Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• • 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
  • A61K47/02—Inorganic compounds
• • 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
  • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P13/00—Drugs for disorders of the urinary system
  • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers

Definitions

• the present invention relates to 2-chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide, or a pharmacologically acceptable salt thereof, or a
• the present invention relates to a coating preparation containing a hydrate as an active ingredient.
• azosemide 2-chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide, or a pharmaceutically acceptable salt thereof, or a hydrate thereof
• azosemide is a compound described in Patent Document 1 and is known as a continuous loop diuretic.
• the pharmacological action is considered to suppress the reabsorption of sodium ions and chloride ions in renal tubules, mainly Henle's ascending limb, and exert diuretic action.
• oral preparations and injections Patent Document 2 are known, and oral preparations have been manufactured and sold in Japan since 1993.
• titanium dioxide in order to improve the stability of the drug to light, it is a common technique to incorporate titanium dioxide in the coating layer. Crystalline polymorphism exists in titanium dioxide, and among them, anatase type titanium dioxide is known for its high light-shielding ability and whitening ability. For this reason, anatase-type titanium dioxide is usually used in order to improve the stability of the drug to light.
• light-shielding packaging it is a package that can prevent the transmission of light and protect the preparation from the effects of light, or a colored or translucent light that does not allow the passage of light with a wavelength from the ultraviolet to the visible blue region, which causes coloring of the preparation.
• PTP packaging that uses a packaging sheet to stabilize the internal formulation is used.
• a package that prevents light transmission by means of sandwiching a metal foil, such as aluminum, that prevents light transmission with an alkene polymer, etc. is more expensive than a package that consists only of an alkene polymer, etc.
• a packaging sheet that does not transmit light having a wavelength from the ultraviolet to the visible blue region is more expensive than a packaging sheet that transmits light having a wavelength from the ultraviolet to the visible blue region.
• hospitals and dispensing pharmacies sometimes offer a single package service that packs several types of pharmaceutical preparations into a single unit for each dose in consideration of patient convenience.
• a package that normally transmits light and moisture in the air is used. Therefore, the encapsulated pharmaceutical preparation is easily affected by the influence of light and the temperature or humidity due to the climate during storage.
• it is required to be stable not only with respect to light but also with respect to temperature or humidity.
• the present inventors have studied a coating preparation containing azosemide as an active ingredient to be a stable pharmaceutical preparation regardless of the package, and the preparation containing azosemide coated with anatase-type titanium dioxide is a It has been found that the appearance may change depending on temperature or humidity. Then, this invention makes it a subject to provide the formulation which uses azosemide as an active ingredient which is stable with respect to external factors, such as temperature or humidity, irrespective of a package.
• the present inventors diligently investigated the cause of changes in the appearance of coating preparations containing azosemide as an active ingredient depending on temperature or humidity. It was also found that azosemide reacts with anatase-type titanium dioxide under certain conditions and causes a change in formulation. Furthermore, when applying a light-shielding coating to a preparation containing azosemide as an active ingredient, it has been found that by using rutile type titanium dioxide, the preparation is stable not only against light but also against temperature or humidity. Completed.
• the main configuration of the present invention is as follows.
• a coating comprising an active ingredient-containing part containing a Japanese product as an active ingredient, and a coating layer formed on the surface of the active ingredient-containing part, wherein the coating layer contains rutile-type titanium dioxide.
• Formulation. (2) The coating preparation according to (1), wherein the content of the rutile-type titanium dioxide is 0.2% by mass or more based on the active ingredient-containing part.
• the coating layer further contains at least one colorant selected from the group consisting of talc, calcium carbonate, magnesium oxide, kaolin, and iron sesquioxide, according to any one of (1) to (6) Coating formulation.
• the coating layers are all (i) rutile-type titanium dioxide 8 to 50% by mass, (ii) water-soluble polymer 40 to 85% by mass, and (iii) talc, based on the entire coating layer.
• the coating preparation according to any one of (1) to (7) comprising: (9) The coating preparation according to any one of (1) to (8), which is encapsulated in a package that is partially colorless and transparent and allows the contents to be seen.
