Composition for foam formation, foam, and medical material

Abstract

This composition for foam formation includes a urethane prepolymer and a drug, wherein the viscosity of the urethane prepolymer is 10,000 mPa·s or less. This foam is obtained by foaming and curing said composition for foam formation. This medical material comprises said foam.

Description

Foam-forming composition, foam, and medical device

[0001] The present disclosure relates to a foam-forming composition, a foam, and a medical device.

[0002] Foams such as polyurethane are used for medical purposes. For example, polyurethane foams loaded with drugs have absorbency and drug release properties, and are therefore used in antigen testing kits and antibacterial covering materials to prevent catheter infections.

[0003] A polyurethane foam carrying a drug can be produced by forming a foam from an isocyanate-terminated prepolymer, immersing the foam in an aqueous solution containing the drug, and drying it. In recent years, because the above-mentioned step of immersing the foam in the drug is complicated, a technique has been disclosed in which the drug is added to a foam-forming composition and then molded (for example, Patent Document 1).

[0004] Special Publication No. 2007-520614

[0005] However, with the technology of Patent Document 1, in the process of producing a foam, molding of the foam may be difficult due to poor stirring of the foam-forming composition, poor foaming, etc.

[0006] Therefore, an object of the present disclosure is to provide a foam-forming composition that can simplify the manufacturing process and improve the moldability of the foam; a foam obtained by foaming and curing the foam-forming composition; and a medical device that includes the foam.

[0007] One aspect of the present disclosure is a foam-forming composition, the foam-forming composition comprising a urethane prepolymer and an agent, wherein the urethane prepolymer has a viscosity of 10,000 mPa·s or less.

[0008] Another aspect of the present disclosure is a foam obtained by foaming and curing the foam-forming composition of the above aspect.

[0009] In the foam of the above embodiment, the density is 300 kg / m ３ It is preferable that:

[0010] Another aspect of the present disclosure is a foam. The foam contains a urethane foam and a drug, and the drug concentration in the extract 1 hour after the start of stirring is 80% by mass or less relative to the drug concentration in the extract 24 hours after the start of stirring, as measured by the following drug sustained release test. (Drug sustained release test) (1) The extract is added to the foam and stirred at 20°C. (2) One hour after the start of stirring, the drug concentration in the extract is measured by high-performance liquid chromatography (HPLC). (3) Steps (1) and (2) are repeated in the same manner, except that the stirring time is changed to 24 hours.

[0011] Another aspect of the present disclosure is a medical device, the medical device comprising the foam of the above aspect.

[0012] According to the present disclosure, it is possible to provide a foam-forming composition that can simplify the manufacturing process and improve the moldability of the foam; a foam obtained by foaming and curing the foam-forming composition; and a medical device that includes the foam.

[0013] 1 is a graph showing the relationship between each stirring time and the drug release rate of the foam of the example.

[0014] In this specification, the expression "a to b" in the description of a range of values ​​means that the range is from a to b, unless otherwise specified.

[0015] In this specification, when multiple upper limit values ​​and multiple lower limit values ​​are separately described, all numerical ranges that can be set by freely combining these upper limit values ​​and lower limit values ​​are considered to be described in this specification.

[0016] In this specification, when a compound is described, its isomers are also described.

[0017] In this specification, the number average molecular weight is measured by gel permeation chromatography (GPC) (for example, gel permeation chromatography according to ASTM standard test D5296) using polystyrene as a standard polymer.

[0018] In this specification, each viscosity is an E-type viscosity measured in accordance with JIS Z8803:2011 "Method for measuring viscosity of liquids" using a cone-and-plate rotational viscometer.

[0019] The foam-forming composition, foam, uses, etc. of this embodiment will be described in detail below.

[0020] 1. Foam-forming composition The foam-forming composition of this embodiment contains a urethane prepolymer and a chemical. The foam-forming composition may also contain other components. The components and physical properties of the foam-forming composition and the properties of the urethane prepolymer are described below.

[0021] 1-1. Components 1-1-1. Urethane Prepolymer Urethane prepolymers are obtained by a urethane reaction between a polyol compound and a polyisocyanate compound. In other words, urethane prepolymers are reaction products of polyol compounds and polyisocyanate compounds. More specifically, urethane prepolymers are usually isocyanate-terminated urethane prepolymers obtained by a urethane reaction between a polyol compound and a polyisocyanate compound in such a way that the polyisocyanate compound is in excess.

[0022] (Polyol Compound) A polyol compound is a compound having two or more hydroxyl groups in one molecule. The polyol compound is not particularly limited and can be freely selected in consideration of the desired properties of the polyurethane foam. Various polyol compounds may be used alone or in combination of two or more. The polyol compound can be freely selected in consideration of the desired properties of the polyurethane.

