JP6803789B2 - Patch medicated base material - Google Patents

Description

The present invention relates to a patching medicinal base material for applying and forming an adhesive containing various chemicals, and particularly has a composite structure of a film and a non-woven fabric layer, has less drug adsorption to the base material, and serves as a patch. Regarding substrates that are effective for sealing therapy.

Patches in which a medicinal ingredient is applied to a base material are widely used because they are convenient to have an effect only by sticking to the skin or are less invasive than injections. Initially, those with anti-inflammatory and analgesic effects were the mainstream, but nowadays, those with a vasodilator or bronchodilator applied to treat angina and asthma are used. As is well known, a patch is composed of a medicinal ingredient, a drug for stabilizing the drug, and an adhesive for sticking to the skin, which are applied to a base material as a plaster. At the site of application, water derived from sweat secreted from the skin, water contained in the plaster, and auxiliary components such as alcohol permeate into the keratin that constitutes the skin at body temperature, causing a kind of stuffiness. In the keratin in such a state, it is considered that the permeability or permeability of the medicinal ingredient into the body is enhanced, and it is known as so-called sealing therapy (hereinafter, may be referred to as ODT).

Such stuffiness is an important factor, and in order to maximize the permeation amount of the medicinal ingredient, it is necessary to control the moisture permeation of the base material. That is, it is said that insensitive evaporation of a person at rest is about 600 to 700 g / m ² / day, but if the moisture permeability of the base material is too high, the above stuffiness does not occur and water is released to the outside air through the base material. It becomes easy and it becomes difficult to achieve effective drug penetration.

As a technique focusing on the above-mentioned moisture permeability, for example, in Japanese Patent Application Laid-Open No. 2005-343125 (hereinafter, Patent Document 1), as shown in FIG. 1 shown by a schematic cross section, both surfaces of the non-woven fabric 11 made of a polyamide resin are used. A non-woven fabric laminate 15 formed by laminating a resin sheet 13 made of a polyamide elastomer resin has been proposed. The publication technology is used by applying an adhesive layer 17 to a non-woven fabric laminate 15, but conventionally, most skin patches such as emergency adhesive plasters are made of polyvinyl chloride (PVC), polyethylene (PE), polypropylene ( We are paying attention to the fact that a film such as PP) that has been subjected to adhesive processing has poor moisture permeability of the material and causes stuffiness of the skin. Therefore, the moisture permeability of the nonwoven fabric laminate 15 in accordance with the proposed 800g / m 2 ^· 24hr or more (hereinafter, the unit of the moisture permeability herein unifies expressed as "g / m 2 ^/ day" of the publication art synonymous ) Is preferable, and in the Example column showing the preferred embodiment, a non-woven fabric laminate having a moisture permeability of 3000 to 3600 g / m ² / day, which greatly exceeds the above-mentioned insensitive evaporation, is compared and examined. Therefore, there is a disclosure that it is possible to prevent a decrease in the adhesive force by giving the base material a moisture permeability higher than the amount of water generated by the insensitive evaporation described above. Further, in order to cope with the movement of the body at the time of sticking without discomfort, the stiffness (cantilever method) of the non-woven fabric laminate 15 as the base material is preferably 15 mm or more and 50 mm or less, and the base material is It is also possible to prevent the trouble of curling and the adhesive-coated surfaces at both ends sticking to each other. In Patent Document 1, the property of suppressing curl by selecting the rigidity and softness in this way is expressed as "good self-supporting property".

