorb at least a portion of the sorbate to form a second swollen polymer bead. The sorbate usually contains an active agent. The active agent can be a biologically active agent, a non-biologically active agent, or a mixture thereof.

  The amount of polar solvent removed from the first swollen polymer beads to form the dried beads can be any amount desired. The dried beads often contain at least a small amount of polar solvent remaining in the polymeric material. In addition, when the dried beads are contacted with a sorbate to sorb the active agent into or onto the polymer beads, the amount of polar solvent present in the dried beads is generally the mass of the dried polymer beads. Is 25 mass percent or less based on The amount of polar solvent in the dried beads is less than 20 weight percent, less than 15 weight percent, less than 10 weight percent, less than 5 weight percent, less than 2 weight percent, or less than 1 weight percent of the weight of the dried polymer beads. be able to. In general, the more solvent removed from the first swollen beads, the greater the amount of sorbate that can be sorbed by the dried beads.

  The first swollen polymer beads may shrink when the polar solvent is removed, resembling a collapsed or deflated sphere or ellipsoid. Some dry polymer beads may have an oval or elliptical cross section. The cross-sectional shape of the dried polymer beads depends on the cross-sectional shape of the first swollen polymer beads. The amount of shrinkage depends on the volume of polar solvent initially present in the first swollen polymer beads and the degree to which the polar solvent is removed by drying.

  Dry polymer beads (especially in the absence of active agent) generally remain homogeneous and do not contain macroscopic (ie, greater than 100 nm) internal pores or grooves. In general, polymer beads have no porosity or voids that can be identified when viewed using a microscope. For example, even if the polymer beads are observed using an environmentally controlled scanning electron microscope at a magnification of 50 times, there are no holes that can be identified (see FIG. 6B). Some polymer beads have no discernable pores when viewed using a field emission scanning electron microscope with magnification up to 50,000 times. The dried bead may have a high elastic modulus, a high crushing strength, or a combination thereof. These properties can be similar to those of swollen polymer beads or can be greater than those properties.

  The swollen polymer beads can be dried using any of a variety of methods, such as the following (ie, at least a portion of the polar solvent can be removed from the swollen beads). For example, heating in a conventional oven such as a convection oven, heating in a microwave oven, air drying, freeze drying, or vacuum drying. The optimal method for drying a particular bead composition is in addition to the nature and amount of polar solvent present in the swollen polymer beads, as well as the thermal stability of the components in the beads, such as bioactive agents. Dependent. When water is present, preferred drying methods include conventional ovens such as convection oven drying, microwave drying, vacuum oven drying, and freeze drying. A suitable temperature for drying the water at atmospheric pressure is often close to 100 ° C or above 100 ° C. In some cases it may be desirable to heat the dried beads to a higher temperature. This can result in increased bead strength through condensation or other chemical reactions. For example, the beads can be heated to above 140 ° C, above 160 ° C, or even above 180 ° C. The polymer beads do not coalesce when dried to form, for example, a film or sheet. Rather, the dried beads tend to remain as separate particles.

  The dried beads can be easily re-swelled, for example, by impregnating with sorbate. As a result, it can return to its swollen state and approach its original size. Typically, the volume of sorbate that can be sorbed by the dried beads to form the second swollen polymer beads is approximately the polar solvent and other non-polymerized removed from the first swollen polymer beads during the drying process. It is the volume of the sex component. The polar solvent present in the precursor composition, and the polar solvent present in the resulting first swollen bead, is used to perform a second swelling of the bead (eg, swell the dried bead). When different from the solvent in the sorbate, the dried polymer beads may swell little or swell beyond their original polymerization dimensions.

  Dry beads can be loaded with active agents that are particularly sensitive to the heat or radiation that occurs during the formation of swollen polymer beads, such as drugs, pharmaceuticals, insecticides, herbicides. Agents, dyes, aromatic components, or mixtures thereof. To provide the beads with an active agent, the dried beads are contacted with a sorbate containing the active agent. If the activator is not a liquid, the sorbate typically also contains a fluid such as a polar solvent or a supercritical fluid (eg, carbon dioxide). The sorbate can be a solution, suspension, or dispersion. In many embodiments, the sorbate is a solution. The dried beads typically sorb at least a portion of the sorbate. The exposure of the dried beads to the sorbate results in the polymer beads being impregnated with the active agent.

  The sorbate often contains an active agent and a liquid such as a polar solvent. Due to liquid sorption, polymer beads often swell. The liquid usually facilitates the transfer of the active agent into the beads. The liquid often retains the active agent throughout the bead to form a homogeneous bead. However, in some embodiments, the active agent may remain on the surface of the beads, or a gradient of active agent having a higher concentration on the surface may occur across the polymer beads. For example, the composition of the polar solvent in addition to the size of the active agent (eg, molecular size) may affect the transfer (eg, diffusion) of the active agent into the dried beads.

  The amount of sorbate that can be sorbed by the dried polymer beads is often at least 10 percent, at least 20 percent, at least 40 percent, at least 50 percent, at least 60 percent, based on the weight of the dried polymer beads. Percent, at least 80 weight percent, at least 100 weight percent, at least 120 weight percent, at least 140 weight percent, at least 160 weight percent, at least 180 weight percent, or at least 200 weight percent. The increase in weight is typically less than 300 weight percent, less than 275 weight percent, or less than 250 weight percent, based on the weight of the dried polymer beads.

  The polymer beads can be a carrier for the active agent, and the active agent can be present in at least a portion of the interior of the bead or on at least a portion of the surface of the bead. An active agent can be included in the precursor composition used to form the polymer beads. Alternatively, the active agent can be sorbed by at least partially dried polymer beads. With polymer beads, diffusion controlled transfer to and from the bulk can be achieved. That is, in many embodiments, the active agent can be diffused into the polymer beads, out of the polymer beads, or both. The diffusion rate must be controllable, for example, by the following method. That is, changing the polymeric material and its crosslink density, changing the polar solvent, changing the solubility of the active agent in the polar solvent, and changing the molecular weight of the active agent. Diffusion can occur over hours, days, weeks, or months.

  Depending on the intended use, it may be desirable for the polymer beads containing the active agent to be in a dry state. After the active agent is added by exposing the dried beads to sorbate to form a second swollen polymer bead containing the active agent, the second swollen polymer bead can be dried again. When the dried polymer beads are exposed to moisture, the active agent can diffuse out of the polymer beads. The active agent can remain dormant in the bead until exposed to moisture. That is, the active agent can be stored in the dried polymer beads until the beads are exposed to moisture. This prevents wasting or losing the active agent when it is not needed and reduces the stability of the active agent which can be degraded by many moisture sensitive active agents, hydrolysis, oxidation, or other mechanisms. Can be improved. Applications that may utilize diffusion-controlled uptake or delivery of active agents include, for example, drug delivery, wound management, and sustained release antibacterial and antifungal protection, air freshening agents, time release (time release) -released) insecticides, and time-released attractants for higher animals (eg fish or mammals).

  As a wound dressing, the polymer beads can be loaded with various active agents that provide a therapeutic function. Wound dressings containing these active agents can reduce or eliminate wound infection. In addition, these wound dressings can increase the speed of wound treatment when: Therapeutic agents such as anti-inflammatory agents, growth factors, alpha-hydroxy acids, enzyme inhibitors such as matrix metal proteinase (MMP) inhibitors, enzyme activators, vasodilators, chemotactic agents, hemostasis When an agent (eg thrombin), antibacterial agent, antihistamine, antitoxin, anesthetic, analgesic, vitamin, nutrient, or combination is added to the polymer beads. When used in a wound dressing, the polymer beads are usually dry prior to use in highly exuded wounds, but may be used in a swollen state to add moisture to the dried wound.

