Classifications

• • 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
• • 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
• • 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
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin

Definitions

• the present invention relates to a composition and a method for producing the composition.
• cancer treatment affects the mucous membrane of the mouth, and stomatitis is likely to occur.
• anticancer drug therapy when drugs that cause stomatitis are administered, in radiation therapy for head and neck cancer (cancer in the area from the head to the neck), when radiation hits the mucous membrane of the mouth directly. Stomatitis is inevitable. The pain of stomatitis is so strong that I cannot even take food by mouth.
• a patch to be directly applied to the affected area e.g., Aphtaseal (registered trademark) 25 ⁇ g, active ingredient: triamcinolone acetonide, Taisho Pharmaceutical Co., Ltd., etc.
• an ointment to be applied to the affected area e.g., dexartin oral ointment, active ingredient: dexamethasone, manufactured by Nippon Kayaku Co., Ltd., etc.
• a spray to be sprayed onto the affected area e.g., Salcort (registered trademark) capsule external use 50 ⁇ g, active ingredient: beclomethasone propionate, manufactured by Teijin Pharma Co., Ltd., etc.
• the patch pasted on the affected area may come off due to the physical stimulation of the chewing material, or the ointment or spray applied to the affected area may be lost, reducing the pain of stomatitis. may not be restrained.
• a composition that can suppress the pain of such stomatitis during eating and that dissolves and disappears from the oral cavity immediately after eating.
• Patent Document 1 describes "a sustained-release oral ointment characterized by containing a hydrophobic ointment base, a polyhydric alcohol, an adhesive substance, and a drug.” 1).
• a composition comprising an alginate, a carboxyvinyl polymer, and an oily base,
• the content of the alginate is more than 5% by mass and 25% by mass or less with respect to the total mass of the composition
• the content of the carboxyvinyl polymer is more than 5% by mass and 25% by mass or less with respect to the total mass of the composition
• the oily base contains a gelling hydrocarbon, substantially free of aluminum compounds
• a method for producing the composition according to any one of [1] to [5] A method for producing a composition, comprising mixing the alginate, the carboxyvinyl polymer, and the oil base.
• the present invention it is possible to provide a composition capable of forming a gel with excellent dissolution properties and excellent abrasion resistance.
• the present invention can also provide a method for producing a composition.
• the range expressed using “ ⁇ ” shall include both ends of “ ⁇ ”.
• the range represented by “AB” includes A and B.
• composition is a composition comprising an alginate, a carboxyvinyl polymer, and an oleaginous base,
• the alginate content is more than 5% by mass and 25% by mass or less with respect to the total mass of the composition
• the content of the carboxyvinyl polymer is more than 5% by mass and 25% by mass or less with respect to the total mass of the composition
• the oleaginous base comprises a gelling hydrocarbon; substantially free of aluminum compounds, No xylitol or, if xylitol is included, the xylitol content is less than 10% by weight relative to the total weight of the composition.
• the composition is a biocompatible material.
• biocompatible material means a material that adheres well to biological surfaces (eg, skin, mucous membranes (eg, intraoral mucous membranes), eyes, teeth, tongue, nails, hair, etc.).
• the composition has little adverse effect on the living body and is well adapted to the living body.
• the biological surface may be healthy, wounded, or ulcerated.
• the composition may form a gel on contact with water.
• Water that exists on the surface of a living body for example, the surface of the oral cavity, etc.
• the adhesiveness of the formed gel to the biological surface becomes stronger than the adhesiveness of the composition to the biological surface before forming the gel.
• the gel formed from the composition preferably has the function of protecting the biological surface, which is the adhered surface, from external stimuli. In order to achieve this purpose, it is preferable that the gel formed from the composition have a certain level of physical strength.
• the gel formed from the composition may have lubricity on the non-adhesive surface.
• “Living body” means humans and animals other than humans (eg, mammals, etc.).
• Non-human animals include, for example, primates, rodents (eg, mice and rats), rabbits, dogs, cats, pigs, cows, sheep, and horses.
• the composition includes alginate.
• the alginate is not particularly limited as long as it is a salt of alginic acid, but is preferably a monovalent metal salt of alginic acid or an ammonium alginate, and at least one selected from the group consisting of sodium alginate, potassium alginate, and ammonium alginate. is more preferred, and sodium alginate is even more preferred.
