WO2007069662A1 - 貼付製剤 - Google Patents
貼付製剤 Download PDFInfo
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- WO2007069662A1 WO2007069662A1 PCT/JP2006/324875 JP2006324875W WO2007069662A1 WO 2007069662 A1 WO2007069662 A1 WO 2007069662A1 JP 2006324875 W JP2006324875 W JP 2006324875W WO 2007069662 A1 WO2007069662 A1 WO 2007069662A1
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- Prior art keywords
- drug
- adhesive
- pressure
- adhesive layer
- alcohol
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
Definitions
- the present invention relates to a transdermal absorption patch for continuously administering a drug having a liquid property at or near room temperature (except for the free base of pisoprolol) into the body through the skin surface. Relates to the formulation.
- a preparation for treating or preventing a disease by administering a drug into a living body for example, drug metabolism and various side effects due to the first passage of the liver can be avoided, and the drug can be continuously used for a long time.
- transdermal preparations that can be administered. Among them, since the drug application is easy and the dose can be strictly controlled, the development of a patch preparation containing a drug in an adhesive is actively performed.
- patch preparations are designed by selecting the most suitable adhesives and additives according to the drug so as to satisfy these basic characteristics.
- pressure-sensitive adhesives acrylic pressure-sensitive adhesives and rubber-based pressure-sensitive adhesives are mainly used.
- rubber-based pressure-sensitive adhesives that generally do not have functional groups are talyl-based pressure-sensitive adhesives. Is more advantageous.
- rubber adhesives include polyisobutylene (PIB), styrene-isoprene-styrene (SIS), and silicone adhesives. SIS and silicone adhesives promote drug absorption.
- PIB-based adhesive a polyisobutylene-based adhesive (hereinafter sometimes referred to as “PIB-based adhesive”) is easily used as the rubber-based adhesive.
- the PIB adhesive has a low polarity, there is a problem that the solubility of the drug is low! In order to satisfy the drug release and sustainability required for patch preparations, it is desirable to add as much drug as possible, but PIB adhesives are limited. If the drug is solid at room temperature or near room temperature, it is possible to mix a large amount of drug with solubility or higher by dispersing the solid drug in the adhesive. In that case, a part of the drug is dispersed in the pressure-sensitive adhesive in the form of crystals or the like, and the concentration of the drug dissolved in the pressure-sensitive adhesive is low, so that the adhesive strength of the pressure-sensitive adhesive itself is rarely impaired. In other words, it is possible to achieve both the formulation of a sufficient amount of drug necessary for prevention and the practical adhesive properties.
- this bleed-out phenomenon is a force called bleed
- the bleed occurs, the surface of the pressure-sensitive adhesive layer is covered with the drug, and the contact between the pressure-sensitive adhesive and the adherend is inhibited, so that the adhesive strength of the patch preparation is significantly reduced.
- the adhesion of the adhesive to the support that is, the anchoring property, is reduced as well as a decrease in the adhesive strength to the adherend.
- Examples of drugs that are liquid at or near room temperature include emedastine free base and galopamil free base. These salts are crystalline powders, but the percutaneous absorbability is low in salt form drugs. When these free bases are used to improve the transdermal absorbability, the transdermal absorbability is improved, but there is a problem that the stability of the drug is lowered. Therefore, if a patch preparation using a PIB-based adhesive with excellent drug stability in an adhesive can be developed, its technical significance is great.
- Patent Document 1 discloses that at least one of them has a low molecular weight and is liquid at room temperature or almost room temperature. It has a polymer matrix that contains one or more drugs and one or more high shear resistance polymers A transdermal composition is disclosed. This high shear resistance polymer reduces the plasticization effect of low molecular weight drugs and is said to have sufficient tack and shear for human application.
- an acrylic pressure-sensitive adhesive or a pressure-sensitive adhesive obtained by mixing an acrylic pressure-sensitive adhesive and a silicone pressure-sensitive adhesive showed a stringing suppressing effect.
- the high-shear resistance polymer has a high molecular weight, an increased blending ratio of the high-shear resistance polymer, etc. If the adhesive is hardened, it is logically possible to suppress the stringing of the adhesive when the amount of the liquid drug is increased, but if the adhesive is hardened, the adhesive will adhere to the adherend. The adhesiveness of the patch preparation is reduced. Acrylic adhesives originally have a high level of adhesive strength, so even if a liquid drug is contained, a decrease in adhesive strength is not a major problem, but it is less adhesive than acrylic adhesives!