  In some embodiments, swollen polymer beads can be used to deliver antimicrobial agents to either mammalian tissue or other environments outside the polymer beads. Some representative antimicrobial agents that can be added to the polymer beads include various complex forms of iodine and iodine, commonly referred to as iodophors. An iodophor is a complex of iodine or triiodide present in the elemental state with a specific carrier. The function of these iodophors is performed not only by increasing the solubility of iodine, but also by reducing the level of free molecular iodine in the solution and providing a type of sustained release reservoir for iodine. The iodophor can be formed using the following polymer carrier. Thus, for example, polyvinylpyrrolidone (PVP); N-vinyl lactam and other unsaturated monomers such as, but not limited to, copolymers of acrylates and acrylamides; polyether-containing surfactants such as nonylphenol ethoxylate, Various polyether glycols (PEG); polyvinyl alcohol; polycarboxylic acids such as polyacrylic acid; polyacrylamide; and polysaccharides such as dextrose. Other suitable iodophors include protonated amine oxide surfactant-triiodide complexes. This is described in US Pat. No. 4,597,975 (Woodward et al.). Depending on the intended use, the iodophor is popidone iodine. This is commercially available as Popidone Iodine USP. Popidone iodine USP is a complex of K30 polyvinylpyrrolidone and iodide, and the available abundance of iodine is from about 9 weight percent to about 12 weight percent.

  In some embodiments, various combinations of antimicrobial agents can be used in the precursor composition or sorbate. Any other known antimicrobial agent can be used that is compatible with the precursor composition or the resulting hydrogel. These include, but are not limited to: Chlorhexidine salts such as chlorhexidine gluconate (CHG); parachlorometaxylenol (PCMX); triclosan; hexachlorophene; fatty acid monoesters and monoethers of glycerol and propylene glycol such as glycerol monolaurate, glycerol monocaprylate, glycerol monocap Plates, propylene glycol monolaurate, propylene glycol monocaprylate, propylene glycol moncaprate; phenol; (C12-C22) containing hydrophobic substances and quaternary ammonium groups or protonated tertiary amino groups , Surfactants and polymers; quaternary amino-containing compounds such as quaternary silanes and poly-4 such as polyhexamethylene biguanide Amine; silver-containing compounds such as silver metal, silver salts such as silver chloride, silver oxide and silver sulfadiazine; methyl paraben; ethyl paraben; propyl paraben; butyl paraben; octenidine; 2-bromo-2-nitropropane-1,3 diol; It is a mixture of Other antibacterial agents are described, for example, in the following literature. US Patent Application Publication Nos. 2006/0052452 (Scholz), 2006/0051385 (Scholz), and 2006/0051384 (Scholz).

  In addition, polymer beads can be used to concentrate various materials, such as contaminants or toxins. For example, polymer beads can be used to remove contaminants from water systems or ecosystems. Incorporation of various functionalities into polymeric materials such as chelating agents may remove heavy metals, radioactive contaminants, and the like.

  The beads often contain unreacted ethylenically unsaturated groups. These ethylenically unsaturated groups can be reacted with other monomers, such as monomers in the coating composition. The beads can be polymerized into a final coating. In addition, some polymer beads have other functional groups that can be further reacted. For example, some of the poly (alkylene oxide (meth) acrylates) contained in the precursor composition have hydroxy groups that can cause various nucleophilic substitution reactions or condensation reactions.

  Representative cosmetic and personal care applications that may use the bead composition include, but are not limited to: Wound care products such as absorbent wound dressings and wound fillings that absorb excess exudates; first aid dressings, hot / cold packs, baby products such as baby shampoos, lotions, powders and creams; bath preparations such as bath oil, tablets And salts, bubble baths, bath fragrances and bath capsules; eye makeup preparations such as eyebrow pencils, eyeliners, eye shadows, eye drops, eye makeup removers and mascaras; fragrance preparations such as cologne and lotions, powders and sachets; Non-coloring hair preparations such as hair conditioners, hair sprays, straight hair irons, permanent waves, rinses, shampoos, tonics, bandages and other grooming aids; -Cosmetics; hair coloring preparations such as hair dyes, hair tints, hair shampoos, hair color sprays, hair lighteners and hair bleaching agents; makeup preparations such as face powders, foundations, legs and body paints, lipsticks, makeup bases Nail polish preparations such as base coats and undercoats, cuticle softeners, nail creams and lotions, nail extenders, nail polishes and enamels, and nail polishes and enamel removers; oral hygiene products such as dentifrices and Mouthwash; Personal cleansing products such as bath soaps and detergents, deodorants, vaginal washer and feminine hygiene products; shave preparations such as af -Shave lotion, wrinkle softener, talc powder for men, shaving cream, shave soap and pre-shave lotion; skin care preparations such as cleansing preparations, skin disinfectants, hair remover, facial and neck makeup remover, body and hand makeup Removers, foot powders and sprays, moisturizers, night preparations, paste masks, and skin fresheners; and sunscreen preparations such as sun creams, gels and lotions, and indoor suntan preparations.

  Depending on the intended use, the polymer beads contain an indicator that can detect the presence or absence of another compound of interest. Adding the indicator to the dried polymer beads can be done using a sorbate containing the indicator and an optional fluid such as a polar solvent (eg, water, dimethylformamide, etc.). The beads can be contacted with a sample potentially containing the compound to be detected. The indicator can then change color when the sample contains a compound to be detected. If the indicator does not migrate out of the bead when exposed to the sample, the bead may change color. If the indicator moves out of the bead when exposed to the sample, the sample itself may change color.

  In a specific example, the polymer beads can be loaded with an indicator, such as ninhydrin that can detect the presence of an amino-containing material. Ninhydrin can be loaded onto dry, often clear and colorless polymer beads to form yellow polymer beads. The activator can be added to the polymer beads using a sorbate containing ninhydrin in addition to a polar solvent. When the ninhydrin-containing polymer beads come into contact with the amino-containing material, the ninhydrin changes from yellow to a bright purple. Depending on the relative diffusion rate of the ninhydrin and the amino-containing material, the bead color changes from yellow to purple, or the ninhydrin moves out of the bead and changes the color of the amino-containing sample. For example, a small amount of amino-containing material can migrate into ninhydrin-containing polymer beads and change the color of the beads from yellow to purple. However, diffusing a relatively large amount of protein into the polymer beads is not as easy as ninhydrin can move out of the beads. While the color of the sample containing the protein can turn purple, the beads may not turn purple. In some other examples involving a mixture of amino-containing materials, both the polymer beads and the amino-containing sample may turn purple.

  Polymer beads loaded with dyes can be used as saturation indicators. The dye-containing polymer beads can be dried. When the dried beads are contacted with water, the dye can diffuse out of the polymer beads and change the color of the water. Alternatively, dyes can be incorporated that are colorless in the absence of water, but color when water is sorbed into the beads. For example, certain pH indicators, such as phenolphthalein, are colorless when dry, but become colored when wet.

  The foregoing is a perspective of a foreseeable embodiment in which an authoritative description is available by the inventors, even though a non-substantial modification of the invention may not represent the present invention, but may represent an equivalent of the invention. The present invention has been described.

  The invention is further illustrated in the following illustrative examples. In the examples, all parts and percentages are by weight unless otherwise specified.

  All organisms used to make test cultures were obtained from the American Type Culture Collection, Manassas, VA.