• Quantitative analysis and qualitative analysis of monovalent cations constituting alginate can be performed, for example, by ion chromatography under the following measurement conditions. ⁇ Measurement conditions Column: ion exchange resin (inner diameter 4.0 mm, length 25 cm) Mobile phase: methanesulfonic acid solution (20 mmol/L) Flow rate: 1.0 mL/min Sample injection volume: 25 ⁇ L Column temperature: 40°C Suppressor: Electrodialysis type Detector: Conductivity detector (30°C)
• the weight average molecular weight of the alginate is not particularly limited, but is often 500,000 or more, preferably 1,000,000 or more, more preferably 2,000,000 or more, and even more preferably 2,500,000 or more.
• the upper limit of the weight average molecular weight of the alginate is not particularly limited, it is preferably 10 million or less, more preferably 5 million or less, even more preferably 4.5 million or less, and particularly preferably 3 million or less.
• the weight average molecular weight of alginate can be measured using gel permeation chromatography (GPC).
• GPC measurement conditions for measuring the weight average molecular weight of alginate are shown below.
• GPC measurement conditions/column TSKgel G6000+G4000+G2500
• PWXL ⁇ Eluent 0.2 mol/L sodium nitrate
• Flow rate 0.7 mL/min
• ⁇ Injection volume 50 ⁇ L ⁇ Sample concentration: 0.1% by mass Analysis time: 60 minutes
• RI Refractive Index
• the viscosity of the alginate is not particularly limited, but the viscosity of an aqueous solution (25°C) in which 1% by mass of alginate is dissolved in water is often 50 mPa s or more, preferably 100 mPa s or more, and 200 mPa s or more. More preferably, it is 500 mPa ⁇ s or more, even more preferably 800 mPa ⁇ s or more, and particularly preferably 1,000 mPa ⁇ s or more.
• the upper limit of the viscosity of the alginate is not particularly limited, but the viscosity of an aqueous solution dissolved in 1% by mass in water is preferably 10,000 mPa s or less, more preferably 5,000 mPa s or less, and 4,500 mPa s or less. More preferably, 3,000 mPa ⁇ s or less is particularly preferable.
• the alginate preferably has a viscosity of 300 to 400 mPa ⁇ s.
• the viscosity of alginate can be measured using a rotational viscometer or a viscoelasticity measuring device (rheometer).
• the alginate may be particulate.
• the average particle diameter of the alginate particles is not particularly limited, it is preferably 50 ⁇ m or more and less than 300 ⁇ m, more preferably 50 ⁇ m or more and less than 200 ⁇ m, and even more preferably 50 ⁇ m or more and less than 150 ⁇ m.
• the average particle size of alginate particles can be measured using a wet/dry particle size distribution analyzer (LS13320, manufactured by Beckman Coulter, Inc.).
• the content of alginate is more than 5% by mass and 25% by mass or less, preferably 10 to 25% by mass, more preferably 15 to 25% by mass, and 20 to 25% by mass, based on the total mass of the composition. More preferred.
• Alginates may be used singly or in combination of two or more.
• a commercial product can be used for the alginate in the composition.
• Specific examples of commercially available alginates include “Kimica Algin IS”, “Kimica Algin I-8”, “Kimica Algin I-5”, “Kimica Algin I-3” and “Kimica Algin I-1” manufactured by Kimika Co., Ltd. ”, “Snow Argin SSH”, “Snow Argin SH”, “Snow Argin H”, “Snow Argin M”, and “Snow Argin L” manufactured by Fuji Kagaku Kogyo.
• the composition includes a carboxyvinyl polymer.
• a carboxyvinyl polymer is a water-soluble vinyl polymer having a carboxy group, specifically a polymer having a crosslinked structure with acrylic acid and/or methacrylic acid as a main chain.
• the crosslinked structure includes allyl sucrose, allyl ether of pentaerythritol, and the like.
• the viscosity of the carboxyvinyl polymer is not particularly limited, but in an aqueous solution (20° C.) in which 0.2% by mass of the carboxyvinyl polymer is dissolved in water adjusted to pH 7.5, it is preferably 50,000 mPa s or less, 50,000 mPa ⁇ s is more preferable, and 1,000 to 10,000 mPa ⁇ s is even more preferable.
• the viscosity of the aqueous solution (20° C.) at pH 7.5 is 50,000 mPa ⁇ s or less, the wear resistance and dissolution properties of the gelled composition are further improved.