[0023] Examples of polyol compounds include polyester polyols, polycarbonate polyols, polyether polyols, polyester ether polyols, etc. They can be freely selected in consideration of the desired properties of the foam.

[0024] Examples of polyester polyols include aliphatic dicarboxylic acids such as succinic acid, adipic acid, sebacic acid, and azelaic acid; aromatic dicarboxylic acids such as phthalic acid, terephthalic acid, isophthalic acid, and naphthalenedicarboxylic acid; alicyclic dicarboxylic acids such as hexahydrophthalic acid, hexahydroterephthalic acid, and hexahydroisophthalic acid; and acid esters or acid anhydrides thereof, with ethylene glycol, 1,3-propylene glycol, 1,2-propylene glycol, Examples include polyester polyols such as polypropylene glycol obtained by a dehydration condensation reaction with 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 3-methyl-1,5-pentanediol, neopentyl glycol, 1,8-octanediol, 1,9-nonanediol, or a mixture thereof; and polylactone diols obtained by ring-opening polymerization of lactone monomers such as ε-caprolactone and methylvalerolactone.

[0025] Examples of polycarbonate polyols include those obtained by reacting at least one polyhydric alcohol such as ethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 3-methyl-1,5-pentanediol, neopentyl glycol, 1,8-octanediol, 1,9-nonanediol, or diethylene glycol with diethylene carbonate, dimethyl carbonate, diethyl carbonate, or the like.

[0026] Examples of polyether polyols include polyethylene glycol (PEG), polypropylene glycol, polytetramethylene ether glycol, etc., which are obtained by polymerizing cyclic ethers such as ethylene oxide (EO), propylene oxide, tetrahydrofuran, etc., and copolyethers thereof. Polyether polyols can also be obtained by polymerizing the above-mentioned cyclic ethers using polyhydric alcohols such as glycerin and trimethylolethane.

[0027] Examples of polyester ether polyols include those obtained by a dehydration condensation reaction of aliphatic dicarboxylic acids such as succinic acid, adipic acid, sebacic acid, and azelaic acid; aromatic dicarboxylic acids such as phthalic acid, terephthalic acid, isophthalic acid, and naphthalenedicarboxylic acid; alicyclic dicarboxylic acids such as hexahydrophthalic acid, hexahydroterephthalic acid, and hexahydroisophthalic acid; or acid esters or acid anhydrides of these with glycols such as diethylene glycol or propylene oxide adducts, or mixtures thereof.

[0028] The polyol compounds can be used alone or in combination.

[0029] The polyol compound is preferably a diol and / or a triol.

[0030] The polyol compound preferably contains a copolymer of ethylene oxide (EO) and alkylene oxide (AO), more preferably a random copolymer (random polyether polyol). Note that the alkylene oxide (AO) shown here refers to an alkylene oxide other than ethylene oxide (EO).

[0031] Random polyether polyols contain ethylene oxide (EO). Here, the term "random" in random polyether polyol refers to a random copolymer. That is, random polyether polyol refers to a polyether polyol in which ethylene oxide and propylene oxide are randomly copolymerized. Note that polyether polyols in which ethylene oxide and propylene oxide are block copolymerized are referred to as block polyether polyols.

[0032] The content of the random polyether polyol in all polyol compounds constituting the urethane prepolymer is preferably 30% by mass or more, 35% by mass or more, 40% by mass or more, 45% by mass or more, or 50% by mass or more.

[0033] The random polyether polyol preferably has a proportion of ethylene oxide per molecule (hereinafter sometimes referred to as the random polyether polyol EO content or EO content) of 20.0 mass % or more, 25.0 mass % or more, 30.0 mass % or more, etc. By including a random polyether polyol with an EO content within this range as the polyol compound, it becomes easier to adjust the EO content of the urethane prepolymer, and a foam with excellent hydrophilicity can be obtained.

[0034] The random polyether polyol preferably contains a diol compound and a triol compound.

[0035] The average number of functional groups of hydroxyl groups in the whole random polyether polyol is not particularly limited, but is preferably more than 2.0 and less than 3.0, or 2.4 to 2.7. When the average number of functional groups of hydroxyl groups in the whole random polyether polyol is within this range, a foam having excellent water absorbency and the like can be obtained.

[0036] The polyol compound preferably has a number average molecular weight of 200 to 5,000, 300 to 4,500, 400 to 4,000, etc. When the number average molecular weight of the polyol compound is within this range, the number average molecular weight of the urethane prepolymer falls within an appropriate range, making molding easy and enabling the production of a foam with excellent water absorbency.

