Granular carrier, granular pharmaceutical composition and absorbent article containing the same, and method for producing the granular carrier

Abstract

To provide a granular carrier that has both high water absorbency and biodegradability, and has a substantially spherical shape, a uniform particle size, and excellent strength and transparency, and also to provide particulate pharmaceutical compositions and absorbent articles containing the granular carrier, and in addition, to provide a method of easily producing the granular carrier.SOLUTION: Provided is granular carrier containing a crosslinked salt of carboxyalkyl cellulose having a viscosity in a 1-mass% aqueous solution at 25°C of 5 mPa s or more and 300 mPa s or less, which is dispersed in a reverse phase suspension. Granular carriers that are particle-derived gel particles.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a granular carrier, a granular pharmaceutical composition and an absorbent article containing the same, and a method for producing the granular carrier. [Background technology]

[0002] Superabsorbent polymers (SAPs) absorb water upon contact with it and instantly become a transparent hydrated gel. This gel is a type of functional polymer that retains water without releasing water even when pressure is applied. Superabsorbent polymers have a wide range of applications, including, for example, in the field of hygiene products, where they are used as highly absorbent materials in absorbent articles such as disposable diapers and sanitary napkins for women. Superabsorbent polymers are also used as carriers in gel formulations to absorb and support aqueous liquid compositions containing chemicals such as fragrances and deodorants. Gel formulations containing such carriers made of superabsorbent polymers are widely used in stationary air fresheners and deodorants because they eliminate the risk of spillage from the container and have excellent design characteristics.

[0003] Currently, polyacrylic acid-based SAPs are the mainstream of superabsorbent polymers (SAPs) due to their ease of synthesis and cost. However, because polyacrylic acid-based SAPs are made from petroleum, their production costs are affected by fluctuations and increases in crude oil prices, and they also emit a lot of CO2 during production and disposal. In particular, when used in diapers, acrylic acid-based SAPs are disposed of in a water-absorbed state, so incineration requires a large amount of energy and emits particularly large amounts of CO2. Furthermore, when acrylic acid-based SAPs are disposed of in landfills, they are not biodegradable, which can lead to problems such as soil contamination.

[0004] The fact that polyacrylic acid-based SAPs are the mainstream of superabsorbent polymers (SAPs) may cause environmental problems. Given that demand for disposable diapers is expected to rapidly increase in emerging countries in the future, there is a demand for biodegradable natural polymers as superabsorbent polymers. In light of this situation, superabsorbent polymers made from plant-derived materials such as polysaccharides have been proposed.

[0005] For example, Patent Documents 1 to 3 propose a cellulose-based SAP consisting of a crosslinked polymer of carboxymethyl cellulose (CMC) or a CMC salt as a biodegradable, highly water-absorbent polymer to replace polyacrylic acid-based SAP. CMC is a water-soluble cellulose derivative synthesized by etherifying the hydroxyl groups of cellulose with chloroacetic acid or the like. Its aqueous solution exhibits anionic properties and has high viscosity and excellent dispersibility, making it widely used as a thickener, dispersant, and stabilizer.

[0006] CMC is non-toxic and non-allergenic, and is also used as a food additive and pharmaceutical binder. Its physical properties depend strongly on the degree of substitution (DS), which is the average number of carboxymethyl groups substituted per glucose residue (monomer). According to one example, a DS of >0.55 indicates water solubility. For example, Patent Document 1 uses CMC and CMC salts with a degree of substitution of 1.1 or more (see Claim 1, etc.), while Patent Document 2 uses CMC salts with a degree of substitution of 0.65 to 1.4 (see Claim 1, etc.). [Prior art documents] [Patent documents]

[0007] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-140534 [Patent Document 2] International Publication No. 2012 / 147256 [Patent Document 3] Japanese Patent Application Laid-Open No. 2008-285611 Summary of the Invention [Problem to be solved by the invention]

[0008] Stationary products in which gel formulations such as fragrance compositions and deodorant compositions are filled in containers are currently on the market. Many of these products use granular gel formulations in which a liquid composition containing various chemicals is supported on a gel carrier made of a highly water-absorbent polymer. Many of these products utilize air exposure to the surface of the granular gel formulation to allow the various chemicals supported on the gel carrier to function. That is, when the chemical supported on the gel carrier is a volatile chemical such as a fragrance, the surface of the granular gel formulation is exposed to air to volatilize the volatile chemical. Furthermore, when the chemical supported on the gel carrier is a non-volatile chemical, such as a deodorant that uses a chemical reaction to eliminate odors, the surface of the granular gel formulation is exposed to air to bring the malodorous molecules into contact with the non-volatile deodorant, resulting in decomposition and deodorization of the malodorous molecules through a chemical reaction.

[0009] Therefore, in order to allow the drug carried by the gel carrier in a granular gel preparation to function efficiently, it is desirable that air flow easily occurs when the granular gel preparation is filled in a container. To facilitate air flow, it is preferable that the gaps between the granular gel preparations are uniform and have a certain size. For this reason, it is desirable that the granular gel preparations are uniform in size and nearly spherical in shape.

[0010] Furthermore, considering that granular gel preparations such as fragrance compositions and deodorant compositions are distributed as stationary products filled in containers, it is desirable for the granular gel preparations to also have excellent gel strength. Furthermore, in such products, the granular gel preparations are often filled in transparent or translucent containers so that they can be seen from the outside. A granular gel preparation having a uniform size and a nearly spherical shape is preferable not only because it allows the above-mentioned chemicals to function efficiently, but also from the viewpoint of aesthetics. From the viewpoint of aesthetics, it is even more preferable for the granular gel preparation to also have excellent transparency.

[0011] Meanwhile, a conventional method for producing cellulose-based SAP involves polymerizing CMC and / or a CMC salt in an aqueous solution using a crosslinking agent (hereinafter referred to as "aqueous solution polymerization"). For example, a crosslinking agent is added to an aqueous CMC salt solution prepared by dissolving CMC or a CMC salt in an aqueous sodium hydroxide solution to cause a crosslinking reaction, thereby obtaining a hydrogel that uniformly gels the aqueous solution. The hydrogel is then pulverized and subjected to a sorting process such as classification to form a cellulose-based SAP (see, for example, paragraph 0035 of Patent Document 1, paragraph 0024 of Patent Document 2, and paragraph 0044 of Patent Document 3).

