WO2011030659A1 - 制酸・緩下用錠剤 - Google Patents
制酸・緩下用錠剤 Download PDFInfo
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- WO2011030659A1 WO2011030659A1 PCT/JP2010/064066 JP2010064066W WO2011030659A1 WO 2011030659 A1 WO2011030659 A1 WO 2011030659A1 JP 2010064066 W JP2010064066 W JP 2010064066W WO 2011030659 A1 WO2011030659 A1 WO 2011030659A1
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- antacid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
- A61K33/08—Oxides; Hydroxides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
Definitions
- the present invention relates to an antacid / relaxing tablet mainly composed of magnesium oxide particles. More specifically, the present invention relates to a tablet for antacid and laxation in which the content of magnesium oxide particles in the tablet is as high as 85% by weight or more, the disintegration time is as short as 10 seconds or less, and the characteristics of the short disintegration time are maintained for a long time. .
- the present invention also relates to an antacid / relaxing tablet excellent in shape retention stability in which magnesium oxide particles are extremely free from abrasion and chipping in spite of a high content. Furthermore, the present invention relates to a method for producing an antacid / relaxation tablet mainly composed of magnesium oxide particles having the aforementioned characteristics.
- tablets mainly composed of magnesium oxide particles are known as antacid or laxative tablets, and the amount used has been increasing recently.
- Tablets containing the magnesium oxide particles are produced by blending magnesium oxide particles with additives such as a binder and a disintegrant and tableting.
- the present applicant has previously proposed a tablet containing magnesium oxide particles in a high content, which has a short disintegration time of 10 seconds or less and is therefore easy to drink when taken (see Patent Document 1).
- the tablet described in Patent Document 1 contains 88 to 97% by weight of magnesium oxide particles having a specific average secondary particle size, 1 to 10% by weight of crystalline cellulose or starch as a binder, and cloth as a disintegrant. It has a composition containing 1 to 3.5% by weight of carmellose sodium or carboxysteam sodium. This tablet has a composition in which hard magnesium oxide particles are easily tableted, and the disintegration time of the obtained tablet is 10 seconds or less and is easy to take.
- the tablet described in Patent Document 1 is an excellent magnesium oxide-containing tablet that is easy to tablet and easy to drink.
- this tablet has been found that when this tablet is kept in a dry state, its excellent disintegration lasts for a relatively long time, but when held under normal temperature and humidity conditions, the disintegration time is delayed.
- the tablets were found to lose the short disintegration characteristics in 4-6 days. did.
- the reason for this is not clear, but under high humidity conditions, some of the magnesium oxide particle crystals on the tablet surface absorb moisture and change to poorly soluble magnesium hydroxide, and the disintegrant component thickens due to moisture absorption. This is presumably due to reasons such as Further, the tablet has the advantage that it can be easily tableted and easily formed as a tablet, but the resulting tablet is not always broken, worn and chipped, and an improvement has been demanded.
- the present inventors have a long-term persistence of the excellent disintegration property (hereinafter, this property may be abbreviated as “short-time disintegration”) of the tableted tablet, and increase the strength of the tablet.
- short-time disintegration the excellent disintegration property of the tableted tablet
- the obtained tablets can be reduced even if they are kept under normal humidity conditions. It was found that time disintegration is sustained for a long time. The reason is probably that two types of disintegrants and binders interact with each other to prevent a part of the magnesium oxide particle crystals from changing to magnesium hydroxide, and prevent the disintegrant itself from thickening.
- the present inventors infer that. Further, according to the study by the present inventors, by making the shape of the tablet into a specific shape, there is little occurrence of tableting trouble, and the obtained tablet has little wear and end chipping and excellent shape retention stability. It turns out that it is obtained. It is considered that the effect of the shape retention stability contributes not only due to the specific shape but also due to the combination of two types of disintegrant and binder.
- a tablet comprising magnesium oxide particles as a main component, the tablet comprising: (a) the magnesium oxide particles have an average secondary particle diameter of 0.5 to 10 ⁇ m as measured by a laser diffraction scattering method. (B) the content of magnesium oxide particles is 85 to 96% by weight, (c) the content of crystalline cellulose as a binder is 2 to 8% by weight, and (d) disintegrant-I The content of croscarmellose sodium is 0.8 to 2.5% by weight, (e) the content of insoluble polyvinylpyrrolidone as disintegrant-II is 1 to 3.5% by weight, and (f) There is provided a tablet for antacid / relaxation characterized in that the content of the lubricant is 0.5 to 2% by weight.