As can be understood from the above description, Patent Document 1 comprehensively represents a base material mainly suitable for adhesive plaster applications (in the present specification, constituent components excluding the adhesive component of the patch are simply referred to as "base material". ), But is not a technique intended to achieve the ODT effect utilizing the skin permeability of the drug due to stuffiness. On the other hand, in Japanese Patent Application Laid-Open No. 2008-163538 (hereinafter referred to as Patent Document 2), the applicant has stated that fibers containing unstretched polyester fibers on at least one surface of a film made of polyester and having a thickness of more than 6 μm. We are proposing a composite non-woven fabric for patches on which a non-woven fabric layer formed by heat-bonding a web is formed. FIG. 2 is a cross-sectional view shown in the same manner as in FIG. 1 described above. In this technique, a polyester film 21 having less chemical adsorption and a nonwoven fabric layer 23 heat-bonded to the polyester film 21 constitute a composite nonwoven fabric layer 25 as a base material. .. Next, the pressure-sensitive adhesive 27 containing the drug is applied and formed on the non-woven fabric layer 23 side to be used as a patch. According to the literature technology, after the heat bonding step of preparing the composite non-woven fabric layer 25, the heat of crystallization per unit area of the base material itself is set to 3.0 × ^10-2 J / cm ² or less. It is possible to eliminate the drug-adsorbing ability of the unstretched polyester fiber and to impart the anchoring property of the non-woven fabric layer 23 to the pressure-sensitive adhesive 27. In the figure, since the constituent fibers of the non-woven fabric layer 23 are mixed in the layer region of the pressure-sensitive adhesive 27, the interface thereof is shown by a broken line. The preferred form of each component constituting the base material composed of the composite non-woven fabric layer 25 will be described in detail later, but the thickness of the polyester film is 6 to 25 μm, and the surface density of the non-woven fabric layer is 4 to 25 g / m ² . The thickness of the substrate is disclosed as 20 to 100 μm. Further, in the present specification, the constituent component composed of two layers after the "polyester film 21" and the "nonwoven fabric layer 23" are heat-bonded, in other words, the constituent component corresponding to the base material in Patent Document 2 is referred to as the "composite nonwoven fabric layer". It is called "25".

Japanese Unexamined Patent Publication No. 2005-343125 ([Claims], [0002], [0006], [0020], [0046], [Examples], [Fig. 1], etc.) Japanese Unexamined Patent Publication No. 2008-163538 ([Claims], [0012], [0024] to [0027], etc.)

All of the above-mentioned conventional substrates are used with an adhesive. At this time, a predetermined stress is applied to the base material in the direction of the coating surface of the adhesive, and a so-called curl phenomenon may occur. For example, in the technique of Patent Document 1, since the base material 15 has a symmetrical layer structure centered on the non-woven fabric 11 in the thickness direction, when the base material 15 has sufficient bending hardness, the pressure-sensitive adhesive layer Curling is less likely to occur in relation to the stress derived from 17. On the other hand, in the technique of Patent Document 2, since the composite nonwoven fabric 25 as the base material has an asymmetric two-layer structure and has a small thickness of about 20 to 100 μm, the pressure-sensitive adhesive 27 is applied and formed. Later, a stress difference was generated with the base material 25, which may cause curling.

Based on the technique according to Patent Document 2 described above, the inventor of the present application has studied a base material design capable of reducing curl by increasing the thickness of a polyester film having less drug adsorption. However, after the pressure-sensitive adhesive shown in FIG. 2 is applied, a concave curl (hereinafter referred to as a concave curl) appears strongly on the surface side of the polyester film 21, and becomes convex on the 27-side surface side of the pressure-sensitive adhesive, which is different from this, and becomes a patch. In that case, the peripheral edge may be peeled off from the object to be attached. This phenomenon is often extremely disadvantageous for practical use because the dosage form of an adhesive containing an expensive and high-concentration drug is as small as 1 cm square or less, and further, it is caused by rubbing against clothes. The applied formulation may come off. Further, as described above, the moisture permeability of the base material is an important factor in expecting the ODT effect. As an example, a 12 μm thick polyester film may have a moisture permeability of 50 g / m ² / day or more and satisfy the conditions of 10 g / m ² / day or less required for the ODT to function effectively. There was also the problem that it was difficult. The present invention has been made in view of the above-mentioned conventional problems, and an object of the present invention is to provide a base material that reduces concave curl on the surface side of the base material and exhibits the above-mentioned practically sufficient moisture permeability. And.

In order to achieve this object, according to the configuration of the present invention, a non-woven layer formed by heat-bonding a fiber web containing unstretched polyester fibers is provided on one surface of a polyethylene terephthalate film having a thickness of 6 to 25 μm. A patch medicinal base material containing the composite non-woven fabric layer and having a heat of crystallization of 3.0 × ^10-2 J / cm ² or less per unit area of the composite non-woven fabric layer, which is the other of the above-mentioned films. A laminated film is arranged on the surface of the above, and the laminated film is a single-layer film in which a cyclic olefin-based copolymer resin and a low-density polyethylene resin are blended, a single-layer film made of polyethylene resin, and a single-layer film made of polyvinylidene chloride resin. A laminated film having a thickness of 25 μm or less, which is selected from a composite film composed of a low-density polyethylene resin and a linear low-density polyethylene resin laminated, and is determined by a pure bending test (KES-FB2 method) of the KES method. The concave stress is larger than the convex stress. This "concave stress" means an external force equivalent to the stress required when trying to bend the laminated film of the base material as the inside, and "convex stress" means bending the non-woven fabric layer of the base material as the inside. The external force required at the time. The larger the value obtained by the measurement, the more the two types of external forces are bent and hardened in the specified direction, and depend on the weight of the base material, such as the flexibility by the cantilever method specified in JIS L1096. Unlike the static measurement value, it is a value for indicating whether the dynamic bending hardness observable by the repetitive bending operation tends to cause concave curl or convex curl.