[0012] Crushed gel particles (crushed gel) refined by crushing are typically fragmented with sharp edges, and most of the particles are irregularly shaped and far from spherical. When a cellulose-based SAP consisting of a collection of small, irregularly shaped gel fragments rather than spherical is filled in a container, the gel particles are in close contact with each other, making it difficult for air to flow. Furthermore, a cellulose-based SAP consisting of a collection of small, irregularly shaped gel fragments is not desirable from the viewpoint of aesthetics.

[0013] The present invention aims to provide a granular carrier that is highly absorbent and biodegradable, has a substantially spherical shape, uniform particle size, and excellent strength and transparency, as well as a granular pharmaceutical composition and an absorbent article that contain the granular carrier. Another object of the present invention is to provide a method for easily producing the granular carrier. [Means for solving the problem]

[0014] According to a first aspect of the present invention, there is provided a granular carrier comprising a crosslinked salt of carboxyalkyl cellulose, the viscosity of which in a 1% by mass aqueous solution at 25°C is in the range of 5 mPa·s to 300 mPa·s, and the granular carrier is a gel particle derived from dispersed particles in a reverse phase suspension.

[0015] In an embodiment of the first aspect of the present invention, the dispersion medium of the reversed phase suspension may be a low-polarity organic solvent having a relative dielectric constant of 10 or less.

[0016] In another embodiment of the first aspect of the present invention, the dispersion medium of the reverse phase suspension may be liquid paraffin or silicone oil.

[0017] In another embodiment of the first aspect of the present invention, the viscosity of the carboxyalkyl cellulose and / or salt thereof may be 5 mPa·s or more and 100 mPa·s or less.

[0018] In another embodiment of the first aspect of the present invention, the granular carrier is used for carrying a drug.

[0019] According to a second aspect of the present invention, there is provided a granular drug composition comprising a granular carrier according to the first aspect and a liquid composition supported on the granular carrier and containing at least one drug selected from drugs having aromatic, deodorizing, deodorizing, insect repellent, insecticidal or antifungal properties.

[0020] In an embodiment of the second aspect of the present invention, the granular pharmaceutical composition may be an air freshener composition or a deodorant composition.

[0021] According to a third aspect of the present invention, there is provided an absorbent article comprising a granular carrier according to the first aspect.

[0022] According to a fourth aspect of the present invention, there is provided a method for producing a granular carrier comprising gel particles containing a crosslinked product of a carboxyalkyl cellulose salt, comprising: preparing a carboxyalkyl cellulose salt aqueous solution by dissolving a carboxyalkyl cellulose and / or a salt thereof, the viscosity of which of a 1 mass% aqueous solution at 25°C is in the range of 5 mPa·s or more and 300 mPa·s or less, in an alkaline aqueous solution; preparing a mixture of the aqueous carboxyalkyl cellulose salt solution and a crosslinking agent; and the mixture is dispersed in a low-polarity organic solvent to form a suspension, and crosslinking polymerization of the carboxyalkyl cellulose salt is allowed to proceed in the suspension to form dispersed particles containing a crosslinked product of the carboxyalkyl cellulose salt. The low-polarity organic solvent has a relative dielectric constant of 10 or less at 25°C and a kinematic viscosity of 10mm at 37.8°C. 2 / s or more.

[0023] In an embodiment of the fourth aspect of the present invention, the low polarity organic solvent may be liquid paraffin or silicone oil.

[0024] In another embodiment of the fourth aspect of the present invention, the kinematic viscosity of the low-polarity organic solvent at 37.8°C is 10 mm 2 / s or more 100mm 2 / s or less.

[0025] In another embodiment of the fourth aspect of the present invention, the cross-linking polymerization of the carboxyalkyl cellulose salt in the suspension is carried out under stirring at a rotation speed of 50 rpm or more and 500 rpm or less.

[0026] In another embodiment of the fourth aspect of the present invention, the viscosity of the carboxyalkyl cellulose and / or salt thereof may be 5 mPa·s or more and 100 mPa·s or less.

[0027] In another embodiment of the fourth aspect of the present invention, the mass ratio (X / Y) of the carboxyalkyl cellulose and / or salt thereof (X) to the crosslinking agent (Y) in the mixture may be in the range of 10 / 2 to 10 / 5.

[0028] In another embodiment of the fourth aspect of the present invention, the crosslinking agent may be a compound having two or more epoxy groups in the molecule.

[0029] In another embodiment of the fourth aspect of the present invention, the granular carrier is used for carrying a drug.

[0030] In another embodiment of the fourth aspect of the present invention, the granular carrier is used as a water-absorbing material in an absorbent article. [Effects of the Invention]

[0031] The present invention provides a granular carrier that is both highly absorbent and biodegradable, has a substantially spherical shape and uniform particle size, and is also excellent in strength and transparency, as well as a granular pharmaceutical composition and an absorbent article that contain the granular carrier. The present invention also provides a simple method for producing the granular carrier. [Brief explanation of the drawings]

[0032] [Figure 1] FIG. 1 is a flow diagram showing an example of a method for producing a granular carrier according to an embodiment of the present invention. [Figure 2] 2 is a photograph of the granular carrier 12 produced in Example 3-4 of the [Examples]. (a) shows the dried gel particles, and (b) shows the water-absorbed gel particles. [Figure 3A] 3A is a photograph comparing the particle shape of the granular carrier according to the embodiment of the present invention with the particle shape of crushed gel particles for comparison. (a) shows the crushed gel particles (dry state) produced in Example 4-1 of the [Examples], and (b) shows the granular carrier 2 (dry state) produced in Example 1-2 of the [Examples]. [Figure 3B] 3B is a photograph comparing the particle shape of the granular carrier according to the embodiment of the present invention with the particle shape of crushed gel particles for comparison. (a) shows the crushed gel particles (water-absorbed state) produced in Example 4-1 of the [Examples], and (b) shows the granular carrier 2 (water-absorbed state) produced in Example 1-2 of the [Examples]. [Figure 4] FIG. 4 is a particle size distribution showing the relationship between the particle diameter D (mm) and the frequency (mass %) of the granular carrier 2 produced in Example 1-2 of the [Example]. DETAILED DESCRIPTION OF THE INVENTION

[0033] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. The embodiments described below are more specific embodiments of any of the above aspects.

