JP2007145920A - Method for antisepticizing aqueous emulsion type adhesive for medical treatment - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for antisepticizing an aqueous emulsion type adhesive for medical treatments, by which the aqueous emulsion type adhesive substantially not containing an antiseptic, having excellent adhesiveness to the surfaces of the skins, little irritating the skins and safe for human bodies can be antisepticised, while solving problems found in the aqueous emulsion type adhesive for the medical treatments. <P>SOLUTION: This method for preserving the aqueous emulsion type adhesive for the medical treatments, containing a resin emulsion having an average particle diameter of 80 to 150 nm as an adhesive resin and substantially not containing an antiseptic at a temperature of 1 to 12°C. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for preserving a medical aqueous emulsion-type pressure-sensitive adhesive used for forming a pressure-sensitive adhesive layer of a patch used for application to a human skin in the medical field.

Medical adhesives are used in the field of medicine for emergency bandages, surgical tapes, dressing tapes, haps, transdermal absorbents, and the like. In recent years, in medical adhesives, there is a demand for a shift from solvent-based adhesives to water-based adhesives in order to reduce environmental problems, resource saving, and skin irritation. As for the aqueous pressure-sensitive adhesive, for example, JP-A-9-87172 (Patent Document 1) contains a cross-linked product of polyacrylic acid and polyacrylic acid salt as an aqueous pressure-sensitive adhesive composition with little skin irritation. In an aqueous adhesive base, polyacrylic acid and / or polyacrylate having a weight average molecular weight of 50,000 to 300,000 and polyacrylic acid and / or polyacrylate having a weight average molecular weight of 500,000 to 2,000,000 An aqueous pressure-sensitive adhesive composition characterized by being used in combination is disclosed.
Japanese Patent Laying-Open No. 2003-64336 (Patent Document 2) discloses an aqueous emulsion acrylic pressure-sensitive adhesive having excellent skin adhesiveness.
As a water-based pressure-sensitive adhesive composition, for example, in the case of a water-soluble pressure-sensitive adhesive mainly composed of polyacrylic acid, sufficient adhesive strength cannot be obtained, and its use is limited to use as a haptic agent, and water-resistant skin adhesive strength is required. It cannot be used for other purposes. On the other hand, the water-based emulsion type adhesive is excellent in adhesiveness to the skin surface, but the surfactant essential for the production of the water-based emulsion type adhesive is a nutrient source when bacteria are mixed, There is a problem that bacteria grow after the production of the adhesive, leading to spoilage.

As for the water-based emulsion type adhesive, it is known that a method for preventing decay due to bacterial contamination by adding a preservative is effective for those used for medical purposes other than medical use.
These preservatives include halogen-based, imidazole-based, thiazole-based, pyridine-based, imide-based, sulfamide-based, nitrogen-sulfur-based compounds, etc., but problems remain with regard to skin irritation and human safety. . Some paraben compounds, inorganic compounds and natural products with low skin irritation have antiseptic action, but when these are used in aqueous emulsion adhesives, there is a problem that sufficient antiseptic effects are not observed. .
The term “preservative” as used in the present invention is a substance for the purpose of bacteriostatic action to suppress the growth of microorganisms, and is intended to prevent product deterioration, odor, mold generation, etc. that can be caused by microorganisms. Refers to a drug formulated as
JP-A-9-87172 JP 2003-64336 A

  The present invention solves the above-mentioned problems found in aqueous emulsion pressure-sensitive adhesives used for medical purposes, is substantially free of preservatives, has excellent adhesion to the skin surface, low skin irritation, and is safe for the human body. An object of the present invention is to provide a method for preserving an aqueous emulsion-type pressure-sensitive adhesive.

As a result of intensive studies to solve the above problems, the present inventors have completed the present invention.
That is, the present invention comprises a resin emulsion having an average particle diameter of 80 to 150 nm as an adhesive resin, and a medical aqueous emulsion adhesive that contains substantially no preservative at a temperature of 1 to 20 ° C. It relates to the method of saving.

  Moreover, this invention contains the resin emulsion which is 80-150 nm in average particle diameter as an adhesive resin, and is medical aqueous emulsion type adhesive which does not contain a preservative substantially at the temperature of 1-20 degreeC. It relates to the method of transport.

  Furthermore, the present invention comprises a resin emulsion having an average particle size of 80 to 150 nm as an adhesive resin, and stores and / or transports a medical aqueous emulsion adhesive that does not substantially contain a preservative. Furthermore, the present invention relates to a method for preserving an aqueous medical emulsion pressure-sensitive adhesive, characterized in that the environmental temperature and the temperature of the medical aqueous emulsion pressure-sensitive adhesive are 1 to 20 ° C.

