JP2006518773A - Compound comprising alumina and a compound confined to the alumina surface, system and method for supplying the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a delivery system for various functional materials.
A delivery system for various functional compounds. The delivery system incorporates a composition containing silica and / or alumina. Various functional materials containing specific components can be adsorbed onto silica and / or alumina and used as desired. Functional compounds can be, for example, pharmaceuticals, xenobiotics, antimicrobial agents, antiviral agents, UV absorbers, odor modifiers, and fragrances. In one particular embodiment, for example, several dyes can be adsorbed onto the alumina surface. With the dye adsorbed on the alumina surface, the resulting particles can be combined with a liquid excipient for use in any suitable printing process.

Description

  The present invention generally relates to delivery systems for various functional materials.

  Delivery system generally refers to a system that helps or otherwise facilitates delivery of the functional material to a desired location. The functional material can be any material that acts on or otherwise benefits the substrate as delivered to the desired location. Examples of functional materials that can benefit from use in delivery systems include pharmaceuticals, fragrances, vitamins and nutrients intended to be taken orally, applied topically, or injected subcutaneously into a patient. And various other and many additives.

  For example, in one particular application, the functional material can be a dye that is intended to be printed or otherwise applied to the substrate. In the past, various delivery systems have been proposed for dyes that are intended to facilitate the application of the dye to a substrate such as a textile material. For example, the delivery system secures the dye to the substrate and does not fade when exposed to sunlight, does not degrade when exposed to the environment, facilitates the addition of the dye to the substrate, or For example, it is intended to make the dye more stable.

  In view of recent advances in the art, there is still a need for further improvements in delivery systems for functional materials. For example, there is a need for a delivery system that can be bonded to a variety of functional materials that currently do not incorporate relatively expensive chemical formulations and does not require any of the complex process steps to incorporate the functional material into the delivery system. Exists. With respect to dyes, the art also requires a delivery system for dyes that can fix the dye to a negatively charged surface. For example, there currently exists a need for a delivery system for dyes that can fix the dyes to a textile material containing natural or synthetic polymer fibers having a negative surface charge. With respect to pharmaceutical and nutritional materials, there is also a need in the art for delivery systems for materials that can be accompanied by pharmaceutical compounds or other health-related compounds to the delivery system. There is also a need for a delivery system that will readily and / or selectively release such pharmaceutical material when a selected event or trigger occurs. There is a further need for a method that selectively triggers the release of pharmaceutical materials or other health-related compounds at the required location and time.

US Pat. No. 5,681,380 US Pat. No. 5,964,926

  The present invention generally relates to delivery systems for various functional materials. Functional materials may be, for example, colorants, UV absorbers, pharmaceuticals, odor modifiers, fragrances, antimicrobial agents, antiviral agents, antibiotics, xenobiotics, and nutritional supplements (nutrient materials). it can. According to the invention, the functional material is adsorbed on the particles. For example, the functional material is absorbed onto silica particles or alumina contained within / on particles. The resulting particles can then be used as is or in combination with an excipient such as a liquid excipient to deliver the functional material to the desired location. Furthermore, the resulting particles or particles containing excipients can be incorporated into drug delivery devices such as bandages or tampons.

  For example, if the functional material is a colorant, the particles of the present invention can be incorporated into a liquid excipient and applied to the substrate using any conventional printing means. If the functional material is a health-related compound such as a pharmaceutical or nutritional compound, the particles are also incorporated into the excipient and can be in close proximity to, in contact with, or into the patient's body. Can be applied to a substrate such as a dressing or drug delivery device. In this application, the term “patient body” means the human or animal body. In this way, the functional material can be delivered to a selected location on or within the patient's body. Alternatively, such particles could be taken up internally by the patient if appropriate to deliver the functional material to the desired location. In an alternative embodiment, the functional material is triggered from the particle at a selected location or time after a triggering event has occurred, such as exposure to chemicals, body exudates or moisture, or environmental stimuli such as pH changes. Can be released as possible.

That is, in one embodiment, the present invention relates to particles containing alumina. At least a part of the alumina contained in the particles is present on the surface of the particles. The functional compound is bound to alumina on the surface of the particles. The functional compound prior to binding to alumina contains a component comprising one or more of the following, tautomers thereof, or functional equivalents thereof, where R and R ′ are independently: Including hydrogen, an alkyl group, or an aryl group.

The said component can exist on a functional compound as it is. However, alternatively, each of the above components can further comprise an R group attached to the carbon chain described above. In general, any such R group can be present in association with the component as long as the R group does not interfere with the binding of the component to alumina.
The above ingredients have been found to form bonds with alumina in constituting the compositions of the present invention. Of particular importance, it has been found that functional compounds can bind to alumina in some embodiments without significantly altering the positive charge properties of alumina. For example, under some conditions, alumina can have a positive surface charge. It has been found that even after the functional material is bonded to alumina, the resulting structure still maintains a positive charge. That is, in one embodiment of the present invention, positively charged particles are formed. Due to their positive charge, the particles can be reliably fixed to the surface of the negatively charged substrate through Coulomb attraction.

  In one particular embodiment of the present invention, nanoparticles containing new recording media, inks, and colorant compounds can be formed. According to the present invention, such a recording medium exhibits improved water and detergent resistance when added to a substrate. For example, the delivery system of the present invention can improve the durability of the recording medium, particularly for substrates having a negative charge. For example, in one embodiment, a recording medium such as an inkjet ink that is directly dyed to a substrate containing synthetic polymer fibers such as polypropylene fibers, polyethylene fibers, and polyester fibers can be produced in accordance with the present invention. .

  In one embodiment of the present invention, a functional agent such as a pharmaceutical agent is selectively selected from carrier particles (such as alumina, silica, or alumina-coated silica particles) to release the pharmaceutical agent at a target / desired body location or at a desired time. Can be released. In one such embodiment, such selective release can be achieved by exposing the particles to changes in environmental conditions such as pH changes. For example, such selective release can be achieved by exposure to an alkaline environment. Alternatively, such selective release can be achieved by exposure to an acidic environment. Further, such selective release can be the result of exposing the carrier particles to a specific chemical stimulus. In an alternative embodiment of the invention, the method of adding a health-related compound uses health-related compound coated particles and selects the compound when the particles are exposed to changes in environmental conditions or to chemical stimuli. Release.

  Functional compounds can be selectively released in either basic or acidic environmental conditions in one embodiment. For example, in one particular embodiment of the present invention, the functional compound can be released in a basic / alkaline environment of a cocoon that has undergone yeast infection. In a second embodiment, the functional compound can be released in the basic environment of the small intestine after passing through the acidic environment of the stomach to treat the infection. In yet another alternative embodiment, the functional compound may be combined with the completion of delivery of the pharmaceutical material as a result of environmental stimulation as a warning or to provide an indication of the success of such delivery or such treatment. Can be released. Alternatively, such indicators can be released as a result of the appearance of moisture or body fluids. Such indicators or signals can be in the form of dyes or fragrances. In most of these situations, while the functional compound is being released, the particles still remain on the substrate or alternatively pass through the patient's body.

  In yet another alternative embodiment, such indicator or signal may be the result of a functional material contained on the first type of particles, such coated particles It can be included with different types of additional particles containing related compounds (pharmaceuticals and / or nutritional compounds). In yet another alternative embodiment, the functional material can be released in response to a specific chemical stimulus intentionally applied to the site of the carrier particles. In yet another alternative embodiment, a method of utilizing a triggerably releasable delivery system for treatment of a patient's body provides at least one type of particle selected from alumina particles, alumina-coated particles, and silica particles. Adsorbing at least one health-related functional compound to the surface of the one or more particles to form one or more particles that are at least partially coated; Exposing one or more particles at least partially coated to the patient's body, such as by transdermal transfer or transmucosal transfer, and exposing the one or more particles to environmental or chemical conditions, thereby Releasing a health-related compound from the surface of the particle to the patient's body (which can be either an animal or a human body). In an alternative embodiment, such health-related compounds are released from the particles contained on the drug delivery device, but because of the charge attraction (as described above), the particles themselves are in the drug delivery device. It remains attached.

