JP2003192580A - Film for cataplasm - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a film for cataplasms having softness and stretchability, excellent in strength and scarcely causing release of the film by contact or friction with clothing when attaching to the skin. <P>SOLUTION: This film for cataplasms is obtained by laminating a surface layer comprising 50-99 wt.% ethylene-3-12C α-olefin copolymer obtained by carrying out polymerization by using a metallocene catalyst on at least one side of a base layer containing 70-100 wt.% thermoplastic elastomer. In the film, at least the surface layer comprises 0.1-1 wt.% fatty acid amide-based lubricant, and a layer thickness ratio of the base layer to the surface layer is (1/5) to (40/1). <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a patch film, and more specifically, it is a flexible and stretchable drug, a dissolving agent for applying a drug or a drug to a substrate, and a sub-agent for enhancing a transdermal absorption effect. It has excellent resistance to swelling by organic compounds such as agents, has excellent strength and skin adhesion, and is unlikely to peel off due to contact friction with clothing etc. when applied to the skin, suitable for transdermal absorption preparations and bandages. The present invention relates to a film for patch material used.

[0002]

2. Description of the Related Art Conventionally, many percutaneous absorption preparations containing a drug in an adhesive layer and medical patch materials such as adhesive plasters have been manufactured. Generally, a bandage is obtained by applying an adhesive on one surface of a soft film layer, further adhering a gauze or the like on the adhesive, stacking a release paper on the adhesive, and then punching it to a predetermined size. As the above-mentioned soft film used for this adhesive plaster, many soft vinyl chloride films have been used. The transdermal preparation is composed of a pressure-sensitive adhesive layer containing a drug or a drug layer containing a drug and a pressure-sensitive adhesive layer applied to a support. , Can be treated by directly absorbing the drug from the skin, mucous membranes, etc., and is conventionally used as a local therapeutic agent such as an anti-inflammatory analgesic, a tape for skin diseases, an antipruritic patch, and an agent for wounds. With the development of transdermal therapeutic systems (TTS), their use as systemic therapeutic agents, such as sickness remedy, is increasing. As such a support for percutaneous absorption preparations, a lot of films made of soft vinyl chloride have been used as in the case of the above plaster.

However, since the soft vinyl chloride film contains a large amount of plasticizer, the plasticizer migrates from the film to the pressure-sensitive adhesive layer, the adhesive strength of the pressure-sensitive adhesive layer is lowered, or the film and the pressure-sensitive adhesive layer are combined. The adhesive strength between the two decreases, and there are drawbacks such as percutaneous absorption preparations and adhesive bandages peeling off, and the adhesive migrates to the periphery and stains.Therefore, as a material that replaces the above soft vinyl chloride, it is flexible and stretchable. Although the use of a polyolefin resin film, etc. that has properties has been studied, the film does not have sufficient stretchability and stress relaxation property at the time of attachment necessary for the film, and the film may have a tight tightening feeling. , The film does not follow the skin easily in the bending part such as the elbow and the film peels off, and further the organic compound contained in the adhesive layer or the drug layer migrates to the film, and the film swells and becomes wrinkled. Like there was a problem that.

Various improvements have been made in order to solve such problems. For example, it is possible to make a considerable improvement by using a film made of a thermoplastic elastomer having a narrow molecular weight distribution as a film for patch. However, since the surface is sticky when it is actually used, there is a problem that when it comes into contact with clothes or the like, the edges are flipped up and finally peeled off from the skin.

[0005]

DISCLOSURE OF THE INVENTION The present invention is flexible and stretchable, fits the affected area and the like and does not exert strong pressure, has excellent followability when the affected area is moved, and further has an adhesive layer or a drug layer. It is an object of the present invention to provide a film for an adhesive patch, which has excellent resistance to swelling by an organic compound contained in, and which has improved surface stickiness and strength and is hardly peeled off even when contacted with clothes or the like. .