[0034] The granular carrier according to an embodiment of the present invention is a gel particle containing a crosslinked carboxyalkyl cellulose salt, and as described below, is a gel particle derived from dispersed particles formed by suspension polymerization (i.e., reverse-phase suspension polymerization) in a suspension using a low-polarity organic solvent as a dispersion medium. The granular carrier derived from dispersed particles obtained through the formation of crosslinked carboxyalkyl cellulose salt by reverse-phase suspension polymerization has a substantially spherical shape, a uniform particle size, and excellent strength and transparency. According to the manufacturing method according to an embodiment of the present invention, a granular carrier having such properties can be easily obtained without undergoing the steps of crushing the gel body, classifying, etc., that are required in the conventional manufacturing methods described above.

[0035] In an embodiment of the present invention, the carboxyalkyl cellulose or salt thereof used as the raw material is preferably a carboxyalkyl cellulose or salt thereof having an alkyl group having 1 to 3 carbon atoms, for example, from the viewpoint of production costs, etc. Specific examples include carboxymethyl cellulose, carboxyethyl cellulose, carboxybutyl cellulose, or salts thereof. The carboxyalkyl cellulose and / or salt thereof may be used alone or in combination of two or more.

[0036] In embodiments of the present invention, it is important to select carboxyalkyl cellulose and / or its salts as raw materials, whose 1% by weight aqueous solution has a viscosity within a predetermined range. The longer the polymer chain of the carboxyalkyl cellulose, the higher the viscosity when dissolved, which reduces the handling properties when injected into the low-polarity organic solvent used as the dispersion medium. This may adversely affect the uniformity of the particle shape and particle size of the resulting granular carrier. On the other hand, the longer the polymer chain of the carboxyalkyl cellulose, the greater the water absorption, which means that when the granular carrier according to this embodiment is used as a drug carrier, it can carry a large amount of drug. However, excessive water absorption can cause problems such as a decrease in gel strength and increased syneresis. From these perspectives, embodiments of the present invention use carboxyalkyl cellulose and / or its salts whose 1% by weight aqueous solution has a viscosity of 5 mPa·s to 300 mPa·s.

[0037] Here, the viscosity of a 1% by mass aqueous solution of carboxyalkyl cellulose and / or its salt is the viscosity value measured using a Brookfield viscometer after preparing a 200 mL aqueous solution of carboxyalkyl cellulose so that the solids content is 1% by mass. Hereinafter, the viscosity of a 1% by mass aqueous solution of carboxyalkyl cellulose and / or its salt measured under these conditions will be simply referred to as the "viscosity of carboxyalkyl cellulose." The viscosity of carboxyalkyl cellulose is preferably 10 mPa·s or more and 100 mPa·s or less, and more preferably 20 mPa·s or more and 50 mPa·s or less.

[0038] In an embodiment of the present invention, the average degree of etherification (average degree of substitution, DS) of the carboxyalkyl cellulose used as the raw material may be, for example, 0.5 to 1.5. The use of carboxyalkyl cellulose having an average degree of etherification in this range can easily improve the water absorption and strength of the gel. The average degree of etherification (average degree of substitution) refers to the average degree of substitution of hydroxyl groups at the 2-, 3-, and 6-positions of the glucose units constituting the cellulose.

[0039] Fig. 1 is a flow diagram showing an example of a method for producing a granular carrier according to an embodiment of the present invention. The production method shown in Fig. 1 includes the steps of: Step S1: dissolving carboxyalkyl cellulose and / or a salt thereof in an alkaline aqueous solution to prepare an aqueous carboxyalkyl cellulose salt solution; Step S2: preparing a mixture of the aqueous carboxyalkyl cellulose salt solution obtained in Step S1 with a crosslinking agent; Step S3: dispersing the mixture obtained in Step S2 in a low-polarity organic solvent to form a suspension (reverse phase suspension); Step S4: forming dispersed particles containing crosslinked carboxyalkyl cellulose salt; and Step S4: filtering, washing, and drying the dispersed particles formed in Step S3.

[0040] 1 is one example, as described above. In other examples, the manufacturing method according to the embodiment of the present invention may further include other steps not shown in FIG. 1. Furthermore, step S4 is an optional step that is performed as needed, as will be described later. Therefore, in still another example, the manufacturing method according to the embodiment of the present invention may not include step S4.

[0041] In step S1, carboxyalkyl cellulose and / or its salt are added (injected) into an alkaline aqueous solution and completely dissolved while stirring at room temperature to prepare an aqueous carboxyalkyl cellulose salt solution. The time required to prepare the aqueous carboxyalkyl cellulose salt solution in step S1 can be set appropriately, but in one example, it can be set to 1 to 5 hours. After adding the carboxyalkyl cellulose to the alkaline aqueous solution, a degassing treatment can be performed, if necessary, by reducing the pressure or by leaving the solution at normal pressure for a predetermined time.

[0042] The carboxyalkyl cellulose and / or salt thereof used in step S1 may be one obtained by using cellulose such as pulp as a starting material and carboxyalkylating it using a conventional method, or a commercially available carboxyalkyl cellulose and / or salt thereof may be used.

[0043] The carboxyalkyl cellulose salt contained in the carboxyalkyl cellulose salt aqueous solution obtained in step S1 may be, for example, an alkali metal salt or alkaline earth metal salt of carboxyalkyl cellulose. In this case, the alkaline aqueous solution to which the carboxyalkyl cellulose and / or its salt is added is an alkaline aqueous solution containing an alkali metal or alkaline earth metal. Examples of carboxyalkyl cellulose salts include sodium salts, potassium salts, and calcium salts. In this case, the alkaline aqueous solution to which the carboxyalkyl cellulose is added is an aqueous solution of sodium hydroxide, potassium hydroxide, or calcium hydroxide. According to one example, sodium carboxymethyl cellulose (CMC-Na) is used as the carboxyalkyl cellulose and / or its salt, and sodium hydroxide is used as the alkaline aqueous solution to prepare the CMC-Na aqueous solution in step S1.