Inhibition Zone Assay Candida albicans test: Candida albicans (ATCC 90028) was grown overnight in DIFCO Sabouraud dextrose (SD) broth. The broth is sold by Voigt Global Distribution, Inc. (Lawrence, Kansas). Cells are diluted and concentrations are approximately 1 × 10 ⁶ colony forming units per milliliter (mL) in phosphate buffered saline (PBS) (obtained from EMD Biosciences (Darmstadt, Germany)). (CFU) was performed using a 0.5 McFarland standard turbid solution. The flora was prepared by immersing a sterile cotton applicator in the cell suspension and spreading the dry surface of the DIFCO SD agar plate in three different directions with a cotton swab. The agar medium was obtained from Voith Global Distribution. Three beads from each bead sample were placed on the inoculated plate and then pressed firmly against the agar using sterile forceps to ensure complete contact with the agar. Plates were cultured at 28 ° C. ± 1 ° C. for 24 hours. The area under the beads and the area surrounding the beads were examined for the growth of fungi. The diameter of the inhibition zone was also recorded.

Aspergillus niger test: A suspension of 1 × 10 ⁵ spores of Aspergillus niger (ATCC 16404) in PBS was added to a DIFCO potato dextrose agar (PDA) plate using a sterilized diffuser. . Agar plates were obtained from Voith Global Distribution. One bead from each bead sample was placed on the inoculated plate and then pressed firmly against the agar using sterile forceps to ensure complete contact with the agar. Plates were cultured at 28 ° C. ± 1 ° C. for 7 days. Next, the area under the beads and the area surrounding the beads were examined for the growth of fungi. The diameter of the inhibition zone was also recorded.

Staphylococcus aureus (ATCC 6538), Gram-positive test: The preparation of an inoculum suspension containing a concentration of approximately 1 × 10 ⁸ colony forming units (CFU) per milliliter (mL) in PBS Land standard turbidimetric solution was used. The fungal moss was prepared by immersing a sterile swab-applied body in the suspension and smearing the dry surface of the Mueller Hinton II plate with a cotton swab in three different directions. Plates were obtained from Teknova (Hollister, Calif.). Three beads from each bead sample were placed on the inoculated plate and then pressed firmly against the agar using sterile forceps to ensure complete contact with the agar. Plates were cultured at 28 ° C. ± 1 ° C. for 24 hours. The area under the bead and the area surrounding the bead were examined for bacterial growth. The diameter of the inhibition zone was also recorded.

Pseudomonas aeruginosa (ATCC 9027), Gram negative test: preparation of an inoculum suspension containing a concentration of approximately 1 × 10 ⁸ colony forming units (CFU) per milliliter (mL) in PBS This was done using a Farland standard turbidimetric solution. The fungal moss was prepared by immersing a sterile swab-applied body in the suspension and smearing the dry surface of the Mueller Hinton II plate with a swab in three different directions. Plates were obtained from Teknova (Hollister, Calif.). Three beads from each bead sample were placed on the inoculated plate and then pressed firmly against the agar using sterile forceps to ensure complete contact with the agar. Plates were cultured at 28 ° C. ± 1 ° C. for 24 hours. The area under the bead and the area surrounding the bead were examined for bacterial growth. The diameter of the inhibition zone was also recorded.

For each antifungal agent with liquid broth test testing growth inhibition of the fungus, the flask replication housing the DIFCO malt extract broth 50 mL, was inoculated with approximately 10 ⁵ spores of Aspergillus niger (ATCC 16404). Ten beads were added to each flask and the samples were incubated in the dark on a shaker for 7 days at 28 ° C. ± 1 ° C. (until visible growth was observed in the control flasks). ) On day 7, a sample flask was photographed. Weighing the fungal biomass recovered by filtering the contents of the flask was performed both immediately after collection and after drying for 4 hours.

ASTM E2149-01: Standard Test Method for Determining Antimicrobial Activity of Immobilized Antimicrobial Agents Under Dynamic Contact Conditions This method involves inoculating a buffer with an overnight culture of bacterial cells. It was. The buffer was 0.3 mM KH ₂ PO4 (obtained from EM Science (Gibbstown, NJ)). Bacterial cells were either Pseudomonas aeruginosa (ATCC 9027) or S. aureus (ATCC 6538). The final concentration of bacteria in the buffer was 1 × 10 ⁶ CFU / mL. For each 50 mL of buffer, 10 hydrogel beads from each sample were tested. Samples were incubated for 24 hours at 28 ° C. ± 1 ° C. with constant agitation. After 24 hours, surviving microorganisms were plated and counted. Counting was performed using M Petrifilm Aerobic Count (AC) Plates. It is sold from 3M (Saint Paul, Minnesota). Incubation of 3M Petrifilm AC plates was performed at 35 ° C. ± 1 ° C. for 48 hours. Calculations of percent reduction of bacteria from treated vs. untreated samples were made.

Example 1 Basic Bead Formation Process Beads were produced on the equipment illustrated in FIG. Referring to the various elements of FIG. 2, reference numerals are shown in parentheses.

  A homogeneous precursor composition (50) was prepared by mixing: 40 grams of 20 mole ethoxylated trimethylolpropane triacrylate (TMPTA) (SR415, sold by Satomer, Exeter, PA), 60 grams of deionized (DI) water, and 0.8 grams of light initiation Agent (sold from Irgacure 2959, Ciba Specialty Chemicals, Taritown, NY). The average number of functional groups of ethoxylated TMPTA used in this and all subsequent examples was determined from HPLC data. According to HPLC data, the monomer was 53.6 weight percent trifunctional acrylate (52.5 mole percent), 45.3 weight percent bifunctional acrylate (46.5 mole percent), and 1.0 weight percent. Percent monofunctional acrylate (1.1 mole percent). Using this information and assuming an average value of 20 mole ethoxylation for each species, the average number of functional groups was calculated to be about 2.5. The precursor composition (50) was poured into the funnel (32) such that the precursor composition (50) exited the funnel (32) through a 2.0 millimeter diameter orifice (34). The precursor composition (50) dropped along the vertical axis of a 0.91 meter long, 51 millimeter diameter quartz tube (46). A quartz tube (46) extends through the UV exposure zone. The UV exposure zone consists of a light shield (44) and a 96 W / cm (240 W / inch) irradiator (sold from Fusion UV Systems, Gaithersburg, MD). It is prescribed by. The irradiator is equipped with a 25 cm long “H” bulb (42). The bulb (42) is coupled to the integrated rear reflector (44) so that the orientation of the bulb is parallel to the falling precursor composition (50). Polymer beads (10) were obtained under the irradiator (40). The entire process was operated under ambient conditions.

  The clear, free flowing polymer beads (10) showed a glossy appearance and the porosity was not visibly visible. Bead diameters ranged from approximately 1 millimeter to 4 millimeters. The beads (10) were collected in a plastic bag attached to the base of the quartz tube (46). The yield was essentially quantitative. It was found that the beads were elastic but could be crushed and had a homogeneous composition throughout their construction. FIG. 4 shows an optical micrograph of a typical bead.

Example 2 Polymer Beads Containing Acrylate Blend Repeating the process of Example 1 was repeated using 5 grams of the precursor composition (SR415), 5 grams of tetrahydrofurfuryl acrylate (SR285, manufactured by Satmer), 0. Performed with 2 grams of Irgacure 2959 and 30 g of deionized (DI) water. The average number of functional groups of the monomer by calculation was 1.2. The formed beads were similar in appearance and size to those of Example 1.

Example 3: Impregnating polymer beads with a water soluble solute A sample of beads (5 grams) prepared as described in Example 1 is placed in a vial and placed in an oven at 100 ° C for 2 Dry for hours. When dried, the resulting mass loss was 60 weight percent. This corresponded to a quantitative loss of water present in the original beads. The dried beads looked like spheroids but no signs of porosity.

  The dried beads were covered with an aqueous solution of methyl red. Within 1 hour, most of the solution was absorbed by the polymer beads. The red colored beads were then filtered and rinsed with deionized water.

Example 4 Preparation of Polymer Beads with Smaller Average Diameter The process of Example 1 was repeated. However, the precursor composition exited the funnel through a micropipette tip with an inner diameter of 0.75 millimeters. The liquid level in the funnel was maintained at a constant level to maintain a steady flow of precursor composition flowing through the exit orifice. The average bead diameter was about 700 micrometers.