In yet another alternative embodiment of the present invention, the triggerable delivery system includes particles selected from silica, alumina, or alumina-coated particles and a health-related compound adsorbed on the surface of the particles, Are those that can be released from the particles when exposed to either pH changes, moisture, chemical irritation, or body exudates.
In yet another alternative embodiment, the triggerable delivery system includes particles containing alumina at least partially present on the surface of the particles and a health-related compound adsorbed on the alumina surface of the particle, Before adsorbing to the alumina on the surface of the particles, contains at least one of the following components, or tautomers thereof, or functional equivalents thereof, wherein R and R ′ are independently , Hydrogen, an alkyl group, or an aryl group.

In yet another alternative embodiment, a drug delivery device, such as a topical bandage or tampon, includes a triggerable delivery system. The triggerable delivery system includes a particle and a health-related compound adsorbed on the surface of the particle, the health-related compound being removed from the particle when exposed to either a change in pH, moisture, chemical irritation, or body exudate. It can be released.
Other features and aspects of the present invention are described in further detail.

What has been described is merely illustrative of embodiments, and is not intended to limit the broad aspects of the present invention, and the broad aspects are specifically illustrated in exemplary configurations. It will be understood by those skilled in the art.
In general, the present invention relates to a delivery system for functional compounds. The functional compound can be any suitable substance that can benefit the delivery location. In accordance with the present invention, the delivery system generally relates to the composition of the particles. For example, such particles can be silica, and preferably contain alumina. When alumina is contained in the particle, a binding site for the functional compound is generated on the surface of the particle. More specifically, the functional compound is adsorbed on the surface of alumina (or silica if it is completely silica particles). With the functional compound bound to alumina, the functional compound can be delivered to a specific position using the resulting particles. The particles can be used as is, for example, depending on the particular application, can be combined with a liquid excipient that can facilitate delivery of the particles. The particles or liquid excipient containing the particles can be further placed in a drug delivery device, such as a tampon, bandage, or other transdermal delivery device.

本明細書で用いる場合、上記成分の１つに対する機能的均等物とは、上述のものと同様の反応基を含むが、正確に上記のようには分子上に位置決めされておらず、しかも、依然として同じようにアルミナと結合することになる機能性材料を意味する。 Functional compounds well suited for use in the present invention include compounds containing at least one of the following components, which are one or more of the following, tautomers thereof, or functional equivalents thereof: And R and R ′ independently include hydrogen, an alkyl group, or an aryl group.

As used herein, a functional equivalent for one of the components includes a reactive group similar to that described above, but is not positioned on the molecule exactly as described above, and It means a functional material that will still bind to alumina in the same way.

  With respect to the above components, component (1) can be considered a carboxy-hydroxy component. Component (2) can be considered a hydroxy-hydroxy component and component (3) can be considered a carboxy-carboxy component. On the other hand, components (4) and (5) can be considered “vinyllogous” amide components. In components (4) and (5) above, the amine group can be a primary amine, a secondary amine, or a tertiary amine. Components (6) and (7) can be considered hydroxylcarbonyl components. Component (8) can be considered a carboxyamine. Components such as (8) can be found in amino acids. Component (9) can be considered a hydroxyimine. In general, according to the present invention, any suitable functional compound containing the above components or one of its functional equivalents can be used. Furthermore, it should be understood that various additional R groups can be included in the above components as long as the R groups do not interfere with the bond formed with the alumina.

  The inventors have discovered that the above components can form a relatively strong bond at least on the alumina surface. Functional compounds can be bound to the alumina surface to change the properties of the resulting particles or to perform a specific function. While not wishing to be bound by theory, it is believed that the above components form a bidentate ligand binding system with the alumina surface. For example, alumina is believed to form covalent and coordinate bonds with the above components. Furthermore, it is believed that a surface reaction occurs and the functional compound is retained on the surface of the particle, forming a coating thereon. The functional material can cover the entire resulting particle or can be positioned at a specific location on the particle. Further, it is understood that the particles of the present invention can contain more than one functional compound, or alternatively, many different particles can contain / include different functional compounds. Should.

  As a particular advantage in many embodiments, it has also been found that functional compounds can also bind to alumina without significantly affecting the positive surface charge of alumina, which can be measured as zeta potential. Yes. The term “zeta potential” is used herein to mean, but is not limited to, a potential gradient that occurs across an interface. This term refers in particular to the potential gradient that occurs across the interface between the Stern layer in contact with the particles of the invention and the diffusion layer surrounding the particles. Zeta potential measurements can be made, for example, using a “Zetapals” instrument available from “Brookhaven Instrument Corporation”, Holtsville, NY. For example, zeta potential measurements can be made by adding 1-3 drops of sample to a cuvette containing a 1 mM KCl solution using the instrument's default function preset for an aqueous solution.

  Thus, when alumina is bound to a functional material, the resulting molecule continues to maintain a relatively strong positive charge. For example, the zeta potential of particles made according to the present invention can be greater than 20 mV, specifically greater than 30 mV, and in some embodiments greater than 40 mV. By maintaining a positive charge, the particles are well suited for fixing to a substrate having a negative surface charge through Coulomb attraction. Depending on the charge difference between the particles of the present invention and the surface of the substrate, in some applications, the bonding of the particles can be relatively permanent and directly dyeable. As a result, the delivery system of the present invention can be used to immobilize functional compounds on a variety of substrates without using chemical binders or other attachment structures. In some situations, the functional compound / drug can be selectively released from the particles while the particles are immobilized on the substrate, as described below.

  As an example, a carrier particle (delivery system) can include a pharmacologically functional compound along its surface, and the particle still retains a sufficient positive charge and is a negatively charged bandage or other Can adhere to a layer of the locally contacted substrate. Second, when certain chemical or environmental stimuli occur, the functional material contained on the particles can be selectively released to the patient's body, while the carrier particles are applied to the bandage or other charged surface. It remains fixed.

A variety of different particles and compositions can be used in the present invention. For example, alumina or silica particles can be used based on the functional compound and the trigger to release it. Silica particles are available under the name “SNOWTEX-C” from “Nissan Chemical America” (Houston, Texas, USA). In the present invention, compositions containing a variety of different particles and alumina can be used. For example, in one embodiment, the functional material is combined with an alumina sol. Many different types of alumina sols with various particle sizes are commercially available. As a particular advantage, an alumina sol having a relatively strong positive surface charge or zeta potential can be prepared. In this embodiment, the particles that react with the functional compound contain primarily alumina, and in some embodiments, contain only alumina. Examples of alumina particulate materials include “Alumina Sol-100” and “Alumina Sol-200” available from “Nissan Chemical America” (Houston, Texas, USA).
However, in other embodiments, the alumina particles that react with the functional compound can contain a variety of other ingredients. In general, the particles can contain any material that does not interfere with the function of the functional material binding to the alumina. In this regard, at least a portion of the alumina contained in the particle should be present on the surface of the particle so that the alumina is available to adsorb the functional compound.

  In one particular embodiment of the present invention, the particles can contain a core material coated with alumina. Alumina can form a continuous coating over the particles, or it can form a discontinuous coating. The core material can be, for example, an inorganic oxide such as silica. For example, in one embodiment, a sol containing silica nanoparticles having an alumina surface coating can be used. Such sols are currently commercially available from, for example, “Nissan Chemical America”, Houston, Texas. Silica is coated with alumina and imparts stability to the sol over several pH ranges. Indeed, silica sols coated with alumina can be more stable than alumina sols for some applications of the present invention. Specific examples of alumina particle materials having a silica core include "Snowtex-AK" obtained from "Nissan Chemical America" (Houston, Texas) and "Ludox" obtained from "Grace Davison", Columbia, Maryland, USA. Cl "is included.

As described above, according to the present invention, any suitable functional compound containing one of the above components, a tautomer thereof, or a functional equivalent thereof can be used. Examples of functional compounds include health related compounds such as pharmaceuticals, and xenobiotics. Xenobiotic is a general term used to describe any chemical interaction with a living body that does not occur in the body's normal metabolic pathways. Other functional compounds can include UV absorbers, odor modifiers, fragrances, therapeutic agents, nutritional supplements, antiviral agents, antimicrobial agents, signaling agents, and the like. One example of a therapeutic agent that can be used in the present invention is hydrocortisone. Examples of nutritional supplements include ascorbic acid and aspartame. In one particular embodiment, the functional compound can be tetracycline, a known antimicrobial agent.
In yet another embodiment of the present invention, the functional compound can be a colorant such as a dye. Specific examples of dyes that can be used in accordance with the present invention are described in more detail below.