- the antacid / relaxing tablet of the present invention preferably has the following mode.
- the magnesium oxide particles have an average secondary particle diameter of 1 to 7 ⁇ m measured by a laser diffraction scattering method.
- the content of the magnesium oxide particles is 88 to 92% by weight, (3)
- the content of crystalline cellulose as a binder is 4 to 6% by weight, (4)
- the content of croscarmellose sodium as disintegrant-I is 1.2 to 1.8% by weight, (5)
- the content of insoluble polyvinylpyrrolidone as disintegrant-II is 1.5 to 2.8% by weight, (6)
- the lubricant is calcium stearate, (7)
- the cylindrical plate-like vertical and horizontal planes have a dome shape, and the vertical and horizontal dome shapes are the following (a), (b) and (c) Requirements, (A) Corner angle is 25 to 45 ° (b) Corner angle horizontal distance is 0.30 to 1.0 mm (C) Cup depth 0.6-1.2mm Be satisfied
- the present invention is a tablet containing magnesium oxide particles at a high content, and disintegrates in the oral cavity in a short time by taking it, and its short-time disintegration lasts for a long time and is easy to drink for antacid and laxative use Tablets are provided. Moreover, the tablet of the present invention is easy to compress, and the obtained tablet is hardly worn or chipped and has excellent shape retention stability. Moreover, according to this invention, the manufacturing method of the said tablet is also provided.
- the tablet which has a preferable shape is shown,
- the tablet of this preferable shape has a dome shape in the columnar plate-like vertical and horizontal plane.
- a vertical cross-sectional structure along the center line is shown.
- the magnesium oxide particles used in the present invention have an average secondary particle diameter of 0.5 to 10 ⁇ m, preferably 1 to 7 ⁇ m, measured by a laser diffraction scattering method.
- the magnesium oxide particles in the tablet are 85% to 96% by weight, preferably 88% to 92%. Tablets with a high content percentage by weight are obtained.
- Magnesium oxide particles to be used for tableting may be in powder form or in any form of granules, but the granular form described below is more effective in preventing tablet wear and more excellent in shape retention stability. High content tablets can be obtained.
- Magnesium oxide particles are usually obtained by firing magnesium hydroxide particles. Magnesium oxide particles obtained by firing magnesium hydroxide having an average secondary particle size of 1 to 10 ⁇ m by a laser diffraction scattering method at 700 to 1,000 ° C. A tablet having the above-mentioned average secondary particle diameter and having excellent disintegration when tableted is obtained.
- crystalline cellulose is used as a binder.
- Crystalline cellulose is used in a proportion of 2 to 8% by weight, preferably 4 to 6% by weight in the tablet.
- croscarmellose sodium is used as the disintegrant-I
- insoluble polyvinylpyrrolidone is used as the disintegrant-II.
- Croscarmellose sodium as disintegrant-I is used in a proportion of 0.8 to 2.5% by weight, preferably 1.2 to 1.8% by weight in the tablet.
- the insoluble polyvinylpyrrolidone as the disintegrant-II is used in a proportion of 1 to 3.5% by weight, preferably 1.5 to 2.8% by weight in the tablet.
- the insoluble vinylpyrrolidone as the disintegrant-II is obtained by cross-linking soluble polyvinylpyrrolidone to insolubilize it.
- insoluble means slightly insoluble or insoluble in water, methanol, ethanol or diethyl ether.
- Soluble polyvinyl pyrrolidone has no effect of sustaining disintegration for a short time when used as a disintegrant in the tablet of the present invention.
- Insoluble polyvinylpyrrolidone as the disintegrant-II is commercially available under the common name Crospovidone, and specifically, sold by BASF JAPAN as Kollidone CL (trade name).
- a lubricant is blended in the tablet of the present invention.
- this lubricant include stearic acid and its salts (Na, Mg, Ca salts). Preferred are stearates, especially calcium stearate and magnesium stearate, but the most effective is calcium stearate. When these lubricants are too much, they are delayed in disintegration, and when they are too little, they adhere to the pestle and die. Therefore, the amount of lubricant added is preferably 0.5 to 2% by weight, more preferably 0.8 to 1.5% by weight.