  According to the present invention, it is possible to provide a method for preserving a medical aqueous emulsion adhesive that is excellent in skin adhesiveness, has low skin irritation, and is safe for the human body even though it contains substantially no preservative. became.

It is important that the medical aqueous emulsion-type pressure-sensitive adhesive used in the present invention is composed of a resin emulsion having an average particle size of 80 to 150 nm as the pressure-sensitive adhesive resin, and is preferably in the range of 100 to 120 nm. When the average particle diameter is smaller than 80 nm, the viscosity of the resin emulsion becomes too high and the productivity is remarkably lowered. When it exceeds 150 nm, the resistance of the resulting adhesive layer to sweat, skin secretions, and the like decreases, and the skin adhesiveness decreases.
Furthermore, the size of a general bacterium is about 1 to 3 μm, and it is presumed that the effect of suppressing the growth of bacteria by adsorbing emulsion particles on the bacterium surface decreases when the average particle diameter exceeds 150 nm.
Note that a general aqueous emulsion-type pressure-sensitive adhesive has an average particle diameter of about 500 nm, and there is almost no effect of inhibiting bacterial growth by the emulsion particles.

It is important to store and transport a medical aqueous emulsion-type pressure-sensitive adhesive containing a resin emulsion having an average particle size of 80 to 150 nm, which contains substantially no preservative, in the range of 1 to 20 ° C. It is preferable that it is the range of 5-15 degreeC. When the temperature is lower than 1 ° C., the emulsion may be frozen and broken. When the temperature is higher than 20 ° C., the bacteria grow and decay.
As a method of storing and transporting at a temperature of 1 to 20 ° C., a method of storing in a warehouse equipped with a cooler and an environmental temperature of 1 to 20 ° C., or a cold insulation with an environmental temperature of 1 to 20 ° C. Transportation by car is effective. The resin emulsion constituting the medical aqueous emulsion type pressure-sensitive adhesive used in the present invention is, for example, by a conventionally known emulsion polymerization method in which a monomer is radically polymerized in the presence of water, a surfactant and a polymerization initiator. can get.
In the present invention, an aqueous emulsion acrylic resin obtained by known emulsion polymerization is preferably used as the adhesive resin having good skin adhesiveness.

As a main monomer for obtaining an aqueous emulsion acrylic resin, (a) (meth) acrylic acid alkyl ester having 4 to 12 carbon atoms of alkyl group is preferably used. Examples of the alkyl group include butyl group and pentyl. (Meth) acrylic acid alkyl ester to which an alkyl group having 4 to 12 carbon atoms such as a hexyl group, a hexyl group, a nonyl group, an octyl group, a decyl group, or a dodecyl group is bonded can be used, and these alkyl groups are linear. Or it may be branched. Among these, more preferable monomers include 2-ethylhexyl acrylate and isooctyl acrylate, and 2-ethylhexyl acrylate is particularly preferable.
These monomers are contained in an amount of 60 to 98.5% by weight in a total of 100% by weight of the monomers, and can be used alone or in combination of two or more.

The monomer (a) is copolymerized with (b) a (meth) acrylic acid alkyl ester having 1 to 4 carbon atoms in the alkyl group and (c) an ethylenically unsaturated monomer having a carboxyl group. Is preferred. As the monomer (b), (meth) acrylic acid alkyl ester to which an alkyl group having 1 to 4 carbon atoms such as methyl group, ethyl group, propyl group, butyl group and isobutyl group is bonded can be used. These alkyl groups may be linear or branched. Of these, methyl methacrylate is particularly preferred. These monomers (b) are contained in an amount of 1 to 30% by weight in a total of 100% by weight of the monomers, and can be used alone or in combination of two or more.
As the monomer (c), that is, an ethylenically unsaturated monomer having a carboxyl group, acrylic acid, methacrylic acid, maleic acid, fumaric acid, itaconic acid and the like can be used, and acrylic acid is particularly preferable. These monomers (c) are contained in an amount of 0.5 to 10% by weight in a total of 100% by weight of the monomers, and can be used alone or in combination of two or more.
Furthermore, if necessary, a monomer having an alcoholic hydroxyl group that does not affect skin irritation, a monomer having a carbonyl group, a polyfunctional monomer, or the like can be used.
When obtaining the aqueous emulsion acrylic resin used in the present invention, as a method of controlling the particle size of the emulsion, a method of increasing the amount of surfactant used during polymerization, a method of charging a surfactant in a reaction vessel in advance, a single amount A method of previously charging the body emulsion into the reaction flask can be employed.