[0006]

The gist of the present invention is to obtain (a) ethylene obtained by polymerizing at least one side of a base material layer containing 70 to 100% by weight of a thermoplastic elastomer with a metallocene catalyst. And an α-olefin having 3 to 12 carbon atoms, having a (b) density of 0.88.
˜0.93 g / cm ³ , (c) Melt flow rate is 0.
Ethylene-α-of 5 to 50 g / 10 minutes, and (d) the ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) (hereinafter referred to as "Mw / Mn") is 1.5 to 5. Olefin copolymer (hereinafter referred to as "metallocene polyethylene")
A surface layer containing 50 to 99% by weight of
At least the surface layer contains a fatty acid amide-based lubricant in an amount of 0.1 to 1% by weight, and the layer thickness ratio between the base material layer and the surface layer is base material layer / surface layer = 1/5 to 40/1. Exists in the film. The present invention is described in detail below.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Examples of the thermoplastic elastomer used in the base material layer of the film of the present invention include styrene-based thermoplastic elastomer, polyolefin-based thermoplastic elastomer, and a mixture thereof.

Examples of the styrene thermoplastic elastomer include styrene-butadiene copolymer rubber, styrene-butadiene block copolymer and styrene-isoprene copolymer rubber. Of these, styrene-budadiene type thermoplastic elastomers such as styrene-butadiene copolymer rubber and styrene-butadiene block copolymer are preferable. The styrene-based thermoplastic elastomer is preferably hydrogenated. These styrene-based thermoplastic elastomers may be used alone or as a mixture.

As the thermoplastic polyolefin-based elastomer, ethylene-propylene copolymer rubber, ethylene-propylene non-conjugated diene rubber, ethylene-butadiene copolymer rubber, and a density obtained by polymerization using a metallocene catalyst are 0.900 g. Examples thereof include ethylene-α-olefin copolymers having a content of less than / cm ³ or a mixture thereof.

In the above base material layer, it is possible to mix up to 30% by weight of other resin such as polyethylene resin, polypropylene resin and a mixture thereof with the thermoplastic elastomer. If it exceeds 30% by weight, the film may swell remarkably due to the organic compound contained in the pressure-sensitive adhesive or the like and may not be suitable for use.

The polyethylene resin is a homopolymer of ethylene and / or a copolymer of ethylene as a main component with ethylene and another monomer copolymerizable therewith, such as low density polyethylene (LDPE). , Linear low density polyethylene (LLDPE), high density polyethylene (HDP)
E), polyethylene obtained by polymerization using a metallocene catalyst, a mixture thereof, and the like. As the polypropylene resin, propylene homopolymer and /
Or a copolymer etc. can be illustrated. As the copolymer, a random copolymer of propylene and another α-olefin,
Examples thereof include block copolymers, graft copolymers and mixtures thereof.

The surface layer of the film of the present invention is a copolymer of ethylene (a) obtained by polymerization using a metallocene catalyst and an α-olefin having 3 to 12 carbon atoms, and ) The density is 0.88 to 0.93 g / cm ³ , (c)
Melt flow rate is 0.5 to 50 g / 10 minutes, and (d)
The ratio of the weight average molecular weight (Mw) to the number average molecular weight (Mn) (hereinafter referred to as “Mw / Mn”) is 1.5 to 5 and the ethylene-α-olefin copolymer (metallocene polyethylene) is 50. ˜99% by weight. The mixing ratio of α-olefin is preferably 5 to 40% by weight with respect to ethylene. When the density of the metallocene-based polyethylene is less than 0.88 g / cm ³ , blocking of the film is likely to occur, and when it exceeds 0.93 g / cm ³ , the flexibility of the film is poor. Further, if the melt flow rate is less than 0.5 g / 10 minutes, the workability is poor, and if it exceeds 50 g / 10 minutes, stickiness due to the blowing out of the low molecular weight component becomes severe. Mw /
If the Mn is less than 1.5, the workability is poor, and if it exceeds 5, the low molecular weight component may bloom. Density of metallocene polyethylene is 0.900 to 0.918
It is particularly preferable for it to be g / cm ³ because suitable rigidity and mechanical strength as a patch can be obtained.