- Patent Document 1 Japanese Patent Laid-Open No. 2005-23088
- the present invention has been made in view of such circumstances, and the problem to be solved is to develop a patch preparation for transdermally administering a drug that is liquid at or near room temperature into a living body.
- an adhesive preparation using a polyisobutylene-based adhesive as an adhesive can provide a patch preparation that can suppress drug bleeding and has sufficient adhesive properties.
- the present inventors include a specific alcohol in a pressure-sensitive adhesive layer containing a PIB pressure-sensitive adhesive and a drug that is liquid at or near room temperature, thereby providing a polyisobutylene pressure-sensitive adhesive, It was found that the compatibility with drugs was specifically enhanced, and as a result, the above problems could be solved. did. Upon further examination, the present inventors have found that the present invention is particularly effective for a drug whose logPow and viscosity at 40 ° C. are in a specific range. Based on these findings, the present invention has been completed.
- the present invention has the following features.
- a patch preparation comprising
- Branched monohydric alcohol is selected from 2 hexyl 1 decanol, 2 octyl 1-de strength diol, 2—hexyl 1 dodecanol, 2 octyl 1 dodecanol and 2 decyl 1 tetradecanol
- the patch preparation according to any one of (1) to (5) above, which is a seed.
- the patch preparation of the present invention contains a branched monohydric alcohol having 12 to 28 carbon atoms in the pressure-sensitive adhesive layer as a solubilizing agent, so that it is liquid at room temperature or near room temperature.
- Compatibility with drugs can be specifically increased.
- the amount of the drug can be increased, the drug bleeding from the pressure-sensitive adhesive layer can be suppressed, and a sufficient adhesive property can be obtained in terms of practical use. Therefore, it is possible to provide a patch preparation that can achieve both a high level of pharmacological action and adhesive properties.
- FIG. 1 is a cross-sectional view showing one embodiment of a patch preparation of the present invention.
- FIG. 1 is a cross-sectional view showing a preferred embodiment of the patch preparation of the present invention.
- the patch preparation 10 comprises a support 1, a pressure-sensitive adhesive layer 2 laminated on one side of the support 1, and a release liner 3 laminated on the pressure-sensitive adhesive layer 2.
- the pressure-sensitive adhesive layer 2 comprises a branched monohydric alcohol having 12 to 28 carbon atoms, a polyisobutylene-based pressure-sensitive adhesive, and a drug that is liquid at or near room temperature (except for the free base of pisoprolol. “)”).
- the branched monohydric alcohol contained in the pressure-sensitive adhesive layer functions as a solubilizing agent. Surprisingly, only the branched monohydric alcohol having 12 to 28 carbon atoms (preferably 16 to 24 carbon atoms) can be used. The compatibility between the IB adhesive and the drug can be specifically improved. As a result, it is possible to suppress the bleeding of the drug and to secure sufficient adhesive properties in practical use.
- the branched monohydric alcohols can be used alone or in combination of two or more.
- the carbon number means the total carbon number of the carbon skeleton constituting the alcohol.
- the compatibility can be improved to some extent by using a solubilizing agent having a polarity approximately intermediate between that of the drug and the PIB adhesive. It is guessed. Therefore, compared with the above alcohol, even if the number of carbon atoms, the type or number of polar groups, or the bonding position of the polar group is slightly different, the effect on the compatibility is small. It is estimated that acid) can be used. However, the use of fatty acid esters, diesters, organic acids, etc., having the same number of carbon atoms and the same polarity in place of the above-mentioned alcohol, strangely has no effect on the suppression of drug bleeding.
- the primary alcohol power is easily exposed to the surface of the alcohol molecule because its hydroxyl group is easily exposed to the surface of the alcohol molecule. Is significantly improved.
- 2-alkyl 1 alkanol which is excellent in the balance between the hydroxyl group and the carbon skeleton, is more preferable.
- Such an alcohol has one branch point of the carbon chain, two long carbon chains from the strong base point, one short and short carbon chain, and a hydroxyl group bonded to the tip of the carbon chain. It has a structure.
- the alcohol molecule as a whole becomes bulky, the intermolecular interaction between the alcohol molecules weakens, and the fluidity of the alcohol molecules increases.
- the two long carbon chains interact efficiently with the PIB molecule as a hydrophobic part, thereby improving the compatibility between the alcohol molecule and the PIB molecule.