• the coating preparation of the present invention comprises 2-chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide, or a pharmaceutically acceptable salt thereof, Or those hydrates are included as an active ingredient.
• 2-Chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide is generally called azosemide, but in this specification, the salts and the like are also summarized. This is called azosemide.
• Azosemide-containing preparations are loop diuretics and are used as effective preparations for cardiac edema (congestive heart failure), renal edema, hepatic edema, and the like. Azosemide can be produced according to the synthesis method described in US Pat. No. 3,665,002.
• the pharmacologically acceptable salt of 2-chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide is considered in consideration of its use.
• Pharmaceutically acceptable salts are preferred. Specific examples include pharmacologically acceptable inorganic and organic base salts such as sodium, lithium, potassium, magnesium, ammonium, quaternary ammonium salts, hydrochlorides, diethylamine, and diethanolamine. These pharmacologically acceptable salts can be obtained by known methods.
• the hydrate in the present invention includes not only hydrates of 2-chloro-5- (2H-tetrazol-5-yl) -4-[(thiophen-2-ylmethyl) amino] benzenesulfonamide, but also It also includes a hydrate of a pharmacologically acceptable salt and can be obtained by a known method.
• the content (ratio) of the active ingredient azosemide is preferably 10 to 70% by mass, more preferably 20 to 40% by mass as a whole.
• the content of azosemide can be set in an amount suitable for actual use, and it is appropriate to set it in the range of 10 mg to 200 mg in one preparation.
• the content of azosemide per tablet is Since it is 30 mg or 60 mg, it is practically preferable to set the content according to these.
• the coating preparation of the present invention can be produced by coating the surface of an active ingredient-containing part containing azosemide (hereinafter referred to as azosemide-containing part) with a coating layer containing rutile titanium dioxide.
• azosemide-containing part examples include uncoated tablets containing azosemide. Further, a coated tablet may be used instead of the uncoated tablet.
• the core part can be made into an azosemide-containing part by using the technology for producing dry-coated tablets described in WO 01/98067 pamphlet or the like.
• the uncoated tablet usually means a tablet before coating.
• the manufacturing method of a plain tablet is not specifically limited, It can manufacture by the method used normally. For example, it can be produced by kneading a drug, a binder, and a disintegrant, sizing after drying, and mixing or tableting with a lubricant as it is or further.
• titanium dioxide is mainly used for the coating layer. Titanium dioxide is classified into three types: rutile type (R type), anatase type (A type), and brookite type (B type), depending on the difference in crystal structure and properties. Tetragonal rutile-type titanium dioxide and orthorhombic brookite-type titanium dioxide have low light-shielding and whitening effects, and tetragonal anatase-type titanium dioxide has high light-shielding and whitening ability. It is known that. Therefore, in order to improve the stability of the drug to light, titanium dioxide containing a large amount of anatase type crystals tends to be selected first.
• R type rutile type
• a type anatase type
• B type brookite type
• titanium dioxide in the coating layer preferably contains a lot of rutile crystals. This is because a tablet containing azosemide is affected by temperature, humidity, or the like, and the active ingredient and anatase-type titanium dioxide undergo a blending change, resulting in a color change on the preparation surface and poor stability.
• this inventor discovered for the first time that an azosemide and anatase type titanium dioxide cause a mixing
• Rutile-type titanium dioxide can be obtained as a commercial product. Further, it can be obtained by heating the anatase type crystal to 900 ° C. or higher, or heating the brookite type crystal to 650 ° C. or higher. Therefore, different crystal systems may coexist in rutile titanium dioxide. In that case, the ratio of the rutile type titanium dioxide to the titanium dioxide content other than the rutile type is preferably in the range of 100: 0 to 90:10. That is, titanium dioxide containing 90% or more of rutile type titanium dioxide is preferable. Furthermore, rutile type titanium dioxide obtained by chemically modifying the surface of rutile type titanium dioxide with other additives is also included in the rutile type titanium dioxide of the present invention.
• the X-ray diffraction pattern of rutile-type titanium dioxide in the coating layer was 27.5 ⁇ 0.5 °, 36.0 ⁇ 0.5 °, and 54.3 ⁇ under the measurement conditions shown in Table 1 using powder X-ray diffraction by Cu—K ⁇ ray. It has a characteristic peak of diffraction angle 2 ⁇ at 0.5 °. More specifically, it has characteristic peaks of diffraction angle 2 ⁇ at 41.4 ⁇ 0.5 °, 56.7 ⁇ 0.5 °, 63.1 ⁇ 0.5 °, 69.3 ⁇ 0.5 °, and 140.3 ⁇ 0.5 °.