  As the surfactant used in obtaining the aqueous emulsion acrylic resin of the present invention, a reactive surfactant, a non-reactive surfactant, etc. can be used alone or in combination of two or more. In view of the properties, it is preferable to use a reactive surfactant.

The following compounds can be illustrated as a reactive surfactant.
Examples of anionic surfactants include “Aqualon KH-05, KH-10” manufactured by Daiichi Kogyo Seiyaku Co., Ltd., “Adekalia Soap SR-10N” manufactured by Asahi Denka Kogyo Co., Ltd. Examples include “KAYARAD” manufactured by Nippon Kayaku Co., Ltd. having an ester skeleton.

  Among the reactive surfactants, nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene phenyl ethers, sorbitan higher fatty acid esters, and glycerin higher fatty acid esters at the molecular ends or in the middle. Examples thereof include those having a heavy bond and capable of copolymerizing with a monomer. For example, “Adekaria Soap NE-10” manufactured by Asahi Denka Kogyo Co., Ltd., “Aqualon RN-10, RN-20, RN-50” manufactured by Daiichi Kogyo Seiyaku Co., Ltd., “Antox manufactured by Nippon Emulsifier Co., Ltd.” NA-16 "and the like.

When obtaining an aqueous emulsion acrylic resin, it is possible to use a non-reactive surfactant in combination as long as it does not interfere with the skin adhesive force.
Examples of the non-reactive surfactant include “New Coal 2360”, “RA-9614”, “RA-9607” and the like manufactured by Nippon Emulsifier Co., Ltd. Such a non-reactive surfactant is preferably used in a proportion of 50% by weight or less in a total amount of 100% by weight of the surfactant.

  As the polymerization initiator used in the present invention, a persulfate such as potassium persulfate or ammonium persulfate, or a water-soluble thermal decomposition polymerization catalyst such as an azobis cation salt or a hydroxylated substance, or a redox polymerization catalyst may be used. Can do. The redox polymerization catalyst includes a combination of an organic peroxide such as t-butyl hydroperoxide, benzoyl peroxide, cumene hydroperoxide and a reducing agent such as Rongalite, sodium metabisulfite, or potassium persulfate or ammonium persulfate. And Rongalite, a combination of sodium thiosulfate and ascorbic acid.

  Further, in the case of emulsion polymerization, various chain transfer agents can be used in order to control the molecular weight and molecular weight distribution of the resulting aqueous emulsion acrylic resin. As the chain transfer agent, mercaptan-based, thioglycol-based, β-mercaptopropionic acid-based alkyl esters, and the like can be used. The amount used is preferably 0.01 to 0.3 parts by weight, more preferably 0.05 to 0.2 parts by weight, based on 100 parts by weight of the total amount of monomers.

Next, the medical aqueous emulsion type adhesive used in the present invention will be described.
The medical aqueous emulsion-type pressure-sensitive adhesive comprises the above-mentioned aqueous emulsion acrylic resin as a main component, and this aqueous emulsion acrylic resin is suitable for adjusting the adhesive force while considering skin irritation as necessary. An appropriate amount of a tackifier such as rosin resin, phenol resin, polyterpene, acetylene resin, petroleum hydrocarbon resin, ethylene vinyl acetate copolymer, synthetic rubber, natural rubber, etc. can be added. Further, a viscosity modifier, an antifoaming agent, a leveling agent, a plasticizer, a filler, a neutralizing agent, a colorant, a silane coupling agent, and the like may be added.
Further, as a crosslinking agent, ethyleneimine, oxazoline, carbodiimide, zirconylammonium carbonate, an epoxy compound, and the like that can react with the functional group in the aqueous emulsion acrylic resin may be appropriately added.
The optional components added for the above various purposes are excluded from the category of the preservative of the present invention, even if they themselves exhibit a preservative effect.

  As for the medical aqueous emulsion type adhesive used in the present invention, it is preferable to use an aseptic manufacturing facility, an aseptic filling device, and an aseptic container for manufacturing, but it is not limited to these. The medical aqueous emulsion-type pressure-sensitive adhesive is preferably placed in an environment of 1 to 20 ° C. immediately after filling the container.

  The following examples further illustrate the present invention, but the present invention is not limited thereto. In the examples, “parts” means parts by weight, and “%” means percent by weight.

