JP2013082650A - Gel for use in adhesive patches and adhesive patch having the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a gel for use in adhesive patches which is high in heat stability and is excellent in shape retentivity.SOLUTION: The gel for use in adhesive patches containing cellulose nanofibers, glycerol or a derivative thereof, and a functionalizing agent. This gel is produced desirably by mixing cellulose nanofibers, glycerol or a derivative thereof, and the functionalizing agent in a dispersion medium to obtain a composition for the preparation of the gel and removing the dispersion medium from the composition. Further, there is provided a composition for the preparation of the gel, which is the composition containing cellulose nanofibers, glycerol or a derivative thereof, and a dispersion medium.

Description

  The present invention relates to a gel for patches used in various patches including tapes, poultices, haps and the like. The present invention also relates to a patch containing the gel.

  Patches are used as tapes, poultices, poultices and the like for the treatment of low back pain, stiff shoulders, bruises, sprains, inflammation, etc., and healing foot fatigue. Further, in recent years, it is also used as a sheet-like pack agent for the purpose of facial and body beauty, a face mask, a cooling sheet, and the like. Typically, a layer structure having a gel-like pressure-sensitive adhesive layer containing various active ingredients is formed on a sheet substrate such as a nonwoven fabric or a tape. The gel-like adhesive layer is required to have various performances such as shape retention, water retention, skin adhesion, stability, comfort, flexibility, and sustained release of active ingredients.

  Among various patches, when the adhesive layer is made of an aqueous gel, the active ingredients that are lipophilic and their solubilizers generally bleed from the gel gradually by phase separation and feel as an unpleasant surface stickiness. May affect comfort. In addition, when the patch is packaged in a bag, the inside of the bag becomes sticky due to bleed, and it is difficult to remove it from the bag, or the patch may be torn off when removed from the bag. Arise.

  Typical examples of gelling agents for gel-like adhesive layers that have been used in the past include gelatin, carboxymethylcellulose sodium salt, sodium alginate, starch, and other natural polymers or natural polymer derivatives, polyvinyl alcohol, and polyacrylic acid. Synthetic polymers such as sodium, polyvinylpyrrolidone, carboxyvinyl polymer. However, gels using these materials are easily affected by changes in the external environment such as temperature or the properties of the material, so that the gel softens and bleeds the ingredients when exposed to high temperatures in the summer and distribution. As a result, there is a problem of causing unpleasant stickiness on the skin.

  In addition, the patch may be packaged by folding the sheet base material at least in half, but when the sheet base material is brought into close contact with the bleed as described above and the patch is to be developed. It is difficult to peel off, and if it is attempted to be forcibly developed, the adhesive layer and the sheet base material may be separated and become unusable. Therefore, Patent Document 1 proposes a medical patch in which a patch comprising an adhesive layer provided on one side of a support is folded and pasted so as to cover both sides of a separator that has been subjected to double-sided release treatment. Yes. However, it cannot be said that the above bleed itself is suppressed.

  In addition, the patch gel needs to retain its shape because it may be repeatedly deformed such as stretching or shrinking due to exercise while attached to the body surface. On the other hand, it is preferable that the gel precursor for a patch (raw material before gelation) has high fluidity from the viewpoint of workability during the production of the sheet gel. However, the fluidity of the gel precursor and the shape retention of the gel are generally contradictory properties and are difficult to achieve at the same time. That is, when considering the shape retention of the gel for patches, the mechanical strength can be improved by, for example, adding a large amount of gelling agent. On the other hand, when considering the fluidity of the gel precursor, using a large amount of gelling agent may increase the viscosity of the gel precursor and reduce the workability. Moreover, it is not preferable to mix | blend many gelatinizers also from a viewpoint of sustained release of an active ingredient, and a softness | flexibility.

  For example, Patent Document 2 discloses a base material for a haptic agent characterized by comprising a thermally crosslinked carboxymethylcellulose sodium salt.

  Patent Document 3 discloses a polymer gel composition containing a copolymer of N-vinylacetamide, acrylic acid and / or acrylate, an epoxy compound, and a wetting agent as essential components. However, this composition has room for improvement in heat resistance.

  Patent Document 4 discloses an invention relating to fine cellulose fibers, and describes the possibility of using fine cellulose as a gelling agent. However, this document does not describe the specific production method and characteristics of the gel and the use of the gel in a patch gel.

Japanese Utility Model Publication No. 52-1877 JP 2000-95678 A JP-A-5-271517 JP 2008-1728 A

  The base for hap agents obtained using the technique described in Patent Document 2 is composed of a thermally crosslinked carboxymethylcellulose sodium salt, and a hap agent base having excellent shape retention and fluidity is disclosed. However, since the carboxymethyl cellulose sodium salt, which is a conventional polymer gelling agent, is used, it cannot be said that the above-described bleed problem has been improved.

  Further, in the gel composition described in Patent Document 2, the amount of the polymer used as the gelling agent is substantially relatively large as 5 to 10% by mass of the whole, which is preferable from the viewpoint of fluidity. Absent.

  Therefore, the first problem of the present invention is to provide a gel for a patch having high heat stability and excellent shape retention.

  Moreover, the 2nd subject of this invention is providing the composition for preparation of the gel for patchs excellent in fluidity | liquidity.

  As a result of various studies on the novel gel for patches using the fine cellulose fiber (cellulose nanofiber) described in Patent Document 4, the present inventors have found that the fine cellulose fiber, that is, a specific gel obtained by the method described later. It has been found that gels using cellulose nanofibers have high heat stability and excellent shape retention. Specifically, it has been found that the gel has few bleeds of various components even under a high temperature environment, and has high shape stability against deformation with a small amount of cellulose nanofiber blended. Moreover, it discovered that the gel precursor using the said cellulose nanofiber was excellent in fluidity | liquidity. Specifically, it has been found that when the gel precursor is spread into a film having a certain size, the gel precursor has a viscosity characteristic capable of forming a film uniformly.

  This invention is made | formed based on the said knowledge, and solves the said subject by providing the gel for patchs containing a cellulose nanofiber, glycerol or its derivative (s), and a functionalizing agent.

  Moreover, this invention provides the composition for preparation of the gel for patch which contains a cellulose nanofiber, glycerol or its derivative (s), and a dispersion medium as a suitable composition used for preparation of the gel for said patch. This solves the problem.

  In addition, the present invention provides a preparation method for a patch gel by mixing cellulose nanofibers, glycerin or a derivative thereof, and a functionalizing agent in a dispersion medium as a suitable method for producing the above-mentioned patch gel. The above-mentioned problems are solved by providing a method for producing a gel for a patch having a step of obtaining a product and then removing at least a part of the dispersion medium from the composition.

  Furthermore, the present invention provides another preferred method for producing the above gel for a patch, wherein cellulose nanofibers and glycerin or a derivative thereof are mixed in a dispersion medium to obtain a composition, and the dispersion medium is obtained from the composition. It is intended to provide a method for producing a gel for a patch having a step of removing at least a part thereof to obtain a gel and then blending a functional agent into the gel.

  The gel for patch of the present invention has high heat stability and excellent shape retention, and is used for treatment such as low back pain, stiff shoulders, bruises, sprains, etc. It is useful as a material for patches used as an adhesive, a haptic agent and the like. In addition, the composition for preparing a gel for patch of the present invention is excellent in fluidity and is useful as a material for the gel for patch. Moreover, according to the manufacturing method of the gel for patch of this invention, the gel for patch of this invention can be provided stably.