[0044] In step S2, the carboxyalkyl cellulose salt aqueous solution obtained in step S1 is mixed with a crosslinking agent to prepare a mixture of the carboxyalkyl cellulose salt aqueous solution and the crosslinking agent. Hereinafter, when simply referring to the "mixture," this refers to the mixture of the carboxyalkyl cellulose salt aqueous solution and the crosslinking agent prepared in step S2.

[0045] The carboxyalkyl cellulose salt aqueous solution and the crosslinking agent are mixed preferably at 10°C to 80°C, more preferably 20°C to 50°C, while stirring using, for example, a static mixer. At temperatures higher than 80°C, the crosslinking reaction proceeds too quickly, making it difficult to obtain uniform spherical gel particles in the subsequent step S3. At temperatures lower than 10°C, the viscosity of the mixture increases, making it difficult to handle when the mixture is added to a low-polarity organic solvent in the subsequent step S3. The crosslinking reaction of the carboxyalkyl cellulose salt begins immediately after the crosslinking agent is added to the carboxyalkyl cellulose salt aqueous solution in step S2, and the viscosity begins to increase. Therefore, the time from adding the crosslinking agent to the carboxyalkyl cellulose salt aqueous solution to adding the mixture to the low-polarity organic solvent can be appropriately set from the viewpoint of ease of handling when the mixture is added to a low-polarity organic solvent in the subsequent step S3. For example, the reaction temperature can be adjusted within the above range, and the reaction time can be set to within 30 minutes. After stirring, a degassing operation under reduced pressure may be performed as needed.

[0046] The crosslinking agent used in the production method according to the embodiment of the present invention is not particularly limited, and known compounds such as polyepoxy compounds, polyglycidyl compounds, polyaldehyde compounds, polycarboxylic acids, vinyl ether compounds, methylol compounds, polyisocyanates, polyoxazoline compounds, polyvinyl compounds, polyacrylate compounds, polymethacrylate compounds, polyhalogen compounds, methylenebisacrylamide, epichlorohydrin, polyacid anhydrides, methylenebisacrylamide, and glycidyl methacrylate can be used.

[0047] Preferred specific examples of the crosslinking agent include (a) a compound having two or more hydroxyl groups in the molecule, (b) a compound having two or more polymerizable double bonds, and (c) a compound having two or more epoxy groups.

[0048] (a) Examples of compounds having two or more hydroxyl groups in the molecule include ethylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, glycerin, polyglycerin, propylene glycol, diethanolamine, polyoxypropylene, sorbitan fatty acid esters, trimethylolpropane, pentaerythritol, 1,3-propanediol, and sorbitol.

[0049] (b) Examples of compounds having two or more polymerizable double bonds in the molecule include bis(meth)acrylamide, allyl(meth)acrylamide, diethylene glycol diacrylate, trimethylolpropane triacrylate, polyethylene glycol diacrylate, and ethoxylated trimethylolpropane triacrylate.

[0050] (c) Examples of compounds having two or more epoxy groups in the molecule include polyglycidyl ethers such as ethylene glycol diglycidyl ether (EGDE), polyethylene glycol diglycidyl ether, polypropylene glycol diglycidyl ether, glycerin triglycidyl ether, glycerol polyglycidyl ether, polyglycerol polyglycidyl ether, trimethylolpropane polyglycidyl ether, sorbitol polyglycidyl ether, pentaerythritol polyglycidyl ether, resorcinol diglycidyl ether, neopentyl glycol diglycidyl ether, and hydrogenated bisphenol A diglycidyl ether.

[0051] Among these, from the viewpoint of reactivity and the water absorption performance of the resulting granular carrier, (b) compounds having two or more polymerizable double bonds in the molecule and (c) compounds having two or more epoxy groups in the molecule are preferred, (c) compounds having two or more epoxy groups in the molecule are more preferred, polyglycidyl ethers are even more preferred, and ethylene glycol diglycidyl ether (EGDE) is particularly preferred.

[0052] The mass ratio of the carboxyalkyl cellulose and / or its salt to the crosslinking agent can be appropriately set. From the viewpoint of the shape, transparency, and strength of the granular carrier, the mass ratio (X / Y) of the carboxyalkyl cellulose and / or its salt (X) to the crosslinking agent (Y) is preferably in the range of 10 / 2≧X / Y≧10 / 5, and more preferably in the range of 10 / 2>X / Y≧10 / 4.

[0053] In step S3, the mixture obtained in step S2 is added (injected) into a low-polarity organic solvent and dispersed to form a suspension (reverse phase suspension), and dispersed particles containing crosslinked bodies of carboxyalkyl cellulose salt are formed by crosslinking polymerization in this suspension.

[0054] The low-polarity organic solvent used as the dispersion medium in step S3 is a low-polarity organic solvent with a dielectric constant of 10 or less at 25°C, which is lower in polarity than the above-mentioned mixture of dispersoids. Therefore, the suspension prepared in step S3 is a reversed-phase suspension, and the cross-linking polymerization of the carboxyalkyl cellulose salt is reversed-phase suspension polymerization. Here, the dielectric constant is the dielectric constant at 25°C measured with a capacitance meter. According to one example, the low-polarity organic solvent used as the dispersion medium more preferably has a dielectric constant of 3 or more and 6 or less.

[0055] Examples of low-polarity organic solvents with a relative dielectric constant of 10 or less include aliphatic hydrocarbons, alicyclic hydrocarbons, aromatic hydrocarbons, liquid paraffin, silicone oil, etc., which can be used alone or in combination of two or more.

[0056] The low-polarity organic solvent used in step S3 further has a kinematic viscosity of 10 mm at 37.8°C. 2 When the dispersion medium is a viscous fluid, it is possible to suppress the aggregation of the spherical gel particles produced and the adhesion between the spherical gel particles, thereby suppressing the formation of clumps of the spherical gel particles. 2 / s or more is important in order to obtain high quality granular carriers that are spherical in shape and have a uniform particle size.

[0057] Here, the kinematic viscosity is the kinematic viscosity at 37.8°C measured by a vibration viscometer. According to one example, the low polarity organic solvent used as the dispersion medium has a kinematic viscosity of 10 mm 2 / s or more 100mm 2 / s or less, and according to other examples, 15 mm 2 / s or more 80mm 2 / s or less, and in another example, 20 mm 2 / s or more 50mm 2 / s or less.