• the particle size of rutile-type titanium dioxide is preferably 50% to 10 ⁇ m, more preferably 0.5 ⁇ m to 5 ⁇ m, as a 50% particle size measured by laser diffraction.
• a material having a high refractive index such as titanium dioxide has a large ability to prevent incident light from being transmitted by irregular reflection when the particle diameter is about 1/2 of the wavelength of incident light (Japanese Patent No. 2525192, JP-B-6). -2562).
• the content (ratio) of rutile-type titanium dioxide is preferably 0.2% by mass or more with respect to the azosemide-containing part (total mass). If the content of rutile-type titanium dioxide relative to the azosemide-containing part is less than 0.2% by mass, it is not sufficient to prevent discoloration of the active ingredient by light.
• a person skilled in the art can implement the present invention by setting the optimum range of the rutile-type titanium dioxide content.
• the content (ratio) of rutile-type titanium dioxide is preferably 8% by mass or less based on the azosemide-containing part.
• the content (ratio) of rutile-type titanium dioxide with respect to the azosemide-containing part is preferably 0.2 to 8% by mass, more preferably 0.3 to 6% by mass, but the upper limit is further preferably 5% or less. Further, it is more preferably 0.4 to 4% by mass.
• the sufficient amount of titanium dioxide is said to be 1 to 5% by mass relative to the tablet before coating, but in the present invention, even if the amount is less than the usual sufficient amount, the azosemide is the active ingredient. It is possible to provide a coating formulation that is stable against environmental factors.
• the content of rutile-type titanium dioxide in the coating layer cannot be generally specified depending on the thickness of the coating layer, but is preferably 8 to 50% by mass, more preferably 9 to 40% by mass with respect to the entire coating layer. More preferably, it is 10 to 25% by mass.
• various excipients and the like can be used for the coating layer according to the common general technical knowledge in the field.
• a water-soluble polymer examples include hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, methyl vinyl ether / maleic anhydride copolymer, carboxymethylcellulose sodium, phthalate acetate
• examples include acid cellulose, xanthan gum, gum tragacanth, gum arabic, agar, gelatin, sodium alginate, polyethylene oxide, polyvinyl pyrrolidone, aminoalkyl methacrylate copolymer, methacrylic acid copolymer, carboxyvinyl polymer, polyvinyl pyrrolidone, polyvinyl alcohol, and macrogol.
• hydroxypropylmethylcellulose, hydroxypropylcellulose, and macrogol are preferred.
• the water-soluble polymer one or more selected from these can be used alone or in appropriate combination.
• the content of the water-soluble polymer is usually 40 to 85% by mass, preferably 45 to 70% by mass, based on the entire coating layer.
• the coating layer includes talc, calcium carbonate, magnesium oxide, kaolin, low-substituted hydroxypropyl cellulose (L-HPC), calcium hydrogen phosphate, magnesium aluminate metasilicate, synthetic aluminum silicate, copper chlorophyll, copper chlorophyllin sodium,
• One or more colorants selected from the group consisting of iron sesquioxide and edible colorants can be further added.
• the content of these colorants is usually 0 to 15% by mass, preferably 0 to 5% by mass, based on the entire coating layer.
• one or more light-shielding agents other than rutile-type titanium dioxide can be further added.
• a light-shielding agent include talc, calcium carbonate, magnesium oxide, kaolin, low-substituted hydroxypropyl cellulose (L-HPC), calcium hydrogen phosphate, magnesium aluminate metasilicate, and synthetic aluminum silicate. it can.
• the classification of additives such as colorants and light-shielding agents is not strict.
• known components generally used in pharmaceuticals can be added to the coating layer in an appropriate combination.
• sweeteners, dispersants, excipients, plasticizers, fragrances, brighteners, anti-adhesive agents, preservatives, preservatives, pH adjusters, and the like can be further added.
• the coating layer in the present invention means a layer that protects azosemide from external factors such as temperature and humidity, and includes not only a uniform coating state as a whole but also a non-uniform coating state as a whole.
• a person skilled in the art can appropriately set the coating state.
• the coating layer may be in a non-uniform coating state as a whole.
• the thickness ratio of the coating layer can be appropriately set by a known method. For example, it is preferably 2% by mass to 20% by mass, more preferably 2% by mass to 15% by mass with respect to the uncoated tablet. More preferably, the content is 3% by mass to 8% by mass.
• the method for coating the azosemide-containing part is not particularly limited, but can be coated by a generally known method. Examples thereof include a coating pan method, a fluidized bed coating method, and a rolling coating method.
• the coating pan method is a method in which an azosemide-containing part is put into a rotating drum (pan), and the coating solution is sprayed and dried on the azosemide-containing part that rolls in the pan.
• the fluidized bed coating method is a method in which an azosemide-containing part is floated or fluidized by an air flow, and the coating solution is sprayed and dried to coat the suspended suspension.