[0037] The raw material for the urethane prepolymer may contain a monool other than the polyol as an alcohol component, as long as the effect of the invention is not impaired.

[0038] (Polyisocyanate Compound) The polyisocyanate compound is a compound having two or more isocyanate groups in one molecule. There are no particular limitations on the polyisocyanate compound, so long as it is a compound that is normally used as a raw material for urethane prepolymers, and it can be freely selected in consideration of the desired foam properties.

[0039] The polyisocyanate compound may be used alone or in combination of two or more kinds. The polyisocyanate compound may be bifunctional, trifunctional or higher functional.

[0040] Examples of bifunctional polyisocyanate compounds include 2,4-toluene diisocyanate (2,4-TDI), 2,6-toluene diisocyanate (2,6-TDI), m-phenylene diisocyanate, p-phenylene diisocyanate, 4,4'-diphenylmethane diisocyanate (4,4'-MDI), 2,4'-diphenylmethane diisocyanate (2,4'-MDI), 2,2'-diphenylmethane diisocyanate (2,2'-MDI), hydrogenated MDI, xylylene diisocyanate, 3,3'-dimethyl-4,4'-biphenylene diisocyanate, and 3,3'-dimethoxy-4,4'-biphenylene diisocyanate. aromatic isocyanates such as cyclohexane-1,4-diisocyanate, isophorone diisocyanate, dicyclohexylmethane-4,4'-diisocyanate, and methylcyclohexane diisocyanate; and alkylene isocyanates such as butane-1,4-diisocyanate, hexamethylene diisocyanate, isopropylene diisocyanate, methylene diisocyanate, and lysine diisocyanate.

[0041] Examples of tri- or higher functional polyisocyanate compounds include 1-methylbenzene-2,4,6-triisocyanate, 1,3,5-trimethylbenzene-2,4,6-triisocyanate, biphenyl-2,4,4'-triisocyanate, diphenylmethane-2,4,4'-triisocyanate, methyldiphenylmethane-4,6,4'-triisocyanate, 4,4'-dimethyldiphenylmethane-2,2',5,5'tetraisocyanate, triphenylmethane-4,4',4"-triisocyanate, polymeric MDI, lysine ester triisocyanate, 1,3,6-hexamethylene triisocyanate, 1,6,11-undecane triisocyanate, bicycloheptane triisocyanate, and 1,8-diisocyanatomethyloctane.

[0042] The polyisocyanate compound may also include modified products and derivatives thereof.

[0043] The polyisocyanate compounds can be used alone or in combination.

[0044] The polyisocyanate preferably contains an aliphatic isocyanate. More specifically, the aliphatic isocyanate preferably accounts for 50% by mass or more, 60% by mass or more, 70% by mass or more, 80% by mass or more, or 90% by mass or more of the total polyisocyanate constituting the urethane prepolymer.

[0045] The amount of polyisocyanate can be adjusted so that the average functionality of the hydroxyl groups in the polyol and the NCO% of the urethane prepolymer fall within desired ranges. For example, the amount of polyisocyanate can be 10 to 40% by mass or 20 to 35% by mass, where the total amount of polyol and polyisocyanate is 100% by mass.

[0046] 1-1-2. Chemicals The chemicals used in this embodiment are not particularly limited and can be appropriately selected from known chemicals depending on the intended use of the foam.

[0047] Examples of the drug are not particularly limited as long as they have antibacterial, disinfecting, bactericidal, antiseptic properties, etc., and include, for example, inorganic drugs whose main component is a metal element such as gold, platinum, silver, silver oxide, copper, copper oxide, zinc oxide, cobalt, nickel, zirconium, palladium, or tungsten; 2-chloro-6-trichloromethylpyridine, 2-chloro-4-trichloromethyl-6-methoxypyridine, 2-chloro-4-trichloromethyl-6-(2-furylmethoxy)pyridine, di(4-chlorophenyl)pyridylmethanol, 2,3,5-trichloro-4-(n-propylsulfonyl)pyridine, 2-pyridylthiol-1-oxo- Examples of the anti-inflammatory agent include 2-pyridylthiol-1-oxide metal salts such as copper cid, zinc 2-pyridylthiol-1-oxide, and sodium 2-pyridylthiol-1-oxide; pyridine compounds such as di(2-pyridylthiol-1-oxide); guanidine compounds such as polyhexamethylene guanidine salts and chlorhexidine salts; phenolic compounds such as 3-methyl-4-isopropylphenol and 2-isopropyl-5-methylphenol; quaternary ammonium salt compounds; organic nitrogen-sulfur compounds; and organic agents such as imidazole compounds; and the like, and these can be used alone or in combination of two or more.