  The gel for patches of the present invention contains (1) cellulose nanofibers, (2) glycerin or a derivative thereof, and (3) a functionalizing agent. In the present invention, it is sufficient that these three components are contained in the gel for patches, and the form of inclusion is not particularly limited, and an appropriate form is selected as long as the gel for patches can have predetermined properties. can do. Moreover, the gel for patch of this invention may contain the liquid medium additionally as needed. The three components will be described in detail below.

  The cellulose nanofibers (hereinafter also simply referred to as “nanofibers”) used in the present invention preferably have an average fiber diameter of 200 nm or less, more preferably 50 nm or less, and particularly preferably 10 to 1 nm. The average fiber diameter is measured by the following measuring method.

<Measurement method of average fiber diameter>
Water is added to cellulose nanofibers having a solid content concentration of 0.0001% by mass to prepare a dispersion. An observation sample is obtained by dropping the dispersion onto mica (mica) and drying it. Using an atomic force microscope (NanoNaVi IIe, SPA400, manufactured by SII Nano Technology Co., Ltd., the probe uses SI-DF40Al manufactured by the same company), the fiber height of the cellulose nanofiber in the observed sample is measured. In a microscopic image in which cellulose nanofibers can be confirmed, five or more cellulose nanofibers are extracted, and the average fiber diameter is calculated from the fiber heights. In general, the smallest unit of cellulose nanofibers prepared from higher plants is a 36 × 36 molecular chain packed in a substantially square shape. Therefore, the height that can be analyzed by the atomic force microscope image is regarded as the fiber diameter. be able to.

  The cellulose nanofiber according to the present invention has an average aspect ratio (fiber length / fiber diameter) of preferably 10 to 1000, more preferably 10 to 500, and particularly preferably 100 to 350. A patch comprising cellulose nanofibers having an average aspect ratio in such a range, the cellulose nanofiber obtained by the method described later, glycerin or a derivative thereof, and a functionalizing agent by using the gel for the patch of the present invention. In the gel for use, even when the content of the cellulose nanofiber is small, high heat stability and shape retention are exhibited. The average aspect ratio is measured by the following measurement method.

<Measuring method of average aspect ratio>
The average aspect ratio is calculated from the viscosity of a dispersion prepared by adding water to cellulose nanofiber (mass concentration of cellulose fiber: 0.005 to 0.04 mass%). The viscosity of the dispersion is measured at 20 ° C. using a rheometer (MCR, DG42 (double cylinder), manufactured by PHYSICA). From the relationship between the mass concentration of the cellulose nanofibers in the dispersion and the specific viscosity of the dispersion with respect to water, the aspect ratio of the cellulose nanofibers is calculated by the following formula (1) to obtain the average aspect ratio. The following formula (1) is obtained from The Theory of Polymer Dynamics, M .; DOI and D.D. F. EDWARDS, CLARENDON PRESS · OXFORD, 1986 , P312 viscosity rigid-rod molecules according to equation (8.138), the relationship wherein the ^{Lb 2 × ρ = M / N} A, L is the fiber length, b is fiber width (The cross section of the cellulose fiber is square), ρ is the concentration of the cellulose nanofiber (kg / m ³ ), M is the molecular weight, and N _A is the Avogadro number. In the viscosity formula (8.138), rigid rod-like molecules = cellulose fibers. In the following formula (1), η _SP is the specific viscosity, π is the circumference ratio, ln is the natural logarithm, P is the aspect ratio (L / b), γ = 0.8, ρ _S is the density of the dispersion medium ( kg / m ³ ), ρ ₀ represents the density of cellulose crystals (kg / m ³ ), and C represents the mass concentration of cellulose (C = ρ / ρ _S ).

  The cellulose nanofiber is a constituent component of the gel for patch of the present invention. In the gel for patch of the present invention, a liquid medium containing glycerin or a derivative thereof and a functionalizing agent described later is held in a large number of minute spaces formed by a network of nanofibers. Therefore, it is considered that the gel for patch has high heat stability and shape retention. The cellulose nanofiber content in the gel for patches of the present invention can be arbitrarily set within a range that can have predetermined properties, but in addition to the properties of heat stability and shape retention, flexibility and In consideration of various properties required for a patch such as sustained release of a functionalizing agent, it is preferably 0.1 to 90% by mass, more preferably 2 to 50% by mass, and still more preferably 2 to 20% by mass. is there. In particular, by using cellulose nanofibers (cellulose nanofibers having an average fiber diameter and a carboxyl group content in a specific range) described below, even if the cellulose nanofiber content is as small as 0.1% by mass, A gel for patch with high elasticity and high heat resistance is obtained. Note that the transparency of the gel for patches is mainly derived from the transparency of the liquid medium, and cellulose nanofibers lose the high transparency of the liquid medium when a highly transparent liquid medium is used. Without realizing high elasticity and high heat resistance. From such a viewpoint, the transmittance of the gel for a patch is preferably 70 to 100%, particularly 80 to 100%, particularly 90 to 100%. The transmittance can be evaluated by measuring the transmittance at a wavelength of 660 nm using an ultraviolet-visible spectral hardness meter (for example, an ultraviolet-visible spectral hardness meter U-3310, manufactured by Shimadzu Corporation). When a liquid medium having a low transmittance is used, the transmittance of the gel for patch may be out of such a range.

  The cellulose nanofiber used in the present invention can be produced, for example, by the following method. That is, the cellulose nanofiber used in the present invention can be obtained by a production method including an oxidation reaction step in which natural cellulose fibers are oxidized to obtain reactant fibers, and a refinement step in which the reactant fibers are refined. Each step will be described in detail below.

  In the oxidation reaction step, first, a slurry in which natural cellulose fibers are dispersed in water is prepared. The slurry is obtained by adding about 10 to 1000 times (mass basis) of water to the natural cellulose fiber (absolute dry basis) as a raw material, and processing with a mixer or the like. Examples of natural cellulose fibers include wood pulp such as softwood pulp and hardwood pulp; cotton pulp such as cotton linter and cotton lint; non-wood pulp such as straw pulp and bagasse pulp; bacterial cellulose and the like. These 1 type can be used individually or in combination of 2 or more types. The natural cellulose fiber may be subjected to a treatment for increasing the surface area such as beating.

  Next, a natural fiber is oxidized in water using an N-oxyl compound as an oxidation catalyst to obtain a reactant fiber. Examples of N-oxyl compounds that can be used as an oxidation catalyst for cellulose include TEMPO (2,2,6,6-tetramethyl-1-piperidine-N-oxyl), 4-acetamido-TEMPO, and 4-carboxy-TEMPO. 4-phosphonooxy-TEMPO can be used. A catalytic amount is sufficient for the addition of these N-oxyl compounds, and is usually in a range of 0.1 to 10% by mass with respect to natural cellulose fibers (absolute dry basis) used as a raw material.

  In the oxidation treatment of the natural cellulose fiber, cooxidation with an oxidizing agent (for example, hypohalous acid or a salt thereof, hypohalous acid or a salt thereof, perhalogenic acid or a salt thereof, hydrogen peroxide, a perorganic acid, etc.) An agent (for example, an alkali metal bromide such as sodium bromide) is used in combination. As the oxidizing agent, alkali metal hypohalites such as sodium hypochlorite and sodium hypobromite are particularly preferable. The amount of the oxidizing agent used is usually in the range of about 1 to 100% by mass with respect to the natural cellulose fiber (absolute dry standard) used as a raw material. Moreover, the usage-amount of a co-oxidant is the range used as about 1-30 mass% normally with respect to the natural cellulose fiber (absolute dry reference | standard) used as a raw material.