- the hydroxyl group of the alcohol molecule is exposed on the surface of the alcohol molecule so as not to be hidden behind the alcohol molecule, the hydroxyl group can interact with the drug, thereby making the alcohol-drug compatible. Get better.
- those having an alkyl group at the 2-position of 2 or more are preferably used.
- 2-octyl 1-decanol, 2-hexyl 1-decanol, 2-octyl 1-decanol, 2-hexyl 1-dodecanol, and 2-decyl-1-tetradecanol are more preferable.
- the content of the alcohol in the total weight of the pressure-sensitive adhesive layer can be appropriately selected depending on the content of the drug and the like, and is not particularly limited, but is usually 0.1 to 40% by weight. %, Preferably 0.5 to 35% by weight, more preferably 0.5 to 30% by weight, and most preferably 0.5 to 20% by weight. If the content is less than 0.1% by weight, the above effects tend to be difficult to obtain. On the other hand, if the content is more than 40% by weight, the cohesive strength and adhesive strength of the entire pressure-sensitive adhesive layer are increased. It tends to decrease.
- the present invention is advantageously implemented in that drug bleeding can be more effectively suppressed than when other organic liquid components such as fatty acid alkyl esters are used. it can.
- the drug contained in the adhesive layer is not particularly limited as long as it is a liquid drug at or near room temperature, but the partition coefficient logPow is -1.0 to 5.0, A drug having a viscosity at 40 ° C of 0.05-100, OOOmPa's is preferred.
- Specific examples include emedastine free base represented by the following formula (1), crotamiton represented by the following formula (2), galapamyl free base represented by the following formula (3), and the like.
- the "drug that is liquid at or near room temperature” means the temperature at which the patch preparation after manufacture is normally stored, that is, at least one temperature in the temperature range of 1 to 40 ° C. It refers to a drug that is a liquid. In the high temperature range, the drug is fluid enough to cause bleeding.
- the viscosity of the drug is measured using an E-type viscometer while keeping the drug at a predetermined temperature. In the present invention, when the viscosity of a drug at a predetermined temperature is 0.05 to 100, OOOmPa's, the drug is a liquid at the predetermined temperature.
- ⁇ logPow '' is an index representing the hydrophilicity or hydrophobicity of a drug
- ⁇ OECD GUIDELIN E FOR THE TESTING OF CHEMICALS 107, Adopted by the Council on 27 th July 1 995, Partition Coefficient ( water) .Shake Flask MethodJ refers to the value measured for each individual drug by the method described in its own manual.
- the logarithmic base of logPow is 10.
- logPow is obtained by calculation after distributing the drug to the water layer and n-octanol layer by the method described in the above guidelines and quantifying the drug concentration in each layer by an appropriate method.
- the drug quantification is not particularly limited as long as it is a method that confirms the quantification by confirming the linearity of the calibration curve, etc., but is usually an absorbance method, a gas chromatography method, or a high performance liquid chromatography method. Is used. When measuring drugs that do not have UV absorption, other methods such as titration may be used as long as the quantification is confirmed. If the drug is a dissociable substance, measure the logPow while suppressing dissociation according to this guideline.
- logPow is measured in a free acid or free base state using a buffer solution having an appropriate pH as an aqueous layer.
- the drug is an acidic drug, use a buffer solution with a pH that is at least one lower than the pKa value of the drug.
- the drug is a basic drug, use a buffer solution with a pH that is at least one higher than the pKa value of the drug.
- the measurement range of log Pow is usually 2-4.
- the sensitivity of quantitative analysis is increased by using a high-sensitivity analysis method such as high-speed liquid chromatography. It can be 2-5.
- logPow is less than -1.0, the hydrophilicity of the drug is too high, and even if the above alcohol is added that has low compatibility with the PIB adhesive, the bleed suppression effect cannot be sufficiently obtained. There are cases. On the other hand, if logPow is larger than 5.0, the bleed suppressing effect and the tackiness may be insufficient. According to the knowledge of the present inventors, logPow is -1.0 to 5.0 (preferably In the case of a drug of 0.0 to 5.0), there is a marked difference in the bleed suppression effect depending on the presence or absence of the above-mentioned alcohol. In this respect, the present invention is of great technical significance.
- the viscosity of a drug at 40 ° C is determined by S'J using an E-type viscometer while the drug is heated to 40 ° C. 40.