- the aforementioned magnesium oxide particles, binder, disintegrant-I, disintegrant-II and lubricant may be mixed in a predetermined ratio and tableted, but preferably described later.
- the tableting pressure is preferably 5 to 12 kN, more preferably 6 to 10 kN as a punching pressure per tablet.
- the shape of the ridge may be any of a corner angle R, a corner plane, a corner round plane, etc. in addition to the R plane.
- the tablet according to the present invention can be blended with magnesium oxide particles at a high content ratio, and when taken with water, it quickly disintegrates in the mouth and becomes an easy-to-drink tablet.
- the tablet of the present invention was excellent in shape retention stability, and as a result of an acceleration test described later, the short-time disintegration property was maintained for a long time.
- the size and shape of the tablet of the present invention are not particularly different from normal oral tablets.
- the diameter is 5 to 12 mm, preferably 6 to 10 mm, particularly preferably 6 to 9 mm.
- the thickness is suitably 2 to 6 mm, preferably 2 to 5 mm, particularly preferably 2.5 to 4.5 mm.
- the weight per tablet is 100 to 1,000 mg, preferably 150 to 800 mg, and most preferably 200 to 600 mg.
- the above-mentioned components are mixed by the method as described below to obtain granules, and the obtained granules are tableted. It has been found that excellent tablets can be obtained.
- the manufacturing method of the following tablet is provided.
- (1) Mixing magnesium oxide particles having an average secondary particle diameter of 0.5 to 10 ⁇ m measured by laser diffraction scattering method, crystalline cellulose as a binder, croscarmellose sodium as a disintegrant-I and a lubricant And dry granulate to make magnesium oxide granules, (2) Next, crystalline magnesium as a binder, insoluble polyvinylpyrrolidone as a disintegrant-II, and a lubricant are blended with the magnesium oxide granules, and (3) the obtained granules are tableted.
- the above production method is characterized in that a granule is once formed, and the obtained granule is tableted, disintegrant-I is blended at the time of preparation of the granule, and disintegrant-II is blended after the granule is formed. ing.
- the crystalline cellulose is blended twice at the time of preparation of the granule and after the granulation, but each may be the same crystalline cellulose, but may be another crystalline cellulose.
- the average particle size of the granule is 250 to 550 ⁇ m, preferably 300 to 500 ⁇ m.
- the tablet since the tablet has the shape shown below, it is easy to tablet and a tablet with a low defect rate is obtained, and the obtained tablet is extremely excellent in shape retention stability. Turned out to be.
- the obtained tablet is a tablet that is less likely to be worn or chipped.
- the cylindrical plate has a dome shape on the vertical horizontal plane, and the dome shape on the vertical horizontal plane is the following (a ), (B) and (c) requirements, (A) Corner angle is 25 to 45 °, preferably 28 to 40 ° (B) The corner horizontal distance is 0.30 to 1.0 mm, preferably 0.35 to 0. 85mm (C) The cup depth is 0.6 to 1.2 mm, preferably 0.65 to 1.1. mm Antacid and laxative tablets are provided (hereinafter this tablet may be referred to as “Tablet A”).
- FIG. 1 shows a vertical cross-sectional structure along the center line 1 in the cylindrical shape of the tablet A.
- the cross-sectional structure in the vertical direction along the center line of the tablet A (hereinafter sometimes simply referred to as “cross-sectional shape”) is intended for the left and right with the center line 1 as the central axis.
- the shape is based on a quadrilateral formed from four sides of an upper horizontal plane 2-a, a lower horizontal plane 2-b, a peripheral side surface 3-a, and a peripheral side surface 3-b, and the upper horizontal plane 2-
- a dome shape is formed on a and a dome shape is also formed on the lower horizontal surface 2-b.
- the dome shape on the upper horizontal surface and the dome shape on the lower horizontal surface have the same shape in the vertical direction.
- Tablet A of the present invention has the following characteristics (a) to (e) in cross-sectional shape.
- the basic skeleton part has a round plate shape)
- the angle ⁇ (referred to as “corner angle”) is 25 to 45 ° from the horizontal plane formed by the dome-shaped linear side 8 from both ends of the upper horizontal plane 2-a.