  Moreover, in the oxidation treatment of the natural cellulose fiber, the pH of the reaction solution (the slurry) is preferably maintained in the range of 9 to 12 from the viewpoint of allowing the oxidation reaction to proceed efficiently. The temperature of the oxidation treatment (the temperature of the slurry) is arbitrary at 1 to 50 ° C., but the reaction is possible at room temperature, and no temperature control is required. The reaction time is preferably 1 to 240 minutes.

  After the oxidation reaction step, a purification step is performed before the miniaturization step to remove impurities other than reactant fibers and water contained in the slurry, such as unreacted oxidant and various by-products. At this stage, the reaction product fibers are usually not dispersed evenly to the nanofiber unit. Therefore, in the purification process, for example, a purification method in which water washing and filtration are repeated can be performed, and the purification apparatus used in that case is not particularly limited. The purified oxidized cellulose fiber (or cellulose nanofiber intermediate) thus obtained is usually sent to the next step (miniaturization step) impregnated with an appropriate amount of water, but dried if necessary. A treated fiber or powder may be used.

  In the refinement process, the oxidized cellulose fiber that has undergone the purification process is dispersed in a solvent such as water and subjected to a refinement process. By passing through this refinement | miniaturization process, the cellulose nanofiber which has an average fiber diameter and an average aspect ratio in the said range, respectively is obtained.

  In the above-mentioned micronization treatment, the solvent as the dispersion medium is usually preferably water, but water-soluble organic solvents (alcohols, ethers, ketones, etc.) may be used in addition to water depending on the purpose. These mixtures can also be suitably used. Examples of the disperser used in the miniaturization process include a disaggregator, a beater, a low pressure homogenizer, a high pressure homogenizer, a grinder, a cutter mill, a ball mill, a jet mill, a short screw extruder, a twin screw extruder, and an ultrasonic stirrer. A home juicer mixer or the like can be used. The solid content concentration of the oxidized cellulose fiber in the refining treatment is preferably 50% by mass or less. When the solid content concentration exceeds 50% by mass, it is not preferable because extremely high energy is required for dispersion.

  As the form of the cellulose nanofibers obtained after the above-mentioned micronization step, the solids concentration is adjusted as required (suspension that is visually colorless and transparent or opaque), or the dried powder (however, cellulose) It is also a powder form in which nanofibers are aggregated and does not mean cellulose particles). In the case of a suspension, only water may be used as a dispersion medium, and a mixed solvent of water and other organic solvents (for example, alcohols such as ethanol), surfactants, acids, bases, etc. May be used.

  By such oxidation treatment and refinement treatment of natural cellulose fibers, the hydroxyl group at the C6 position of the cellulose constituent unit is selectively oxidized to a carboxyl group via an aldehyde group, and preferably the average fiber diameter is 200 nm or less. Finely divided highly crystalline cellulose fibers can be obtained. This highly crystalline cellulose fiber has a cellulose I-type crystal structure. This means that the cellulose nanofiber used in the present invention is a fiber obtained by surface-oxidizing and refining a naturally-derived cellulose solid raw material having an I-type crystal structure. That is, natural cellulose fibers have a high-order solid structure formed by a bundle of fine fibers called microfibrils produced in the process of biosynthesis, and a strong cohesive force between the microfibrils (between surfaces). The cellulose nanofibers can be obtained by weakening the hydrogen bond) by introducing the aldehyde group or carboxyl group by the oxidation treatment, and further through the refinement treatment. Then, by adjusting the conditions of the oxidation treatment, the carboxyl group content is increased or decreased within a predetermined range, the polarity is changed, or the electrostatic repulsion of the carboxyl group or the refinement treatment is performed on the cellulose fiber. The average fiber diameter, average fiber length, average aspect ratio, etc. can be controlled.

  From the viewpoint of the refinement of cellulose fibers and the physical properties of the gel for patches of the present invention, the cellulose nanofibers preferably have a carboxyl group content (carboxyl group content of cellulose constituting the cellulose nanofibers) of 0.1 to 0.1. It is 3 mmol / g, more preferably 0.4 to 1.8 mmol / g, and still more preferably 0.6 to 1.5 mmol / g. The gel for patches of the present invention is produced using cellulose nanofibers having a carboxyl group content in such a range as a raw material, and, as a result, is configured to contain the cellulose nanofibers. Cellulose nanofibers having a carboxyl group content in this range can be suitably obtained, for example, by the production method described above. The carboxyl group content is measured by the following measurement method. The gel for patch of the present invention may unintentionally contain cellulose fibers having a carboxyl group content outside such a range as impurities.

  The carboxyl group content is an important factor for stably obtaining cellulose nanofibers having an average fiber diameter of preferably 200 nm or less. That is, in the process of biosynthesis of natural cellulose, normally, nanofibers called microfibrils are first formed, and these are multi-bundleed to construct a higher-order solid structure. Fine cellulose fibers used in the present invention Is obtained by oxidizing a part of the cellulose solid raw material of natural origin and converting it to a carboxyl group in order to weaken the hydrogen bond between the surfaces, which is the driving force of the strong cohesive force between microfibrils. Therefore, the larger the total amount of carboxyl groups in the cellulose (carboxyl group content), the smaller the fiber diameter, the more stable it can exist, and the electric repulsive force is generated in water. As a result, the tendency of the microfibrils to break apart without maintaining aggregation is increased, and the dispersion stability of the nanofibers is further increased. By making the carboxyl group content preferably 0.1 mmol / g or more, nanofibers having a fine fiber diameter of 200 nm or less can be easily obtained, and dispersed in a polar solvent such as water. Stability can be easily increased. The carboxyl group content is measured by the following measurement method.

<Measurement method of carboxyl group content>
Take a cellulose fiber with a dry mass of 0.5 g in a 100 ml beaker, add ion-exchanged water to make a total of 55 ml, add 5 ml of 0.01 M sodium chloride aqueous solution to prepare a dispersion, and until the cellulose fibers are sufficiently dispersed The dispersion is stirred. 0.1M hydrochloric acid is added to this dispersion to adjust the pH to 2.5-3, and 0.05M sodium hydroxide aqueous solution is waited for using an automatic titrator (AUT-50, manufactured by Toa DKK Co., Ltd.). The solution is dropped into the dispersion under the condition of 60 seconds, and the conductivity and pH values are measured every minute, and the measurement is continued until the pH is about 11, thereby obtaining an conductivity curve. From this conductivity curve, the sodium hydroxide titration amount is obtained, and the carboxyl group content of the cellulose fiber is calculated by the following formula.
Carboxyl group content (mmol / g) = sodium hydroxide titration × sodium hydroxide aqueous solution concentration (0.05 M) / mass of cellulose fiber (0.5 g)

  In addition, as long as the gel for patch of this invention uses the cellulose nanofiber obtained with the manufacturing method containing the said oxidation process as a raw material, carboxyl group content may be outside the said range. For example, in order to improve the affinity between glycerin or a derivative thereof described later and a liquid medium containing a functionalizing agent, a chemical modification treatment is performed on cellulose nanofibers having a carboxyl group content of 0.1 to 3 mmol / g. The carboxyl group may be derivatized into another modifying group. In this case, the carboxyl group content of the modified cellulose nanofiber may fall outside the above range, but this modified cellulose nanofiber is also preferably used in the present invention.