(Adhesive A)
88 parts of 2-ethylhexyl acrylate, 5 parts of ethyl acrylate, 2 parts of methyl methacrylate, 1 part of acrylic acid, 4 parts of methacrylic acid, 0.1 part of octyl thioglycolate as a chain transfer agent for all 100 parts of these monomers A solution prepared by dissolving 2 parts of “Aqualon KH-10” manufactured by Daiichi Kogyo Seiyaku Co., Ltd., which is a reactive ammonia neutralizing anionic surfactant, in 32 parts of ion-exchanged water was added and stirred to emulsify. Product was obtained and placed in a dropping funnel.
A four-necked flask equipped with a stirrer, a condenser, a thermometer and the above dropping funnel was charged with 75 parts of ion-exchanged water and 0.2 part of “RA-9607” manufactured by Nippon Emulsifier Co., Ltd. The inside temperature was raised to 80 ° C. while stirring with gas, and 0.1 part of a 3% aqueous potassium persulfate solution was added as a solid content.
After 5 minutes, dropping of the emulsion was started from the dropping funnel, and in parallel with this, 0.35 part of 3% potassium persulfate aqueous solution was added dropwise from another dropping port over 3 hours.
While maintaining the internal temperature at 80 ° C., 60 minutes after completion of the emulsion dropping, 0.02 parts are divided into three portions with 1% t-butyl hydroperoxide aqueous solution and 1% Rongalite aqueous solution as solids every 30 minutes. Added.
Further, the mixture was aged at 80 ° C. for 60 minutes with stirring and then cooled and neutralized with aqueous ammonia to obtain an aqueous emulsion acrylic resin having an average particle diameter of 100 nm and a solid content of 45%. The average particle size was measured with “Microtrack” manufactured by Nikkiso Co., Ltd.
To the obtained aqueous emulsion acrylic resin, 0.01 part of “Form Star A10” manufactured by Cognis Japan Co., Ltd. was added as an antifoaming agent, and 0.1 part of “Disponyl SUS875” manufactured by Cognis Japan Co., Ltd. was added as a leveling agent. Further, the pH is adjusted to 7.5 to 8 with aqueous ammonia, and the viscosity is further 3000 mPa · s (measured at 60 rpm using a BL type viscometer, # 4 rotor) with a viscosity modifier (“BR125P” manufactured by Coretex). To obtain an aqueous emulsion adhesive for medical use.

(Adhesive B)
88 parts of 2-ethylhexyl acrylate, 5 parts of ethyl acrylate, 2 parts of methyl methacrylate, 1 part of acrylic acid, 4 parts of methacrylic acid, 0.1 part of octyl thioglycolate with respect to 100 parts of these monomers, “AQUALON KH— A solution prepared by dissolving 2 parts of 10 "in 32 parts of ion-exchanged water was added and stirred to emulsify to obtain an emulsion, which was placed in a dropping funnel.
A four-necked flask equipped with a stirrer, condenser, thermometer and dropping funnel was charged with 75 parts of ion-exchanged water and 0.1 part of “RA-9607” manufactured by Nippon Emulsifier Co., Ltd. The inside temperature was raised to 80 ° C. while stirring with gas, and 0.1 part of a 3% aqueous potassium persulfate solution was added as a solid content.
After 5 minutes, dropping of the emulsion was started from the dropping funnel, and in parallel with this, 0.35 part of 3% potassium persulfate aqueous solution was added dropwise from another dropping port over 3 hours.
While maintaining the internal temperature at 80 ° C., 60 minutes after completion of the emulsion dropping, 0.02 parts are divided into three portions with 1% t-butyl hydroperoxide aqueous solution and 1% Rongalite aqueous solution as solids every 30 minutes. Added.
The mixture was further aged at 80 ° C. for 60 minutes with stirring and then cooled and neutralized with aqueous ammonia to obtain an aqueous emulsion acrylic resin having an average particle size of 150 nm and a solid content of 45%. To the obtained aqueous emulsion acrylic resin, 0.01 part of “Form Star A10” manufactured by Cognis Japan Co., Ltd. was added as an antifoaming agent, and 0.1 part of “Disponyl SUS875” manufactured by Cognis Japan Co., Ltd. was added as a leveling agent. Further, the pH is adjusted to 7.5 to 8 with aqueous ammonia, and the viscosity is further 3000 mPa · s (measured at 60 rpm using a BL type viscometer, # 4 rotor) with a viscosity modifier (“BR125P” manufactured by Coretex). To obtain an aqueous emulsion adhesive for medical use.