The metallocene catalyst (also referred to as single-site catalyst or Kaminsky catalyst) is described in JP-A 3-1.
As disclosed in JP-A-63088, JP-A-7-118431, JP-A-7-148895, and the like,
It is a catalyst composed of a metallocene-based transition metal complex and an organoaluminum compound, and may be used by being supported on an inorganic substance. Examples of the metallocene-based transition metal complex include
Transition metals selected from Group IVB (titanium, zirconium,
Hafnium), cyclopentadienyl group, substituted cyclopentadienyl group, dicyclopentadienyl group, substituted dicyclopentadienyl group, indenyl group, substituted indenyl group, tetrahydroindenyl group, substituted tetrahydroindenyl group, One or two fluorenyl groups or substituted fluorenyl groups are coordinated as ligands, or two of these groups are linked by a covalent bond are coordinated, and a hydrogen atom and oxygen are also included. Examples thereof include those having a ligand such as an atom, a halogen atom, an alkyl group, an alkoxy group, an aryl group, and an acetylacetonate group. Examples of the organoaluminum compound include alkylaluminum and chain or cyclic aluminoxane, and as the alkylaluminum, triethylaluminum, triisobutylaluminum, dimethylaluminum chloride, diethylaluminum chloride, methylaluminum dichloride, ethylaluminum dichloride, dimethyl. Aluminum fluoride, diisobutyl aluminum hydride, diethyl aluminum hydride, ethyl aluminum sesquichloride, etc. can be exemplified, and the chain or cyclic aluminoxane can be produced by contacting the above alkyl aluminum with water, for example, during polymerization. Alkyl aluminum is added and water is added later, or water of crystallization of complex salt or The adsorbed water and aluminum alkyl of the machine or inorganic compounds can be obtained by reacting.

Examples of the carrier for supporting the metallocene catalyst include silica gel, zeolite, diatomaceous earth and the like.

Further, in order to improve the moldability of the surface layer, it is preferable to add LDPE to the surface layer. On this occasion,
The blending ratio of LDPE is preferably less than 50% by weight. If it exceeds 50% by weight, the mechanical strength of the surface layer may decrease.

As the fatty acid amide-based lubricant contained in at least the surface layer of the film of the present invention, any higher fatty acid amide compound such as erucic acid amide and oleic acid amide may be used, and its content is 0. 1 ~
It is 1.0% by weight, preferably 0.1 to 0.8% by weight. Also, when both the base material layer and the surface layer contain a fatty acid amide lubricant, it is preferable to add the above amount to each layer. If the content exceeds 1.0% by weight, the pressure-sensitive adhesive may be peeled off due to excessive amount of lubricant blown out on the back surface of the film, resulting in peeling of the film. Further, if it is less than 0.1% by weight, it is difficult to obtain the effect of blending the fatty acid amide lubricant.

In the film of the present invention, the surface layer containing the metallocene-based polyethylene is laminated on at least one surface of the base layer containing the thermoplastic elastomer, and the layer structure is as follows. The ratio is appropriately selected from the range of base material layer / surface layer = 1/5 to 40/1. When the layer thickness ratio is less than ⅕, the flexibility obtained by the base material layer is lowered, and when it exceeds 40/1, the mechanical strength is lowered, which may hinder the use. Further, when the base layer has surface layers on both sides, the layer thickness ratio is as follows: surface layer / base layer / surface layer = 1 to 2.5
/ 1 to 20/1 to 2.5, and the thickness ratio of both surface layers may not be the same, for example, surface layer / base material layer / surface layer = 1/7/2 It may be like. An adhesive layer made of a resin having good adhesiveness to the constituent resins of both layers may be provided between the surface layer and the base material layer in order to improve interlayer adhesiveness.