  Examples of the modification treatment for the carboxyl group of cellulose nanofiber include methyl group, ethyl group, propyl group, 2-propyl group, butyl group, 2-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, Examples thereof include carboxylic acid esterification or carboxylic acid amidation with an alkyl group such as octyl group, nonyl group, decyl group, undecyl group, dodecyl group, myristyl group, palmityl group and stearyl group. Further, a cellulose nanofiber derivative may be obtained by modifying the hydroxyl group on the surface of the cellulose nanofiber. Examples of modification treatment for the hydroxyl group of cellulose nanofiber include acetyl group, acryloyl group, methacryloyl group, propionyl group, propioyl group, butyryl group, 2-butyryl group, pentanoyl group, hexanoyl group, heptanoyl group, octanoyl group, nonanoyl group , Decanoyl group, undecanoyl group, dodecanoyl group, myristoyl group, palmitoyl group, stearoyl group, pivaloyl group, benzoyl group, naphthoyl group, nicotinoyl group, isonicotinoyl group, furoyl group, cinnamoyl group and other acyl groups, 2-methacryloyloxyethyl isocyania Isocyanate group such as noyl group, methyl group, ethyl group, propyl group, 2-propyl group, butyl group, 2-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, octyl , Nonyl group, decyl group, undecyl group, dodecyl group, myristyl group, palmityl group, an alkyl group such as a stearyl group, an oxirane group, an oxetane group, a thiirane group, and esterification or etherification, etc. with thietane group. Cellulose nanofiber derivatives obtained by such various modification treatments are due to the change in hydrophilicity / hydrophobicity with respect to unmodified cellulose nanofibers. The dispersibility may be improved, and can be arbitrarily selected as necessary.

  In addition to cellulose nanofibers, the gel for a patch of the present invention contains glycerin or a derivative thereof (hereinafter collectively referred to as “glycerins”) as a constituent component. Glycerins are mainly used as water retention agents in patches. By using the cellulose nanofiber as a gelling agent, a liquid medium containing glycerins and a functionalizing agent can be made into a gel for patches with high heat stability and shape retention.

Cellulose nanofibers gel a liquid medium containing glycerins and a functionalizing agent, whereby the patch gel of the present invention is obtained. The liquid medium may contain a solvent necessary for obtaining the function of the gel for a patch in addition to the glycerins and the functionalizing agent which are essential components in the present invention. Examples of the liquid solvent include water, lower aliphatic monoalcohol having 1 to 8 carbon atoms such as methanol, ethanol, isopropanol, and butanol, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, 1,3- Examples include alcohol solvents such as polyhydric aliphatic alcohols such as butylene glycol, 1,4-butylene glycol, isobutylene glycol and sorbitol, and dehydration polycondensates of polyhydric aliphatic alcohols such as polyethylene glycol and polypropylene glycol. These liquid media can be used alone or in combination of two or more. These liquid media are the same as or different from the dispersion media used in the method for producing a gel for a patch of the present invention described later. The ratio of the liquid medium contained in the patch gel of the present invention is preferably 0 to 50% by mass from the viewpoint of the strength of the gel for patch and the sustained release of the functional agent, and 1 to 15% by mass. More preferably it is. In addition to the method for calculating the content of the liquid medium from the preparation amount of each component in the method for producing a patch gel described below, the difference in the thermal decomposition temperature of the constituent components in the patch gel is used, for example, by thermogravimetric analysis. And a method of calculating from a change in weight using a difference in solubility and volatility in various solvents.

  The glycerins used in the present invention include unmodified glycerin itself and glycerin derivatives. Examples of glycerin derivatives include glycerin fatty acid esters such as glyceryl monostearate, glyceryl monooleate, glyceryl tri-2-ethylhexanoate, glyceryl monocaprylate, glyceryl tricaprylate and tri (caprylic acid / capric acid) glycerin, poly Examples include glycerin. Glycerin can be used alone or in combination of two or more. Particularly preferred glycerin is unmodified glycerin itself. The glycerin used may contain water and impurities as long as the properties of the gel are not adversely affected.

  The content of glycerins in the gel for patches of the present invention can be arbitrarily set within a range that can have predetermined properties, but in addition to the properties of heat stability and shape retention, flexibility and functionalization Considering each property required for the patch such as sustained release of the agent, it is preferably 1 to 99% by mass, more preferably 10 to 90% by mass, and still more preferably 20 to 90% by mass. The content of glycerin can be calculated from the charged amount of each component in the method for producing a gel for a patch described later. In addition, for example, a thermogravimetric analysis can be calculated from a change in weight by using a difference in pyrolysis temperature of components in the gel or a difference in solubility in various solvents and vapor pressure. .

  The gel for patches of the present invention is characterized by containing a functionalizing agent in addition to the cellulose nanofibers and glycerins described above. The functional agent means an active ingredient for expressing the function of the patch, and is not particularly limited as long as the patch gel of the present invention can be suitably produced. It can be appropriately selected from newly synthesized, semi-synthesized and extracted drugs. Such an active ingredient has a medicinal effect on the human body. Such effects include analgesic anti-inflammatory effect, refreshing effect, anti-inflammatory effect, anti-histamine effect, central nervous system effect, hormone effect, antihypertensive effect, cardiotonic effect, antiarrhythmic effect, coronary vasodilator effect, local anesthetic effect, muscle Relaxation effect, antifungal effect, anti-malignant tumor effect, urination disorder improvement effect, antiepileptic effect, anti-Parkinson disease effect, smoking cessation assist effect, whitening effect, wrinkle improvement effect, ceramide production promotion effect, blood circulation promotion effect, antioxidant effect, A cell activation effect is mentioned.

  Examples of the functionalizing agents include analgesic / anti-inflammatory agents such as methyl salicylate, glycol salicylate, flurbiprofen, and ketoneprofen, refreshing agents such as menthol and xylitol, steroidal anti-inflammatory agents such as prednisolone and hydrocortisone, indomethacin, diclofenac and the like. Non-steroidal anti-inflammatory drugs and their ester derivatives, antihistamines such as diphenhydramine, central nervous system drugs such as isoprenaline hydrochloride, hormones such as estradiol, antihypertensives such as furosemide, cardiotonics such as digitoxin, antiarrhythmic drugs such as disopyramide phosphate Agents, coronary vasodilators such as trazoline hydrochloride, local anesthetics such as lidocaine, analgesics such as acetaminophen, muscle relaxants such as squismethonium chloride, antifungal agents such as clotrimazole, and antineoplastic agents such as fluorouracil , Urinary disorder improving agents such as acid tamsulosin, antiepileptic agents such as diazepam, antiparkinsonian agents such as bromocriptine mesylate, smoking cessation aids such as nicotine, ascorbic acids, hydroquinones, kojic acids, tranexamic acids, ellagic acids, lucinols , Linoleic acids, alkoxysalicylic acids, chamomile extract, glutathione, tocotrienol, ferulic acid, raspberry ketone, adenosine monophosphate, levocarnitine chloride, polyphenols, acerola extract, almond extract, altea extract, aloe extract, age (Neobara) extract, Ogon (Koganebana) extract, fire spine extract, cuckoo (kudzu) extract, kiwi extract, gardenia (sanshin) extract, Clara (kujin) extract, chlora extract, rice bran extract , Peonies Extract, Jiyu extract, Sohakuhi extract, soybean extract, tea extract, safflower extract, Melissa extract, clove extract, Yakuinin extract , Whitening agents such as placenta extract, guanidines and salts thereof, wrinkle improving agents such as ginger extract, maroni extract, lemon extract, yeast extract, ceramide production promoter such as eucalyptus extract, vitamin E ester Nicotinic acid ester, nicotinic acid ester, orotic acid ester, blood circulation promoter such as nicotinic acid amide, methyl nicotinate, astaxanthin, alpha lipoic acid, ergothioneine, carotenoid, carotene, catechin, coenzyme Q10, fullerene, platinum nano Colloid, Inobara extract, Genokosho extract, Watermelons Antioxidants such as La extract, Yukinoshita extract, oil-soluble licorice extract, Artemisia leaf extract, retinol, cyanocobalamin, riboflavin, niacinamide, bilberry extract, soybean isoflavone, camellia extract, beech bud extract, beech sprout extract Examples include cell activators such as liquids, vitamins, prostaglandins and the like, but are not limited thereto.