Example 5: Conductive Beads The process of Example 1 was repeated using a precursor composition containing a 5 weight percent deionized aqueous solution of (+)-glucose. Glucose is a known reducing sugar. After rinsing the resulting beads with fresh deionized water, a small number of beads (ie, covering the spatula) were placed in a 10 weight percent aqueous solution of silver nitrate. Both silver nitrate and (+)-glucose were obtained from Sigma-Aldrich Chemical Co. (Saint Louis, MO). Because the silver ions were reduced to silver metal on the surface of the beads, the surface of the beads was dark. When the electrical resistance was measured, the beads were much more conductive than the beads before silver treatment. When the beads were crushed, it was found that silver was localized near the surface (because it had a darker appearance) and did not penetrate into the bulk inner region. See FIG. This micrograph also shows the property that the inside of the polymer beads is not porous.

Example 6: Preparation of beads with bioactivity Beads were produced according to the process of Example 1. However, a 3 mass percent H ₂ O ₂ solution was used instead of deionized water. Although the resulting beads were not tested, the beads were expected to exhibit bioactivity.

Example 7: Species Transfer from Polymer Beads A spatula tip amount of red colored beads from Example 3 was placed in a vial containing several grams of deionized water. Within a few minutes, there were signs that red color would diffuse into the bulk aqueous phase.

Example 8: Use of an ultrasonic atomization nozzle This example was prepared according to the schematic shown in FIG. An atomization nozzle (Sono-Tek Corp, Milton, NY) operating at 120 kHz was used to produce a 40 weight percent aqueous solution of SR415 containing 1 weight percent Irgacure 2959. The average number of functional groups of the monomer was 2.5. The precursor composition was sprayed into a 76 millimeter diameter quartz tube. In the quartz tube, the precursor composition was exposed to power from an HP-6 irradiator (Made by Fusion UV System (Gaithersburg, Md.)) With a 15 cm long “H” bulb. The formed beads were collected as fine powder on the wall of a plastic bag placed at the exit end of the quartz tube. The produced beads had a maximum diameter of about 0.05 millimeters. FIG. 5 shows the resulting polymer beads. FIG. 5 is a field emission scanning electron micrograph of a plurality of representative polymer beads at a magnification of 50,000 times.

Example 9: Preparation of polymer beads having a high refractive index Example 1 was repeated. However, 44.5 mass percent yttrium-stabilized zirconia sol was used instead of deionized water. The resulting beads had a translucent appearance and contained 27 weight percent ZrO ₂ doped with yttrium. The sol was prepared using the hydrothermal synthesis method described in Example 6 of US 2006/0148950 A1 (Davidson et al.).

Example 10: Production and drying of beads Beads were prepared as described in Example 1 (large beads) and Example 8 (small beads). The beads were then dried for 1.5 hours at 70 ° C. The dried beads were used in Examples 11 to 17 described later. In Examples 11-13, both large and small beads were tested. In Examples 14-17, large beads were tested.

(Example 11): Absorption of iodine from povidone iodine solution into beads A povidone iodine solution was prepared by mixing 10 parts by mass of povidone iodine with 90 parts by mass of water. Povidone iodine, which is a 1-ethenyl-2-pyrrolidone homopolymer compound containing iodine, can be used as a preservative. Povidone iodine is sold by the Prudue Frederick Company (Stamford, Connecticut), under the trade name BetaDINE, and also by Sigma-Aldrich (St. Louis, Missouri). 1 part by weight of the dried beads from Example 10 was placed in a glass jar with 2 parts by weight of the povidone iodine solution. When the solution was absorbed into the beads for 2 hours at room temperature, it turned red. The beads were then removed from the solution, rinsed with deionized water and allowed to air dry. The sample was then transferred to a clean glass vial and capped. These beads were then evaluated against the Candida albicans using the inhibition zone method. The diameter of the inhibition zone ranged from 6 mm (small beads) to 16 mm (large beads).

Example 12: Absorption of miconazole into beads Preparation of a saturated solution of miconazole was performed by adding approximately 1 part by weight of miconazole nitrate to 99 parts of water. Miconazole nitrate (1- [2- (2,4-dichlorophenyl) -2 [(2,4-dichlorophenyl) methoxy] ethyl] imidazole) can be used as an antifungal agent and is available from Sigma-Aldrich Chemical Company, St. Louis, Missouri. It can be obtained from the state. After gently shaking for 3 days, the excess undissolved miconazole was removed by centrifuging the solution with 2900 times the force of gravity for 15 minutes. The supernatant was then passed through a 0.22 micron syringe filter. The filter is commercially available from Whatman (Middlesex, UK). One part by weight of the dried beads from Example 10 was placed in a glass jar with 2 parts by weight of miconazole solution. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then removed from the solution, rinsed with deionized water and allowed to air dry. The sample was then transferred to a clean glass vial and capped. Beads treated with miconazole were evaluated against Candida albicans using an inhibition zone assay. The diameter of the inhibition zone ranged from 9 mm (small beads) to 13 mm (large beads).

Example 13: Absorption of Econazole into Beads A saturated solution of econazole was prepared by adding approximately 1 part by weight of econazole to 99 parts by weight of water. Econazole (1- [2-[(4-chlorophenyl) methoxy] -2 (2,4-dichlorophenyl) -ethyl] imidazole) can be used as an antifungal agent and is available from Sigma-Aldrich Chemical Company (St. Louis, Missouri). Commercially available. After gently shaking for 3 days, the excess undissolved econazole was removed by centrifuging the solution for 15 minutes at a force of 2900 times gravity. The supernatant was then passed through a 0.22 micron syringe filter. One part by weight of the dried beads from Example 10 was placed in a glass jar with 2 parts by weight of an econazole solution. The beads were allowed to absorb the solution for 2 hours at room temperature. Thereafter, the beads were removed from the solution, rinsed with deionized water and allowed to air dry. The sample was then transferred to a clean glass vial and capped. The beads treated with econazole were evaluated against Candida albicans using an inhibition zone assay. The diameter of the inhibition zone ranged from 7 mm (small beads) to 16 mm (large beads).

Example 14: Zinc OMADINE Absorption into Beads A zinc omadin solution was prepared by mixing 5 parts by weight of zinc omadine and 95 parts by weight of water. Zinc omadin is the trade name for pyrithione zinc complex and is commercially available from Arch Biocides (Cheshire, CT). This material is a broad spectrum antibacterial agent usually used as a fungicide-algaecide. Powder is 97 weight percent active zinc pyrithione. One part by weight of large dried beads from Example 10 was placed in a glass jar with 2 parts by weight of zinc omadin mixture. The beads were allowed to absorb the solution for 2 hours at room temperature on a wrist action shaker to prevent the zinc omadin from precipitating. Thereafter, the beads were removed from the solution, rinsed with deionized water and allowed to air dry. The resulting beads turned white, indicating the presence of zinc omadin powder inside the beads. The sample was then transferred to a clean glass vial and capped. Beads treated with zinc omadin were evaluated using an inhibition zone and a liquid broth growth inhibition test. The diameter of the inhibition zone for Candida albicans and the diameter of the inhibition zone for Aspergillus niger were 22 mm and 35 mm, respectively. In the liquid broth growth inhibition test for Aspergillus niger, the mass after filtration was 1.05 grams and the mass after both filtration and drying was 0.95 grams. This compares with the filter paper having a mass after filtration of 0.91 grams and a mass after both filtration and drying of 0.76 grams. In the growth control example, the mass after filtration was 2.91 grams and the mass after both filtration and drying was 2.80 grams.