- the viscosity in C is usually from 0.05 to: LOO, OOOmPa-s, preferably from 0.5 to 50, OOOmPa's. If the viscosity is less than 0.05 mPa's, the fluidity is too high and it tends to evaporate from the pressure-sensitive adhesive layer when the drug is mixed with the pressure-sensitive adhesive solution and applied to the substrate and dried. . On the other hand, if the viscosity force is greater than SlOO, OOOmPa's at 40 ° C, the viscosity is too high, and the weighing operation of the drug tends to be performed accurately and difficult.
- the content of the drug in the pressure-sensitive adhesive layer is not particularly limited, and is a force appropriately selected according to the above-described effects obtained depending on the drug release and solubility, the type of alcohol and the amount added, preferably 0.1 to 40% by weight, more preferably 0.5 to 40% by weight, and more preferably 0.5 to 35% by weight.
- the content of the drug is less than 0.1% by weight, the drug concentration is sufficiently low, so that the bleed is suppressed. The effect of the addition of the alcohol tends not to be sufficiently exhibited.
- the content of the drug exceeds 40% by weight, the drug concentration is too high, and thus the effect of adding the alcohol tends to be hardly exhibited.
- the concentration of the drug is 0.1 to 40% by weight, a remarkable difference is observed in the bleed suppression effect depending on the presence or absence of the alcohol added to the alcohol, and the present invention is technically significant in this respect.
- the PIB adhesive used in the patch preparation of the present invention is required to contain polyisobutylene, and is particularly limited as long as it has appropriate adhesiveness and cohesion as an adhesive itself. It is not used, and it is used alone or in combination of two or more.
- the molecular weight of polyisobutylene is not particularly limited. S, viscosity average molecular weight power is preferably 40, 000-5, 500, 000, more preferably 45, 000. -5, 000, 000.
- the viscosity average molecular weight force is less than 40,000, it may be difficult to impart the necessary internal cohesive force to the pressure-sensitive adhesive layer, while if it exceeds 5,500,000, the adhesiveness of the adhesive layer to the skin or There is a risk that tack will be lowered.
- the butylene is preferably composed of the combination force of the first polyisobutylene and the second polyisobutylene having a lower molecular weight than the first polyisobutylene.
- These polyisobutylenes having different molecular weights can be combined.
- “at least two types of polyisobutylene having different molecular weights” means a poly having a molecular weight distribution peak measured by gel permeation chromatography (GPC) in at least two independent regions. Refers to isobutylene.
- the molecular weight of each polyisobutylene is not particularly limited, but in order to obtain good adhesion, the viscosity average molecular weight of the first polyisobutylene.
- Force S Preferably 1,800,000-5,500,000, more preferably ⁇ 2,000,000-5, 000,000, and the second, the viscosity average molecular weight force of the second positive isobutylene Is preferably from 40,000 to 85,000, more preferably from 45,000 to 65,000.
- the viscosity average molecular weight of the first polyisobutylene is less than 1,800,000, it tends to be difficult to obtain the internal cohesive force required for the pressure-sensitive adhesive layer. If it exceeds, the adhesiveness and tackiness of the pressure-sensitive adhesive layer tend to decrease.
- the viscosity average molecular weight of the second polyisobutylene is less than 40,000, the pressure-sensitive adhesive layer may feel sticky and may contaminate the skin surface, while if it exceeds 85,000, the pressure-sensitive adhesive There is a tendency for the skin adhesion and tackiness of the layer to decrease.
- the viscosity average molecular weight is the Staudinger index ⁇ .
- the blending ratio of the polyisobutylene to the second polyisobutylene is preferably 1: 0.1-1 to 3: 3, more preferably 1: 0.1-1 to 2.5, and more preferably 1: 0 by weight. 3 to 1: 2.
- the blending ratio of the second polyisobutylene is less than the lower limit, the skin adhesive force of the pressure-sensitive adhesive layer tends to decrease greatly.
- the upper limit is exceeded, the pressure-sensitive adhesive layer There is a tendency for the decrease in internal cohesive force to increase.
- the total content of Poriisopuchiren relative to the total weight of the adhesive layer is preferably 15 to 70 weight 0/0, more preferably 15 to 60 wt%. If the polyisobutylene content is less than 15% by weight, it may be difficult to impart the necessary internal cohesive force to the pressure-sensitive adhesive layer. On the other hand, if it exceeds 70% by weight, the adhesiveness and tackiness of the pressure-sensitive adhesive layer may be reduced. May decrease.