Further, in each layer of the film of the present invention, if necessary, other synthetic resins, antioxidants, light stabilizers, UV inhibitors, fillers such as talc, calcium carbonate, mica, titanium oxide, flame retardants, Antistatic agents, colorants and the like can be added.

If the surface roughness (10-point average roughness (Rz) defined in JIS B 0601) of at least one side of the film is 1 to 80 μm, the apparent thickness is increased with respect to the actual thickness of the film. It is preferable because the touch feeling of the film can be further softened. The surface roughness is obtained by forming irregularities on the surface of the film.

The shape of the irregularities may be satin-like, stripe-like, lattice-like, polka-dot-like or the like. Particularly for transdermal preparations, the surface roughness of the film is preferably 30 to 70 μm.

The film of the present invention may be produced by a known extrusion molding machine, a multi-layer coextrusion molding machine or a lamination molding machine. Further, in order to make the film uneven, embossed rolls having a grain mark formed at the time of film formation. The film may be embossed in-line by using, or may be softened by heating so that the film that has been once cooled may be deformed under pressure, and may be pressed against the surface provided with the uneven pattern to transfer the uneven pattern offline. .

The embossing method is not particularly limited, and for example, between a metal roll having a fine uneven pattern on the surface and a silicone rubber roll having elasticity and good releasability. Examples thereof include a method of transferring a fine uneven pattern provided on the surface of the metal roll to the surface of the film by nipping while being heated to a temperature suitable for each composition.

The thickness of the film of the present invention (the thickness of the maximum thickness portion when the film has irregularities) is not particularly limited, but is preferably 20 to 200 μm. If it is less than 20 μm, the strength at the time of use tends to be insufficient, and if it exceeds 200 μm, the film is too hard and the texture may be impaired. The film may be colorless / colored, transparent / opaque.

Further, the swelling ratio of the film is preferably less than 0.2% in both the machine direction and the machine direction.

The film of the present invention is preferably used for percutaneous absorption preparations, adhesive bandages, bandages, wound guard films, protect films and the like.

The adhesive plaster using the film of the present invention is, if necessary, subjected to corona discharge treatment or anchor coating on the surface of the film, then provided with an adhesive layer, and laminating a gauze or the like on the adhesive layer. It is obtained by stacking release paper from the above and punching it into a predetermined size. The type of the pressure-sensitive adhesive is not particularly limited, and for example, various pressure-sensitive adhesives such as natural rubber-based, synthetic rubber-based, acrylic-based, urethane-based, vinyl ether-based, and silicone-based adhesives are preferably used, and their forms May be a solution type, an emulsion type, a hot melt type, or the like. In addition, various types of printing may be performed on either surface of the film depending on the purpose.

The percutaneous absorption preparation using the film of the present invention may be prepared, for example, by laminating a layer containing a drug and an adhesive layer on the film, coating an adhesive containing the drug on the film, or releasing the film. The adhesive can be obtained by laminating a pressure-sensitive adhesive containing a drug, which is previously applied to paper or the like, by laminating or the like.

The above-mentioned drug is not particularly limited as long as it is percutaneously absorbed into the body and exerts a pharmacological effect, and examples thereof include anti-inflammatory agents, analgesics, local stimulants, antihistamines, and local anesthetics. , Blood circulation promoters, hypnotic sedatives, tranquilizers, antihypertensive agents, antibacterial agents and the like. Moreover, as the adhesive, those mentioned in the description of the adhesive bandage can be used.

If necessary, an additional layer may be provided between the film of the present invention and the pressure-sensitive adhesive layer.

[0030]

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded. Evaluation Method (Tensile Modulus) The tensile modulus of the film was measured according to JIS K 7127.

(Initial / Residual stress) JIS K 6732
Using the film of the described shape as a test piece, 300 mm
The test piece was stretched by 10% at a test speed of / min and then held, and the initial stress F (10) and the residual stress f (10) after 5 minutes were measured.