Example 15: Absorption of OMACIDE IPBC into beads Two solutions containing omaside IPBC (available from Arch Chemicals, Cheshire, Connecticut) were prepared. Omaside is a trade name of Arch Chemicals and IPBC is a fungicide based on iodopropylbutylcarbamate. The first solution is a mixture of 1 part by weight of omaside IPBC100 (containing 97 parts by weight of active IPBC) with 20 parts by weight of isopropanol. The second solution is a mixture of 1 part by weight of omaside IPBC40 (containing 40 parts by weight of active IPBC in the solution) with 16 parts by weight of isopropanol. One part by weight of the dried large beads from Example 10 was placed in a glass jar with 2 parts by weight of each omaside solution. The beads were allowed to absorb the solution for 2 hours at room temperature. Thereafter, the beads were removed from the solution, rinsed with deionized water and allowed to air dry. The sample was then transferred to a clean glass vial and capped. Beads treated with each omaside were evaluated using an inhibition zone and a liquid broth growth inhibition test. The diameter of the zone of inhibition for Candida albicans in the case of omaside IPBC100 and omaside IPBC40 was 26 mm and 22 mm, respectively. The zone of inhibition against Aspergillus niger could not be measured. This is because there was no growth zone covering the entire agar plate. In the liquid broth growth inhibition test of Aspergillus niger on beads treated with omaside IPBC40, the mass after filtration was 0.88 grams and the mass after both filtration and drying was 0.69 grams. This compares with the filter paper having a mass after filtration of 0.91 grams and a mass after both filtration and drying of 0.76 grams. In the growth control example, the mass after filtration was 2.91 grams and the mass after both filtration and drying was 2.80 grams.

Example 16: Absorption of triclosan into the beads The triclosan solution was prepared by mixing 0.5 parts by weight of triclosan with 10 parts by weight of IPA. Triclosan has the chemical formula 2,4,4′-trichloro-2′-hydroxydiphenyl ether and is commercially available from Ciba Specialty Chemicals (Taritown, NY). The solution was stirred until the triclosan was completely dissolved. One part by weight of the large dried beads from Example 10 was placed in a glass jar with 3 parts by weight of the triclosan solution. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then filtered from the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. Beads treated with triclosan were evaluated using an inhibition zone and a liquid broth growth inhibition test. The diameter of the inhibition zone for Candida albicans was 3 mm. There was no zone of inhibition against Aspergillus niger. In the liquid broth growth inhibition test for Aspergillus niger, the mass after filtration was 1.40 grams and the mass after both filtration and drying was 1.30 grams. This compares with the filter paper having a mass after filtration of 0.91 grams and a mass after both filtration and drying of 0.76 grams. In the growth control example, the mass after filtration was 2.91 grams and the mass after both filtration and drying was 2.80 grams.

(Example 17): Absorption of sorbic acid into beads 1 part by mass of sorbic acid was mixed with 9 parts by mass of IPA, and then dissolved by stirring. Sorbic acid is commercially available from Sigma-Aldrich (St. Louis Missouri) and is often used as a food preservative to suppress the growth of mold, yeast and fungi. Sorbic acid was dissolved in IPA after stirring for 1 hour using a magnetic stir bar. 2 parts by weight of sorbic acid solution was mixed with 1 part by weight of dried large beads from Example 10 and allowed to absorb for 2 hours. The beads were distorted and rinsed with distilled water. The final mass of the beads increased by 58 weight percent. The beads were placed in a glass vial and capped. The beads were evaluated using an inhibition zone and a liquid broth growth inhibition test. There was no zone of inhibition against Candida albicans. The diameter of the zone of inhibition for Aspergillus niger was 7 mm. In the liquid broth growth inhibition test for Aspergillus niger, the mass after filtration was 3.11 grams and the mass after both filtration and drying was 2.80 grams. This compares with the filter paper having a mass after filtration of 0.91 grams and a mass after both filtration and drying of 0.76 grams. In the growth control example, the mass after filtration was 2.91 grams and the mass after both filtration and drying was 2.80 grams.

Example 18: Sustained release of miconazole and econazole from beads The beads from Examples 12 and 13 above were tested for time-dependent active release. After measuring the zone of inhibition for the beads, the same beads were transferred to freshly inoculated agar plates and incubated for 24 hours. At that time, the inhibition zone was measured again as the second day zone and the beads were transferred back to a new plate. This process was repeated daily for a week or until no zones were detected. For small beads treated with econazole (Example 13 above), the inhibition zone decreased from 7 mm on day 1 to zero on day 5. For large beads treated with econazole (Example 13 above), the inhibition zone decreased from 16 mm on day 1 to 12 mm on day 7. For small beads treated with miconazole (Example 12 above), the inhibition zone decreased from 9 mm on day 1 to zero on day 5. For large beads treated with miconazole (Example 12 above), the inhibition zone decreased from 13 mm on day 1 to 11 on day 7.

Example 19: Bead preparation and drying Polymer bead preparation was performed as described in Example 1. The beads were dried at 60 ° C. for 2 hours. After drying, the beads appeared to be reduced in size, resulting in a mass loss of about 60 percent of their original mass. This value corresponded to the amount of polar solvent initially present in the beads. The dried beads were used in various examples described below.

Example 20: Absorption over time Ten dried beads from Example 19 were weighed and then immersed in deionized water for various specific times. The beads were removed from the water after a specified time and weighed to determine the amount of water absorbed in the beads during that time. The weight percent increase was about 175 percent for 30 minutes and about 190 percent for 120 minutes. The procedure was repeated using isopropanol instead of deionized water. The weight percent increase was about 20 percent for 30 minutes and about 25 percent for 120 minutes. The increase in mass is based on the mass of the dried beads.

Example 21: Absorption of silver oxide into beads The preparation of the silver oxide-containing solution is 5 parts by weight of ammonium carbonate (commercially available from Sigma-Aldrich Chemical Company, St. Louis, MO) and 95 parts by weight of water. And stirring until the salt was dissolved. One part by weight of silver oxide (AgO) (Alfa Aesar (commercially available from Ward Hill, Mass.)) Was added to this solution. Stirring of the mixture was oxidized at 60 ° C. for 1 hour. This was done until the silver was dissolved, resulting in a clear and transparent solution containing silver ions.

  One part by weight of the dried beads from Example 19 was placed in a glass jar with 3 parts by weight of silver oxide solution. Within 1 minute, the beads began to develop a gray color indicating silver precipitation within the beads. The beads were allowed to absorb the solution for 2 hours at room temperature and turned dark gray. The beads were then filtered from the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. Beads treated with silver oxide were evaluated using an inhibition zone assay. The diameter of the inhibition zone for S. aureus was 9 mm and the diameter of the inhibition zone for Pseudomonas aeruginosa was 8 mm.

Example 22: Absorption of bronopol (2-bromo-2nitropropane-1,3-diol) into beads The preparation of bronopol solution was 1 part by weight of bronopol (trade name MYACIDE AS PLUS). ) (Commercially available from BASF (Germany)) with 5 parts by weight of IPA. Bronopol can function as an antibacterial agent. The solution was stirred until fully dissolved. 1 part by weight of the dried beads from Example 19 was placed in a glass jar with 3 parts by weight of bronopol solution. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then filtered from the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. The beads were evaluated using an inhibition zone assay. The diameter of the inhibition zone for S. aureus was 34 mm and the diameter of the inhibition zone for Pseudomonas aeruginosa was 36 mm.