  The content of the functional agent in the gel for patches of the present invention can be arbitrarily set within a range that can have a predetermined property, but is preferably 0.01 to 50% by mass, more preferably 0.8. It is 05-20 mass%, More preferably, it is the range of 0.1-10 mass%. The content of the functionalizing agent can also be calculated from the charged amount of each component in the method for producing a gel for patch described later. In addition, for example, a thermogravimetric analysis can be calculated from a change in weight by using a difference in pyrolysis temperature of components in the gel or a difference in solubility in various solvents and vapor pressure. .

  In addition, in the gel for patches of the present invention, in addition to cellulose nanofibers, glycerins and functionalizing agents, cellulose nanofibers such as sodium polyacrylate, gelatin, gum arabic, etc., as an adhesive, if necessary Other polymeric materials, white inorganic pigments such as kaolin, talc, titanium oxide, aluminum hydroxide and aluminum silicate, gelling aids such as crosslinking agents, skin absorption enhancers, antioxidants, solubilizers, coloring Agents, surfactants, stabilizers, preservatives, ultraviolet absorbers, fillers, cold / warmth imparting agents, pH adjusters, perfumes such as limonene, tacking agents used in conventional patch gels, etc. May be included.

  The gel for patch of the present invention containing each of the above components has high shape retention as described above, has high elasticity, high heat resistance, strong mechanical strength, and is resistant to tension, bending, and twisting. Flexible and highly recoverable after deformation. That is, the gel state can be maintained for a long time.

  The gel for patch of the present invention preferably has high heat resistance capable of maintaining constant gel properties in a wide temperature range, and from this viewpoint, it is preferable that the temperature dependence of the elastic modulus is small. . More specifically, the change rate of the elastic modulus (hereinafter also referred to as the temperature dependency change rate of the elastic modulus) in the temperature range of 25 to 110 ° C. is 0.5 to 5, particularly 0.7 to 4, particularly 0. It is preferably 9 to 1.5. The temperature-dependent change rate of the elastic modulus represents a change in storage elastic modulus in the dynamic viscoelasticity of the gel for a patch, which is measured by a method to be described later. This means that there is little change in the heat resistance, that is, heat resistance is high.

  The gel for patch of the present invention preferably has high shape stability capable of maintaining the gel state over a long period of time. From such a viewpoint, it is preferable that the frequency dependence of the elastic modulus is small. More specifically, the gel for a patch of the present invention has an elastic modulus change rate (hereinafter, also referred to as an elastic modulus frequency-dependent change rate) of 0.1 to 20 in a frequency range of 0.01 to 10 Hz. In particular, it is preferably 0.5 to 10, particularly preferably 0.8 to 5. The frequency-dependent change rate of the elastic modulus represents a change in the storage elastic modulus in the dynamic viscoelasticity of the gel-like body measured by the method described later. It means less change. The patch gel of the present invention in which the frequency-dependent change rate of the elastic modulus is within such a range is not easily solated even when an external force is applied, and can maintain a highly elastic gel state for a long period of time.

  The gel for patch of the present invention preferably has a gel state, and from this viewpoint, it is preferable that the loss tangent (tan δ) is small. The loss tangent is the tan value of the phase difference δ between the measured sine strain wave and the detected sine stress wave in dynamic viscoelasticity, and the physical meaning is the viscous response / elastic response ratio. The value of loss tangent is defined as loss elastic modulus / storage elastic modulus. If the value (tan δ value) is larger than 1, the viscous response is dominant, and if the value is smaller, the elastic response is dominant. About a gel, it means that it is a solid gel, so that a tan-delta value is small. More specifically, the gel-like body of the present invention preferably has a loss tangent of less than 0.6, particularly less than 0.1, especially less than 0.07. In general, the gel has a loss tangent of less than 1, and it is considered that the solvent is immobilized by a polymer (cellulose nanofiber in the present invention), but the loss is caused by an external force load (large strain or frequency range). Some have a tangent of 1 or more, that is, a fluidized sol state. The patch gel of the present invention having a loss tangent within such a range has high elasticity, high heat resistance, high mechanical strength, flexibility against tension, bending and twisting, and high resilience after deformation.

From the same viewpoint, the patch gel of the present invention preferably has a small loss tangent temperature change rate. More specifically, the F / E is defined as 0.1 to 5, particularly 0.4 to 2, especially 0.4, as defined by the loss tangent value (E) at 25 ° C. and the loss tangent value (F) at 110 ° C. It is preferable that it is 5-1.5. The loss tangent values E and F are measured by the following measurement method (ii). The patch gel of the present invention having a loss tangent change rate in such a range can maintain a highly elastic gel state regardless of temperature changes.

The storage elastic modulus, loss elastic modulus, and loss tangent are measured as follows using, for example, a rotary rheometer (apparatus: MCR300, manufactured by PHYSICA). The measurement cell is a parallel plate with a diameter of 25 mm, and the sample thickness is 0.5 to 1 mm. When measuring a gel sample, select a measurement control mode in which a force of about 1 N is applied to the sample via the cell surface to suppress slippage at the measurement cell surface and the sample interface and to respond to changes in the sample thickness due to thermal expansion. Use. Since the physical properties of the gel for patch of the present invention are difficult to change due to evaporation of volatile components, rheology measurement is performed while flowing dry nitrogen gas (vaporized liquid nitrogen) controlled in temperature to the measurement cell section. In order to estimate the degree of evaporation of volatile components from the sample, the sample is mounted in a measurement cell that has been controlled to 25 ° C in advance, and the frequency-dependent change rate (frequency dependency) of the elastic modulus is first measured as follows. Measurement is performed according to the method (i), and then the temperature-dependent change rate (temperature dependency) of the elastic modulus is measured according to the following measurement method (ii). For the loss tangent, the measured value at 25 ° C. in the following measuring method (ii) is used.
Measurement method (i): Frequency-dependent change rate (frequency dependency) of elastic modulus is a storage elastic modulus at 0.01 Hz measured when the temperature is varied from 0.01 Hz to 100 Hz at a linear strain of 25 ° C. It is defined by D / C from (C) and the storage elastic modulus (D) at 10 Hz.
Measurement method (ii): The temperature-dependent change rate (temperature dependency) of the elastic modulus is measured when the temperature is increased from 25 ° C. to 110 ° C. at 2.5 ° C./min at a linear strain of 2 Hz. It is defined as B / A from the storage elastic modulus (A) at 100 ° C. and the storage elastic modulus (B) at 110 ° C. It should be noted that the rate of change in elastic modulus of the gel-like body that could not be measured up to 110 ° C. under the same conditions was greatly reduced in the temperature rising process.