- the distance 9 (referred to as “corner horizontal distance”) obtained by projecting the length of the straight side 8 with the corner angle onto the upper horizontal plane is 0.35 to 0.85 mm;
- the length 7 (referred to as “cup depth”) of the center line from the upper horizontal plane to the apex of the dome shape is 0.65 to 1.1 mm;
- the dome shape formed on the upper dome horizontal plane 4-a is preferably a part of a circle having a single curvature R (referred to as “curvature R”),
- the diameter (radius) of the curvature R is advantageously 7 to 25 mm, preferably 8 to 22 mm.
- the tablet A of the present invention is characterized in that the cross-sectional shape has the shape and length shown in the above (a) to (e).
- the corner angle ⁇ is 25 to 45 °, preferably 28 to 40 °, particularly preferably 29 to 33 °, and the side 8 from the end of the horizontal plane forming this corner angle is linear, It is important that the linear length is a certain length.
- the cross-sectional shape of the tablet A of the present invention is a dome-shaped shape that is formed on the upper and lower horizontal planes. It is characterized by having a two-stage structure consisting of parts.
- the tablet A of the present invention has a cross-sectional shape in which the corner horizontal distance 9 is 0.3 to 1.0 mm, preferably 0.35 to 0.85 mm.
- the cup depth 7 is 0.6 to 1.2 mm, preferably 0.65 to 1.1 mm.
- Tablet A of the present invention is mainly composed of magnesium oxide particles, and is intended for tablets each having a weight of about 200 mg to about 600 mg.
- the size of the tablet of the present invention can be changed by changing the thickness and diameter of the tablet.
- the tablet diameter 5 (the length of the upper and lower horizontal surfaces) is 6 to 14 mm, preferably 7 to 11 mm, and the thickness 6 is 4 to 6 mm, preferably 4.2 to 5.6 mm. .
- the diameter 5 and the thickness 6 may be appropriately determined from the above ranges based on the desired weight per tablet.
- a tablet containing a high content of magnesium oxide particles and compressed and compressed and by specifying the shape of the compressed tablet, transport process, storage process, and packaging In a process or a sales process, the tablet can be provided with extremely low shape wear and end chipping and excellent shape retention stability.
- the magnesium oxide particle-containing tablet according to the present invention can have a high content ratio of magnesium oxide particles, and is extremely excellent in shape stability.
- the disintegration time is very short and easy to drink. It has the advantage that its disintegration lasts.
- the tablet of the present invention is orally administered for antacid or laxative use.
- the dose depends on the purpose and the condition. Typically, 2g per day is administered per adult. This 2 g is usually equivalent to 6 to 8 tablets on average, and can be administered once to 3 times a day.
- Formulation Example According to the formulation examples in Table 1, Table 2, and Table 3, the following production method was used.
- the 330 mg and 250 mg preparations are basically the same proportional prescription as the 500 mg preparation.
- the trade names (or trade names) and the sources of the reagents used in the examples and comparative examples are as follows.
- Examples 1, 3, 5 (500 mg, 330 mg, 250 mg formulations)
- Container type mixer with 17.17 kg of magnesium oxide particles with an average secondary particle size of 6.50 ⁇ m, 0.33 kg of crystalline cellulose-I, 0.33 kg of high-formability crystalline cellulose-II, 0.27 kg of croscarmellose sodium, and 0.07 kg of calcium stearate
- the molded product granulated at a roll pressure of 5 MPa with a roll mold dry granulator was granulated with an oscillator grinder.
- Examples 2, 4, and 6 (500 mg, 330 mg, and 250 mg formulations) After mixing 17.17 kg of magnesium oxide particles having an average secondary particle size of 6.50 ⁇ m, 0.17 kg of crystalline cellulose-I, 0.50 kg of crystalline cellulose-II, 0.27 kg of croscarmellose sodium, 0.07 kg of calcium stearate in a container type mixer, Granules were produced from a molded product granulated with a roll mold dry granulator at a roll pressure of 5 MPa with an oscillator grinder.