Example 23: Absorption of Quaternary Amine Biocide into Beads The preparation of two solutions of a quaternary amine biocide (eg, an agricultural pesticide) was conducted using 1 part by weight of BARDAC 208M. Alternatively, Baldak 205M (both commercially available from Lonza Group, Ltd. (Valais, Switzerland)) was mixed with 2 parts by weight of IPA. Baldak 208M and 205M are a blend of twin chain quaternary ammonium compounds and alkyldimethylbenzyl ammonium chloride, with Baldac 208M being 50% more active than Baldak 205M. The solution was stirred until fully dissolved. 1 part by weight of the dried beads from Example 19 was placed in a glass jar with 3 parts by weight of each solution. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then filtered through the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. The treated beads were evaluated using an inhibition zone assay. The diameter of the zone of inhibition against S. aureus was 21 mm for Valdac 208M and 19 mm for Valdac 205M. There was no inhibition zone against Pseudomonas aeruginosa in VALDAQ 208M, but in VALDAC 205M the diameter of the inhibition zone was 3 mm.

Example 24: Absorption of PHMB (polyhexamethylene biguanide) into the beads 1 part by weight of the dried beads from Example 19 was placed in a glass jar with 3 parts by weight of COSMOCIL CQ or Placed with VANTOCIL P. Both Cosmosil CQ and Vantosyl P are commercially available from Arch Chemicals, Inc. (Norwalk, Conn.). These materials are chemically similar antimicrobial substances. However, Cosmocil is FDA approved and is usually used for human skin applications, while Vantosill is EPA registered and is usually used for industrial applications. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then filtered from the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. Treated beads were evaluated using an inhibition zone assay. The diameter of the zone of inhibition against S. aureus was 16 mm for Cosmocil CQ and 18 mm for Vantosyl P. The diameter of the zone of inhibition against Pseudomonas aeruginosa was 8 mm for both cosmosyl CQ and vantosyl P.

(Example 25): Absorption of triclosan into the beads The triclosan solution was prepared by mixing 0.5 parts by mass of triclosan with 10 parts by mass of IPA. Triclosan (sold by Ciba Specialty Chemicals (Taritown, NY)) is 5-chloro-2 (2,4-dichlorophenoxy) phenol and is used as an antibacterial and antifungal agent. The solution was stirred until the triclosan was completely dissolved. 1 part by weight of the dried beads from Example 19 was placed in a glass jar with 3 parts by weight of the triclosan solution. The beads were allowed to absorb the solution for 2 hours at room temperature. The beads were then filtered from the solution, rinsed with deionized water, briefly dried on a paper towel, then transferred to a clean glass vial and capped. Treated beads were evaluated using an inhibition zone assay. The diameter of the inhibition zone for S. aureus was 27 mm and there was no inhibition zone for Pseudomonas aeruginosa.

(Example 26): Adsorption of Au into beads Preparation of a gold chloride solution was performed by dissolving 1 part by mass of gold chloride in 99 parts by mass of deionized water. Gold chloride can be obtained from Sigma-Aldrich (St. Louis, MO). The gold chloride powder was immediately dissolved in water to give a clear and clear solution. One gram of this solution was added to 0.5 gram of dried beads from Example 19. After 15 minutes, the beads turned yellow, but the surrounding solution remained clear and clear. This indicates that gold has been reduced in the beads. After 2 hours, most of the solution was absorbed, so the beads were filtered from the solution, rinsed with deionized water, briefly dried on a paper towel and weighed. The total mass of the beads was 1.28 grams. This indicates a total mass increase of 156 mass percent. The beads can effectively absorb and concentrate metal ions from the solution.

Example 27: Long Delayed Release of Bromopol, Baldac 205M, and Vantosyl P Beads from Examples 22, 23, and 24 above were tested for time-dependent active diffusion. . After measuring the zone of inhibition, the same beads were transferred to freshly inoculated agar plates and incubated for 24 hours. At that time, the inhibition zone was measured again as the second day zone and the beads were transferred back to a new plate. This process was repeated daily until no zones were detected. The inhibition zone for S. aureus decreased from 38 mm to zero in 5 days and the inhibition zone for Pseudomonas aeruginosa decreased from 40 mm to zero in 5 days for the bromopol treated beads. A decrease in the zone of inhibition against S. aureus from 21 mm to 10 mm in about 30 days occurred for beads treated with Baldak 205M. This zone of inhibition lasted until about 110 days to remain fairly constant. At that time, the experiment was stopped. It occurred for Baldac 205M that the zone of inhibition against Pseudomonas aeruginosa remained at about 3 mm for 21 days and then decreased to zero on day 22. The zone of inhibition against Staphylococcus aureus decreases from 19 mm to 6 mm in about 30 days for beads treated with Vantosyl P, and after maintaining a constant value of 6 mm for 32 days, it reaches zero in 68 days. Diminished. For Vantosyl P, the zone of inhibition against Pseudomonas aeruginosa decreases from 9 mm to about 3 mm within 5 days, remains constant at about 3 mm for 21 days, and then decreases to zero at 22 days. woke up.

(Example 28): Adsorption of iodine After preparing the beads as described in Example 10, placing them in a 50 mL plastic centrifuge tube and washing 3 times, the centrifuge tube is almost filled with water. And by shaking for at least 10 minutes. Dry beads weighing 4.27 grams occupied 15 mL of bed volume when swollen with water. This corresponds to a bead volume of 0.284 grams / mL or 3.51 mL / gram. A sample of 5 mL beads (1.42 grams) was mixed with 10 mL of 100 mM I- ³ (100 mM iodine and 200 mM KI solution) and then diluted to 40 mL with water. The sample was rocked slowly for 5 hours. At that time, essentially all of the iodine (purple) was adsorbed by the beads. The calculated volume was 0.39 gram iodine / gram bead.

A second experiment was performed. This is done by washing the undried beads three times by shaking in water for 1 hour (about 10 m beads for 100 mL water), then shaking in 100 mL methanol and shaking in 100 mL water. It was something to do. A 2 mL bed volume of these beads sucked up at least 10 mL of iodine in a 100 mMI- ³ solution. This corresponds to 0.67 grams of iodine / gram of beads.

Example 29: Flavored beads Mixing the dried beads obtained from Example 19 with flavored apple oil, mixing 1 part by weight of polymer beads with 2 parts by weight of flavored oil, And by allowing the beads to absorb oil for 2 hours. The oil is sold as “Applejack and Peel” home fragrance oil and is obtained from Tsumura International, Secaucus, and NJ. The swollen beads were placed on a glass plate. The air around the beads smelled an apple aroma for 2 months.

Examples 30-34: Beads Prepared Using Cationic Monomers Polymer beads were prepared as described in Example 1. However, the precursor composition was changed as shown in Table 1. The various components of the precursor composition were stirred together in an amber jar until the antimicrobial monomer was dissolved.

DMAEMA-C ₈ Br was formed in a three neck round bottom reaction flask fitted with a mechanical stirrer, temperature probe, and condenser. A reaction flask was charged with 234 parts dimethylaminoethyl methacrylate, 617 parts acetone, 500 parts 1-bromooctane, and 0.5 parts BHT antioxidant. The mixture was stirred for 24 hours at 35 ° C. At this point, the reaction mixture was cooled to room temperature and a slightly yellow clear solution was obtained. The solution was transferred to a round bottom flask and acetone was removed by rotary evaporation at 40 ° C. under vacuum. The resulting solid was washed with cold ethyl acetate and then dried at 40 ° C. under vacuum. The formation of DMAEMA-C ₁₀ Br and DMAEMA-C ₁₂ Br was performed using a similar procedure. However, 1-bromodecane and 1-bromododecane were used instead of 1-bromooctane.

  3- (Acrylamidopropyl) trimethylammonium chloride was obtained from Tokyo Kasei Kogyo Limited (Japan). Ageflex FA-1Q80MC was obtained from Ciba Specialty Company.

  The average functional group numbers for the monomers were 2.0 (Examples 30 and 31), 2.1 (Example 32), 1.9 (Example 33), and 1.8 (Example 34).

  Evaluation of the antibacterial performance of the resulting hydrogel beads was performed using both the zone of inhibition assay and the ASTM E2149-01 test method. The results are shown in Table 2.