[0058] Among the above-mentioned specific examples of low-polarity organic solvents having a relative dielectric constant of 10 or less, liquid paraffin and silicone oil are viscous fluids, and therefore are particularly preferable as the low-polarity organic solvent used in step S3.

[0059] The liquid paraffin is not particularly limited as long as it is a paraffin that is liquid at room temperature, and examples thereof include liquid saturated hydrocarbons having 12 to 50 carbon atoms, and may be any of n-paraffin, isoparaffin, and naphthene. Commercially available products that can be used include, for example, Moresco White and Moresco Bioless (all trade names, manufactured by Matsumura Oil Research Institute), Stanol, Krystoll, Esso White Oil, and Purelex (all trade names, manufactured by Esso Oil Co., Ltd.). These may be used alone, or two or more types may be used in combination.

[0060] The silicone oil is not particularly limited as long as it has a siloxane structure that is liquid at room temperature, and examples thereof include polysiloxane oils such as dimethyl silicone oil, and modified silicone oils having functional groups such as hydroxyl groups, carboxyl groups, amino groups, epoxy groups, cyano groups, mercapto groups, trifluoropropyl groups, chlorophenyl groups, and long-chain alkyl groups, or modified with polyethers, alcohols, etc. These may be used alone or in combination of two or more.

[0061] In step S3, the aforementioned crosslinking agent may be further added to the low-polarity organic solvent to perform surface crosslinking (secondary crosslinking) to provide high-crosslink density portions on the surface layer of the gel particles. By performing surface crosslinking (secondary crosslinking), it is possible to improve gel strength while maintaining water absorption.

[0062] In step S3, the low-polarity organic solvent to which the mixture obtained in step S2 is added is at room temperature or heated. In one example, the low-polarity organic solvent is preferably heated to 30°C to 80°C, and in another example, the low-polarity organic solvent is more preferably heated to 50°C to 70°C.

[0063] In step S3, the low-polarity organic solvent to which the mixture obtained in step S2 is added is stirred. Examples of stirring devices include mechanical stirrers, and examples of stirring blades include anchor-type, propeller-type, and paddle-type blades, and these can be appropriately selected and used. In one example, in step S3, the low-polarity organic solvent is stirred at a rotation speed of 50 to 500 rpm, in another example, at a rotation speed of 200 to 500 rpm, and in yet another example, at a rotation speed of 250 to 400 rpm.

[0064] In step S3, the mixture obtained in step S2 is added (injected) into the low-polarity organic solvent, for example, by dripping the mixture drop by drop using a pipette from the liquid surface of the low-polarity organic solvent (hereinafter, sometimes referred to as the "drop-by-drop injection method"). Another example is by continuously injecting the mixture while immersing a pipette in the low-polarity organic solvent (hereinafter, sometimes referred to as the "continuous injection method"). The drop-by-drop injection method is preferred because it makes it easier to obtain uniform particle sizes for the dispersed particles. The continuous injection method is preferred because it can be easily performed in a short time.

[0065] In step S3, the time required for the cross-linking polymerization reaction of the carboxyalkyl cellulose salt can be set appropriately, and according to one example, it can be set to 1 hour to 6 hours.

[0066] The method for producing a granular carrier according to this embodiment typically includes step S4, as shown in FIG. 1 . Specifically, the dispersed particles containing the crosslinked carboxyalkyl cellulose salt formed in the suspension in step S3 of this embodiment are typically removed from the suspension by filtration, and then washed, dried, or otherwise processed as necessary. The washing after filtration involves, for example, washing the low-polarity organic solvent adhering to the gel particle surface with an aqueous detergent solution containing a surfactant or the like, and / or immersing the gel particles in ethanol to dehydrate and dealkalize them. Drying can be performed, for example, by air drying. When a solvent with a low boiling point, such as n-hexane, is used as the low-polarity organic solvent, the solvent on the gel particle surface can be volatilized / removed without washing by using a method such as vacuum distillation.

[0067] However, in the method for producing a granular carrier according to this embodiment, step S4 is an optional step, and the dispersed particles may be distributed as a product in a dispersed state in the suspension without being removed from the suspension. That is, the granular carrier according to this embodiment may be gel particles derived from dispersed particles that have been subjected to reverse phase suspension polymerization in the suspension formed in step S3, and may be in the form of, for example, dispersed particles present in the suspension, water-absorbed gel particles that have been removed from the suspension and not dried, or dried gel particles that have been removed from the suspension and dried.

[0068] The particle diameter of the granular carrier according to this embodiment is not particularly limited, but there are preferred particle diameters depending on the purpose of use. For example, when the granular carrier according to this embodiment is used for carrying a drug, the average particle diameter of the gel particles in a water-absorbed state may be, in one example, 2 mm to 30 mm, and in another example, 2 mm to 20 mm. Here, the average particle diameter means the value measured by measuring the major axis of 30 randomly selected particles using a vernier caliper and averaging the results.

[0069] Furthermore, when the granular carrier according to this embodiment is used for carrying a drug, the average particle size of the gel particles in a dry state may be, for example, 0.2 mm to 6 mm, and in another example, 0.5 mm to 4 mm. Here, the average particle size refers to the value measured by measuring the major axis of 30 randomly selected particles using a vernier caliper and averaging the results.

[0070] For example, the granular carrier of this embodiment can be used in a dry state as a highly absorbent material in absorbent articles such as disposable diapers, sanitary products (napkins, tampons, etc.), pads (sweat pads, breastfeeding pads, incontinence pads, etc.), and pet toilets.

[0071] In another example, the granular carrier according to the present embodiment is used as a drug carrier. That is, a liquid composition containing at least one drug selected from drugs having, for example, aromatic, deodorizing, deodorizing, insect repellent, insecticidal, or antifungal properties is absorbed and carried by the granular carrier made of the dried gel particles according to the present embodiment. This makes it possible to provide gel formulations such as granular drug compositions, such as granular air freshener compositions, granular deodorant compositions, granular deodorizing compositions, granular insect repellent compositions, granular insecticide compositions, and granular antifungal compositions.