Also, per the practice of the present invention, the temperature 40 ° C. of the patch medicinal substrates described above, the moisture permeability being measured under the conditions of a relative humidity of 90% is hereinafter 40 (g ^/ m 2 / day). This value permeates only humidity of about 1/20 or less of the water content due to the above-mentioned insensitive evaporation.

By applying the technique of the present invention, even after the pressure-sensitive adhesive is applied and formed, the concave curl on the surface side of the base material is reduced, and the ODT effect is exhibited by exhibiting sufficient moisture permeability for practical use. It is possible to provide an excellent base material.

Explanatory drawing which shows by schematic cross section of a patch for explaining a background technique. An explanatory diagram shown in the same manner as in FIG. 1 for explaining a preferable form of another background technique. In order to explain the preferred embodiment of the present invention, it is explanatory drawing which shows in the same manner as each above-mentioned figure.

Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings. FIG. 3 is an explanatory view showing a schematic cross section as in FIG. 2, and components having the same function are designated by the same reference numerals and hatches.

First, as disclosed in Patent Document 2, various well-known polyester-based resins can be selected for the polyester film 21, and aromatic dicarboxylic acids can be the main acid component and alkylene glycol can be the main glycol component. Specific examples of the aromatic dicarboxylic acid include terephthalic acid, isophthalic acid, naphthalenedicarboxylic acid, diphenoxyetanedicarboxylic acid, diphenyldicarboxylic acid, diphenyletherdicarboxylic acid, diphenylsulfonedicarboxylic acid, and diphenylketonedicarboxylic acid. Further, as the alkylene glycol, ethylene glycol, trimethylene glycol, tetramethylene glycol, pentamethylene glycol, hexamethylene glycol, hexylene glycol and the like are known. As a combination of these polymerization components, a particularly chemically stable copolymer of terephthalic acid and ethylene glycol can be used. From the viewpoint of process suitability of the base material, it is desirable that the polyester film made of the copolymer is at least uniaxially stretched, and "Tetron film" (manufactured by Teijin DuPont Film Co., Ltd., trade name) is commercially available. ) And "Lumirror" (manufactured by Toray Industries, Inc., trade name) can be used for biaxially stretched films.

Next, a fiber web containing unstretched polyester fibers is heat-bonded to one surface of the film 21, and a non-woven fabric layer 23 having a heat of crystallization of 3.0 × 10-2 J / cm ² or less per unit area is formed. It is provided. Of these, it is preferable that the unstretched polyester fiber, which is one raw material of the non-woven fabric layer 23, is also a resin raw material substantially the same as the polyester film described above. Further, it is preferable that the fiber web contains 35 to 60% by mass of undrawn polyester fibers, and the remaining constituent fibers are polyethylene terephthalate having substantially the same resin composition as the resin composition after the undrawn polyester fibers are heat-crystallized. It is better to use (PET) fiber. As such PET fiber, for example, drawn PET fiber available as "Dacron" (manufactured by DuPont, trade name) or "Tetron" (manufactured by Toray Industries, Inc., trade name) is preferable.

In the present invention, the technique of Patent Document 2 is applied, and the laminate film 31 is arranged on the other surface different from the non-woven fabric layer 23 provided on the film 21 to form the base material 33. The laminated film 31 includes a single-layer film (hereinafter abbreviated as COC / PE-LD), which is a blend of a cyclic olefin-based copolymer resin and a low-density polyethylene resin, which has lower moisture permeability than the polyester film 21, and a polyethylene resin. Single-layer film made of (hereinafter abbreviated as PE), single-layer film made of polyvinylidene chloride resin (hereinafter abbreviated as PVDC), composite film composed of a low-density polyethylene resin and a linear low-density polyethylene resin laminated (hereinafter abbreviated) Hereinafter, it is abbreviated as PE-LD + PE-LLD), or any of the above-mentioned thermoplastic resins can be arbitrarily selected from those subjected to aluminum vapor deposition or aluminum oxide vapor deposition as a base film.