(Tensile Strength of Film) A film having a texture (unevenness) on its surface is difficult to accurately compare with a film without texture because of its apparent thickness when the tensile strength is expressed by stress. Is. Therefore, according to the following conditions, the influence of thickness was excluded and the tensile strength was expressed by the load and elongation per unit width at the time of tensile rupture.

Conditional test piece: The film was formed into a strip of 19 mm and the distance between the marked lines was 4
Measured in cm Tensile tester speed: 200 mm / min (degree of swelling with solvent etc.) A pressure-sensitive adhesive having the following composition was applied on a silicone surface-treated release paper, and the thickness after drying was 1
It was adjusted to be about 5 μm. This was attached to a film to give a patch. Next, the patch was allowed to stand for 1 week in an atmosphere of 50 ° C., and then the dimensional change due to swelling was measured to obtain the dimensional change rate (swelling rate). If it swells by 0.2% or more, it may hinder practical use.

Swelling rate (%): (dimension after 1 week-initial dimension) x 100 / initial dimension Adhesive: 100 parts by weight of natural rubber and 10 parts by weight of hydrogenated rosin acid ester were added to toluene. Concentration is 10
Dissolved to a concentration of 2% by weight, and further dissolved glycol salicylate to a concentration of 2% by weight.

(Peeling off due to friction with clothes) The adhesive was applied to the elbow under the clothes, and after 1 day, the adhesiveness of the adhesive was evaluated.

◯: Good adhesion.

Δ: The edge is slightly turned up.

X: The edge was greatly turned up or completely peeled off.

Examples 1 to 4 and Comparative Examples 1 to 4 <Production of Film> Using the compositions shown in Table 1, a T-die film forming machine (65 mmφ extruder: 500 mm width T-die manufactured by Toshiba Machine Co., Ltd.) was used. ) Each film was made.
Further, the film of Example 1 was textured with a satin embossing roll, and the film of Example 4 was textured with a silk-like embossing roll.

Each of the obtained films was evaluated,
The results are shown in Table-1.

[0041]

[Table 1]

EFFECT OF THE INVENTION The film of the present invention is flexible and stretchable, fits the affected area and does not strongly press, does not have a tight feeling of winding, and has excellent followability when the affected area is moved, and has strength and adhesiveness. Excellent resistance to swelling due to migration of drugs contained in agents, etc., and because peeling is less likely to occur due to contact friction with clothing etc. when applied to the skin, as a film for patches such as transdermal preparations and bandages It is preferably used.

Claims (6)

[Claims] 1. A polymer (a) obtained by polymerizing at least one surface of a base material layer containing 70 to 100% by weight of a thermoplastic elastomer with a metallocene catalyst and α-containing 3 to 12 carbon atoms. A copolymer with an olefin,
(B) a density of 0.88 to 0.93 g / cm ³ , (c) a melt flow rate of 0.5 to 50 g / 10 minutes, and (d) a weight average molecular weight (Mw) and a number average molecular weight (Mn). A surface layer containing 50 to 99% by weight of an ethylene-α-olefin copolymer having a ratio (hereinafter, referred to as “Mw / Mn”) of 1.5 to 5 is laminated, and at least the surface layer is a fatty acid. A patch film containing 0.1 to 1% by weight of an amide-based lubricant and having a layer thickness ratio of a substrate layer to a surface layer of substrate layer / surface layer = 1/5 to 40/1. 2. The film for patch according to claim 1, wherein the thermoplastic elastomer comprises a styrene-based thermoplastic elastomer or a polyolefin-based thermoplastic elastomer. 3. The adhesive film according to claim 1, wherein the thermoplastic elastomer comprises ethylene-propylene copolymer rubber. 4. The film for patch according to claim 1, wherein the fatty acid amide lubricant is oleic acid amide. 5. A percutaneous absorption preparation in which a drug is coated on one surface of the film according to any one of claims 1 to 4. 6. A film for bandages, comprising an adhesive layer provided on one surface of the film according to any one of claims 1 to 4.