[0048] Among the above, organic agents are preferred, and guanidine compounds are more preferred. Among guanidine compounds, chlorhexidine salts are more preferred, and chlorhexidine gluconate (CHG) is particularly preferred. Chlorhexidine gluconate exhibits rapid antibacterial activity and can be used against a wide range of bacteria.

[0049] When the content of the urethane prepolymer is taken as 100 parts by mass, the lower limit of the content of the agent is preferably 0.1 parts by mass or more, 1 part by mass or more, 3 parts by mass or more, 5 parts by mass or more, 10 parts by mass or more, etc. Furthermore, the upper limit is preferably 25 parts by mass or less, 20 parts by mass or less, 18 parts by mass or less, etc. By setting the lower limit of the content of the agent to the above-mentioned value, the antibacterial effect and other properties of the agent can be appropriately exhibited. Furthermore, by setting the upper limit of the content of the agent to the above-mentioned value, inhibition of foaming can be suppressed. Furthermore, in this embodiment, since the agent is contained in the foam-forming composition, the step of soaking the agent in the agent after foam formation can be omitted, thereby simplifying the manufacturing process.

[0050] 1-1-3. Other Components Examples of other components include resin components other than the above-mentioned urethane prepolymer and chemicals, and known additives. Examples of known additives include catalysts, pH adjusters, antifoaming agents, foam stabilizers, surfactants, antioxidants, and ultraviolet absorbers.

[0051] The content of the other components can be 30 parts by mass or less, 25 parts by mass or less, 22 parts by mass or less, etc., when the content of the urethane prepolymer is 100 parts by mass.

[0052] 1-2. Physical Properties 1-2-1. pH In the foam-forming composition of this embodiment, the pH of the foam-forming composition excluding the urethane prepolymer is preferably 7.0 or less, 6.5 or less, 6.0 or less, etc. The pH of the foam-forming composition excluding the urethane prepolymer can be adjusted with a pH adjuster (e.g., citric acid, sodium bicarbonate, etc.) described in "1-1-3. Other Components" from among the components of the foam-forming composition described above.

[0053] 1-3. Properties of Urethane Prepolymer 1-3-1. Viscosity With regard to the viscosity of the urethane prepolymer at 25°C, the lower limit is preferably 2,000 mPa·s or more, 2,500 mPa·s or more, 3,000 mPa·s or more, or 3,500 mPa·s or more. Furthermore, the upper limit is preferably 10,000 mPa·s or less, 9,000 mPa·s or less, 8,000 mPa·s or less, 7,000 mPa·s or less, or 6,000 mPa·s or less. Having the urethane prepolymer's 25°C viscosity within the above range allows the above-mentioned chemicals to be uniformly dispersed in the foam-forming composition. Furthermore, molding is facilitated, and particularly when producing long roll-molded products, it is easy to adjust the thickness and product width using a roll coater. In other words, since the thickness is highly accurate and the product can be molded to the desired width, products with superior appearance can be produced. The term "long" means that the length in the longitudinal direction is 5 m or more. There is no particular upper limit, but from the viewpoint of handling of the molded product, it is preferably 500 m or less, 100 m or less, 50 m or less, etc.

[0054] The viscosity of the urethane prepolymer can be changed by adjusting, for example, the number average molecular weight, the average number of functional groups, etc. of the urethane prepolymer.

[0055] The number average molecular weight of the urethane prepolymer is not particularly limited as long as it does not impair the effects of the invention, and is preferably, for example, 500 to 10,000, 750 to 7,500, 1,000 to 5,000, or 1,200 to 2,500. By setting the number average molecular weight within such a range, the viscosity of the foam-forming composition containing the urethane prepolymer does not become too high, making it easy to mold, and also making it possible to obtain a foam with excellent water absorbency.

[0056] 1-3-3. Average Number of Functional Groups (Number of Isocyanate Groups) The average number of functional groups (number of isocyanate groups) of the urethane prepolymer is usually 2 or more, preferably more than 2 and less than 3, and more preferably 2.2 or more and 2.7 or less.

[0057] Here, when a bifunctional polyisocyanate compound is used as the polyisocyanate compound and three types of polyol compounds, namely polyol (a), polyol (b), and polyol (c), are used, the average number of functional groups of the urethane prepolymer can be calculated by the following formula, which takes into account the number of functional groups of each of the polyols (a) to (c) contained in the entire polyol compounds used and the molar fraction of each of the polyols (a) to (c):

[0058] (Equation 1) [Average number of functional groups in urethane prepolymer]=[((Fa×Wa) / Ma)+(Fb×Wb / Mb)+(Fc×Wc / Mc)) / (Wa / Ma+Wb / Mb+Wc / Mc)]

[0059] Fa represents the number of functional groups of polyol (a), Wa represents parts by mass of polyol (a), Ma represents the number average molecular weight of polyol (a), Fb represents the number of functional groups of polyol (b), Wb represents parts by mass of polyol (b), Mb represents the number average molecular weight of polyol (b), Fc represents the number of functional groups of polyol (c), Wc represents parts by mass of polyol (c), and Mc represents the number average molecular weight of polyol (c).