• the viscosity of the carboxyvinyl polymer was measured by using a viscoelasticity measuring device (MCR301, manufactured by Anton Paar) with a 0.2% by mass aqueous solution of the carboxyvinyl polymer adjusted to pH 7.5, at a shear rate of 1 (1/s).
• GAP is a value measured at 0.05 mm and 20°C.
• carboxyvinyl polymer A commercial product can be used as the carboxyvinyl polymer in the composition.
• Commercially available carboxyvinyl polymers include, specifically, Lubrizol's "Carbopol 971", “Carbopol 974", “Carbopol 980” and “Carbopol 981”; Fuji Film Wako Pure Chemical Industries, Ltd.
• Hi-Vis Wako 103 "Hi-Vis Wako 104" and “Hi-Vis Wako 105" manufactured by Toagosei; "Junron PW-120”, “Junron PW-121” and “Junron PW-312S” manufactured by Toagosei; "AQUPEC HV-501E”, “AQUPEC HV-505E”, and “AQUPEC HV805" manufactured by Sumitomo Seika; "Syntaren K” and “Syntaren L” manufactured by 3V Sigma; Examples include “NTC-CARBOMER 380” and “NTC-CARBOMER 381".
• the content of the carboxyvinyl polymer is more than 5% by mass and 25% by mass or less, preferably 10 to 25% by mass, more preferably 10 to 20% by mass, and 10 to 15% by mass, based on the total mass of the composition. is more preferred.
• the carboxyvinyl polymer may be used singly or in combination of two or more.
• the content of alginate is 15 to 25% by weight relative to the total weight of the composition, and the content of carboxyvinyl polymer is 10 to 15% by weight relative to the total weight of the composition. preferable.
• the composition contains an oleaginous base.
• the oleaginous base includes gelled hydrocarbons.
• the spreadability of the composition becomes more excellent.
• oleaginous base is meant a component that is immiscible with water.
• the viscosity of the oily base material is not particularly limited, but is preferably 100 to 1,000,000 mPa ⁇ s, more preferably 1000 to 500,000 mPa ⁇ s, in terms of better adhesion when the composition of the present invention is gelled. is more preferred.
• the viscosity is measured using a viscoelasticity measuring device (MCR302, manufactured by Anton Paar) at a measurement temperature of 25° C. and a shear rate of 1 (1/s).
• the consistency of the oil base is preferably 200 to 400, more preferably 250 to 370, from the viewpoint of easy application of the composition of the present invention.
• the consistency is measured using an automatic consistency meter (RPM-201, manufactured by Rigosha) with a needle penetration time of 5 seconds.
• the gelling hydrocarbon those conforming to the standards for pharmaceutical excipients "gelating hydrocarbon" can be used. More specifically, the gelling hydrocarbon is polyethylene equivalent to 5-10% by mass of liquid paraffin can be preferably used.
• the gelling hydrocarbon Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.), Hicol Gel (manufactured by Kaneda Corporation), or Hydrocarbon Gel 55W (manufactured by Contract Pharmaceuticals Limited) is preferable.
• the oleaginous base may contain other oleaginous bases in addition to the gelling hydrocarbon.
• Other oil-based bases include raw materials used in ordinary oil-based ointments, such as hydrocarbons, waxes, vegetable oils, animal oils, neutral lipids, synthetic oils and fats, sterol derivatives, monoalcohol carboxylic acid esters, oxyacids. Examples include esters, polyhydric alcohol fatty acid esters, silicones, higher alcohols, higher fatty acids, and fluorine oils.
• hydrocarbons examples include liquid paraffin (mineral oil), heavy liquid isoparaffin, light liquid isoparaffin, ⁇ -olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, olive-derived squalane, squalene, vaseline, and solid paraffin.
• the petrolatum is preferably selected from those complying with the Japanese Pharmacopoeia or equivalent standards of "vaseline”, “white petrolatum”, or "yellow petrolatum”.
• Waxes include, for example, candelilla wax, carnauba wax, rice wax, Japan wax, beeswax, montan wax, ozokerite, ceresin, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene wax, and ethylene/propylene copolymer. mentioned.
• Vegetable oils include soybean oil, sesame oil, olive oil, coconut oil, palm oil, rice bran oil, cottonseed oil, sunflower oil, rice bran oil, cocoa butter, corn oil, safflower oil, and rapeseed oil.