The gel for patch of the present invention is preferably a highly elastic gel, and from this viewpoint, it is preferable that the value of the storage elastic modulus is large. More specifically, the storage elastic modulus at 25 ° C. measured in (ii) is preferably 10 ² Pa or more, more preferably 10 ³ Pa or more, and particularly preferably 10 ⁴ Pa or more. The gel for patches of the present invention having a storage elastic modulus in such a range can be used as a high-strength gel.

  In addition, the gel for a patch of the present invention preferably has a high heat resistance in which the liquid medium to be contained is not easily eluted by heating, and more specifically, the liquid medium measured by the following measurement method. The elution amount is preferably 20% by mass or less, particularly preferably 5% by mass or less.

<Measurement method of elution amount of liquid medium>
The gel to be measured is heated by being left for 30 minutes in a thermostatic chamber set at a bath temperature of 105 ° C. This operation can be carried out, for example, by storing about 2 g of gel in a glass petri dish, putting the glass petri dish together with the glass petri dish in a constant temperature bath, and allowing it to stand for 30 minutes. After 30 minutes, the glass petri dish is removed from the thermostat and left at room temperature until the temperature of the gel reaches room temperature. Then, after removing the eluate (liquid medium etc.) on the surface of the gel, the mass of the gel is measured, and the measured value (mass B) is recorded. The eluate can be removed by, for example, absorbing the surface eluate by sandwiching the gel with paper (Kimwipe, Nippon Paper Crecia). Then, the elution amount of the liquid medium is calculated from the mass B and the previously measured mass of the gel before heating (mass A, about 2 g in the specific example) by the following equation.
Elution amount of liquid medium (%) = {(A−B) / A} × 100

  In addition, the gel for patch of the present invention preferably has flexibility in addition to having high elasticity and high heat resistance. From this viewpoint, it conforms to the standard of ASTM D 2240. It is preferable that the hardness measured by the method is 20 degrees or less, particularly 0.1 to 15 degrees, particularly 1 to 10 degrees. The hardness is measured using a generally used rubber or plastic hardness meter (for example, a rubber hardness meter GS-709 A type, manufactured by Teclock Corporation).

  The gel for patch of the present invention can be produced, for example, as follows. The production method of this embodiment includes (i) a step of mixing cellulose nanofibers and glycerin in a dispersion medium to obtain a composition for preparing a gel for a patch, and (ii) the dispersion medium from the composition. A step of removing at least a part thereof to obtain a gel for patch.

  In the step (i), the composition for preparing a gel for a patch of the present invention contains cellulose nanofibers and glycerols, and a dispersion medium (liquid medium) for mixing them. The functionalizing agent that is a constituent of the gel for a patch of the present invention can be blended in this composition, or can be blended later after forming the gel in the step (ii) as described later. .

  As the dispersion medium, water is usually preferably used. However, as long as it does not adversely affect the production of the gel for patch and the physical properties of the gel, for example, a water-insoluble organic solvent, a water-soluble organic solvent, or these and water A mixed medium etc. can be mentioned. The type of dispersion medium to be used may be appropriately determined according to the solubility and dispersibility of cellulose nanofibers, glycerin and functionalizing agent, or workability for removing the dispersion medium, which will be described later. As described above, since the gel is preferably obtained by drying the dispersion medium, the vapor pressure is higher than that of the glycerin that is a constituent of the gel, that is, only the dispersion medium is volatilized in the drying process, and the glycerin remains. It is preferable to use one having such a relationship.

  As the water-insoluble organic medium used for the dispersion medium, for example, toluene, chloroform, ethyl acetate, hexane or the like can be used. These can be used alone or in combination of two or more. As the water-soluble organic medium used for the dispersion medium, for example, ethanol, methanol, isopropanol, t-butyl alcohol, acetone, N-methyl-2-pyrrolidone, tetrahydrofuran and the like can be used. These can be used alone or in combination of two or more.

  The proportion of the dispersion medium contained in the composition is preferably 50 to 99% by mass from the viewpoints of fluidity for application to equipment, retention during use as a gel for patches, and flexibility. 60 to 90% by mass is even more preferable.

In the step (i), for example, cellulose nanofibers, glycerols, and a dispersion medium can be mixed to prepare the composition. The dispersion medium used here should just be able to disperse | distribute or melt | dissolve cellulose nanofiber and glycerol substantially as above-mentioned. Dispersion of cellulose nanofibers is preferably achieved particularly with water or a hydrophilic organic solvent because the main reason is the surface carboxyl group as described above. Therefore, the dispersion medium is preferably water or a hydrophilic organic solvent.

  The said composition can be manufactured by mixing the cellulose nanofiber previously disperse | distributed to the dispersion medium, and the glycerol dissolved in the dispersion medium, for example. It can also be produced by mixing dried cellulose nanofibers or undissolved glycerins alone in a dispersion medium.

  Whatever dispersion medium is used, the concentration of cellulose nanofibers in the composition is 0.1 to 30% by mass, particularly 0.2 to 10% by mass, especially 0.5 to 10% by mass. From the viewpoint of fluidity of the composition and uniform dispersibility of cellulose nanofibers and glycerins. Moreover, it is preferable that the density | concentrations of glycerol are 0.1-90 mass%, especially 0.2-80 mass%.

  A target composition is obtained by mixing the cellulose nanofiber, glycerin, and a dispersion medium. The composition thus obtained is excellent in fluidity. Specifically, on the condition that the ratio of cellulose nanofibers contained in the composition is within the above range, the viscosity of the composition is preferably 10 to 1000 mPa · s at 23 ° C. and a rotation speed of 50 rpm, More preferably, it is 20-500 mPa * s, More preferably, it is 20-100 mPa * s. By setting the viscosity of the composition within this range, the composition is excellent in coatability and easily forms a uniform gel. In addition, the fluidity becomes appropriate, and for example, it is effectively prevented that the composition spreads and spreads during the time from when the composition is spread into a desired film shape to gelation, A gel having a desired shape can be easily obtained. It was an extremely surprising finding that even when the ratio of cellulose nanofibers, which are gelling agents contained in the composition, is low, the viscosity can be increased to the above-mentioned viscosity of the composition. The viscosity of the composition is measured at 23 ° C. and a rotational speed of 50 rpm using an E-type viscometer VISCONIC manufactured by TOKIMEC.

  In addition to having the above-mentioned viscosity and appropriate fluidity, the composition is also characterized by being transparent in the visible wavelength region. When the composition is transparent, for example, when a patch containing a gel obtained from the composition is attached to the affected area, there is an advantageous effect that changes in the affected area can be observed while the patch is attached. Is done. Moreover, that the said composition is transparent means that the cellulose nanofiber is fully refined | miniaturized and the coarse thing is not contained. From this, the gel for patches obtained from the composition has an advantageous effect of improving adhesion to the skin and touch.

  Moreover, the functional agent which is one of the structural components of the gel for patch of this invention can be mix | blended with this composition. In addition to cellulose nanofibers, glycerins and dispersion media, polymer materials other than cellulose nanofibers such as sodium polyacrylate, gelatin and gum arabic as adhesives, kaolin, talc, oxidation White inorganic pigments such as titanium, aluminum hydroxide and aluminum silicate, gelling aids such as cross-linking agents, skin absorption enhancers, antioxidants, solubilizers, colorants, surfactants, stabilizers, preservatives, Ultraviolet absorbers, fillers, cold / warmth imparting agents, pH adjusters, fragrances such as limonene, and the like may be included. Even when these components are contained in the composition, the viscosity of the composition is preferably within the above-mentioned range.