[0072] In a gel preparation consisting of such a granular pharmaceutical composition, various commonly used drugs can be used as the pharmaceutical component contained in the liquid composition absorbed and carried by the granular carrier depending on the purpose. Specific examples of aromatic agents include animal fragrances such as musk, spirit cat fragrance, and dragon jasmine fragrance, and plant fragrances such as abies oil, accion oil, almond oil, angelica root oil, peper oil, bergamot oil, perch oil, bois rose oil, kayabuchi oil, gananga oil, capsicum oil, caraway oil, cardamom oil, cassia oil, celery oil, cinnamon oil, citronella oil, cognac oil, coriander oil, cumin oil, camphor oil, basil oil, estugolan oil, eucalyptus oil, fennel oil, garlic oil, ginger oil, grapefruit oil, hop oil, lemon oil, lemongrass oil, nutmeg oil, mandarin oil, peppermint oil, orange oil, sage oil, star anise oil, turpentine oil, rosemary oil, eucalyptus oil, anise oil, lavender oil, cumin oil, cinnamon oil, and hiba oil. Artificial fragrances such as synthetic fragrances or extracted fragrances can also be used. Specific examples include hydrocarbon fragrances such as pinene and limonene; alcohol fragrances such as linalool, geraniol, citronellol, menthol, borneol, benzyl alcohol, anise alcohol, and β-phenethyl alcohol; phenol fragrances such as anethole and eugenol; aldehyde fragrances such as n-butyraldehyde, isobutyraldehyde, hexylaldehyde, citral, citronellal, benzaldehyde, and cinnamic aldehyde; ketone fragrances such as carvone, menthone, camphor, acetophenone, and ionone; lactone fragrances such as γ-butyrolactone, coumarin, and cineole; and ester fragrances such as octyl acetate, benzyl acetate, cinnamyl acetate, butyl propionate, and methyl benzoate. These may be used alone or in any combination of two or more.

[0073] The deodorizing agent may be a volatile agent or a non-volatile agent, and specific examples include metal oxides such as titanium oxide and zinc oxide, flavonoid compounds, plant extracts such as catechin and polyphenols or derivatives thereof, cyclodextrin or derivatives thereof, amine compounds, etc. These may be used alone or in any combination of two or more.

[0074] Specific examples of deodorizing agents include carbon-based adsorbents such as activated carbon from coconut shells and charcoal such as binchotan charcoal, and silica-based adsorbents such as zeolite, silica gel, and layered zinc aluminosilicate. These may be used alone or in any combination of two or more.

[0075] Specific examples of insecticides having insect repellent or insecticidal properties include pyrethroid insecticides such as empenthrin, transfluthrin, allethrin, fenothrin, eminence, and profluthrin, and volatile insect repellent or insecticides such as paradichlorobenzene, naphthalene, camphor, 2-phenoxyethanol, hinokitiol, and allyl isothiocyanate. These can be used alone or in any combination of two or more.

[0076] In addition to the above-mentioned drugs, various additives may be used in the liquid composition, such as surfactants, colorants, preservatives, and pH adjusters.

[0077] The granular pharmaceutical composition according to this embodiment can be produced, for example, by impregnating dry gel particles into a liquid pharmaceutical composition.

[0078] As described above, the granular carriers according to this embodiment, which are gel particles derived from dispersed particles formed by reverse-phase suspension polymerization using a low-polarity organic solvent as a dispersion medium, are approximately spherical in shape and have uniform particle sizes. Therefore, the granular pharmaceutical composition obtained by loading a liquid pharmaceutical composition onto the granular carriers according to this embodiment is prone to air flow when filled into a container, allowing the pharmaceutical loaded onto the granular carriers to function efficiently. Furthermore, the granular pharmaceutical composition according to this embodiment also has excellent strength and transparency. Therefore, the granular carriers according to this embodiment are suitable for use as pharmaceutical carriers for granular gel formulations loaded into containers in stationary products such as air fresheners and deodorants. [Example]

[0079] ≪Example 1≫ CMC-Na viscosity <Example 1-1: Production of Granular Carrier 1> The raw material used was sodium carboxymethylcellulose (CMC-Na) (Daicel 1110, manufactured by Daicel Miraize Co., Ltd.) with a viscosity in the range of 10 to 20 mPa s. The viscosity here was measured by the above-mentioned method for the viscosity of a 1% by mass aqueous solution of CMC-Na at 25°C.

[0080] 10.0 g of the above CMC-Na (Daicel 1110) was dissolved in 100 mL of 0.5 mol / L aqueous sodium hydroxide. 4.0 g of ethylene glycol diglycidyl ether (EGDE) (Denacol EX-810, Nagase ChemteX Corporation) was added dropwise to the resulting solution as a crosslinker. After stirring for 20 minutes, the solution was degassed under reduced pressure for 5 minutes. This yielded a mixture of an aqueous CMC-Na solution and EGDE. In this example, the mass ratio of CMC-Na to the crosslinker EGDE (CMC-Na / EGDE) was 10 / 4.

[0081] The resulting mixture was then poured into a liquid paraffin (Moresco White P-100, manufactured by MORESCO Corporation; kinematic viscosity 20.5 mm) heated to 60°C and stirred at a stirring speed of 250 rpm. 2 The mixture was injected into a liquid paraffin (1 / s). A high-viscosity pipette was used to inject the mixture, and the tip of the pipette was immersed in the liquid paraffin while it was being injected. The reaction was allowed to proceed in the liquid paraffin for 4 hours. After the reaction, the gel particles that had formed were filtered off, and the liquid paraffin adhering to the surface of the gel particles was washed off with an appropriate amount of aqueous surfactant solution. The gel particles were then immersed in ethanol to dehydrate and dealkalize them, and then air-dried to obtain a white to pale yellow solid (granular carrier 1).

[0082] <Examples 1-2 to 1-6: Production of Granular Carriers 2 to 6> Granular carriers 2 to 6 were produced in the same manner as in Example 1-1, except that CMC-Na (Daicel 1110, viscosity 10-20 mPa·s) was changed to CMC-Na shown in Table 1 below.