[0060] 1-3-4. NCO % (Isocyanate Content) The NCO % (isocyanate content) of the urethane prepolymer is preferably 3.0 to 10.0%, more preferably 4.0 to 10.0%. By setting the NCO % of the urethane prepolymer within this range, it becomes possible to obtain a foam that is excellent in balance of properties such as water absorption when the foam is made hydrophilic.

[0061] The NCO % of the urethane prepolymer is measured in accordance with Method A (toluene / dibutylamine, hydrochloric acid method) of JIS K1603-1:2007 "Plastics - Polyurethane raw material aromatic isocyanate test method, Part 1: Determination of isocyanate group content."

[0062] 2. Foam The structure, properties, and production method of the foam of this embodiment will be described below.

[0063] 2-1. Structure The size, thickness, etc. of the foam of this embodiment are not particularly limited and can be changed appropriately depending on the application. For example, when the foam is used as a medical device, a foam formed into a sheet shape may be cut into single plates and then cut to a convenient size. The thickness of the foam is preferably 0.1 to 15 mm, more preferably 0.5 to 10 mm, and even more preferably 1.0 to 5 mm.

[0064] The foam of this embodiment may have a closed cell structure or an open cell structure.

[0065] 2-2. Physical Properties 2-2-1. Density The lower limit of the density of the foam of this embodiment is 30 kg / m ３ Above, 50kg / m ３ Above, 70kg / m ３ The upper limit is preferably 300 kg / m ３ Below 250kg / m ３ Below, 200kg / m ３ Below, 150kg / m ３ The following are preferred:

[0066] (Measurement Method) The density is measured in accordance with JIS K7222:2005 "Foamed plastics and rubber - Determination of apparent density".

[0067] The foam of the present embodiment preferably has a water absorption capacity of 8.0 g / g or more, 8.5 g / g or more, 10 g / g or more, 15 g / g or more, etc., as measured by the following method. There is no particular limitation on the upper limit.

[0068] (Measurement method) Measure the mass A of the foam in a dry state. Immerse the foam in distilled water at 25°C for 1 hour. After immersion, remove the foam from the distilled water and hang it for 20 seconds, then measure the mass B of the foam. Calculate the amount of water absorption using the following formula: (Amount of water absorption) = (Mass B - Mass A) / (Mass A)

[0069] 2-2-3. Concentration of Decomposition Products The foam of this embodiment preferably has a concentration of drug decomposition products of 0.1% by mass or less, as measured by the following method.

[0070] (Measurement method) Formic acid and acetonitrile are mixed in a mass ratio of 80:20 to synthesize an extract. The extract is added to a predetermined mass of foam and stirred for 2 hours. The concentration of the drug decomposition products in the extract is then measured by high performance liquid chromatography (HPLC).

[0071] The sustained drug release of the foam of this embodiment can be evaluated by the drug release rate (% by mass). The drug release rate is calculated using the following formula from the drug concentration in the extract after stirring the foam in the extract, which is measured using the test method described below.

[0072] (Drug sustained release test method) The extract is added to a foam of a predetermined size placed in a storage container, and stirring is initiated at 20°C. One minute after the start of stirring, the drug concentration in the extract is measured by high performance liquid chromatography (HPLC). The same procedure is repeated for 30 minutes, 1 hour, 2 hours, and 24 hours, and the drug (CHG) concentration in the extract at each stirring time is measured.

[0073] The foam of this embodiment preferably has a drug release rate (mass%) of 10% or less by mass of the drug concentration in the extract 1 minute after stirring relative to the drug concentration in the extract 24 hours after stirring, 70% or less by mass of the drug concentration in the extract 30 minutes after stirring, 80% or less by mass of the drug concentration in the extract 1 hour after stirring, and 99% or less by mass of the drug concentration in the extract 2 hours after stirring. Therefore, the foam of this embodiment can improve the sustained release of the drug.

[0074] 2-3. Manufacturing Method The foam of this embodiment can be manufactured based on a known method. For example, it can be obtained by foaming and curing the foam-forming composition described above. More specifically, the manufacturing method of the foam of this embodiment includes a step of manufacturing a urethane prepolymer, a step of preparing a raw material composition, and a foaming / curing step. Below, a preferred manufacturing method of the foam of this embodiment will be described by dividing it into each step.