Examples 35 to 45: Reaction of polymer beads with cationic monomer (propylene glycol solvent)
The bead preparation was performed as described in Example 19. The beads were reacted with various cationic monomers. Examples 35-43 included using a cationic monomer of the formula

  Here, n was 4, 6, 8, 10, 12, 16, 18, or 20.

  Each of these cationic monomers was prepared using a similar process. A three-necked round bottom reaction flask was equipped with a mechanical stirrer, temperature probe, and condenser. A reaction flask was charged with 234 parts by weight of dimethylaminoethyl methacrylate, 617 parts by weight of acetone, 500 parts by weight of 1-bromoalkane, and 0.5 parts by weight of BHT antioxidant. The mixture was stirred for 24 hours at 35 ° C. At this point, the reaction mixture was cooled to room temperature and a slightly yellow clear solution was obtained. The solution was transferred to a round bottom flask and acetone was removed by rotary evaporation at 40 ° C. under vacuum. The resulting solid was washed with cold ethyl acetate and then dried at 40 ° C. under vacuum. The 1-bromoalkane used had 4, 6, 8, 10, 12, 16, 18, 20, or 22 carbon atoms.

  Examples 44 and 45 were prepared using two other commercially available cationic monomers. (3-Acrylamidopropyl) trimethylammonium chloride is commercially available from Tokyo Chemical Industry (Japan). Ageflex FA-1Q80MC is N, N-dimethylaminoethyl acrylate methyl chloride and is commercially available from Ciba Specialty Chemicals (Taritown, NY).

  The preparation of each example was performed by forming a cationic monomer solution as shown in Table 3. All the components shown in Table 3 for each example were mixed in an amber jar. The resulting mixture was stirred until the cationic monomer (usually solid powder) was dissolved.

The monomer solutions listed in Table 3 (2 grams for each solution) were each mixed with 1 gram of dried beads and then contacted with the beads for 2 hours. After the beads were filtered and rinsed, the mass was measured to determine the amount of monomer solution sorbed into the beads. Table 4 shows the increase in mass percent of beads. The beads were placed in a shallow aluminum pan and post cured by passing twice over a conveyor belt UV processor under a medium pressure Hg bulb. The total UVA energy was 354 mJ / cm ² .

Evaluation of the antibacterial performance of beads treated with a cationic monomer solution was performed using both the inhibition zone test method and the ASTM E2149-01 test method. Table 4 shows the results of antibacterial agent performance. The results suggest that medium size monomers (DMAEMA-C ₁₂ and DMAEMA-C ₁₆ ) give the best antimicrobial performance.

Examples 46 to 53: Reaction of polymer beads with cationic monomer (isopropyl alcohol solvent)
The bead preparation was performed as described in Example 19. The beads were reacted with various cationic monomers. All the components shown in Table 5 for each example were mixed in an amber jar. The resulting mixture was stirred until the cationic monomer (usually a solid powder) was dissolved. The various DMAEMA-containing monomers are the same as those described for Examples 35-43. Ageflex FA-1Q80MC for Example 52 is N, N-dimethylaminoethyl acrylate methyl chloride, commercially available from Ciba Specialty Chemicals (Taritown, NY). The cationic monomer MP-8275 for Example 53 is N, N-dimethylaminoethyl acrylate methosulfate (40% aqueous solution), commercially available from ABCR GmbH and Co. KG (Karlsruhe, Germany). Has been. There was no IPA in these samples.

The monomer solutions listed in Table 5 (4 grams of each solution) were each mixed with 2 grams of dried beads and then contacted with the beads in a dark drawer for 4 hours without any premature curing under visible light I did it. The beads were filtered and rinsed, and then weighed to determine the amount of monomer solution absorbed in the beads (shown in Table 6). The beads were placed in a shallow aluminum pan and then post cured by passing twice using a conveyor belt UV processor. Total UVA energy was 445 mJ / cm ² .

  Evaluation of the antibacterial performance of the beads was performed using both the inhibition zone test method and the ASTM E2149-01 test method. The results are shown in Table 6 below.

  The data in Table 6 shows that the bead absorption mass is increased compared to the data in Table 4. This may be due to the use of IPA instead of propylene glycol as the monomer solvent. In addition, the last two samples in Table 6 show much higher absorbed mass. This is because water was used as a solvent. Although the total capacity absorbed is not so different, the mass increase is significantly greater due to the higher density when using water rather than IPA.

Antibacterial performance for medium size monomers (DMAEMA-C ₁₂ and DMAEMA-C ₁₆ ) is best as seen in previous examples.

Examples 54-63: Addition of humectants Hydrogel beads were made from homogeneous precursor compositions containing the components shown in Table 7 according to Example 1. SR415 is a 100 percent solid (ethoxylated (20) trimethylolpropane triacrylate) and is commercially available from Satomer (Exton, PA). The average number of functional groups of the monomer was 2.5. Various humectants were added to the polymer beads during the formation of the polymer beads.

  Examples 54-56 included various levels of COLAMOIST 200, while Examples 57-59 included various levels of coramoist 300P. Both Coramoist 200 and Coramoist 300P are commercially available from Colonial Chemical, Inc. (South Pittsburg, Tennessee). Coramoist 200 is a 73.1 percent solids hydroxypropyl bis-hydroxyethyl diammonium chloride, and Coramoist 300P is a polymeric material containing multiple quaternary ammonium ions at 69.4 percent solids. . This polymer material is (poly (hydroxypropyltetra (2-hydroxypropyl) ethylenediammonium) chloride). Examples 60-62 contain various levels of sodium lactate. Sodium lactate was obtained from Purac America (Lincolnshire, Ill.). No humectant was added to Example 63. Example 63 is a control example.

  The water activity of the beads was tested using an Aqua Lab CX-2 model water activity meter. The meter was obtained from Decagon Devices, Inc. (Pullman, WA). The instrument was first calibrated with a saturated NaCl solution and then operated with a deionized water sample. The activity of the saturated NaCl solution should be close to 0.753, while the activity of pure deionized water should be 0.99-1.00.

Approximately 1.0 grams of beads were weighed directly into a disposable active sample cup (circular cup approximately 2.5 (1 ") diameter, approximate depth 0.6 cm (1/4")). The exact mass was recorded. The sample was immediately loaded into the activity meter and operated until the reading was stable. When the interval between the two measurements of A _w is below 0.001, the device showed the end of the operation. Temperature measurements were made using an activity meter and recorded at the end of the run. Water activity decreased significantly with increasing moisturizer levels.

Example 64: Ninhydrin containing hydrogel beads Dry beads (0.95 grams) were prepared as described in Example 19, followed by 1 weight percent aqueous ninhydrin solution (3 mL) at room temperature for 24 hours. Made contact. Ninhydrin was obtained from Aldrich Chemical Co. (Milwaukee, Wis.). After exposure to the ninhydrin solution, the beads were rinsed with water and ethanol and then dried in air for 4 hours. The dried ninhydrin-containing beads were stored in closed vials for future use.

  A first sample of ninhydrin-containing beads was contacted with buminate albumin. A second sample of ninhydrin-containing beads was contacted with pork broth solution. Buminate albumin (25 weight percent) was obtained from Baxter Healthcare Co. The pork broth solution was prepared by extracting from about 16 grams of fresh pork slices with 20 mL of water over 16 hours and filtering the resulting mixture. Measurement of total protein in the broth was performed according to the Pierce assay. Protein ranged from approximately 17 mg / mL to 37 mg / mL.