[0083] <Evaluation> [Handling when pouring into liquid paraffin (ease of pouring)] During the manufacturing process of each granular carrier, the handling characteristics of the mixture of CMC sodium salt and EGDE when pouring it into the liquid paraffin were evaluated based on the ease of drawing it into the pipette and the ease of pouring it from the pipette into the liquid paraffin, according to the following criteria. The evaluation results are shown in Table 1. A: It can be easily aspirated and injected. B: Suction and injection take some time, but are not difficult. C: Difficult to suction and inject.

[0084] [Shape of granular carrier (dry gel)] The shape of each of the resulting granular carriers (dry gels) was visually evaluated according to the following criteria. The evaluation results are shown in Table 1. A: Spherical dry gels account for almost the entire sample, and dry gels of other shapes are hardly observed. B: Mostly spherical dry gel. Flat or thread-like dry gel is mixed in, but not noticeable. C: Most of the dry gel is thread-like, with few spherical dry gels.

[0085] [Transparency] Each of the obtained granular carriers (dry gels) was immersed in ion-exchanged water to absorb the maximum amount of water possible, and the transparency of the water-absorbed gel particles was evaluated visually according to the following criteria. The evaluation results are shown in Table 1. A: There is no cloudiness and the overall transparency is high. B: Some parts are cloudy, but more than 80% is transparent, and the overall appearance is transparent. C: Many areas are cloudy or the entire surface is cloudy, with low transparency overall.

[0086] [Strength] One gram of each of the resulting granular carriers (dried gel particles) was placed in a 200 mL beaker, 150 mL of ion-exchanged water was added, and the mixture was left overnight to obtain water-absorbed gel particles carrying the maximum amount of water they could absorb. The water-absorbed gel particles were then filtered to remove excess water, and the water-absorbed gel particles were then re-filled into the 200 mL beaker. At this point, the container contained approximately six layers of particles stacked from bottom to top. These were used as evaluation samples, and their strength was evaluated according to the following criteria. The evaluation results are shown in Table 1. A: The strength at which particles located at the bottom of the container, bearing a weight approximately six times their own weight, maintain their spherical shape and create uniformly sized gaps between particles throughout the particle-packed structure. B: Strength at which at least some of the particles located at the bottom of the container, which are subjected to a weight approximately six times their own weight, are unable to maintain their spherical shape, and there are areas where no gaps are formed between the particles at the bottom. C: The strength that cannot maintain a spherical shape even under its own weight.

[0087] [Table 1]

[0088] Table 1 shows that granular carriers 1 to 5 of Examples 1-1 to 1-5 according to the embodiment of the present invention are excellent in particle shape, transparency, and strength. Furthermore, Examples 1-1 to 1-5 also have excellent handling properties when the mixture is poured into liquid paraffin, demonstrating that granular carriers (gel particles) with excellent particle shape, transparency, and strength can be easily obtained by reversed-phase suspension polymerization. On the other hand, it is clear that it is difficult to produce spherical gel particles by reversed-phase suspension polymerization in Example 1-6 (Comparative Example), which uses highly viscous CMC.

[0089] Example 2: CMC-Na / crosslinking agent (mass ratio) <Examples 2-1 and 2-2: Production of Granular Carriers 7 and 8> Granular carriers 7 and 8 were produced in the same manner as in Example 1-2, which used Daicel 1120 (viscosity 20 to 50 mPa s) as the raw material (CMC-Na), except that the blending mass ratio of CMC-Na to EGDE was changed as shown in Table 2. The dried gel shape, transparency, and strength of each granular carrier were evaluated in the same manner as in Example 1-1. The evaluation results are shown in Table 2.

[0090] [Table 2]

[0091] In addition, although Example 2-1 was rated as B in strength, the portion where no gaps occurred between particles was only a part of the bottom of the packed particles, and air fluidity was ensured.

[0092] <Example 3> Dynamic viscosity of liquid paraffin and stirring speed <Examples 3-1 to 3-5: Production of Granular Carriers 9 to 13> Granular carriers were produced in the same manner as in Example 1-2 (granular carrier 2) above, using Daicel 1120 (viscosity 20 to 50 mPa s) as the raw material (CMC-Na), except that the liquid paraffin and stirring speed were changed as shown in Table 3. The dried gel shape of each granular carrier was evaluated in the same manner as in Example 1-1. The evaluation results are shown in Table 3.

[0093] However, low viscosity (kinematic viscosity 4.51 mm 2 In Examples 3-1 and 3-2, in which liquid paraffin (1 / s) was used, the mixture accumulated at the bottom and coalesced, and granular gel particles could not be obtained.

[0094] [Table 3]

[0095] In addition, although Example 3-3 was rated as B in strength, the portion where no gaps occurred between particles was only a part of the bottom of the packed particles, and air fluidity was ensured.

[0096] Example 4 Comparison of particle shapes between granular carrier according to the embodiment and crushed gel particles <Example 4-1: Production of crushed gel> 10.0 g of CMC-Na (Daicel 1120, Daicel Miraize Co., Ltd.) was dissolved in 100 mL of 0.5 mol / L aqueous sodium hydroxide solution. 4.0 g of EGDE (Denacol EX-810, Nagase ChemteX Corporation) was added dropwise and stirred for 20 minutes. After 5 minutes of degassing under reduced pressure, the mixture was allowed to react for 4 hours in a constant temperature bath at 60°C. After the reaction, the resulting gel-like substance was removed from the beaker and roughly crushed using a mixer. The crushed gel obtained was immersed in ethanol to dehydrate and dealkalize it, and then air-dried to obtain a white to pale yellow solid.

[0097] <Evaluation> Figure 3A(a) is a photograph of the dried and crushed gel particles produced in Example 4-1, and Figure 3B(a) is a photograph of the water-absorbed state of the particles. Figure 3A(b) is a photograph of the granular carrier 2 (dried gel particles) produced in Example 1-2, and Figure 3B(b) is a photograph of the water-absorbed state of the particles. Comparing (a) and (b) in Figure 3A and (a) and (b) in Figure 3B, it is clear that the particle shape of the granular carrier in this embodiment is completely different from the particle shape of the crushed gel particles. 3A(a) and 3B(a) show that the pulverized gel particles obtained by conventional methods of pulverizing a hydrogel formed by aqueous solution polymerization are fragmented with sharp edges, and most of the particles are irregularly shaped and far from spherical. On the other hand, 3A(b) and 3B(b) show that the gel particles according to the present embodiment, which are derived from dispersed particles formed by reversed-phase suspension polymerization, are spherical and have a uniform particle size. Thus, it can be seen that the production method according to the present embodiment allows high-quality gel particles to be easily obtained.