Further, the moisture permeability of the laminated film naturally differs depending on the constituent resin of the film, but in general, the thicker the film, the lower the moisture permeability and the greater the contribution to the ODT effect. As an example, the moisture permeability of PVDC is 1.0 (g / m ² / day) when the film thickness is 15 μm, 0.6 (g / m ² / day) when the film thickness is 25 μm, and 38 μm. In some cases, it is known to be 0.4 (g / m ² / day). However, if the base material exceeds a predetermined thickness, the base material itself may be peeled off due to the force applied to the end portion of the patch. Therefore, the thickness of the laminated film is 10 μm or more, more preferably 15 μm or more, and 25 μm or less to prevent the peeling, in order to avoid the occurrence of pinholes in the bonding and to satisfy the processing suitability in consideration of the film tension applied in the process. Is preferable.

Further, when the above-mentioned laminated film is attached to the surface of the film 21, a so-called thermal laminating method in which a resin component that can be thermally adhered to the film 21 is adopted, or after various hot melt resins are applied in a spray form. Well-known techniques can be applied, such as a method of laminating, a direct laminating method of extruding a heat-melted resin to a predetermined thickness and directly pasting it as a film, and a method of preliminarily applying plasma treatment to the film 21 to increase the laminating adhesive strength. it can.

As can be understood from the numerical relationship by the KES-FB2 method, the patch medicated base material of the present invention configured in this way is bent and hard in the direction in which the above-mentioned concave curl is likely to occur, and the force of bending in the direction opposite to the concave curl is strong. It will show a small value. Therefore, "the concave stress is larger than the convex stress" in the present invention represents a state in which the above-mentioned concave curl is unlikely to occur, and the above-mentioned "concave curl" tends to occur after the adhesive is applied and formed. Low.

Hereinafter, the results of evaluating an example to which the preferred embodiment of the present invention is applied and a comparative example to which the background technology is applied will be described.

(Example 1 and Comparative Example 1)
First, the various base materials used for the evaluation will be described. The thickness is 12.0 (μm) and the surface density is 16.8 (g / g / g /), which is made of commercially available polyethylene terephthalate (hereinafter, may be abbreviated as PET). It was prepared biaxially stretched film of m ^2). Undrawn PET fibers (fineness 4.0 (decitex) x fiber length 38 (mm)) and drawn PET fibers (fineness 1.3 (decitex) x fiber length 38 (mm)) are used as fiber webs that heat-adhere to this film. And were mixed at a mass ratio of 40:60 to form a web with a flat card machine. The thermal adhesion between these fiber webs and the film was performed at a linear pressure of 30 (kg / cm) and a production rate of 5 (m / min) using a calendar composed of a metal roll and an elastic roll at 195 (° C.), and the above-mentioned film was formed. A composite non-woven fabric layer (base material) of Comparative Example 1 having a thickness of 50 (μm) provided with a non-woven fabric layer having a surface density of 12 (g / m ² ) was obtained. Next, a hot melt resin made of an acrylic rubber resin was sprayed onto the PET film surface of the composite non-woven fabric layer according to Comparative Example 1 so as to have a coating amount of about 2 (g / m ² ), and a commercially available PVDC film was applied. A laminated film was arranged by laminating and crimping (thickness 25 μm) to obtain a base material according to Example 1.

(Examples 2 to 4)
Instead of the laminated film in Example 1 described above, a PVCD film having a thickness of 15 μm (Example 2), a film prepared by adjusting the molten resin of COC / PE-LD to a thickness of 20 μm (Example 3), and having a thickness of 25 μm. Commercially available PE film (Example 4) was used as a base material.

(Examples 5 to 6)
A base material (Example 5) in which a molten resin of PE-LD + PE-LLD was directly laminated on the PET film surface of the composite non-woven fabric layer according to Comparative Example 1 so as to have a thickness of 15 μm, and a molten resin of PE-LD + PE-LLD were applied. A base material (Example 6) directly laminated so as to have a thickness of 20 μm was used as a base material.

(Comparative Example 2 and Comparative Example 3)
Comparative Example 2 (fiber web basis weight 18 g / m ² ) and Comparative Example 3 (fiber web basis weight 30 g / m ² ), which differed only from Comparative Example 1 in the basis weight of the fiber web, were obtained.