• Animal oils include mink oil, turtle oil, fish oil, beef oil, horse oil, pork oil, and shark squalane.
• Neutral lipids include triolein, trilinolein, trimyristin, tristearin, and triarachidonine.
• Synthetic fats and oils include, for example, phospholipids and azone.
• Sterol derivatives include dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterols, cholic acid, and cholesteryl linolate.
• Monoalcohol carboxylic acid esters include octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, and cetyl palmitate.
• the oxyacid esters include cetyl lactate, diisostearyl malate, and hydrogenated castor oil monoisostearate.
• Polyhydric alcohol fatty acid esters include glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, glyceryl diisostearate, and glyceryl tri(caprylate/caprate).
• Silicones include dimethicone (dimethylpolysiloxane), highly polymerized dimethicone (highly polymerized dimethylpolysiloxane), cyclomethicone (cyclic dimethylsiloxane, decamethylcyclopentasiloxane), and phenyltrimethicone.
• Higher alcohols include cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, and stearyl alcohol.
• Higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, undecylenic acid, 12-hydroxystearic acid, and palmitoleic acid.
• Fluorinated oils include perfluorodecane, perfluorooctane, and perfluoropolyether.
• the content of the oily base material is not particularly limited, but is preferably 40% by mass or more, more preferably 50% by mass or more, relative to the total mass of the composition.
• the upper limit is not particularly limited, it is preferably 90% by mass or less, more preferably 80% by mass or less, and even more preferably 75% by mass or less, relative to the total mass of the composition.
• the oil base may be used alone or in combination of two or more.
• the composition is substantially free of aluminum compounds.
• substantially free means that the inclusion of a small amount of aluminum compound (for example, a trace amount of aluminum contained in the raw material of the composition) that does not affect the effects of the present invention is within the allowable range.
• substantially free of aluminum compounds means that the content of aluminum compounds in the composition is less than 0.1% by mass with respect to the total mass of the composition. . Especially, it is preferably 0.01% by mass or less with respect to the total mass of the composition.
• the lower limit is not particularly limited, it may be 0% by mass or more based on the total mass of the composition.
• the aluminum compound is not particularly limited as long as it contains aluminum (aluminum atom).
• specific examples include water-soluble aluminum compounds.
• water-soluble aluminum compounds include aluminum chloride (AlCl 3 ), aluminum sulfate (Al 2 (SO 4 ) 3 ), aluminum nitrate (Al(NO 3 ) 3 ), ammonium alum (AlNH 4 (SO 4 ) 2 12H2O ), potassium alum ( AlK ( SO4 ) 2.12H2O ), aluminum acetate, aluminum propionate, aluminum glycolate (aluminum hydroxyacetate), aluminum lactate, aluminum malate, aluminum tartrate, aluminum citrate , and aluminum isocitrate.
• HPLC high performance liquid chromatography
• the HPLC measurement conditions for measuring the content of aluminum compounds are shown below. (HPLC measurement conditions) ⁇ Column: Inert Sustain swift C18 4.6 ⁇ 150 mm, 3 ⁇ m - Column temperature: constant temperature around 30 ° C.
• - Mobile phase A Bis-Tris buffer (pH 7) and acetonitrile mixture (4: 1), containing 8-quinolinol 1.5 mM
• Mobile phase B Bis-Tris buffer ( pH 7) and acetonitrile mixture (1:9), containing 8-quinolinol 1.5 mM
• Mobile phase liquid transfer mobile phase A and mobile phase B at a mixing ratio of 4: 1 Flow rate: 1.0 mL / min ⁇ Injection volume: 20 ⁇ L ⁇ Analysis time: 30 minutes ⁇ Detection: UV ⁇ Preparation of measurement sample: After extraction with water/acetonitrile, 900 ⁇ L is mixed with 100 ⁇ L of 8-quinolinol 15 mM acetonitrile solution prepared in advance.
• the composition is free of xylitol or, if xylitol is included, contains less than 10% by weight of xylitol relative to the total weight of the composition.
• the content of xylitol is within the above range, both elution and abrasion resistance of the composition can be achieved.
• the xylitol content is preferably 1% by mass or less, more preferably less than 0.5% by mass, and further preferably 0.1% by mass or less, relative to the total mass of the composition. preferable.
• the composition is substantially free of water.