  In the step (ii), the dispersion medium is removed from the composition thus obtained to obtain the patch gel of the present invention. The method for removing the dispersion medium is not particularly limited, but is mainly performed by drying. The dispersion medium may be naturally dried, or a known drying method such as heat drying, vacuum drying, freeze drying, or spray drying may be used. When these drying methods are used, it is preferable from the viewpoint of drying efficiency that the composition is cast (cast) and dried. Whichever drying method is used, a gel having high heat stability and high shape retention can be obtained. The reason for this is that the cellulose nanofibers are uniformly disposed in a liquid medium containing glycerin without aggregation of the cellulose nanofibers even during the drying process due to the electrostatic repulsion of the carboxyl groups of the cellulose nanofibers. This is considered to form a structure in which a liquid medium containing glycerins is held in a large number of minute spaces formed by a network-like network. In addition, the cellulose nanofibers obtained by the above-described method have high crystallinity, and in the liquid medium, the above-described electrostatic repulsion force is weakened, and hydrogen bonds (so-called cross-linking points) between the nanofibers are strongly fixed. This is considered to be the cause of no structural change with respect to stress and thermal load.

  The dispersion medium may be removed entirely or partially. When removing the whole dispersion medium, the gel obtained is used suitably for a tape agent. When a part of the dispersion medium is removed, the obtained gel is suitably used as a haptic agent or a poultice. When a part of the dispersion medium is removed, the dispersion medium remains in the obtained patch gel. The remaining dispersion medium is the liquid medium described above. What is necessary is just to set suitably the grade which removes a dispersion medium in a process (ii) according to the ratio of the liquid medium contained in the gel for target patches.

  In the step (i), if a functional agent is added to the composition, the gel obtained in the step (ii) contains cellulose nanofibers, glycerin and a functional agent. A gel for patch is obtained. On the other hand, when a functional agent is not added to the composition in the step (i), the functional agent is added later to the gel obtained in the step (ii), whereby the patch of the present invention is added. An agent gel can be obtained. Examples of the method of blending the functional agent later include a method of impregnating the obtained gel into a functional agent solution or injecting the functional agent into the gel with a device such as a syringe.

  The form of the gel for patch is not particularly limited. Usually, since the patch is in a sheet form, for example, a sheet-like gel for patch can be obtained by casting (casting) on a sheet substrate such as a nonwoven fabric or a film and drying. Moreover, granular gel can also be obtained by using spray drying, and this can adhere to skin etc. as it is, and can also be used as a raw material before making it into a sheet form. In spray drying, the above-mentioned composition for gel preparation may be ejected from a nozzle to form fine droplets, and then heated and dried in convection air. Further, a three-dimensional gel for a patch can be produced by pouring the composition for gel preparation into a mold having an arbitrary shape and drying it.

  The degree of drying can be arbitrarily selected as long as the gel for patch obtains predetermined physical properties. That is, in the drying of the dispersion medium, the dispersion medium may be completely removed, or the drying may optionally be stopped with the dispersion medium remaining in the patch gel.

  In addition to drying, the dispersion medium can be removed by dialysis (removing only the dispersion medium using the osmotic pressure difference), precipitation (gelation by pouring the composition into a poor solvent), dehydrating agents such as molecular sieves. Can also be used.

  Moreover, the gel for patch of this invention is not restricted to the manufacturing method containing the process of (i) and (ii) mentioned above, It can manufacture by various gelation methods.

  For example, the gel for patch of the present invention can also be produced by the following method. A composition for preparing a gel for a patch containing cellulose nanofibers, glycerin, a dispersion medium and a functionalizing agent is applied on a sheet substrate. Then, by applying a gelation accelerator in multiple layers, the applied film of the composition becomes a stable gel, and the gel for a patch of the present invention is produced. In this case, as the dispersion medium, water or a mixed solvent of primary alcohol such as water and ethanol is preferably used. Gelation accelerators include sodium, potassium, lithium, silver, magnesium, calcium, zinc, copper, gold, aluminum and other halides (chlorides, etc.), carbonates, sulfates, phosphates, etc. Poly [(meth) acryloyloxyalkylammonium quaternary salt], poly [(meth) acrylamide alkylammonium quaternary salt], poly [alkenylammonium quaternary salt], poly [vinyloxyalkylammonium quaternary salt], poly [ Vinylbenzylammonium quaternary salt], poly [diallylammonium quaternary salt], poly [vinylpyridinium quaternary salt], poly [vinylimidazolinium quaternary salt], poly [alkylated quaternary ammonium] ("ionene") , Poly [condensed ammonium quaternary salt], poly [(meth) acryloyloxyethylsulfonium Grade salt], poly [vinyl benzylsulfonium quaternary salt], poly [diallylsulfonium quaternary salt], poly [vinyl phosphonium quaternary salt], poly [acrylic phosphonium quaternary salt], poly [vinyl benzylphosphonium quaternary salt] , Poly [condensed phosphonium quaternary salts], homopolymers such as polyethyleneimine (hydrochloride), and copolymers of monomers constituting the homopolymer with vinyl monomers such as (meth) acrylamide, styrene and (meth) acrylate A solution of a cationic polymer such as is preferably used.

  Furthermore, the patch gel of the present invention can also be produced by the following method. The gel preparation composition containing cellulose nanofibers, glycerin, a functionalizing agent and a dispersion medium is stirred and mixed while heating. Thereafter, the composition is formed into a desired shape and then cooled to form a stable gel, whereby the patch gel of the present invention is produced. In this case, the heating temperature may be in a range in which the composition can obtain fluidity, and the cooling temperature may be in a range in which the gel can obtain predetermined heat stability and shape retention. At this time, a crosslinking agent or a polymer may be used in combination as a gelation accelerator. The gelation accelerator is not particularly limited as long as a gel is suitably obtained. Examples thereof include sodium alginate, carboxymethylcellulose, gelatin, sodium polyacrylate, hydroxymethylcellulose, hydroxyethylcellulose, a copolymer of acrylic acid and acrylamide, and montmorillonite. Plate-like inorganic particles, polyvinyl alcohol, gellan gum, agarose, xanthan gum, pectin, carrageenan and the like are used.

  In addition, a dripping method in which cellulose nanofiber dispersion liquid is dropped onto a liquid medium containing glycerins and a functionalizing agent, or an airgel in which cellulose nanofibers prepared in advance are arranged in a network form, and functionalized with glycerins. It can also be produced by impregnating a liquid medium containing an agent.

  The gel for patch of the present invention obtained as described above has high heat stability and excellent shape retention. As a material for patches that are used as tapes, poultices, haptics, etc. for the treatment of low back pain, stiff shoulders, bruises, sprains, inflammation, etc. and healing foot fatigue due to its high heat stability and shape retention Useful.

  The patch gel of the present invention having high heat stability is highly effective in suppressing bleeding of the liquid medium contained in the gel. The suppression of bleed becomes more pronounced as the cellulose nanofiber content in the gel increases, but considering the properties required for patches such as flexibility and sustained release of functional agents, The cellulose nanofiber content is preferably set within the range described above. When the cellulose nanofiber content is in this range, the gel for a patch of the present invention has the above-described preferable numerical value for the amount of elution of the liquid medium containing glycerins and the functionalizing agent in the evaluation method described below. Fill the range.