  With any of the functional compounds described above bound to alumina (or, in some cases, silica), the particles serve as delivery excipients for delivering the functional compound to the desired location. Once bound to the particles, the functional compound may be easier to handle, increase stability, or improve other properties, depending on the application. Furthermore, the resulting particle structure can be incorporated into a variety of other media. For example, the particle structure can be incorporated into liquid excipients, formed into capsules, combined with gels, pastes, or other solid materials. As described above, the particles can be incorporated into drug delivery devices such as bandages and tampons.

The particles and functional compounds formed according to the present invention can exist in various forms, shapes and sizes depending on what results are desired. For example, the particles can be of any shape, for example, spheres, crystals, rods, disks, tubes, or strings. Also, the size of the particles can be changed dramatically. For example, in one embodiment, the average particle size may be less than about 1 mm, specifically less than about 500 microns, and more specifically less than about 100 microns. However, in other embodiments, a smaller size may be desirable. For example, the average diameter of the particles can be less than about 1,000 nm, specifically less than about 500 nm. As used herein, the average particle diameter means the average length, width, height, or diameter of the particles.
As described above, the particles of the present invention include a surface layer containing one or more functional compounds. The coating on the particles can be continuous or discontinuous. The particles themselves are considered amorphous.

  In one particular embodiment, the present invention relates to a delivery system for dyes. More specifically, it has been found that using alumina as described above provides various advantages and benefits when attempting to add dye to a substrate. For example, it has been found that an alumina delivery system can provide a means for permanent printing on substrates having negatively charged surfaces such as substrates containing thermoplastic polymers as well as natural fibers. The ink is fixed to the substrate in a relatively low cost and less complicated manner without using chemical binders and without pre-treatment or post-treatment steps.

  For example, with the dye adsorbed on alumina according to the present invention, in many applications, the resulting particles have a positive charge. Thus, the particles can be fixed to the negatively charged surface by Coulomb attraction. Depending on the difference in charge between the particles and the substrate, the dye can exhibit permanent properties such as washfastness due to its elasticity to water and detergents. For example, wash fastness is generally obtained when the charge difference between the substrate and the particles is greater than about 42 mV.

In general, the process of the present invention includes a carbonyl-hydroxy component, a hydroxy-hydroxy component, a carbonyl-carbonyl component, a “vinyllogous” amide component, a tautomer thereof, or a functional equivalent thereof, or Any dye containing any other component can be used. Various examples of dyes that can be adsorbed on alumina are as follows. However, it should be understood that the following list is not exhaustive and does not limit the invention.

数字は、アントラキノン構造の置換位置を示す。この表は、アントラキノン構造の１、４、５、又は８位で起こる染料置換基を示す。言い換えると、この表は、アルミナ結合成分１〜５を形成する基の存在を示すものである。




































Anthraquinone (5) Dye containing chromophore

The number indicates the substitution position of the anthraquinone structure. This table shows the dye substituents that occur at the 1, 4, 5, or 8 position of the anthraquinone structure. In other words, this table shows the presence of groups that form alumina binding components 1-5.

Salicylate or 3-hydroxy-2-naphthoic acid component-containing dye Further, according to the present invention, salicylate (6, R = OH), salicamide (6, R = NH2, NHAr, NHAlk) as shown below, Alternatively, a BON acid (3-hydroxy-2-naphthoic acid) (7, R = OH) or a nitrogen-containing BON acid derivative (7, R = NH2, NHAr, NHAlk) component-containing dye can also be used. These dyes often fall under the category of “color index mordanting”.

Chromotropic acid based dyes In addition, chromotropic acid 8 based dyes are also directly dyeable to alumina. An azo dye is formed when chromotropic acid reacts with a diazonium salt. The azo bond occurs at the 2 and / or 7 position.

Acetoacetanilide-containing dyes Further, the dyes containing the acetoacetanilide component 9 include the correct geometry for bonding to alumina. Azo dyes link acetoacetanilide beta to two carboxyl groups. An example is Cl Acid Yellow 99 (10). Acetoacetanilide will adsorb on the surface of the alumina.

Ｃｌナチュラルブラック１（ヘマトキシリン）は、キノイド基を含有してアルミナに直接染色的である染料の別の例である。 Naphthoquinone (11) type structures are also useful for forming complexes with the surface of the naphthoquinone colorant alumina.

Cl natural black 1 (hematoxylin) is another example of a dye that contains a quinoid group and is directly dyeable to alumina.

Aluminum dyes: There are several dyes known to be useful for dyeing dye- anodized aluminum that are known to be useful for dyeing anodized aluminum, including Cl Mordant Red 7 ( Eriochrome Red B) is included (12). It is believed that the geometry of the five-membered pyrazolone ring oxygen atom leads it to the exact position of the β-naphthol group for complexing alumina. Thus, the following structure can be considered a functional equivalent for the carbonyl-hydroxy component. The structure also contains an “iminalogous” amide component that is functionally equivalent to the “vinalogous” amide.

Aluminum lake-forming dyes Some anionic dyes can be precipitated with some metal ions to form insoluble colored compounds known as "lake pigments". For example, erythrosine (tetraiodofluorescein) forms an insoluble salt with aluminum ions. This salt is known as Cl Pigment Red 172.
Cl pigment blue 36 is an aluminum lake of indigo disulfonate as follows (FD + C Blue 1).

  In addition to the dyes described above, in some embodiments it may be desirable to bind other functional compounds or additives to the alumina. For example, if the additive contains components as described above, an additive that aids in the dyeing process that stabilizes the dye can also be bound to the alumina. Functional additives that can be used in this way include charge carriers, thermal oxidation stabilizers, crosslinkers, plasticizers, charge control additives, flow control additives, fillers, surfactants, chelating agents, colorants. Stabilizers or combinations thereof are included.

Various methods can be used to construct the dye particles according to the present invention containing the dye adsorbed on alumina. For example, in some applications, a dye containing alumina and a reactive component can be combined and reacted in an aqueous solution.
However, in some embodiments, it may be difficult for the dye to dissolve in water. In this embodiment, the dye can be first dissolved in a minimal amount of solvent. The solvent can be, for example, acetone, ethanol, or a similar water miscible liquid. After combining the dye with the solvent, the surfactant can be added, if desired, in an amount greater than about 0% to greater than about 50% by weight of the added dye solids. In general, the amount of surfactant added to the solvent should be minimized. One suitable surfactant that can be used is, for example, “SURFYNOL 440” surfactant sold by “Air Products and Chemicals, Inc.”, Allentown, Pa., USA.

The dissolved dye solution can then be added to a dilute aqueous suspension containing particles comprising alumina with rapid stirring. Although not critical, good results may be achieved if the aqueous suspension is heated slightly.
After continuous stirring for a sufficient time, the dye is dispersed throughout the mixture by precipitation and slowly dissolves in water. In the dissolved state in water, the dye can be adsorbed by the alumina contained in / on the particles.
With the dye adsorbed on the alumina, the resulting particles can be used to formulate a suitable colorant composition for use in various processes such as a suitable printing process.

  The colorant composition can include an aqueous or non-aqueous medium, although an aqueous medium is useful for applications using liquid print media. The colorant composition of the present invention contains particles and desirable colorant stabilizers and additives. For example, the colorant composition may be a combination of a second colorant, a colorant stabilizer such as porphine, a molecular inclusion, a prepolymer, and any of the above optional additives. Particles can be included.

  The present invention includes recording media such as inkjet inks comprising the nanoparticles disclosed herein. Inks for use in inkjet printers are described in US Pat. No. 5,681,380 assigned to “Kmberly-Clark World”, the entire contents of which are incorporated herein by reference. Ink jet inks typically contain water as the main solvent, preferably about 20 to about 95 percent deionized water by weight, various cosolvents in an amount between about 0.5 and about 20 percent by weight, and the present invention. Of particles.