- a tackifier may be included as necessary.
- the tackifier those known in the field of patch preparations can be appropriately selected and used.
- petroleum-based, terpene, rosin-, coumarone-indene, and styrene-based resins Alicyclic hydrocarbon rosin and the like.
- alicyclic saturated hydrocarbon resins are preferable because the storage stability of the drug becomes good.
- a tackifier having a softening point of preferably 90 to 150 ° C, more preferably 95 to 145 ° C is used.
- the softening point refers to a value measured by the ring and ball method CFIS K6863).
- Examples of the alicyclic saturated hydrocarbon resin include Alcon P-100, Alcon P-115, Alcon P-125, Alcon P-140 (trade name, manufactured by Arakawa Chemical Industries) as commercially available products. I can get lost.
- Tatsuki Fire can be used singly or in combination of two or more, and when used in combination of two or more, for example, the types of rosin and varieties having different softening points may be combined.
- the content of the tacky ear in the total weight of the pressure-sensitive adhesive layer is preferably 15 to 55% by weight %, More preferably 20 to 50% by weight.
- the content of Tatsuki Fire is less than 15% by weight, the tack may be poor, while when it exceeds 55% by weight, the adhesive layer becomes hard and the skin adhesion tends to be lowered.
- an organic liquid component other than the above alcohol or drug may be contained as necessary.
- the organic liquid component is not particularly limited as long as it is compatible with polyisobutylene and tackifier, and examples thereof include fatty acid alkyl esters.
- fatty acid alkyl ester examples include fatty acid alkyl esters obtained from a higher fatty acid having 12 to 16 carbon atoms, preferably 12 to 14 carbon atoms, and a lower monohydric alcohol having 1 to 4 carbon atoms.
- the higher fatty acid lauric acid (C12), myristic acid (C14) and palmitic acid (C16) are preferable, and myristic acid is more preferable.
- the monohydric alcohol include methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol and the like, and preferably isopropyl alcohol.
- the most preferred fatty acid alkyl ester is isopropyl myristate.
- the organic liquid component may be used alone or in combination of two or more.
- the content of the organic liquid component in the total weight of the pressure-sensitive adhesive layer is preferably 1 to 40% by weight, more preferably 3 to 25% by weight. If the content of the organic liquid component is less than 1% by weight, effects such as absorption promotion tend not to be fully exerted, while if it exceeds 40% by weight, the adhesive force and cohesive force of the entire adhesive will decrease. There is a tendency.
- the support is not particularly limited, but a material that is substantially impermeable to drugs or the like, that is, a drug or additive that is an active ingredient of the adhesive layer passes through the support and is back. Those that lose power and do not cause a decrease in content are preferred.
- the support include polyester, nylon, polyvinylidene chloride, polyethylene, polypropylene, polybutyl chloride, ethylene ethyl acrylate copolymer, polytetrafluoroethylene, ionomer resin, and metal foil. A single film or a laminated film of these can be used.
- the support is made up of a non-porous plastic film having the above material strength and a porous film.
- a laminated film is preferable.
- the pressure-sensitive adhesive layer is preferably formed on the porous film side.
- a porous film one having improved anchoring property with the pressure-sensitive adhesive layer is employed. Specifically, paper, woven fabric, non-woven fabric, knitted fabric, mechanically perforated treatment is performed. Sheet. Of these, paper, woven fabric, and non-woven fabric are particularly preferable from the viewpoint of handleability. A porous film having a thickness of 10 to 200 / ⁇ ⁇ is adopted from the viewpoint of improvement in anchoring property, flexibility of the whole patch preparation, and sticking operability. In the case of thin patch preparations such as plaster type and adhesive tape type, a thickness of 10 ⁇ : LOO / zm is used.
- the basis weight is 5 to 30 gZm 2 , preferably 6 to 15 gZm 2 .
- a non-woven fabric made of a polyester film (preferably polyethylene terephthalate film) having a thickness of 1.5 to 6 ⁇ m and a polyester (preferably polyethylene terephthalate) having a basis weight of 6 to 12 gZm 2 is used. And a laminated film.
- the adhesive preparation of the present invention is preferably laminated with a release liner in order to protect the adhesive surface of the adhesive layer until use.