[0098] Example 5: Uniformity of particle size The granular carrier 2 (dried gel particles) obtained in Example 1-2 was classified using sieves with openings of 4 mm, 2 mm, 1 mm, and 0.25 mm to obtain particles with D (particle size) > 4 mm, 4 mm ≥ D > 2 mm, 2 mm ≥ D > 1 mm, 1 mm ≥ D > 0.25 mm, and 0.25 mm ≥ D. Figure 4 shows the results, a graph showing the particle size distribution of granular carrier 1-2. From FIG. 4, it can be seen that 90% by mass or more of the frequency (mass%) of the granular carrier 2 has a particle size D in the range of 2 mm or more and less than 4 mm, and that the granular carrier 2 has excellent uniformity of particle size.

[0099] Example 6: Uniformity of particle shape and particle size Figure 2 is a photograph of the granular carrier 12 obtained in Example 3-4. (a) shows the dried gel particles, and (b) shows the water-absorbed gel particles. From the photograph in Figure 2, it can be seen that the granular carrier 12 is dominated by roughly spherical particles and has excellent particle size uniformity.

[0100] The present invention is not limited to the above-described embodiments, and various modifications can be made in the implementation stage without departing from the spirit of the invention. Furthermore, the embodiments may be implemented in appropriate combinations, in which case the combined effects can be obtained. Furthermore, the above-described embodiments include various inventions, and various inventions can be extracted by combining selected elements from the disclosed elements. For example, if the problem can be solved and the desired effect can be obtained even if some elements are deleted from all elements shown in the embodiments, the configuration from which these elements are deleted can be extracted as an invention.

Claims

1. A granular carrier containing a crosslinked salt of carboxyalkyl cellulose, the viscosity of which when in a 1% by weight aqueous solution at 25°C is in the range of 5 mPa·s or more and 300 mPa·s or less, and which is a gel particle derived from dispersed particles in a reverse phase suspension, and which is used as a drug carrier.

2. A granular carrier as described in claim 1, having an average particle diameter in a dry state in the range of 0.2 mm or more and 6 mm or less.

3. A granular carrier as described in claim 1 or 2, having an average particle diameter in a water-absorbed state in the range of 2 mm or more and 30 mm or less.

4. 4. The granular carrier according to claim 1, wherein the dispersion medium of the reversed phase suspension is a low-polarity organic solvent having a relative dielectric constant of 10 or less.

5. 5. The granular carrier according to claim 1, wherein the dispersion medium of the reversed phase suspension is liquid paraffin or silicone oil.

6. 6. The granular carrier according to claim 1, wherein the viscosity of the carboxyalkyl cellulose and / or salt thereof is 5 mPa·s or more and 100 mPa·s or less.

7. A granular carrier described in any one of claims 1 to 5, wherein the viscosity of the carboxyalkyl cellulose and / or its salt is 5 mPa·s or more and 50 mPa·s or less.

8. A granular pharmaceutical composition comprising a granular carrier described in any one of claims 1 to 7 and a liquid composition supported on the granular carrier and containing at least one pharmaceutical selected from pharmaceuticals having aromatic, deodorizing, deodorizing, insect repellent, insecticidal or antifungal properties.

9. 9. The granular pharmaceutical composition according to claim 8, which is an air freshener composition or a deodorant composition.

10. An absorbent article comprising a granular carrier comprising a crosslinked salt of carboxyalkyl cellulose, the viscosity of which when in a 1% by mass aqueous solution at 25°C is in the range of 5 mPa·s or more and 300 mPa·s or less, and which is a granular carrier that is a gel particle derived from dispersed particles in a reverse phase suspension.

11. The absorbent article according to claim 10, which is any one selected from disposable diapers, sanitary products, sweat pads, breastfeeding pads, incontinence pads, and pet toilets.

12. A method for producing a granular carrier comprising gel particles containing a crosslinked product of a carboxyalkyl cellulose salt, comprising: A carboxyalkyl cellulose and / or a salt thereof having a viscosity of 5 mPa s or more and 300 mPa s or less in a 1 mass% aqueous solution at 25°C is dissolved in an alkaline aqueous solution to prepare a carboxyalkyl cellulose salt aqueous solution; preparing a mixture of the aqueous carboxyalkyl cellulose salt solution and a crosslinking agent; and the mixture is dispersed in a low-polarity organic solvent to form a suspension, and crosslinking polymerization of the carboxyalkyl cellulose salt is allowed to proceed in the suspension to form dispersed particles containing a crosslinked product of the carboxyalkyl cellulose salt. The low-polarity organic solvent has a relative dielectric constant of 10 or less at 25°C and a kinematic viscosity of 10 mm at 37.8°C. ２ / s or more.

13. The method according to claim 12, wherein the low-polarity organic solvent is liquid paraffin or silicone oil.

14. The kinematic viscosity of the low-polarity organic solvent at 37.8°C is 10 mm ２ / s or more 100mm ２ / The method according to claim 12 or 13, wherein the saturation temperature is 1000°C or less.

15. The method according to any one of claims 12 to 14, wherein the cross-linking polymerization of the carboxyalkyl cellulose salt in the suspension is carried out under stirring at a rotation speed of 50 rpm or more and 500 rpm or less.

16. The method according to any one of claims 12 to 15, wherein the viscosity of the carboxyalkyl cellulose and / or salt thereof is 5 mPa·s or more and 100 mPa·s or less.

17. 17. The method according to claim 12, wherein the mass ratio (X / Y) of the carboxyalkyl cellulose and / or salt thereof (X) to the crosslinking agent (Y) in the mixture is in the range of 10 / 2 to 10 / 5.

18. 18. The method according to claim 12, wherein the crosslinking agent is a compound having two or more epoxy groups in the molecule.

19. The method according to any one of claims 12 to 18, wherein the granular carrier is used for carrying a drug.

20. 19. The method according to any one of claims 12 to 18, wherein the granular carrier is used as a water-absorbing material in an absorbent article.

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