  In addition, the ink formulation can include various co-solvents. Examples of such cosolvents include lactams such as N-methylpyrrolidone. However, other examples of optional co-solvents include N-methylacetamide, N-methylmorpholine-N-oxide, N, N-dimethylacetamide, N-methylformamide, propylene glycol monomethyl ether, tetramethylene sulfone, And tripropylene glycol monomethyl ether. Still other solvents that can be used include propylene glycol and triethanolamine (TEA). If an acetamide-based co-solvent is also included in the formulation, it is present in the range between about 1.0-12 percent by weight, typically about 5 percent by weight.

  Optionally, the ink formulation can include one or more wetting agents in an amount between about 0.5 and 20 percent by weight. Additional wetting agents for optional use in the formulation include, but are not limited to, ethylene glycol, diethylene glycol, glycerin, and polyethylene glycol 200, 400, and 600, propane 1,3 diol, etc. A propylene glycol monomethyl ether such as “Dowanol PM” (“Gallade Chemical Inc., Santa Ana, Calif.”), Polyhydric alcohols, or combinations thereof.

  Also, to improve ink performance, for example, chelating agents for isolating metal ions that may be involved in chemical reactions that may damage the ink over time for use with metal complex dyes, Corrosion inhibitors that help protect the metallic components of the printer or ink delivery system, biocides or bacteriostatic agents to control the growth of unwanted bacteria, fungi, or yeast in the ink, and ink surface tension Other additives such as surfactants for adjusting the viscosity can also be included. However, the usage of the surfactant may depend on the type of print head used. When a surfactant is included, it is generally present in an amount of about 0.1 to about 1.0 percent by weight. If a corrosion inhibitor is included, it is generally present in an amount between about 0.1 and about 1.0 percent by weight. When a biocide or a bacteriostatic agent is included, it is generally present in an amount between about 0.1 and about 0.5 percent by weight.

  When a biocide or a bacteriostatic agent is added to the ink formulation, as an example, "Proxel GXL" ("Zeneca Corporation", Wilmington, Del.) Can be included. Other examples include “Bioban DXN” (“Angus Chemical Company”, Buffalo, Illinois, USA). If a corrosion inhibitor is added to the formulation, it can include "Cobratec" ("PMC Specialty Group Distributing", Cincinnati, Ohio, USA) as an example. Other corrosion inhibitors include sodium nitrite, triethanolamine phosphate, and n-acyl sarcosine. Yet another example includes benzotriazole (“Aldrich Chemical Company”, Milwaukee, Wis.). If a surfactant is included in the formulation, it is typically a nonionic surfactant represented by “Surfynol 504” (“Air Products and Chemicals, Inc.”, Allentown, Pa.). is there. Still other examples include “Surfynol 465” and “Dynol 604” also available from “Air Products”. When a chelating agent is included in the preparation, ethylenediaminetetraacetic acid (EDTA) can be included as an example. In addition, depending on the application of the product, the formulation may include a pH stabilizer / buffer (eg, citric acid and acetic acid, and alkali metal salt derivatives thereof), a viscosity modifier, and a defoaming agent such as “Surfynol DF-65”. Other additives can be included.

  Depending on how the colorant composition is formulated, the composition can be used in various printing processes. For example, in addition to inkjet printing and other non-impact printers, the colorant composition can be used in screen printing processes, offset lithographic printing processes, flexographic printing processes, rotogravure printing processes, and the like. In some of the printing processes described above, it may be necessary to add a thickener to the colorant composition. The thickener can be, for example, an alginate.

  The recording medium or colorant composition of the present invention can be added to any substrate to color the substrate. Substrates to which the composition is applied include, but are not limited to, paper, wood, wood products or composites, woven fabrics, non-woven fabrics, woven fabrics, films, plastics, glass, metals, human skin, animals Skin, leather and the like. In one embodiment, the colorant composition or recording medium can be added to a woven article such as clothing.

  In one particular embodiment, a colorant composition containing the particles of the present invention can be applied to a substrate having a negative surface charge. As described above, the alumina contained in the particles of the present invention retains a positive charge even after the dye is adsorbed. As a result, the particles remain immobilized on the negatively charged surface. Indeed, the wash resistance of the colorant composition will occur when there is a significant amount of charge difference between the substrate and the particles of the present invention.

In view of the above, the colorant composition produced according to the present invention is particularly suitable for addition to natural and synthetic substrates having negative surface charges. For example, natural materials that generally contain negative surface charges include cotton fibers, cellulose fibers, and substrates made therefrom. Such substrates include all kinds of fabrics, clothes and accessories, paper products and the like.
In addition to the natural materials described above, in one particular embodiment, the colorant composition produced according to the present invention is also well suited for addition to a substrate made of a synthetic polymer such as a thermoplastic polymer. It has been found to be suitable. Such substrates can include, for example, woven and non-woven materials made from polyolefin polymers such as polypropylene or polyethylene, and polyesters. In the past, there have been various problems when trying to fix dyes to this type of material. As a result, either complex dye structures were used, or dyes and / or pigments were added in combination with chemical binders. However, the particles of the present invention can be permanently affixed to these materials without the use of chemical binders or complex chemical structures.

  Although not necessary, in some embodiments it may be desirable to pre-treat or post-treat the polymer substrate, thereby further fixing the dye or other functional compound described to the material. I can help. For example, a substrate made of a synthetic polymer can be pretreated to increase the negative surface charge. For example, such a pretreatment process includes a step of performing corona treatment or electret treatment on the substrate. Electret processing is disclosed, for example, in US Pat. No. 5,964,926 issued to Cohen, the entire contents of which are incorporated herein by reference. Such pretreatments have been found not only to increase the negative surface charge of the polymeric material, but also to wet the polymer to help enhance surface adhesion between the polymer and the particles of the present invention.

  In addition to the pretreatment step, the substrate in contact with the particles of the present invention can be subjected to various post-treatments that are further useful for fixing the particles to the substrate. For example, in one embodiment, the treated substrate can be subjected to radio frequency radiation or microwave radiation. Alumina is known to heat particles by adsorbing radio frequency radiation and microwave radiation. In the heated state, the particles are believed to be further embedded in the polymer substrate. Furthermore, the particles can be heated to a temperature higher than desired without heating the substrate together.

In addition to the above embodiments, a functional compound (health-related compound) can be adsorbed to the particles described above and then utilized while it is on the particles to treat a condition or symptom, or particles Can be selectively released from to treat medical conditions or symptoms. Such selective release can be achieved by environmental triggers or chemical stimuli. Such coated particles can be administered directly or locally to the patient's body with the aid of a drug delivery device such as a modified bandage, tampon, or other known transdermal delivery device. Alternatively, such coated particles can be taken by various mechanisms.
The invention can be better understood with reference to the following examples.

カルミン酸を測定セル内に滴下する時に、アルミナゾル中のアルミナ粒子のゼータ電位がモニタされた。ゼータ電位は、カルミン酸を更に加えても変化しなかった。カルミン酸（赤／オレンジ）をアルミナゾル（青みがかったマゼンタ）に加えると有意な色のシフトが見られた。以下のゼータ電位の結果が得られた。 “Alumina sol 200” (Nissan Chemical America) was diluted with deionized water to obtain a 2% “alumina sol 200” suspension. Meanwhile, carminic acid (0.02 g) was suspended in deionized water (1 g). Carminic acid contains a hydroxy-carbonyl component and can be represented as follows:

When carminic acid was dropped into the measurement cell, the zeta potential of the alumina particles in the alumina sol was monitored. The zeta potential did not change with further addition of carminic acid. When carminic acid (red / orange) was added to alumina sol (bluish magenta), a significant color shift was seen. The following zeta potential results were obtained.

  As described above, positively charged alumina can adsorb carminic acid without going through a charge reversal step.

“Alumina sol 200” (“Nissan Chemical America”, 2 g) was diluted with deionized water (98 g) with good stirring. Carminic acid (“Aldrich”, # 22, 925-3) (0.5011 g) was suspended in deionized water (23.7135 g) with good stirring. Carminic acid did not dissolve completely at this concentration, so it was taken with vigorous stirring so that whenever a portion was taken, the suspended solids were also removed. 1 ml of carminic acid suspension was withdrawn using a hypodermic syringe. This was added to the diluted “alumina sol 200” with good stirring. The suspension changed from white to bluish red.
The following changes were investigated by monitoring the zeta potential after the addition.

  The mixture was stirred overnight. The next morning, all the dye was dissolved and no dye crystals were seen.