- the release liner is not particularly limited as long as it has been subjected to a release treatment and a sufficiently light release force can be ensured.
- a silicone resin or a fluorine resin is applied to the contact surface with the pressure-sensitive adhesive layer.
- Polyester, polyvinyl chloride, polyvinylidene chloride, polyethylene terephthalate, etc., high quality paper, paper such as dalasin paper, or high quality paper or lamellar paper and laminate film of polyolefin, etc. are used.
- the thickness of the release liner is usually 10 to 200 111, preferably 25 to: LOO / z m.
- the release liner is preferably made of polyester (particularly, polyethylene terephthalate) resin from the viewpoint of barrier properties, cost, and the like. Further, in this case, a thickness of about 25 to 100 / ⁇ ⁇ is more preferable from the viewpoint of handleability.
- the patch preparation of the present invention can be obtained by, for example, dissolving an adhesive containing two types of polyisobutylene having different molecular weights and a tackifier, the monohydric alcohol, and the drug in an appropriate solvent such as toluene.
- the pressure-sensitive adhesive layer forming composition solution is applied on a release liner and dried to form a pressure-sensitive adhesive layer, and a support is laminated on the pressure-sensitive adhesive layer.
- the thickness of the pressure-sensitive adhesive layer is usually 10 to 300 111, preferably 20 to 250 m.
- the shape of the patch preparation is not particularly limited, and may be, for example, a tape shape or a sheet shape.
- the patch preparation of the present invention is preferably stored or transported in a sealed package until use.
- the packaging method include a method in which a single patch preparation or a plurality of patch preparations are wrapped with a packaging material, and the periphery is sealed by heat sealing.
- the packaging material include, but are not particularly limited to, sheet-like or film-like materials, but those that can be heat-sealed from the viewpoint of ease of packaging and airtightness are desirable.
- a plastic sheet having heat sealing properties such as polyethylene, ionomer resin, ethylene acetate butyl copolymer, ethylene vinyl alcohol copolymer, polyacrylonitrile copolymer, poly butyl alcohol copolymer is used.
- Suitable packaging materials are suitable.
- a laminate of a gas-impermeable film such as a polyester film or a metal foil in order to prevent contamination of the active ingredient contained in the patch preparation by the outside air and decomposition of acid and sour.
- the packaging material one having a thickness of 10 to 200 m is usually used. It is more preferable to use a polyacrylonitrile copolymer having a high barrier property as the innermost layer of the packaging material.
- the patch preparation of the present invention can be used by tearing off the above-mentioned package immediately before use, removing the release liner, and sticking the exposed adhesive surface to the skin surface or the like.
- the patch preparation of the present invention varies depending on the patient's age, weight, symptoms, etc. In this case, apply it to the skin surface once every 1-2 days.
- B200 Oppanol (R) B200 (BASF) Polyisobutylene Viscosity average molecular weight 4,000,000 6H: HIMOL6H (Nippon Petrochemical Co., Ltd.) Polyisobutylene Viscosity average molecular weight 60,000 P140: ARKON (R) P140 (Arakawa Chemical Co., Ltd.) Tatsuki Fireer Alicyclic saturated hydrocarbon resin Softening point 140 ° C
- IPM CRODAMOL IPM (Croda Japan Co., Ltd.)
- the adhesive layer forming composition formulated according to Table 1 was dissolved in toluene to prepare a viscous solution.
- the resulting solution was applied onto a polyethylene terephthalate (PET) liner (75 m) that had been subjected to silicone release treatment so that the thickness strength after drying was O / zm, and this was applied to a hot-air circulating dryer. It was dried in to remove toluene and form an adhesive layer.
- PET polyethylene terephthalate
- a 25-m thick PET film was bonded as a support on the pressure-sensitive adhesive layer to obtain a sheet-like patch preparation.
- Example 1 5 2-year-old cutyl-1-dote "power-'les 1 5 PIB (7 7.5)
- Example 2 5 2—Hexilous 1 Te, Power Knoll 1 5 PTB (7 7.5)
- Example 3 7. 5 2— - ⁇ -sil— 1-tetrathe '—' canol 1 5 PIB (7 7.5)
- the medicated patch strength was visually observed to determine whether the liner had a liquid adhesion, and evaluated according to the following criteria. Table 2 shows the evaluation results. ⁇ : The liquid material did not adhere to the liner.
- A The pressure-sensitive adhesive layer was cast on the support in both the liner peeling operation and the adhesion test.