(Measurement of moisture permeability)
The moisture permeability of each of the base materials of Examples 1 to 6 and Comparative Examples 1 to 3 was measured according to 7.1.1 "Calcium chloride method (A-1 method)" of JIS L 1099 2012. .. First, each base material is cut into a circle having a diameter of 98 mm. Calcium chloride, which is a hygroscopic agent, is stored flat in an aluminum cylindrical moisture-permeable cup (inner diameter 60 mm, outer diameter 90 mm, height 22 mm) prepared in advance at about 40 ° C. so as to create a space of 3 mm at the upper end of the cup. , Weighed. Next, the upper end of the moisture permeable cup was covered with a base material to be evaluated, and the cylindrical moisture permeable cup was sealed using packing or the like to prepare a test piece. The test piece in this state was placed in a constant temperature and humidity device kept at a temperature of 40 ° C. and a relative humidity of 90%, which was close to the state of being attached to a human body, allowed to stand for 1 hour, taken out and weighed. After recording this weighing value, the device was allowed to stand in the constant temperature and humidity device for 1 hour again to perform the second weighing. For each substrate, such two weighing values were recorded. Of these weighed values, as shown in the following formula, the first weighed value 1 hour after the start of measurement is a ₁ (g), and the second weighed value 2 hours after the start of measurement is a. ₂ (g), and the difference between these weighing values was divided by the moisture permeation area S (m ² ) and converted into the moisture permeation amount per 24 hours to obtain the moisture permeation P (g / m ² / day).
P = [(a _2- a ₁ ) / S] × 24

(Measurement of KES-FB2)
Using a commercially available pure bending tester (KES-FB2, manufactured by Kato Tech Co., Ltd.), each base material cut into 20 cm squares was cut into 20 cm squares [curvature K = -2.5 to 2.5 cm ^-1 ], [deformation speed]. The flexural rigidity per unit length was measured 3 times each under the condition of [0.5 cm ^-1 / sec]. From the obtained chart, the maximum value of flexural rigidity when bent toward the non-woven fabric surface side of the base material is defined as "convex stress", and the maximum value when bent toward the laminated film (or film) surface side is defined as "concave stress". , Obtained by the average value of each.
[Table 1] shows the composition of each evaluation base cloth, the moisture permeability, and the measurement results of KES-FB2 described above.

As can be understood from Table 1, in each example in which the present invention is applied and a laminated film is arranged, the convex stress is relatively low as compared with each comparative example, and curls are generated with the laminated film inside. Therefore, it was confirmed that a larger external force was required. From this, it can be understood that the patch coated with the medicinal ingredient using the base material of the present invention can be expected to eliminate the peeling from the sticking target due to the concave curl. Further, from the comparison between each example and each comparative example, it is possible to reduce the moisture permeability in any of the examples as compared with the case where the PET film contained in the composite non-woven fabric layer is used alone. In particular, although Example 5 and Comparative Example 3 have the same basis weight, by adopting the configuration of the present invention, about half the moisture permeability is achieved, and the ODT effect is effectively exhibited. Understand what you get.

11: Non-woven fabric, 13: Resin sheet, 15: Non-woven fabric laminate, 17: Adhesive layer, 21: (Polyester) film, 23: Non-woven fabric layer, 25: Composite non-woven fabric layer (base material), 27: Adhesive, 31: Laminated film, 33: Substrate.

Claims (1)

A composite non-woven fabric layer provided with a non-woven fabric layer formed by heat-bonding a fiber web containing unstretched polyester fibers is provided on one surface of a polyethylene terephthalate film having a thickness of 6 to 25 μm , and the unit area of the composite non-woven fabric layer. A patched medicinal substrate having a heat of crystallization of 3.0 × ^10-2 J / cm ² or less.
A laminated film is placed on the other side of the film,
The laminated film is a single layer film in which a cyclic olefin copolymer resin and a low density polyethylene resin are blended, a single layer film made of a polyethylene resin, a single layer film made of a polyvinylidene chloride resin, a low density polyethylene resin and a linear low density film. A laminated film having a thickness of 25 μm or less, which is selected from a composite film formed by laminating a density polyethylene resin.
It is a patch medicinal base material characterized in that the concave stress obtained by the pure bending test (KES-FB2 method) of the KES method is larger than the convex stress .
A patch medicinal base material having a moisture permeability of 40 (g / m ² / day) or less at a temperature of 40 ° C. and a relative humidity of 90% .

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