In addition to the mechanical properties, the gel for patches of the present invention is also characterized in that it can retain a liquid organic solvent at a high concentration. For example, by encapsulating a functional agent having a high affinity for water in the gel for patch of the present invention, the functional agent can be distributed and transferred from an organic medium to a highly water-containing surface such as skin, and a high sustained release property can be achieved. It can also be set as the base material which has.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the scope of the present invention is not limited to such examples.

[Method for producing oxidized cellulose fiber]
Soft cellulose bleached kraft pulp (Fletcher Challenge Canada, CSF 650 ml) is used as the raw natural cellulose fiber, TEMPO (ALDRICH, Free radical, 98%) is used as the oxidation catalyst, and sodium hypochlorite (Japanese sum) Kobunyaku Kogyo Co., Ltd., Cl: 5%) was used, and sodium bromide (manufactured by Wako Pure Chemical Industries, Ltd.) was used as a co-oxidant. 9900 g of ion-exchanged water is added to 100 g of natural cellulose fibers and sufficiently stirred to obtain a slurry. In the slurry, TEMPO is 1.25% by mass of pulp, sodium bromide is 12.5% by mass of pulp, hypochlorite. 28.4% by mass of sodium acid to pulp was added in this order, and the pH of the slurry was maintained at 10.5 by adding 0.5 M sodium hydroxide dropwise using a pH stud, and the temperature was 20 to 0. The natural cellulose fiber was oxidized at 0 ° C. The dropping of sodium hydroxide was stopped after an oxidation time of 120 minutes. The natural cellulose fiber after the oxidation treatment was thoroughly washed with ion exchange water and dehydrated. Thus, an oxidized cellulose fiber having a carboxyl group content of 1.2 mmol / g was obtained.

[Method for producing cellulose nanofiber]
Oxidized cellulose fiber 10 g (converted to solid content) obtained in [Oxidized cellulose fiber production method] and 990 g of ion-exchanged water were mixed for 120 minutes with a mixer (Vita-mix-Blender ABSOLUTE, manufactured by Osaka Chemikel Co., Ltd.). Stirring was performed (that is, the fine processing time was 120 minutes). Thus, an aqueous suspension (solid content concentration: 1.0% by mass) of cellulose nanofibers having an average fiber diameter of 4 nm and a carboxyl group content of 1.2 mmol / g was obtained.

[Example 1]
Using the cellulose nanofibers obtained in [Method for producing cellulose nanofiber], using glycerin (manufactured by Wako Pure Chemical Industries, Ltd.), using ion-exchanged water as a dispersion medium, and methyl salicylate (Japanese The patch gel was manufactured by the method according to the manufacturing method of the gel for patch of this invention mentioned above using the Koyo Pure Chemical Industries Ltd. make. More specifically, 48 parts by mass of glycerin and 0.9 parts by mass of methyl salicylate are added to 100 parts by mass of the aqueous suspension of cellulose nanofibers (solid content concentration: 1.0% by mass). It stirred with the tic stirrer and the composition for preparation of the gel for patch was obtained. This composition was transparent in the visible light wavelength region. 30 g of the composition was poured into a polystyrene petri dish (φ80 mm) and left to stand in a room temperature environment (23 ° C., 50% RH) for 2 weeks to volatilize part of the ion-exchanged water and perform a drying treatment. A gel for patch of the present invention having a thickness of about 0.8 mm was obtained. The patch gel and the composition for preparing the patch gel thus obtained were used as the sample of Example 1. Table 1 below shows the evaluation results of each item. In the same table, the shape retention, water content, and cellulose nanofiber content were evaluated according to the following criteria.

[Evaluation criteria for shape retention]
Even if it is picked with a finger, the sheet form can be maintained, and it is resilient to bending deformation.
Even if it is picked with a finger, the sheet form can be maintained, but there is no resilience to bending deformation.
Viscous or flowable gel that cannot maintain sheet form when picked with fingers △
In addition, bending deformation evaluated the case where a sheet-like gel was bend | folded at 180 degrees, and the case where it did not cut | disconnect has resilience.

<Measurement method of moisture content and calculation method of cellulose nanofiber content>
The gel was heated at 105 ° C. for 40 minutes using a moisture meter (halogen moisture meter HR83, manufactured by METTLER TOLEDO), and its moisture content was evaluated. Moreover, the cellulose nanofiber content in the gel for patches was calculated from this water content.

[Example 2]
A composition for preparing a gel for a patch was obtained in the same manner as in Example 1 except that 32 parts by mass of glycerin and 0.6 parts by mass of methyl salicylate were added. Using the obtained composition, the patch gel of the present invention was obtained in the same manner as in Example 1. The patch gel and the composition for preparing the patch gel thus obtained were used as the sample of Example 2. Table 1 below shows the evaluation results of each item.

[Comparative Example 1]
1 g of carboxymethylcellulose (abbreviation: CMC, trade name: Cellogen HE1500F, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) was added to 99 g of ion-exchanged water and stirred to obtain a CMC aqueous solution having a solid content concentration of 1% by mass. A gel for patch and a composition for preparing a gel for patch were obtained in the same manner as in Example 2 except that the CMC aqueous solution was used instead of the cellulose nanofiber dispersion, and this was designated as Comparative Example 1. Table 1 below shows the evaluation results of each item.

As described in Table 1, the viscosities of the gel preparation compositions obtained in Examples 1 and 2 are all in the range of 20 to 100 mPa · s, and are suitable as a preparation composition for gels for patches. Showed sex. On the other hand, Comparative Example 1 was blended with the same amount of CMC as the cellulose nanofiber used in Example 2, and showed a very high viscosity as compared with Example 2.
Moreover, all the gels for patches obtained in Examples 1 and 2 showed an extremely high heat stability because the amount of elution of the liquid medium containing glycerin was 10% or less. On the other hand, in Comparative Example 1 using CMC instead of cellulose nanofibers, the solid gel part and the liquid medium containing glycerin were separated by heating. The reason for this is considered to be that, as described above, highly crystalline cellulose nanofibers form a strong network network in the gel, and a liquid medium containing glycerin is retained in the network.
Regarding shape retention, Examples 1 and 2 had high shape stability higher than the extent that the sheet form could be maintained even when picked with a finger, despite the low cellulose nanofiber content. In particular, in Example 2 where the cellulose nanofiber content was 3% by mass or more, the resilience to bending deformation was also high. On the other hand, in Comparative Example 1 using CMC instead of cellulose nanofiber, the shape retention was low as compared with Examples 1-2.

Claims (5)

  A gel for patch comprising cellulose nanofiber, glycerin or a derivative thereof, and a functionalizing agent. A composition for preparing a gel for a patch according to claim 1,
A composition for preparing a gel for a patch comprising cellulose nanofibers, glycerin or a derivative thereof, and a dispersion medium.   A patch comprising an adhesive layer comprising the gel for a patch according to claim 1 provided on one surface of a sheet substrate. A method for producing a gel for a patch according to claim 1,
Cellulose nanofibers, glycerin or a derivative thereof, and a functionalizing agent are mixed in a dispersion medium to obtain a composition for preparing a gel for a patch, and then at least a part of the dispersion medium is removed from the composition. The manufacturing method of the gel for patches which has a process. A method for producing a gel for a patch according to claim 1,
Cellulose nanofibers and glycerin or a derivative thereof are mixed in a dispersion medium to obtain a composition, and at least a part of the dispersion medium is removed from the composition to obtain a gel, and then a functional agent is added to the gel. The manufacturing method of the gel for patchs which has the process to mix | blend.