- Example 1 (N / 24mm) Example 1 ⁇ ⁇ 7.7 Example 2 ⁇ ⁇ ⁇ 1.8 Example 3 ⁇ ⁇ ⁇ 6.6 Example 4 ⁇ ⁇ ⁇ 1.3
- Example 5 ⁇ ⁇ ⁇ 0 .2 2
- Example 6 ⁇ ⁇ ⁇ 0.72 Comparative example 1 X ⁇ X measurement; impossible Comparison example 2 X ⁇ X impossible to measure Comparative example 3 XXX impossible to measure Comparative example 4 ⁇ ⁇ X impossible to measure Comparative example 5 ⁇ ⁇ ⁇ 0.
- the patch preparation of Comparative Example 5 containing hexadecane 8-ol which is structurally similar to 2-xyl-1-decanol but is a linear secondary alcohol, has an appropriate anchoring property.
- the adhesive strength was inferior to that of the patch preparation of Example 14.
- Example 5 In the patch preparation of Example 5 having a viscosity (40 ° C) of 16 mPa's, logPow containing 3.1 crotamiton and 2 octyl 1-dodecanol, bleeding was observed. It was not observed, and the anchoring property and tackiness were both good and had sufficient adhesive strength.
- Example 6 In the case of the patch preparation of Example 6 having a viscosity (40 ° C) of 4500 mPa's, logPow of 4.8 containing galapamyl free base and adding 2-octyl-1-dodecanol, No stickiness was observed, and the anchoring property and stickiness were both good.
- the adhesive preparation of the present invention contains a branched monohydric alcohol having 12 to 28 carbon atoms as a dissolution aid in the adhesive layer, so that the PIB-based adhesive and a drug that is liquid at or near room temperature. Compatibility can be specifically increased. As a result, the amount of the drug can be increased, the drug bleeding from the pressure-sensitive adhesive layer can be suppressed, and a sufficient adhesive property can be obtained in terms of practical use. Therefore, it is possible to provide a patch preparation that can achieve both a high level of pharmacological action and adhesive properties.
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Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2006800468551A CN101330908B (zh) | 2005-12-13 | 2006-12-13 | 粘贴制剂 |
EP06834630A EP1961415A4 (en) | 2005-12-13 | 2006-12-13 | ADHESIVE PREPARATION |
US12/097,220 US20090169603A1 (en) | 2005-12-13 | 2006-12-13 | Adhesive Pharmaceutical Preparation |
CA2633027A CA2633027C (en) | 2005-12-13 | 2006-12-13 | Adhesive pharmaceutical preparation |
KR1020087016979A KR101166599B1 (ko) | 2005-12-13 | 2006-12-13 | 접착 제제 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2005-358469 | 2005-12-13 | ||
JP2005358469 | 2005-12-13 | ||
JP2006-328952 | 2006-12-06 | ||
JP2006328952A JP5015562B2 (ja) | 2005-12-13 | 2006-12-06 | 貼付製剤 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2007069662A1 true WO2007069662A1 (ja) | 2007-06-21 |
Family
ID=38162965
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2006/324875 WO2007069662A1 (ja) | 2005-12-13 | 2006-12-13 | 貼付製剤 |
Country Status (7)
Country | Link |
---|---|
US (1) | US20090169603A1 (ja) |
EP (1) | EP1961415A4 (ja) |
JP (1) | JP5015562B2 (ja) |
KR (1) | KR101166599B1 (ja) |
CN (1) | CN101330908B (ja) |
CA (1) | CA2633027C (ja) |
WO (1) | WO2007069662A1 (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008102880A1 (ja) * | 2007-02-23 | 2008-08-28 | Nichiban Company Limited | 抗真菌症用貼付剤 |
WO2011105457A1 (ja) * | 2010-02-26 | 2011-09-01 | 日東電工株式会社 | 貼付製剤 |