[0075] 2-3-1. Urethane Prepolymer Production Process A predetermined amount of polyol compound and, if necessary, a catalyst are added dropwise to a reaction vessel containing a predetermined amount of polyisocyanate compound. The reaction vessel is then heated and stirred to react the polyisocyanate compound with the polyol compound, producing an isocyanate-terminated urethane prepolymer. The reaction temperature is not particularly limited, but is typically 50 to 120°C, preferably 60 to 100°C. The reaction time is not particularly limited, but is typically 1 to 15 hours.

[0076] The polyol compound, polyisocyanate compound, etc. are as described above in "1-1-1. Urethane prepolymer."

[0077] (Catalyst) Any known catalyst used in the production of polyurethanes can be used, including, for example, amine-based catalysts and organometallic catalysts.

[0078] Examples of the amine catalyst include triethylenediamine, diethanolamine, dimethylaminomorpholine, and N-ethylmorpholine.

[0079] Examples of organometallic catalysts include Bi catalysts such as bismuth carboxylate and bismuth octoate; Sn catalysts such as sternium octoate and dibutyltin dilaurate; and Pb catalysts such as lead octenate and lead naphthenate.

[0080] The catalysts can be used alone or in combination.

[0081] 2-3-2. Raw material composition preparation step In the raw material composition preparation step, a raw material composition containing a urethane prepolymer and, for example, chlorhexidine gluconate (CHG) as an agent is prepared. The raw material composition may contain other components (catalyst, antifoaming agent, etc.) as necessary. The urethane prepolymer, agent, and other components are as described above in "1-1-1. Urethane prepolymer," "1-1-2. Agent," and "1-1-3. Other components."

[0082] 2-3-3. Foaming / Curing Step The foaming / curing step includes first, as needed, mixing and stirring the foam-forming composition described above (stirring step), then coating the foam-forming composition on a substrate (coating step), and then, as needed, heating the foam-forming composition to complete foaming and curing and produce a foam (reaction step). Each step of the foaming / curing step will be described below.

[0083] (Stirring Step) In the stirring step, the components of the foam-forming composition are stirred so as to be uniformly mixed. If the components in the foam-forming composition are sufficiently uniform, there is no need to perform the stirring step. The stirring step can be performed using a known stirring means such as a mixer. The stirring conditions for the stirring step may be appropriately selected depending on the viscosity of the foam-forming composition, the components to be blended, etc.

[0084] (Coating Step) In the coating step, the foam-forming composition mixed in the stirring step is coated onto a substrate. The material of the substrate is not particularly limited, and known materials (PET film, silicone release film, PP laminate film, release paper, etc.) can be used.

[0085] In the coating step, the surface of the foam-forming composition opposite to the surface in contact with the substrate may be further coated with another substrate.

[0086] As the coating means, for example, known coating means such as an air knife coater, blade coater, knife coater, roll coater, cast coater, etc. Coating conditions (such as coating speed) can be appropriately adjusted depending on the desired shape of the foam, etc.

[0087] (Reaction Step) In the reaction step, the raw material composition applied to the substrate in the application step is heated to foam and cure. The reaction is usually carried out at a temperature of 15 to 120°C, preferably 15 to 90°C. The reaction time is usually 60 to 120 minutes.

[0088] The foam obtained in the reaction step may be subjected to a drying step, if necessary, such as exposing the foam to an environment of 80 to 120°C using a heating furnace, microwave oven, high-frequency induction heating, hot air drying, or the like.

[0089] After the reaction step and the production of the foam, the chemicals described in "1-1-2. Chemicals" may be applied to the surface of the foam by spraying or the like. This can further increase the concentration of the chemicals in the foam.

[0090] The foam of the present embodiment can be used in a variety of applications because it can simplify the manufacturing process and inhibit decomposition of drugs. For example, it is preferably used in medical devices such as antibacterial testing kits, antibacterial dressings, and wound dressings.

[0091] The medical device of this embodiment includes the foam described above, which simplifies the manufacturing process and improves the moldability of the foam.

[0092] The foam of the present embodiment will be specifically described below with reference to examples and comparative examples. However, the present disclosure is not limited to the following examples and can be embodied in various forms with various modifications and improvements based on the knowledge of those skilled in the art.