０．２００８ｇＣｌアシドブルー２５（Ａｌｄｒｉｃｈ）を１９．７７３５ｇ脱イオン水に加えて撹拌し、懸濁液を得て、それを３０分間撹拌した。この１ｍｌを２ｇのアルミナゾル及び９８ｇの脱イオン水を含有する混合物に加えた。混合物を一晩撹拌し、全ての染料が確実に溶解するようにした。

０．２５０７ｇのＣｌアシドブルー４５（Ａｌｄｒｉｃｈ）を２０．１７５１ｇ脱イオン水に３０分間撹拌しながら懸濁した。１ｍｌ（注射器）を２ｇのアルミナゾル及び９８ｇの脱イオン水の混合物に加えて青い錯体を得た。混合物を一晩撹拌して全ての染料が確実に溶解するようにした。 In this example, according to the invention, in addition to carminic acid, Cl Acid Blue 25 and Cl Acid Blue 45 were bound to alumina. Cl acid blue 25 and Cl acid blue 45 have the following structures.

0.2008 g Cl Acid Blue 25 (Aldrich) was added to 17.7735 g deionized water and stirred to give a suspension which was stirred for 30 minutes. 1 ml of this was added to a mixture containing 2 g of alumina sol and 98 g of deionized water. The mixture was stirred overnight to ensure that all dye was dissolved.

0.2507 g Cl acid blue 45 (Aldrich) was suspended in 20.1751 g deionized water with stirring for 30 minutes. 1 ml (syringe) was added to a mixture of 2 g alumina sol and 98 g deionized water to give a blue complex. The mixture was stirred overnight to ensure that all dye was dissolved.

  In the following samples, high concentration “Alumina sol 200” was combined with carminic acid. More specifically, 0.111 g of glacial acetic acid (“Fischer”, ACS plus reagent grade) was diluted with 29.795 g of deionized water. This was added to 49.941 g of “alumina sol 200” with slow and good stirring. The mixture is stirred for 20 minutes, at which time 4 ml (measured using a syringe) of a carminic acid deionized water suspension (0.5011 g carminic acid in 23.7135 g water) is stirred at once. added. The mixture was stirred overnight.

Next, the 4th sample which contains the same raw material (carminic acid) listed by the above-mentioned Example 2 in the same quantity was comprised.
All mixtures appeared homogeneous in that the mud did not settle and no dark dye crystals were observed after standing for 3 hours. The analysis of zeta potential and particle size was performed on all samples except those containing Cl Acid Blue 25 using a “Brookhaven Instrument” “PALS Zeta” potential analyzer. The following results were obtained.

  The above three solutions were then subjected to a dialysis test to actually show that the dye was adsorbed on the alumina surface. More specifically, the three solutions are “Sigma Dialysis Tube” (“Cellulose”, 12,000 mw cutoff, “Sigma D-0655”) against 3% glacial acetic acid, and the tube is deionized before use. Dialyzed using 2 hour soak in water to remove glycerin to make the tube flexible. As a control, a small amount of carminic acid was added to the dialysis tubing and placed in a bath containing 3% acetic acid. Within 2 hours, carminic acid crossed the cellulose membrane and colored a 3% acetic acid solution. No coloration was seen from the alumina sol mixture, suggesting that the colorant was strongly absorbed by the particles as the color changed. The next morning, the 50% alumina sol / carminic acid solution colored the water bluish red. However, it seems that the bag was torn. Further, the dialysis solution of alumina sol acid blue 45 dialysis showed a very faint blue color that was hardly visible, suggesting that this colorant was not strongly adsorbed on alumina.

The following tests were conducted to determine the wash fastness of the particles of the present invention on cotton.
Three compositions prepared in Example 3 above containing 2% alumina sol / acid blue 45, 2% alumina sol / carminic acid, and 50% alumina sol / carmic acid, with cotton poplin fabric (0.01198 g / cm ² , “ Stained on Yuhan-Kimberly, uncoated) and dried at 60 ° C. overnight. It was observed that when the alumina sol-containing mixture was dropped onto cotton, only the area overflowing the fabric was colored. Colorless water was wicked around the dyed area, suggesting that i) no non-adsorbing dye was present in the mixture, and ii) nanoparticles were absorbed and fixed by cotton.

In addition, a control sample was prepared. More specifically, a carminic acid solution containing 0.5011 grams of carminic acid in 23.7135 grams of deionized water was first formulated. The carminic acid solution was dropped on a cotton poplin cloth using a pipette and dried at 60 ° C. overnight.
Samples were i) rinsed under hot running water, then stirred (mechanical paddle stirrer), 1 g / liter of “Aerosol OT” (“Cytec Industries”, Paterson, NJ, USA) Washed by stirring in 2 liters of water containing dioctyl sodium surfactant) and 1 g / liter of sodium bicarbonate for 2 hours. The sample was placed in a 60 ° C. wash bath and the bath was cooled to 30 ° C. over 2 hours. The fabric was rinsed with cold water and then dried with ambient air.
A control sample, carminic acid, was rinsed from the cotton. Almost all dye / alumina sol complexes remained as bluish red dyeings.

The following tests were conducted to determine the wash fastness of the particles produced according to the invention on a polypropylene nonwoven spunbond fabric. The basis weight of the spunbond fabric tested was 2 osy.
Polypropylene spunbond includes i) carminic acid, ii) concentrated 50% alumina sol / carmic acid complex suspension prepared in Example 3, and iii) 2% alumina sol / carmic acid complex suspension prepared in Example 3. Smeared. In all cases, polypropylene was difficult to wet with these materials, so it was necessary to wear rubber gloves to apply and liquid was added using a test pipette. When the material was forcibly applied, the material hardly regressed. The sample was dried at 60 ° C. overnight.
More polypropylene was smeared with 50% alumina sol / carminic acid complex. These samples were dried at 60 ° C. and cut in half. Half of the sample received microwave radiation (“Sharp” rotating household microwave oven, model number R-410CK, output 1100 watts) over a range of time (10 seconds, 20 seconds, 28 seconds) It was.

All polypropylene samples were laundered using the same procedure as in Example 4 above. The following results were obtained.
i) Carminic acid in the control sample was rinsed out of PP.
ii) Some but not all of the alumina sol / carmic acid ink was retained on polypropylene. The nature of the washout was not a general fade of the area. However, in some areas it seemed that all material was lost, but in other areas it was not. In other words, it appeared as if the ink did not wet the polypropylene.
iii) A significant amount of alumina sol / carminic acid was retained on the sample irradiated with microwaves before washing. Microwave treatment is believed to have the potential to heat colored particles and embed them in polypropylene. Irradiation with microwaves for a long time did not significantly improve the printing fastness to washing.

In this example, instead of using an alumina sol, a sol containing silica particles surface-coated with alumina was used. The surface-coated silica suspension was obtained from “Nissan Chemical America”, Houston, Texas. The suspension is sold under the trademark “SNOWTEX-AK”.
50 ml of a 20% wt / wt suspension of “SNOWTEX-AK” (“Nissan Chemical America”, Houston, Tex., USA) was stirred at ambient temperature during which 0.2 grams of carminic acid dye (Milwaukee, Wis., USA, "Aldrich Chemical Company") was added. With continued stirring overnight, the color changed dramatically from dark red to blue / purple.
The physical parameters of the nanoparticles are as follows.
“SNOWTEX-AK” —size: 62 nm, zeta potential: +36 mV
“SNOWTEX-AK” with carminic acid—size: 83 nm, zeta potential: +35 mV
The zeta potential did not change upon bond formation of the aluminum dye complex.

  The “ink” solution was added to a 4 ″ × 4 ″ piece of untreated cotton cloth and allowed to air dry. A similar control sample was constructed using only carminic acid. The dry fabric was then subjected to a wash cycle with 2 liters of water containing “Ajax” liquid detergent and sodium bicarbonate for 2 hours at 60 ° C. The fabric sample was then air dried. The “SNOWTEX-AK” / carminic acid sample had no wash cycle regression color. In contrast, the control sample (stained with 50 g aqueous solution of 0.2 g carminic acid and dried under the same conditions) lost all color after washing under the same conditions.