JP2011195565A (ja) * | 2010-02-26 | 2011-10-06 | Nitto Denko Corp | ビソプロロール含有貼付製剤 |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP5058531B2 (ja) * | 2005-09-09 | 2012-10-24 | 日東電工株式会社 | ビソプロロール含有貼付製剤 |
JP4945228B2 (ja) * | 2005-12-13 | 2012-06-06 | 日東電工株式会社 | ビソプロロール含有貼付製剤 |
BRPI0807662A2 (pt) * | 2007-03-08 | 2014-06-10 | Nitto Denko Corp | Dispositivo de administração percutânea de bisoprolol |
CN101862478B (zh) * | 2010-06-12 | 2013-01-02 | 上海交通大学医学院附属新华医院 | 一种具有药物温敏控释作用支架的制备方法 |
KR102071744B1 (ko) * | 2012-09-21 | 2020-01-30 | 닛토덴코 가부시키가이샤 | 부착제 또는 부착 제제용 지지체 및 그것을 사용한 부착제 및 부착 제제 |
JP5925903B2 (ja) * | 2012-10-11 | 2016-05-25 | 久光製薬株式会社 | 貼付剤 |
US20160354322A1 (en) | 2014-01-31 | 2016-12-08 | Hisamitsu Pharmaceutical Co., Inc. | Emedastine-Containing Tape Preparation |
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JPH04321624A (ja) * | 1991-04-19 | 1992-11-11 | Hisamitsu Pharmaceut Co Inc | 消炎鎮痛貼付剤 |
JPH0733665A (ja) * | 1993-05-18 | 1995-02-03 | Kanebo Ltd | エメダスチンを含有する粘着性貼付剤 |
JP2002542277A (ja) * | 1999-04-22 | 2002-12-10 | エルティエス ローマン テラピー−ズュステーメ アーゲー | 中和されたアクリル性粘着パッチを備えた経皮治療システム |
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US20040142024A1 (en) | 1999-07-27 | 2004-07-22 | Hisamitsu Pharmaceutical Co., Inc. | Patch formulation for external use |
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JP2005023088A (ja) | 1995-06-07 | 2005-01-27 | Noven Pharmaceuticals Inc | 室温で液体である低分子量薬を含む経皮組成物 |
WO2005072716A1 (ja) * | 2004-01-30 | 2005-08-11 | Hisamitsu Pharmaceutical Co., Inc. | 貼付剤入り包装袋 |
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-
2006
- 2006-12-06 JP JP2006328952A patent/JP5015562B2/ja not_active Expired - Fee Related
- 2006-12-13 KR KR1020087016979A patent/KR101166599B1/ko active IP Right Grant
- 2006-12-13 US US12/097,220 patent/US20090169603A1/en not_active Abandoned
- 2006-12-13 CN CN2006800468551A patent/CN101330908B/zh not_active Expired - Fee Related
- 2006-12-13 CA CA2633027A patent/CA2633027C/en active Active
- 2006-12-13 WO PCT/JP2006/324875 patent/WO2007069662A1/ja active Application Filing
- 2006-12-13 EP EP06834630A patent/EP1961415A4/en not_active Withdrawn
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JPH04321624A (ja) * | 1991-04-19 | 1992-11-11 | Hisamitsu Pharmaceut Co Inc | 消炎鎮痛貼付剤 |
JPH0733665A (ja) * | 1993-05-18 | 1995-02-03 | Kanebo Ltd | エメダスチンを含有する粘着性貼付剤 |
JP2005023088A (ja) | 1995-06-07 | 2005-01-27 | Noven Pharmaceuticals Inc | 室温で液体である低分子量薬を含む経皮組成物 |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008102880A1 (ja) * | 2007-02-23 | 2008-08-28 | Nichiban Company Limited | 抗真菌症用貼付剤 |
WO2011105457A1 (ja) * | 2010-02-26 | 2011-09-01 | 日東電工株式会社 | 貼付製剤 |
JP2011195565A (ja) * | 2010-02-26 | 2011-10-06 | Nitto Denko Corp | ビソプロロール含有貼付製剤 |
US9326952B2 (en) | 2010-02-26 | 2016-05-03 | Nitto Denko Corporation | Adhesive skin patch |
Also Published As
Publication number | Publication date |
---|---|
CA2633027C (en) | 2012-01-10 |
JP2007186500A (ja) | 2007-07-26 |
EP1961415A1 (en) | 2008-08-27 |
CN101330908B (zh) | 2011-01-12 |
CA2633027A1 (en) | 2007-06-21 |
KR20080079311A (ko) | 2008-08-29 |
US20090169603A1 (en) | 2009-07-02 |
CN101330908A (zh) | 2008-12-24 |
JP5015562B2 (ja) | 2012-08-29 |
KR101166599B1 (ko) | 2012-07-18 |
EP1961415A4 (en) | 2013-02-27 |
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