[0093] <Foam-forming composition> ● Urethane prepolymer ・ Random polyether polyol A (number average molecular weight: 1,250, EO content: 62 mass%, number of functional groups: 2.5) ・ Random polyether polyol B (number average molecular weight: 1,500, EO content: 70 mass%, number of functional groups: 3.0) ・ Polyethylene glycol (PEG) (number average molecular weight: 1,000) ・ Hexamethylene diisocyanate (HDI) ・ Toluene diisocyanate (TDI) ・ Bi catalyst (Bi neodecanoate) ● Chemicals ・ 20% chlorhexidine gluconate (CHG) aqueous solution {manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.} ・ 40% chlorhexidine gluconate (CHG) aqueous solution {the above 20% CHG aqueous solution has been concentrated to a concentration of 40%} ● Other ingredients ・ Foaming agent: water ・ pH adjuster: sodium bicarbonate, citric acid Foam stabilizer: Pluronic (registered trademark) L-64 manufactured by ADEKA Corporation

[0094] <Production of Urethane Prepolymer A> 48.82 parts by mass of random polyether polyol A was charged into a flask while nitrogen was flowing in through the three-way stopcock. Next, 25.40 parts by mass of hexamethylene diisocyanate (HDI) was added dropwise while stirring and nitrogen was flowing in. After the completion of the dropwise addition, 0.002 parts by mass of Bi catalyst was added while stirring for 10 minutes. After the reaction for 2 hours, 25.78 parts by mass of polyethylene glycol (PEG) was added dropwise. The resulting product was designated Urethane Prepolymer A. The number average molecular weight of Urethane Prepolymer A was 5,500, the EO content was 56.1, and the average functionality was 2.3.

[0095] <Production of Urethane Prepolymer B> 3.59 parts by mass of toluene diisocyanate was charged into a flask while nitrogen was flowing through the three-way stopcock. Next, 29.34 parts by mass of random polyether polyol B was added dropwise while stirring and nitrogen was flowing. After the completion of the addition, 0.002 parts by mass of Bi catalyst was added dropwise for 10 minutes while stirring. After reacting for 1 hour, 22.20 parts by mass of HDI was added dropwise. After reacting for 1 hour, 44.87 parts by mass of polyethylene glycol (PEG) was added dropwise. The resulting product was designated Urethane Prepolymer B. The number average molecular weight of Urethane Prepolymer B was 5,800, the EO content was 65.4, and the average functionality was 2.3.

[0096] <Evaluation of Urethane Prepolymers A and B> Each of the urethane prepolymers A and B was evaluated according to the methods described below. The evaluation results are shown in Table 1 below.

[0097] (Viscosity Measurement) The viscosity of each of the urethane prepolymers A and B at 25°C was measured as an E-type viscosity using a cone-plate rotational viscometer (RE-85R manufactured by Toki Sangyo Co., Ltd.) in accordance with JIS Z8803:2011 "Method for measuring viscosity of liquids."

[0098] (Measurement of NCO%) The NCO% of each of the urethane prepolymers A and B was measured in accordance with Method A (toluene / dibutylamine, hydrochloric acid method) of JIS K1603-1:2007 "Test methods for aromatic isocyanates used as raw materials for plastics polyurethanes, Part 1: Determination of isocyanate group content".

[0099] *In Table 1, the amounts of ingredients are expressed in parts by mass.

[0100] <Preparation of Foam> [Example 1] A foam-forming composition containing urethane prepolymer A shown in Table 2 below was stirred for 5 seconds and applied to a release-treated release paper (thickness 100 μm) at room temperature (25° C.) without heating. It was then heated under the following heating conditions to foam and cure to a thickness of 2 mm, thereby obtaining the foam of Example 1. (Heating conditions) Temperature: 60° C. Time: 1 hour

[0101] [Example 2] A foam of Example 2 was obtained in the same manner as in Example 1, except that the foaming and curing were carried out under the following heating conditions: (Heating conditions) Temperature: 80°C Time: 5 minutes

[0102] [Example 3] The foam of Example 3 was obtained in the same manner as in Example 1, except that a 40% CHG aqueous solution was used instead of the 20% CHG aqueous solution, and the mass ratio of urethane prepolymer A to the other foam-forming composition was 100:40.

[0103] Comparative Example 1 A foam of Comparative Example 1 was obtained in the same manner as in Example 1, except that urethane prepolymer B was used instead of urethane prepolymer A.

[0104] [Reference Example 1] The foam of Reference Example 1 was obtained in the same manner as in Example 3, except that the foam of Example 3 was foamed and cured by heating, and then dried under the following drying conditions: (Drying conditions) Temperature: 100°C Time: 1 hour

[0105] <Evaluation of reactivity> For the foams of each Example, Comparative Example, and Reference Example, the cream time (CT) and gel time (GT) were measured when the foam-forming composition was prepared. Cream time (CT) refers to the time from stirring to the start of foaming. Gel time (GT) refers to the time from stirring to the start of gelation. CT and GT are shown in Table 2 below.

[0106] <Calculation of CHG Content> For the foams of each Example, Comparative Example and Reference Example, the drug (CHG) content was calculated using the following formula: The drug (CHG) content is shown in Table 2 below.