The following examples demonstrate the application of the present invention to other functional compounds as opposed to dyes.
Tetracycline is an antimicrobial agent containing a carbonyl-hydroxy functional group that can be bound to alumina according to the present invention. Tetracycline is a series of cyclomycin isomers. Tetracycline has 4S- (4,4,5,6,12) -4- (dimethylamino) -1,4,4,5,5,6,11, represented by the following chemical structure as a main constituent. Contains 12-octahydro-3, 6,10,12,12-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide.

  The UV-visible absorption spectrum of tetracycline was measured using a UV-visible spectrophotometer (“UV-Visible” spectrophotometer manufactured by “Perkin-Elmer”). Tetracycline was found to absorb at 357 nm in water. When the “SNOWTEX AK” suspension (explained in Example 6) is added to the tetracycline solution, a deep color shift occurs and absorption occurs at 365 nm. It was suggested that it was.

Yet another pharmaceutical example In yet another example, the ability of an additional pharmaceutical agent to bind strongly to alumina particles was evaluated. This included the drugs described in the table below, which revealed a significant shift. These agents are considered anti-neoplastic agents for use as agents that kill cancer cells or stop spreading. Baicalein has been tested for anti-proliferative effects on human T-lymphoid leukemia cells.

Still other pharmaceutical agents that can be used in combination with the present invention include the following materials.

Similar to the system described above, examples of medicinal nutrients with desirable functional ingredients were evaluated for their ability to bind to alumina particles. Examples of such compounds were ascorbic acid (vitamin C) and phenylalanine (a sweetener found in “Equal®”). The structural formulas of these materials and their function to bind such particles were revealed as seen in the table below.

  Here, it should be noted that when “SNOWTEX-AK” was added to the ascorbic acid solution, a shift was observed in the absorption maximum, but a blue shift was observed (light color). This shift is due to conjugation because no shift is seen when dilute acid is added to another solution of ascorbic acid. Similarly, even when phenylalanine was bound to “SNOWTEX-AK”, a blue shift (a shallow color shift) was observed.

In an example of the adsorption of various pharmaceutical or nutritional materials onto carrier nanoparticles and the selective release of such materials upon actuation of a trigger mechanism, in yet another set of examples, the pharmaceutical material is incorporated into carrier alumina particles After adsorption, it was selectively released from the carrier particles. More specifically, 50 ml of separate aqueous solutions of tetracycline and hydrocortisone drug (0.01 g) were prepared, to which was added an alumina nanoparticle (SNOWTEX-AK) suspension (5 ml of 20% wt / wt). A deep color shift (red shift) was again observed at the “UV-VIS Lambda” maximum, indicating that these pharmaceutical agents were strongly bound to the surface of the alumina particles. The following table shows the shift of the recorded “UV-VIS” spectrum. With the pharmaceutical agents bound to the particles, they are selectively released by a controlled pH trigger mechanism. That is, by changing the pH of the modified nanoparticle suspension to a higher pH value, the pharmaceutical agent was released as observed at the second redshift of the “UV-VIS Lambda” maximum. In particular, an alkaline agent, ie dilute sodium hydroxide (0.1N), was added to the sample in an amount of 0.5 ml. Tetracycline was released from the alumina surface when the modified nanoparticle suspension changed to pH 9/10 or higher. The shift seen here corresponds to the absorption maximum of the free pharmaceutical agent.

Thus, these two examples of pharmaceutical agents demonstrate the ability to selectively release pharmaceutical agents from carrier particles. By using a “pH trigger”, a functional compound can be released in a controlled manner when needed.
Such triggering of the delivery system is achieved by environmental changes such as infections that will change the pH, taking advantage of the inherent differences in pH due to body location, and chemistry such as pH changing materials. It should be noted that an intentional action that directs a substance to the delivery system can trigger the release of the functional compound. Chemicals that can be directed to the delivery system include bicarbonates, carbonates, and buffer salts that will cause a pH change when wet with water or biological fluids.

  In yet another alternative embodiment, signaling agents such as fragrances are used together to treat conditions together with health-related compounds on various types of particles, and the effectiveness of such treatments Alternatively, the patient can be notified that a particular event has occurred. As an example, the fragrance can be adsorbed on one type of particles and the antibiotic can be adsorbed on a second type of particles. The particles can be delivered to the site of infection at the same time. If the site of infection is alkaline, the release of antibiotics will be facilitated. When the infection is removed and returned to a near normal acidic environment, the fragrance can be released, which provides an indication of effective treatment of the infection. In yet another example, a signal may be used to generate an indication of a specific event, such as the release of fluid or exudate, in a bandage or personal care product such as a feminine care product or a pediatric care diaper product. it can.

  The method used to prepare alumina nanoparticles having functional compounds bound to the surface involved the following steps. That is, the functional compound was dissolved in water while stirring. To this stirred solution, alumina nanoparticles were slowly added and the resulting mixture was stirred for about 5-10 minutes to bind the functional compound to the surface of the nanoparticles. An “UV-VIS” spectrum of this aqueous solution was obtained by taking an aliquot of the stirred mixture and placing it in a quartz cell. The “UV-VIS” spectrum was obtained using a “UV-VIS” spectrophotometer “model number UV-1601” (Shimadzu Corporation) with water as a standard. Zeta potential and particle size measurements were determined using the “ZetaPals Instrument” (“Brookhaven Instrument Company”, Holtsville, NY).

  The method used to release the binding functional compound using a pH trigger included the following steps. The alumina nanoparticles having the functional agent bonded to the surface are put into an aqueous solution (suspension) with stirring. Dilute sodium hydroxide (0.1N) was slowly added dropwise to the stirred suspension, and then the pH was measured. An aliquot of this suspension was taken to measure the “UV-VIS” spectrum. In this way, it can be observed that the lambda maximum peak of the binding function drug decreases, and that the lambda maximum peak of the free function drug appears and increases.

  In yet another embodiment, the delivery system may be incorporated into a tampon. Healthy liquid smoke is acidic and is generally in the range of 3-5 pH. However, when a yeast infection or other microbial infection occurs, the pH changes to the alkaline range. This variation in pH triggers the release of drugs or buffering agents such as tetracycline and restores the filtrate and bacterial flora to a healthy pH. For example, medicinal tampons contain bound antibiotics ("bound" means that the functional compound is adsorbed on the surface of the nanoparticles that are themselves attached to the tampon substrate by a charged attractive force). Can do. When the pH of the patient's sputum changes to alkaline due to yeast infection, the tampon is triggered to release bound antibiotics to control the yeast infection, thereby returning the pH to a normal acidic environment. In yet another alternative embodiment, such a nanoparticle delivery system is used to carry a pharmaceutical agent through the stomach (having an acidic environment) and then the drug is taken into the small intestine (having a basic / alkaline environment). ). In yet another alternative embodiment, such a nanoparticle delivery system can be triggered when water or body exudates appear or when a pH-changing chemical is administered. In these cases, the functional material contained in the carrier nanoparticles of the dressing can be selectively released into or on the wound site.

Example of a signaling system that can be used to indicate the release of a pharmaceutical agent upon changes in environmental conditions
Silica Particle Binding and Release The following examples illustrate the use of silica nanoparticles (as opposed to alumina particles) and the binding of signal functional agents to the particle surface. The pH-triggered silica-coated particle release is activated by adding acid to lower the pH to the silica particle environment. In these examples, dilute acid is used.
The method used to prepare silica nanoparticles with functional agents bound to the surface involved the following steps. That is, the functional drug is dissolved in water while stirring. Silica nanoparticles were slowly added to this stirred solution, and the resulting mixture was stirred for about 5-10 minutes to bind the functional agent to the surface of the nanoparticles. The “UV-VIS” spectrum of the aqueous solution was obtained by taking an aliquot of the stirred mixture and placing it in a quartz cell. The “UV-VIS” spectrum was obtained using a “UV-VIS” spectrophotometer “model number UV-1601” with water as a reference. Zeta potential and particle size measurements were performed using a “ZetaPals Instrument” (“Brookhaven Instrument Company”, Holzville, NY, USA).

  The method used to release the binding agent from the silica surface using a pH trigger included the following steps. That is, the silica nanoparticles having the functional agent bonded to the surface are put into an aqueous solution (suspension) while stirring. Dilute hydrochloric acid (0.1N) was slowly added dropwise to this stirred suspension, and the pH was measured. An aliquot of this suspension was taken and the “UV-VIS” spectrum was measured. In this way, it can be observed that the lambda maximum peak of the bound functional drug decreases and the lambda maximum peak of the free function drug appears and increases.