• substantially free of water means that it is acceptable to contain a small amount of water (for example, a trace amount of water contained in the ingredients of the composition) that does not affect the effects of the present invention. means that Specifically, “substantially free of water” means that the water content in the composition is 3% by mass or less with respect to the total mass of the composition. Especially, it is preferably 1% by mass or less with respect to the total mass of the composition. Although the lower limit is not particularly limited, it may be 0% by mass or more based on the total mass of the composition. When the composition does not substantially contain water, when the composition is applied to the living body, the adhesion of the formed gel is further improved, and the protective performance is also improved.
• Methods for measuring the content of water in a composition include, for example, the water content measurement method (Karl Fischer method) described in the Japanese Pharmacopoeia. However, it is preferable to add a step of dispersing the sample in methanol for moisture measurement and extracting the moisture, and subjecting the extracted liquid to a coulometric titration test.
• composition may contain other ingredients than those mentioned above.
• the composition may further contain at least one selected from the group consisting of sugar alcohols and sugars. If the composition contains at least one selected from the group consisting of sugar alcohols and sugars, the composition will have better scratch resistance when gelled. As used herein, xylitol is not included in sugar alcohols.
• Sugar alcohol is an organic compound having a structure in which the carbonyl group of aldose or ketose is reduced, and specific examples thereof include erythritol, mannitol and sorbitol, and the group consisting of erythritol, mannitol and sorbitol. At least one selected from is preferred.
• Sugars are not particularly limited, but are, for example, monosaccharides or disaccharides, and specific examples include glucose, galactose, sucrose, trehalose, and lactose, consisting of glucose, galactose, and trehalose. At least one selected from the group is preferred, and trehalose is more preferred.
• At least one selected from the group consisting of sugar alcohols and sugars is at least one selected from the group consisting of erythritol, mannitol, sorbitol, glucose, galactose, sucrose, trehalose and lactose. preferable.
• the total content of the sugar alcohols and sugars in the composition is not particularly limited; On the other hand, 0.5 to 20.0% by mass is preferable, and 5.0 to 15.0% by mass is more preferable. When the total content of sugar alcohols and sugars is within the above range, the effect of including at least one selected from the group consisting of sugar alcohols and sugars in the composition will be more pronounced. .
• a method for producing the composition preferably includes a step of mixing an alginate, a carboxyvinyl polymer, and an oily base. Moreover, you may implement a dehydration process as needed.
• the mixing method is not particularly limited, and conventionally known methods used when mixing powder components can be used.
• a stepwise mixing method may be implemented in which some of the components constituting the composition are mixed in advance and then mixed with the remaining components. Alternatively, all components may be mixed at the same time.
• a composition in which the components are more uniformly dispersed can be obtained.
• the mixture and the oily base material may be mixed together, or the mixture may be divided into multiple portions and added to the oily base material for mixing.
• a gel is formed by contacting the composition with water.
• the absorption of water by the composition causes the spontaneous formation of a gel.
• the composition may be applied onto a biological surface to form a gel.
• methods for forming a gel include a method of forming a gel on the surface of a living body by placing the composition on the surface of the living body and bringing the composition placed on the surface of the living body into contact with water.
• Suitable biological surfaces on which the composition is placed include intraoral mucosal surfaces.
• the viscosity of the composition is not particularly limited, it is preferably from 100,000 to 1,000,000 mPa ⁇ s in terms of better spreadability of the composition.
• the viscosity is measured using a viscoelasticity measuring device (MCR302, manufactured by Anton Paar) at a measurement temperature of 25° C. and a shear rate of 1 (1/s).
• the form (property) of the composition is not particularly limited, but examples include ointment, cream, and semi-solid.
• compositions include bioprotective applications.
• the composition can be used as a mucosal protective agent such as an oral mucosal protective agent, a wound dressing, a drug sustained release substrate, an oral moistening agent, and a hemostatic agent.
• the composition When the composition is applied to mucous membranes, the composition is placed on mucous membranes and water or a solution containing water is added to form a gel that adheres more firmly to mucous membranes. That is, as a method of using the composition (or a method of producing a gel), the composition is placed on the mucous membrane and the composition placed on the mucous membrane is brought into contact with water to form a gel on the mucous membrane. method.
• the composition when the composition is applied to the oral mucosa, if the composition is adhered to the oral mucosa, the composition gels with the water in the saliva, which facilitates handling. If the amount of saliva is small, water may be supplied by, for example, spraying water or artificial saliva after applying the composition to the oral mucosa.