[0107] <Evaluation of Foam> The foams of each of the Examples, Comparative Examples, and Reference Examples were evaluated according to the methods described below. The evaluation results are shown in Table 2 below.

[0108] (Moldability) For the foams of each Example, Comparative Example, and Reference Example, the moldability when the foam-forming composition was foamed and cured was evaluated according to the following evaluation criteria. Shrinkage refers to a change in the thickness or shape of the foam due to foaming and curing. Evaluation criteria A: Moldable and no shrinkage occurred. B: Moldable and shrinkage occurred. C: Unmoldable (due to poor stirring, poor foaming, etc.).

[0109] (Density) The density of the foams in each of the Examples, Comparative Examples, and Reference Examples was measured in accordance with JIS K7222:2005 "Foamed plastics and rubber - Determination of apparent density."

[0110] (Water absorption amount) The water absorption amount was measured for the foams of each Example, Comparative Example, and Reference Example. More specifically, the mass A of each foam sample (50 mm x 50 mm x 2 mm) in a dry state was measured. Each sample was immersed in distilled water at 25°C for 1 hour. Each sample immersed in distilled water was removed from the distilled water and hung for 20 seconds, after which the mass B of the sample was measured. The water absorption amount was calculated using the following formula: (Water absorption amount) = (Mass B - Mass A) / (Mass A)

[0111] (Decomposition Product Concentration) The concentration of drug decomposition products was measured for the foams of each Example, Comparative Example, and Reference Example. More specifically, an extract was synthesized by mixing 1% formic acid and acetonitrile in a mass ratio of 80:20. 25 g of the extract was added to 0.5 g of each foam sample and stirred for 2 hours. The concentration of drug decomposition products in the extract was then measured by high performance liquid chromatography (HPLC). (HPLC Measurement Conditions) The HPLC used was an LC-Net II / ADC manufactured by JASCO Corporation. Column used: Supelco Discovery C18 column (250 mm x 4.0 mm, 5 μm) Extraction solvent: 1% formic acid / acetonitrile = 80 / 20 Developing solvent: acetonitrile / buffer = 35 / 65 Buffer: 85% phosphoric acid, sodium dihydrogen phosphate, triethylamine Flow rate: 0.6 ml / min *In Table 2, the amounts of ingredients are expressed in parts by mass.

[0112] (Drug-Sustained Release Test) A drug-suspension release test was conducted on the foams of Examples 1 to 3 and a frozen-thawed product (HALOGUARD, manufactured by ATTWILL). More specifically, the above-mentioned extract was added to a sample of each foam of a predetermined size placed in a storage container, and stirring was initiated at 20°C. One minute after the start of stirring, the drug (CHG) concentration in the extract was measured by high-performance liquid chromatography (HPLC). The stirring time was changed to 30 minutes, 1 hour, 2 hours, and 24 hours, and the same procedure was performed. The drug (CHG) concentration in the extract measured at each stirring time was measured. The drug release rate at each stirring time was calculated using the following formula. Table 3 below shows the calculated drug (CHG) release rate (% by mass). Figure 1 is a graph showing the relationship between each stirring time and the drug (CHG) release rate (% by mass).

[0113]

[0114] The foam-forming composition and foam of the present disclosure can simplify the manufacturing process and improve the moldability of the foam, and therefore can be used, for example, in medical devices such as antibacterial testing kits, antibacterial dressings, and wound dressings.

[0115] The disclosure of Japanese Patent Application No. 2024-090297, filed on June 3, 2024, is incorporated herein by reference in its entirety. In addition, all documents, patent applications, and technical standards described herein are incorporated herein by reference to the same extent as if each individual document, patent application, and technical standard were specifically and individually indicated to be incorporated by reference.

Claims

1. A foam-forming composition comprising a urethane prepolymer and a drug, wherein the viscosity of the urethane prepolymer is 10,000 mPa·s or less.

2. A foam obtained by foaming and curing the foam-forming composition according to claim 1.

3. Density is 300 kg / m ３ 3. The foam of claim 2, wherein:

4. A foam containing a urethane foam and a drug, wherein the drug concentration in the extract 1 hour after the start of stirring is 80% by mass or less of the drug concentration in the extract 24 hours after the start of stirring, as measured by the following drug sustained release test. (Drug sustained release test) (1) The extract is added to the foam, and stirring is initiated at 20°C. (2) One hour after stirring is initiated, the drug concentration in the extract is measured by high-performance liquid chromatography (HPLC). (3) Steps (1) and (2) are repeated in the same manner, except that the stirring time is changed to 24 hours.

5. A medical device comprising a foam according to any one of claims 2 to 4.

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