Similarly, binding of active fragrance compounds to silica nanoparticles (“SNOWTEX C”, “Nissan Chemicals America”, Houston, Texas, USA) was revealed. That is, a solution of salicylaldehyde (used in the perfume industry as a base fragrance) in a solution of 0.01 g salicylaldehyde in 50 ml water (“Snowtex C”, “Nissan Chemicals America”, Houston, Texas, USA) Diluted suspension (3 ml of 2% wt / wt) was added with stirring. The “UV-VIS” absorption of salicylaldehyde was red-shifted at the lambda maximum (see table below) and the characteristic aroma disappeared. The red shift is a characteristic that indicates that the arylaldehyde functional group is bonded to the silica surface. When dilute acid (hydrochloric acid described above) is added, the aldehyde is released and the fragrance returns. Also, the “UV-VIS” absorption shifts blue and returns to the starting aldehyde. Such chemicals can be used in combination with pharmaceuticals that are released when environmental conditions change to signal / signal that the pharmaceutical material has been delivered. For example, such a signal agent can be adsorbed on silica particles. The pharmaceutical compounds can be adsorbed separately on the alumina particles. The particles can be used together in a delivery vehicle or in combination as part of a modified drug delivery device. Thus, functional agents are considered to be triggered upon the occurrence of separate chemical events.
Similarly, it has been found that a sequestering agent called salicylaldoxime is also bound to the surface of the silica particles and pH triggered release. The structural formula and exemplary data are shown in the following table.

  Further, a titration test using the “UV-VIS” spectral method was performed to determine the pH at which all salicylaldehyde was released. This was found to be pH 6.

In an additional alternative embodiment, the functional compound is released from the substrate, but the particles will remain behind when exposed to changes in conditions (eg, pH) after being immobilized on such a substrate. .
In particular embodiments, carrier particles comprising pharmaceutical compounds (desirably nanoparticles, i.e. less than about 1 micron in size, desirably between about 5 nm and 500 nm, more desirably between about 10 nm and 200 nm). Intermediate size particles) can be applied to the local bandage by various application methods. Application methods may include placing a gel, aqueous suspension, dry coating, or powder between the bandage layers if the particles are included in an excipient to facilitate addition. it can. The bandage can then be dried, if appropriate, so that the charge of the particles will maintain the particles in close association with the bandage substrate.

It should be appreciated that the bound pharmaceutical or nutritional chemical can be used with or without triggerable release. Alternatively, some of the binding chemicals in the multiple chemical particle system can be triggerably released while intentionally holding other binding chemicals on the carrier particles. Thus, the binding chemistry can perform its advantageous function while still attached to the carrier particles to facilitate removal or reduce the local toxicity of the functional agent / compound. An example of such usage would be to use bound salicylaldoxime to remove heavy metals from the body or wastewater without losing or being exposed to free complexing agents.
In another example, tetracycline can function as an antibiotic while still attached to the particle. This allows antibiotics to function in the stomach and intestine without entering the patient's bloodstream (due to particle size). Controlling the release of antibiotics in this way may help to reduce the risk of sensitization in patients who are allergic to such drugs.

  These and other modifications and variations to the present invention may be practiced by those skilled in the art without departing from the spirit and scope of the invention as set forth in more detail in the claims. Furthermore, it should be understood that aspects of the various embodiments may be interchanged both in whole or in part. Moreover, those skilled in the art will recognize that the foregoing description is exemplary and is not intended to limit the invention as further described in the claims.

Claims (114)

Particles containing alumina, at least a portion of which is present on the surface of the particles;
A functional compound bound to the alumina on the surface of the particles;
Including
The functional compound before binding to the alumina has the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, or an aryl group,
A composition of the material, characterized in that   The composition of claim 1, wherein the particles containing alumina bonded to the functional compound are positively charged.   The composition of claim 1, wherein the particles consist essentially of alumina.   The composition of claim 1, wherein the particles comprise a core material coated with alumina.   The composition according to claim 4, wherein the core material includes silica.   The functional compound includes a UV absorber, a pharmaceutical product, an odor adjusting agent, a fragrance, a therapeutic agent, a nutritional supplement, an antibacterial agent, an antimicrobial agent, an antiviral agent, or a xenobiotic. A composition according to 1.   The composition of claim 1, wherein the average size of the particles containing alumina bound to the functional compound is less than about 1 mm.   2. The composition of claim 1, wherein the average size of the particles containing alumina bound to the functional compound is less than about 100 microns.   The composition of claim 1 wherein the average size of the particles containing alumina bound to the functional compound is less than about 1,000 nm.   The composition according to claim 1, wherein the functional compound includes hydrocortisone.   The composition according to claim 1, wherein the functional compound includes ascorbic acid.   The composition according to claim 1, wherein the functional compound includes aspartame.   The composition according to claim 1, wherein the functional compound includes cyclomycin.   The composition according to claim 1, wherein the functional compound includes tetracycline.   The composition of claim 1, wherein the particles are amorphous.   The composition according to claim 1, wherein the particles containing alumina bound to the functional compound have a zeta potential of at least 20 mV.   The composition of claim 1, wherein at least two functional compounds are bound to the alumina.   The composition according to claim 1, wherein the functional compound contains a colorant.   The composition according to claim 1, comprising a plurality of the particles containing alumina bound to the functional compound contained in a liquid excipient. Particles containing alumina, at least a portion of which is present on the surface of the particles;
A colorant compound bound to the alumina on the surface of the particles;
Including
The colorant compound before binding to the alumina has the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, and an aryl group.
Nanoparticles for the printing process, characterized in that   21. Nanoparticles according to claim 20, wherein the particles containing alumina bound to the colorant compound are positively charged.   21. A nanoparticle according to claim 20, wherein the particle consists essentially of alumina.   The nanoparticle of claim 20, wherein the particle comprises a core material coated with alumina.   The nanoparticle according to claim 23, wherein the core material includes silica.   21. The nanoparticle of claim 20, wherein the average size of the nanoparticle is less than about 1,000 nm.   21. The nanoparticle of claim 20, wherein the average size of the nanoparticle is less than about 500 nm.   21. Nanoparticles according to claim 20, wherein the particles containing alumina bound to the colorant compound have a zeta potential of at least 20 mV.   21. The nanoparticle of claim 20, wherein both the alumina and the colorant compound have a positive zeta potential.   21. The nanoparticle of claim 20, wherein the alumina on the surface of the particle is further bound to a functional additive.   The functional additive includes a charge carrier, a thermal oxidation stabilizer, a viscoelastic property modifier, a crosslinking agent, a softener, a charge control additive, a flow control additive, a filler, a surfactant, a chelating agent, a leuco dye, 30. The nanoparticle of claim 29, comprising: and a colorant stabilizer, or a combination thereof.   The nanoparticle according to claim 20, wherein the colorant compound includes a dye.   32. The nanoparticle of claim 31, wherein the dye contains an anthraquinone chromophore.   32. The nanoparticle according to claim 31, wherein the dye contains a salicylate or a 3-hydroxy-2-naphthoic acid component.   32. Nanoparticles according to claim 31, wherein the dye is based on chromotropic acid.   32. The nanoparticle according to claim 31, wherein the dye contains acetoacetanilide.   The nanoparticle according to claim 31, wherein the dye contains naphthoquinone.   The nanoparticle according to claim 31, wherein the dye comprises a mordant dye.   32. Nanoparticles according to claim 31, wherein the dye comprises "Cl Mordant Red 7" or "Eriochrome Red B". A plurality of particles containing alumina, at least a portion of which is present on the surface of the particles;
A colorant compound bound to the alumina on the surface of the particles;
Including
The colorant compound before binding to the alumina has the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include a hydrogen, an alkyl group, or an aryl group,
Liquid excipients,
A recording medium further comprising: The colorant compound has the following components:

The recording medium according to claim 39, wherein the recording medium contains a tautomer. The colorant compound has the following components:

40. The recording medium according to claim 39, wherein R and R 'are hydrogen. The colorant compound has the following components:

The recording medium according to claim 39, wherein the recording medium contains a tautomer.   40. The recording medium of claim 39, wherein the particles consist essentially of alumina.   40. The recording medium according to claim 39, wherein the particles include a core material coated with alumina.   The recording medium according to claim 44, wherein the core material includes silica.   40. The recording medium of claim 39, wherein the average size of the particles is less than about 1,000 nm.   40. The recording medium of claim 39, wherein a zeta potential of the particles containing the alumina bound to the colorant compound is greater than about 20 mV.   40. The recording medium of claim 39, wherein the alumina and the colorant compound both have a positive zeta potential.   The recording medium according to claim 39, wherein the colorant compound contains a dye.   The recording medium according to claim 49, wherein the dye contains an anthraquinone chromophore.   The recording medium according to claim 49, wherein the dye contains a salicylate or a 3-hydroxy-2-naphthoic acid component.   The recording medium according to claim 49, wherein the dye is based on chromotropic acid.   The recording medium according to claim 49, wherein the dye contains acetoacetanilide.   The recording medium according to claim 49, wherein the dye contains a mordant dye.   50. The recording medium according to claim 49, wherein the dye is "Cl Mordant Red 7".   The recording medium according to claim 49, wherein the dye contains naphthoquinone.   40. A printing method comprising ejecting the recording medium according to claim 39 from the orifice in the form of droplets according to a recording signal for forming an image on a substrate.   58. The printing method according to claim 57, wherein the substrate includes a woven fabric, a nonwoven fabric, a polymer film, glass, or paper.   The printing method according to claim 57, wherein the printing method is an inkjet process. A substrate having a receiving surface containing a negative charge;
A plurality of positively charged particles containing alumina coupled to the receiving surface of the substrate through a Coulomb attractive force, at least a portion of which is present on the surface of the particles;
Including
The functional compound is bonded to the alumina on the surface of the particles, and the functional compound before binding to the alumina has the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, or an aryl group,
A manufactured product characterized by that.   61. The article of claim 60, wherein the particles comprise a core material coated with alumina.   61. The article of claim 60, wherein the core material comprises silica.   The functional material contains a colorant, UV absorber, pharmaceutical, odor adjusting agent, fragrance, therapeutic agent, nutritional supplement, antibacterial agent, antimicrobial agent, antiviral agent, or xenobiotic. 61. The article of claim 60.   61. The article of claim 60, wherein the average size of the particles containing alumina bound to the functional compound is less than about 1 mm.   61. The article of claim 60, wherein the average size of the particles containing alumina bound to the functional compound is less than about 1,000 nm.   61. The article of claim 60, wherein the functional compound comprises hydrocortisone, ascorbic acid, or aspartame.   61. The article of claim 60, wherein the functional compound comprises tetracycline.   61. The article of claim 60, wherein the particles containing alumina bound to the functional compound have a zeta potential of at least 20 mV.   61. The article of claim 60, wherein the plurality of particles are included in a liquid excipient when added to the substrate.   The article according to claim 60, wherein the functional compound contains a dye.   71. The article of claim 70, wherein the substrate comprises a woven or non-woven material comprising synthetic polymer fibers.   72. The article of claim 71, wherein the substrate is subjected to a corona treatment prior to bonding to the plurality of positively charged particles.   72. The article of claim 71, wherein the substrate undergoes electret processing prior to bonding to the plurality of positively charged particles.   72. The article of claim 71, wherein the substrate and the plurality of charged particles are exposed to microwave radiation or radio frequency radiation after being bonded together.   71. The article of claim 70, wherein the substrate comprises a natural fiber having a negative charge.   76. The article of claim 75, wherein the natural fibers comprise cotton or cellulose fibers.   71. The article of claim 70, wherein the dye contains an anthraquinone chromophore.   71. The article of claim 70, wherein the dye contains a salicylate or 3-hydroxy-2-naphthoic acid component.   71. The article of claim 70, wherein the dye is based on chromotropic acid.   The article of claim 70, wherein the dye comprises acetoacetanilide.   71. The article of claim 70, wherein the dye contains naphthoquinone. The colorant compound has the following components:

The article according to claim 70, wherein the article contains tautomers of the components. The colorant compound has the following components:

71. The article of claim 70, wherein R and R 'are hydrogen. The colorant compound has the following components:

The article according to claim 70, wherein the article contains tautomers of the components.   71. The article of claim 70, wherein the plurality of particles have an average size less than about 1,000 nm.   61. The article of claim 60, wherein the receiving surface and the particles of the substrate have a surface charge difference of at least 42 mV.   71. The article of claim 70, wherein the receiving surface and the particles of the substrate have a surface charge difference of at least 42 mV. A method for producing a composition of materials comprising:
Providing a plurality of particles containing alumina, at least a portion of which is present on the surface of the particles;
Binding a functional compound to the alumina on the surface of the particles;
Including
The functional compound before binding to the alumina has the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, or an aryl group,
A method characterized by that.   90. The method of claim 88, wherein the particles consist essentially of alumina.   90. The method of claim 88, wherein the particles comprise a core material coated with alumina.   The method of claim 90, wherein the core material comprises silica.   The functional material contains a colorant, UV absorber, pharmaceutical, odor adjusting agent, fragrance, therapeutic agent, nutritional supplement, antibacterial agent, antimicrobial agent, antiviral agent, or xenobiotic. 90. The method of claim 88.   90. The method of claim 88, wherein the average size of the particles containing alumina bound to the functional compound is less than about 1 mm.   90. The method of claim 88, wherein the average size of the particles containing alumina bound to the functional compound is less than about 1,000 nm.   90. The method of claim 89, wherein the functional compound comprises hydrocortisone, ascorbic acid, or aspartame.   90. The method of claim 88, wherein the functional compound comprises tetracycline.   90. The method of claim 88, wherein the particles are amorphous.   90. The method of claim 88, wherein the particles containing alumina bound to the functional compound have a zeta potential of at least 20 mV.   90. The method of claim 88, wherein at least two functional compounds are bound to the alumina.   90. The method of claim 88, further comprising combining the particles bound to the functional compound with a liquid excipient.   The method of claim 100, wherein the composition comprises an ink composition.   90. The method of claim 88, wherein the functional compound comprises a dye.   103. The method of claim 102, wherein the dye contains an anthraquinone chromophore.   103. The method of claim 102, wherein the dye comprises a salicylate or 3-hydroxy-2-naphthoic acid component.   103. The method of claim 102, wherein the dye is based on chromotropic acid.   103. The method of claim 102, wherein the dye comprises acetoacetanilide.   103. The method of claim 102, wherein the dye comprises naphthoquinone. A method of utilizing a triggerable releasable delivery system to treat a patient's body, comprising:
a) providing at least one type of particles selected from alumina particles, alumina-coated particles, and silica particles;
b) adsorbing at least one functional compound to the surface of the one or more particles to form at least one partially coated particle or particles;
c) exposing the at least partially coated one or more particles to the patient's body;
d) exposing the one or more particles to environmental or chemical conditions, thereby releasing the health-related compound from the surface of the particles to the patient's body;
A method comprising the steps of:   109. The method of claim 108, wherein the environmental or chemical condition is selected from the group consisting of a chemical trigger, a change in pH, and the introduction of the particles into moisture or body exudates.   109. The method of claim 108, wherein a plurality of types of particles are coated with a functional compound. The particles contain alumina, at least a portion of which is present on the surface of the particles;
Before the functional compound is adsorbed on the alumina particles, the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, or an aryl group,
109. The method of claim 108. Particles,
A health-related compound that is adsorbed on the surface of the particle and can be released from the particle when exposed to any of pH changes, moisture, chemical irritation, or body exudates;
A triggerable delivery system comprising: The particles contain alumina, at least a portion of which is present on the surface of the particles;
Before the health-related compound is adsorbed to the alumina on the surface of the particles, the following structural formula:

Or a tautomer thereof, or a component containing a functional equivalent thereof, wherein R and R ′ independently include hydrogen, an alkyl group, or an aryl group,
113. A triggerable delivery system according to claim 112. A drug delivery device including a triggerable delivery system comprising:
A triggerable delivery system that is adsorbed to the particle and the surface of the particle and can be released from the particle when exposed to any change in pH, moisture, chemical irritation, or body exudate And related compounds,
A device characterized by that.