  To expose the ninhydrin-containing beads to these two samples, six ninhydrin-containing beads (approximately 100 mg) were added to two separate vials (4 mL). Then 1 mL pork broth was added to the first vial and 1 mL of buminate albumin protein aqueous solution (5 weight percent) was added to the second vial. After about 40 minutes, both vials began to turn blue and eventually turned purple. In the vial with pork broth, the beads turned purple, but the color of the pork broth did not change. However, in the vial containing buminate albumin, the solution turned purple while the beads did not show purple.

The invention has been described with reference to various embodiments and techniques. However, it will be apparent to those skilled in the art that many modifications and variations can be made without departing from the spirit and scope of the invention. A part of the embodiment of the present invention is shown in the following item 1-21.
[1]
A method for producing polymer beads, comprising:
As a precursor composition,
a) a polar solvent greater than 10 weight percent based on the total weight of the precursor composition;
b) a polymerizable material capable of free radical polymerization and having an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2, the polymerizable material miscible with the polar solvent. Preparing the precursor composition;
Forming the droplet of the precursor composition, wherein the droplet is entirely surrounded by the gas phase;
Exposing the droplet to radiation for a time sufficient to at least partially polymerize the polymerizable material to form a first swollen polymer bead.
[2]
Item 2. The method according to Item 1, wherein the polymerizable material comprises poly (alkylene oxide (meth) acrylate) having an average number of (meth) acryloyl groups per monomer molecule of at least 2.
[3]
Item 3. The method according to Item 2, wherein the poly (alkylene oxide (meth) acrylate) has a weight average molecular weight of 2000 g / mol or less.
[4]
The method of claim 1, further comprising the step of removing at least a portion of the polar solvent from the first swollen beads to form dried beads.
[5]
The method of claim 1, wherein the precursor composition further comprises an active agent.
[6]
6. The method of item 5, wherein the active agent comprises a bioactive agent.
[7]
The method of claim 1, wherein the precursor composition further comprises a photoinitiator and the radiation comprises actinic radiation.
[8]
Removing at least a portion of the polar solvent from the first swollen beads to form dry beads;
Contacting the dried beads with the sorbate for a time sufficient to sorb at least a portion of the sorbate comprising at least one active agent to form a second swollen polymeric bead. The method according to Item 1, further comprising:
[9]
9. The method of item 8, further comprising the step of drying the second swollen polymer bead.
[10]
A method for preparing an article comprising polymer beads, comprising:
As a precursor composition,
a) a polar solvent of greater than 10 to 85 weight percent based on the total weight of the precursor composition;
b) 15 weight percent to less than 90 weight percent polymerizable material based on the total weight of the precursor composition, the polymerizable material being capable of free radical polymerization and having an ethylene-based polymer per monomer molecule. The average number of saturated groups is at least 1.2, miscible in the polar solvent, and
i) a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl functional groups and having at least five alkylene oxide units;
ii) 0 to less than 20 weight percent anionic monomer, based on the total weight of polymerizable material in the precursor composition, in addition to acidic groups, salts of acidic groups or mixtures thereof, ethylenically unsaturated Providing the precursor composition comprising the polymerizable material comprising the anionic monomer comprising a group; and
Forming the droplet of the precursor composition, wherein the droplet is entirely surrounded by the gas phase;
Exposing the droplet to radiation for a time sufficient to at least partially polymerize the polymerizable material to form a first swollen polymer bead.
[11]
11. The method of item 10, further comprising the step of removing at least a portion of the polar solvent from the first swollen beads to form dry beads.
[12]
11. The method of item 10, wherein the precursor composition comprises less than 1 weight percent anionic monomer based on the weight of the polymerizable material.
[13]
Item 11. The method according to Item 10, wherein the poly (alkylene oxide (meth) acrylate) has a weight average molecular weight of less than 2000 g / mol.
[14]
12. The method of item 10, wherein the precursor composition further comprises an active agent.
[15]
15. A method according to item 14, wherein the active agent comprises a bioactive agent.
[16]
The method of item 10, wherein the precursor composition further comprises a photoinitiator and the radiation comprises actinic radiation.
[17]
Removing at least a portion of the polar solvent from the first swollen beads to form dry beads;
Contacting the dried beads with the sorbate for a time sufficient to sorb at least a portion of the sorbate comprising the active agent to form a second swollen polymeric bead. Item 15. The method according to Item10.
[18]
18. The method of item 17, wherein the activator comprises an ethylenically unsaturated group and a photoinitiator, and the method further comprises exposing the second swollen polymer bead to actinic radiation.
[19]
18. A method according to item 17, further comprising the step of drying the second swollen polymer bead.
[20]
An article comprising polymer beads comprising a free radical polymerization reaction product of a precursor composition, the precursor composition comprising:
a) a polar solvent of greater than 10 to 85 weight percent based on the total weight of the precursor composition;
b) 15 weight percent to less than 90 weight percent polymerizable material based on the total weight of the precursor composition, the polymerizable material being capable of free radical polymerization and ethylenically unsaturated per monomer molecule The average number of groups is at least 1.2, miscible in the polar solvent, and
i) a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups and having at least five alkylene oxide units;
ii) 0 to less than 20 weight percent anionic monomer, based on the total weight of polymerizable material in the precursor composition, in addition to acidic groups, salts of acidic groups or mixtures thereof, ethylenically unsaturated The polymerizable material comprising the anionic monomer comprising a group.
[21]
An article comprising polymer beads, wherein the polymer beads are
a) a free radical polymerization reaction product of a precursor composition comprising a polymerizable material capable of free radical polymerization and having an average number of ethylenically unsaturated groups per monomer molecule of at least 1.2, The polymerizable material is
i) a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl groups and having at least five alkylene oxide units;
ii) 0 to less than 20 weight percent anionic monomer, based on the total weight of polymerizable material in the precursor composition, in addition to acidic groups, salts of acidic groups or mixtures thereof, ethylenically unsaturated The free radical polymerization reaction product comprising the anionic monomer comprising a group;
b) an article comprising an active agent.

FIG. 4 is a schematic drawing of a plurality of polymer beads according to the present invention, illustrating one of the polymer beads in cross-section. 1 is a schematic diagram of a first embodiment of a process and apparatus for producing polymer beads. FIG. FIG. 2 is a schematic diagram of a second embodiment of a process and apparatus for producing polymer beads. An optical micrograph of a plurality of typical polymer beads at a magnification of 50 times. An optical micrograph of a plurality of other representative polymer beads at a magnification of 200 times. Environmentally controlled scanning electron micrograph of representative swollen polymer beads at 50x magnification. Environmental control scanning electron micrograph of representative dried polymer beads at 50x magnification. Optical micrograph (100x magnification) of representative beads milled to show a silver coating on the surface.

Claims (2)

A method for preparing an article comprising polymer beads, comprising:
As a precursor composition,
a) a polar solvent of greater than 10 to 85 weight percent based on the total weight of the precursor composition;
b) 15 weight percent to less than 90 weight percent polymerizable material based on the total weight of the precursor composition, the polymerizable material being capable of free radical polymerization and having an ethylene-based polymer per monomer molecule. The average number of saturated groups is at least 1.2, miscible in the polar solvent, and
i) a poly (alkylene oxide (meth) acrylate) having at least two (meth) acryloyl functional groups and having at least five alkylene oxide units;
ii) 0 to less than 20 weight percent anionic monomer, based on the total weight of polymerizable material in the precursor composition, in addition to acidic groups, salts of acidic groups or mixtures thereof, ethylenically unsaturated Providing the precursor composition comprising the polymerizable material comprising the anionic monomer comprising a group; and
Forming the droplet of the precursor composition, wherein the droplet is entirely surrounded by the gas phase;
Exposing the droplet to radiation for a time sufficient to at least partially polymerize the polymerizable material to form a first swollen polymer bead. The article comprising polymer beads that are first swollen polymer beads prepared by the method of claim 1, wherein the polar solvent is water, a water-miscible organic solvent, or a mixture thereof.

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