• the rolling coating method is a method in which a horizontal disk is rotated and a coating solution is sprayed and dried on an azosemide-containing portion that rolls on the upper surface of the disk.
• a production apparatus such as a fluidized granulator or a rolling granulator can be used.
• the core part can be an azosemide-containing part and the outer layer part can be a coating layer.
• the coating preparation of the present invention can be obtained, for example, by preparing uncoated tablets containing azosemide and then coating the uncoated tablets using a coating solution in which the additives shown in Table 2 are dissolved in water. Can do.
• the mass% of each additive in Table 2 represents mass% relative to the azosemide-containing part (uncoated tablet).
• a person skilled in the art can appropriately set the content of each additive in the coating layer in addition to those shown in Table 2.
• the coating preparation containing the azosemide of the present invention can be encapsulated in a package that is partially transparent and visible.
• the package in which the contents are visible refers to a package that has a transparent portion in a part of the package and can confirm the color change of the contents.
• the discoloration of the pharmaceutical preparation due to the external environment can be suppressed as compared with the conventional preparation even in a non-packaging state, and therefore the packaging body itself does not have to have a light-shielding function or a moisture-proof function. Have.
• ⁇ Color difference measurement> The color difference was evaluated using a spectrocolorimeter (CM-3500d, manufactured by Konica Minolta). D65 was used as the reference light source at the time of measurement, the color of the object was measured with the L * a * b * color system, and the color difference ⁇ E between the two at the start and after storage for a certain period of time was calculated by the following formula 1. . If ⁇ E exceeds 3.0, the color change can be visually identified.
• CM-3500d manufactured by Konica Minolta
• ⁇ Test 1> Mixed powder blending change test Methods Three types of mixed powders were prepared : azosemide alone, a mixture of azosemide and rutile titanium dioxide, and a mixture of azosemide and anatase titanium dioxide.
• Each mixed powder was stored for 3 weeks under the following conditions (a) in an open state or in an airtight container (glass bottle). Airtight container is a state where the glass bottle is sealed with a polypropylene cap and stored, and the humidity of the gas entering the container does not reach the sealed container specified by the Japanese Pharmacopoeia. This means a storage state with extremely little influence.
• the color difference change of each mixed powder at the first week, the second week, and the third week was measured by the method of color difference measurement.
• the rutile type titanium dioxide used in the following examples was purchased from Toho Titanium Co., Ltd., and the anatase type titanium dioxide was purchased from Wako Pure Chemical Industries, Ltd.
• Table 3 shows the color difference ( ⁇ E) of each mixed powder after the results were stored.
• Azosemide alone was stable against temperature and humidity both in an airtight container and in an open state, and the color difference ⁇ E between the first week and the third week was 3.0 or less.
• the color differences ⁇ E from the first week to the third week all greatly exceeded 3.0, and the color change on the powder surface could be confirmed visually.
• the color difference ⁇ E was 3.0 or less even after 3 weeks in the airtight container, and no color change could be confirmed visually.
• the degree of discoloration in the open state was about 1 ⁇ 2 compared to ⁇ E when azosemide and anatase type titanium dioxide were mixed under the same conditions. That is, when rutile type titanium dioxide was used, an improvement effect of reducing discoloration to about 1/2 to 1/5 was seen compared to the case of using anatase type titanium oxide.
• the amount of progress of the reaction is calculated using the Arrhenius equation.
• the amount of reaction progress corresponds to the amount of reaction progress for 36 months at a temperature of 25 ° C. or for 6 months at a temperature of 40 ° C.
• Example 1 The additives shown in Table 4 were dissolved in water to form a coating solution, and the uncoated tablets were coated using a fluid bed granulator to obtain each preparation of Example 1 and Comparative Example 1.
• the mass% of each additive in Table 4 indicates mass% with respect to the azosemide-containing part (uncoated tablet).
• Each preparation was stored for 3 weeks under the condition (a) in an open state or in an airtight container (glass bottle). The color difference changes on the surface of the preparations at 1 week, 2 weeks and 3 weeks were measured by the above color difference measurement method.
• Table 4 shows the color difference ( ⁇ E) of each preparation after storage of the results .
• rutile type was added as titanium dioxide
• the color difference ⁇ E from the first week to the third week was 3.0 or less even in a high temperature (humidity) environment in the light-shielding state and even when a large amount of titanium dioxide was added.