(Adhesive C)
88 parts of 2-ethylhexyl acrylate, 5 parts of ethyl acrylate, 2 parts of methyl methacrylate, 1 part of acrylic acid, 4 parts of methacrylic acid, 0.1 part of octyl thioglycolate with respect to 100 parts of these monomers, “AQUALON KH— A solution prepared by dissolving 2 parts of 10 "in 32 parts of ion-exchanged water was added and stirred to emulsify to obtain an emulsion, which was placed in a dropping funnel.
A four-necked flask equipped with a stirrer, a condenser, a thermometer and the above dropping funnel was charged with 75 parts of ion-exchanged water and 0.05 part of “RA-9607” manufactured by Nippon Emulsifier Co., Ltd. The inside temperature was raised to 80 ° C. while stirring with gas, and 0.1 part of a 3% aqueous potassium persulfate solution was added as a solid content.
After 5 minutes, dropping of the emulsion was started from the dropping funnel, and in parallel with this, 0.35 part of 3% potassium persulfate aqueous solution was added dropwise from another dropping port over 3 hours.
While maintaining the internal temperature at 80 ° C., 60 minutes after completion of the emulsion dropping, 0.02 parts are divided into three portions with 1% t-butyl hydroperoxide aqueous solution and 1% Rongalite aqueous solution as solids every 30 minutes. Added.
The mixture was further aged at 80 ° C. for 60 minutes with stirring and then cooled and neutralized with aqueous ammonia to obtain an aqueous emulsion acrylic resin having an average particle size of 200 nm and a solid content of 45%.
To the obtained aqueous emulsion acrylic resin, 0.01 part of “Form Star A10” manufactured by Cognis Japan Co., Ltd. was added as an antifoaming agent, and 0.1 part of “Disponyl SUS875” manufactured by Cognis Japan Co., Ltd. was added as a leveling agent. Further, the pH is adjusted to 7.5 to 8 with aqueous ammonia, and the viscosity is further 3000 mPa · s (measured at 60 rpm using a BL type viscometer, # 4 rotor) with a viscosity modifier (“BR125P” manufactured by Coretex). To obtain an aqueous emulsion-type pressure-sensitive adhesive.

Example 1
After measuring the number of bacteria after 1 month storage of medical aqueous emulsion-type PSA A immediately in containers 10 ° C. after production, dry coating amount peelable sheet with a comma coater to 25 g / m ² Then, it was dried in a drying oven at 100 ° C. for 60 seconds, laminated with a polyethylene terephthalate (PET) film having a thickness of 25 μm, and wound to obtain a pressure-sensitive adhesive coated product.
(Examples 2-4, Comparative Examples 1-4)
As shown in Table 1, the type or storage temperature of the water-based emulsion type adhesive was changed.

[Test method]
(1) Adhesive strength The adhesive coated product was cut into a strip with a width of 9 mm, the release paper was peeled off, attached to a phenolic resin laminate in an atmosphere at 23 ° C., measured once 20 minutes after reciprocating with a 2 kg roll. It was used for. The adhesive strength was measured when peeled in the 90 ° direction at a speed of 300 mm / min in an atmosphere of 23 ° C.

(2) Adhesive residue Attached to the skin of the human body and peeled off after 6 hours, and whether the adhesive remained on the skin was visually evaluated.
○: No adhesive residue.
X: There is adhesive residue.

(3) Bacterial evaluation Culture medium: Standard agar medium The adhesive sample was diluted with physiological saline to prepare a preparation (10-fold dilution series), and 1 ml thereof was poured into a sterilized petri dish. Thereafter, 15-20 ml of culture medium was poured into a petri dish and solidified. The petri dish was inverted and cultured in a funnel at 35 ° C. for 48 hours to evaluate whether colonies were generated in the petri dish (n = 2).

  The test results are shown in Table 1.

As shown in Table 1, in Comparative Examples 1 to 4, bacterial growth is observed. In contrast, in each of the examples, the skin adherence is excellent, and the growth of bacteria is not recognized even though no preservative is used.

Claims (3)

A method of storing a medical aqueous emulsion type pressure-sensitive adhesive containing a resin emulsion having an average particle size of 80 to 150 nm as an adhesive resin and containing substantially no preservative at a temperature of 1 to 20 ° C. A method of transporting a medical aqueous emulsion pressure-sensitive adhesive comprising a resin emulsion having an average particle size of 80 to 150 nm as an adhesive resin and containing substantially no preservative at a temperature of 1 to 20 ° C. When storing and / or transporting a medical aqueous emulsion type adhesive comprising a resin emulsion having an average particle size of 80 to 150 nm as an adhesive resin and containing substantially no preservative, the environmental temperature and the medical A method for preserving an aqueous emulsion adhesive for medical use, characterized in that the temperature of the aqueous emulsion adhesive for medical use is set to 1 to 20 ° C.