• the composition When the composition is applied to the oral mucosa, the composition begins to dissolve and swell due to water in saliva, and at the same time, the mucin on the oral mucosa surface and the alginate or carboxyvinyl polymer form hydrogen bonds. Glue. It is presumed that the gel formed from the composition of the present invention has excellent wear resistance due to such a mechanism.
• the type of drug to be sustained-released is not particularly limited, and known drugs are included.
• Examples C1 to C16, Comparative Examples R1 to R10 ⁇ Preparation of composition>
• compositions of Examples C1 to C16 and Comparative Examples R1 to R10 were prepared.
• the content of the aluminum compound in the compositions of Examples C1 to C16 was in each case 0.01% by mass or less with respect to the total mass of each composition. That is, the compositions of any of the Examples were substantially free of aluminum compounds.
• the procedure for producing the composition of Example C1 will be described below as a representative example.
• Examples C2 to C16 and Comparative Examples R1 to R10 were prepared in the same manner as in Example C1 except that the content of each component was adjusted.
• Gelling hydrocarbon (Hydrocarbon Gel 55W, manufactured by Contract Pharmaceuticals Limited) (134.0 g) and carboxyvinyl polymer (Carbopol 971P NF, manufactured by Lubrizol) (30.0 g) were mixed in a mixer (model: HP-2P- 03, manufactured by Primix) and stirred at room temperature at 50 rpm for 2 minutes. Further, sodium alginate (Kimika Algin I-SF, Kimika Co., Ltd.) (36.0 g) was put into the mixer and stirred at room temperature at 50 rpm for 10 minutes.
• Example C1 an aluminum tube ( ⁇ 12.8 ⁇ 86 mm, manufactured by Takeuchi Press Industry Co., Ltd.) was filled with 5 g of the mixture, and sealed using a tube bending machine (manufactured by Nakanishi Seisakusho) to obtain the composition of Example C1.
• Carboxyvinyl polymer Carboxyvinyl polymer: Carbopol (registered trademark) 971PNF (manufactured by Lubrizol), pH 7.5 of 0.2% by mass aqueous solution, viscosity at 20 ° C. 1,500 to 5,000 mPa s
• TDAB 50 mg, tetradodecylammonium bromide, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.
• polyvinyl chloride 800 mg, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.
• DOPP 0.6 mL, di-n-octylphenylphosphonate, FUJIFILM Wako Pure Chemical Industries, Ltd.
• THF 10 mL, tetrahydrofuran, FUJIFILM Wako Pure Chemical Industries, Ltd.
• agar 0.5 g, Calicolican (registered trademark), manufactured by Ina Food Industry Co., Ltd.
• gellan gum 0.1 g, Kelcogel (registered trademark), manufactured by CP Kelco
• distilled water 49.4 g.
• MPC 2-methacryloyloxyethylphosphorylcholine
• Dissolution properties were evaluated using each composition before high-temperature storage and each composition after high-temperature storage as compositions to be evaluated for dissolution properties.
• a washer inner diameter: 10 mm, thickness: 0.5 mm
• artificial saliva Surfactant (registered trademark)
• the prepared dissolution evaluation sample and artificial saliva were placed in a tapper, and the amount of artificial saliva was adjusted so that the surface of the artificial saliva was between the simulated biological membrane and the gelled composition.
• the prepared abrasion resistance evaluation sample was repeatedly worn with an abrasion tester (TRIBOGEAR TYPE-40, manufactured by Shinto Kagaku Co., Ltd.), and the number of times (reciprocating) until the gel completely disappeared from the pseudo biological membrane was measured.
• Abrasion resistance was evaluated according to the standard. An aluminum head (0.114 mm grind) was set as the head of the abrasion tester, and the test was conducted under the conditions of a load of 0.3 N, an amplitude of 30 mm, and a speed of 6000 mm/min.
• B 100 times or more and less than 200 times
• C Less than 100 times
• each entry indicates the following.
• the content of each component represents parts by mass.
• Each numerical value in the column of "dissolution” indicates the time (unit: hour) for the gel to dissolve and disappear in the evaluation of dissolution.
• Each numerical value in the "Abrasion resistance” column indicates the number of times (reciprocating) until the gel completely disappears in the evaluation of abrasion resistance.

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• 2022
  • 2022-07-14 JP JP2023534846A patent/JPWO2023286820A1/ja active Pending
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