• anatase type was added as titanium dioxide
• the formulation with anatase-type titanium dioxide added to the coating layer undergoes a color change under high-temperature and high-humidity conditions, while the tablet with the rutile-type titanium dioxide added to the coating layer has an anatase type. Even if it was added in a larger amount than titanium dioxide, it was shown that it was difficult to cause a change in color tone. Even with the same titanium dioxide, it became clear that the stability of the preparation was remarkably different due to the difference in crystal form.
• Example 3 Long-term stability to temperature and humidity
• 180 mg / tablet or 125 mg / tablet azosemide-containing uncoated tablets were produced, and then the uncoated tablets were prepared using a coating solution in which the additives shown in Table 5 were dissolved in water. Coating was carried out to give Example 2.
• the mass% of each additive in Table 5 represents mass% relative to the azosemide-containing part.
• Each formulation of Example 1 and Example 2 was stored for 3 months in the open state or in an airtight container (glass bottle) under the following condition (b). After storage, changes in the color difference on the surface of the preparations at 1 month, 2 months and 3 months were measured by the method of color difference measurement.
• the resultant color difference of each formulation after storage shown in Table 5.
• the color difference ⁇ E between Example 1 and Example 2 was about 0.2 to 0.7, which was significantly lower than 3.0, where the color change can be identified visually. That is, the azosemide preparation containing rutile-type titanium dioxide in the coating layer was found to be stable even when stored for a long time under high humidity.
• Example 4 Temperature, humidity, and light stability
• 180 mg / tablet azosemide-containing uncoated tablets were produced, and then the uncoated tablets were coated using a coating solution in which the additives shown in Table 6 were dissolved in water. It was set as Example 3 and Comparative Example 2.
• the mass% of each additive in Table 6 represents mass% relative to the azosemide-containing part.
• Example 3 and Comparative Example 2 all have the same formulation except that the crystal form of titanium dioxide is different.
• Each of these preparations was stored under the following conditions (c) in an open state or in an airtight container (glass bottle) until the total illuminance reached 1.2 million lx, and then the color difference change on the preparation surface was measured by the color difference measurement method.
• the period until the total illuminance reaches 1.2 million lx is about 25 days.
• Table 6 shows the color difference ⁇ E of each preparation after the results were stored.
• Example 3 where the coating containing rutile-type titanium dioxide was applied, the color difference ⁇ E was significantly less than 3.0 under any condition, indicating that it was sufficiently stable against light.
• Comparative Example 2 containing anatase-type titanium dioxide in the coating layer, when stored in an airtight container having extremely little influence of humidity or the like, the color difference ⁇ E is significantly lower than 3.0, which is as good as Example 3. Despite this result, the color difference ⁇ E in an open state affected by humidity exceeded 3.0. This indicates that it is important to apply a coating using rutile type titanium dioxide in order to obtain a preparation that is stable not only to light and temperature but also to humidity.
• Table 6 shows the color difference ⁇ E value of each preparation after the results were stored.
• the color difference ⁇ E between Example 4 and Example 5 was less than 3.0. This indicates that the formulation of the present invention coated with rutile titanium dioxide is stable after storage at high humidity (75% RH).
• Titanium dioxide particle size Method The particle size of rutile titanium dioxide used for coating in the Example was measured by laser diffraction. Measurement was performed using a laser diffraction particle size distribution analyzer (Mastersizer 2000, manufactured by Malvern Instruments) with water as the dispersion medium and a rutile-type titanium dioxide having a refractive index of 2.7. The results are shown in Table 8.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Inorganic Chemistry (AREA)
• Urology & Nephrology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Dermatology (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (4)

Applications Claiming Priority (2)

Publications (1)

Family

ID=47668194

Family Applications (1)

Country Status (5)

Cited By (5)

Families Citing this family (1)

Citations (3)

Family Cites Families (2)

• 2012
  • 2012-01-11 JP JP2012515842A patent/JP5270798B1/ja active Active
  • 2012-01-11 KR KR1020137033940A patent/KR101877868B1/ko active IP Right Grant
  • 2012-01-11 CN CN201280000333.3A patent/CN103096888B/zh not_active Expired - Fee Related
  • 2012-01-11 WO PCT/JP2012/050305 patent/WO2013021660A1/ja active Application Filing
• 2013
  • 2013-06-13 HK HK13106980.4A patent/HK1179534A1/xx not_active IP Right Cessation

Patent Citations (3)

Non-Patent Citations (5)

Also Published As

Similar Documents

Legal Events