- Comparative Example 1 (500 mg formulation) After mixing 17.17 kg of magnesium oxide particles with an average secondary particle size of 6.50 ⁇ m, 1.19 kg of crystalline cellulose-I and 0.59 kg of croscarmellose sodium in a container type mixer, the roll pressure is 5 MPa in a roll molding type dry granulator. Granules were produced from the molded product granulated in step 1 using an oscillator grinder. This granulated granule (19.15 kg) and calcium stearate (0.20 kg) were mixed with a container-type mixer to obtain tablet granules (see Table 4). Table 5 shows the physical properties of the tablet granules.
- Comparative Example 2 (330 mg formulation) After mixing 17.17 kg of magnesium oxide particles with an average secondary particle size of 6.50 ⁇ m, 1.20 kg of crystalline cellulose-I, 0.36 kg of corn starch and 0.59 kg of croscarmellose sodium in a container type mixer, a roll molding type dry granulator Granules were formed from the molded product granulated with a roll pressure of 5 MPa using an oscillator type pulverizer. This granulated granule (19.3 kg) and calcium stearate (0.21 kg) were mixed with a container-type mixer to obtain tablet granules (see Table 4). Table 6 shows the granule physical properties of the tablet granules.
- Comparative Example 3 (250 mg formulation) After mixing 17.17 kg of magnesium oxide particles with an average secondary particle size of 6.50 ⁇ m, 1.24 kg of crystalline cellulose-I, 0.34 kg of corn starch and 0.62 kg of croscarmellose sodium in a container type mixer, a roll molding type dry granulator Granules were formed from the molded product granulated with a roll pressure of 5 MPa using an oscillator type pulverizer. This granulated granule (19.37 kg) and calcium stearate (0.21 kg) were mixed with a container-type mixer to form tablet granules (see Table 4). Table 7 shows the physical properties of the tablet granules.
- Examples 7 and 8 and Comparative Example 4 500 mg formulation
- the diameter is 10.5 mm and the corner angle R is effective for suppressing edge wear (corner angle 30 °, corner horizontal distance 0.8 mm, cup depth 0.94 mm, R20
- using the granules produced in Comparative Example 3 using a single R punch (diameter 10.5 mm, cup depth 0.78 mm, R17.5), 580 mg / tablet, 5.1 mm thick magnesium oxide tablets were obtained ( Comparative Example 3).
- “single R” means a shape having no corner angle and no corner horizontal distance.
- Table 8 shows the physical property values of the tablets.
- Examples 9, 10 and Comparative Example 5 (330 mg formulation) Using the granules produced in Examples 3 and 4, a diameter of 9.0 mm, a corner angle R which is effective in suppressing edge wear (corner angle 30 °, corner horizontal distance 0.68 mm, cup depth 0.87 mm, R14 7) was tableted with a tableting pressure of 9 to 10 KN using a rotary tableting machine equipped with 24 tablets to obtain magnesium oxide tablets weighing 376 mg and having a thickness of 4.7 mm.
- Examples 11 and 12 and Comparative Example 6 250 mg formulation
- a single corner angle R effective for suppressing edge wear (corner angle 30 °, corner horizontal distance 0.61 mm, cup depth 0.78 mm, R12 .8) was tableted with a tableting pressure of 9 to 10 KN using a rotary tableting machine equipped with 24 tablets to obtain magnesium oxide tablets with a weight of 285 mg and a thickness of 4.4 m per tablet.
- Tables 11 to 13 show the relationship between the formulation of the formulation and the combination of tablet-shaped glaze forms (single R and corner single R) and tablet physical properties (tablet hardness and friability).
- the 250 mg formulation, 330 mg formulation, and 500 mg formulation were reduced in friability in the tablet-shaped form of the present invention, confirming the superiority.
- the friability was greatly reduced.
- Examples 16 and 17 and Comparative Example 10 (Investigation of inhibition of disintegration delay over time of uncoated tablets) Stability evaluation was performed using the tablets of Examples 7 and 8 and Comparative Example 4. The test was carried out under accelerated aging conditions (40 ° C-RH75%), and the delay suppression state of the disintegration time in the uncoated tablet was measured. The results are shown in Table 14.
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Abstract
Description
また前記錠剤は打錠化が容易で錠剤として成形し易いという利点をしていたが、得られた錠剤の割れ、摩損および端欠けが少なからず発生し、その改良が要望されていた。
また本発明者らの研究によれば、錠剤の形状を特定形状とすることにより、打錠障害の発生が少なく、得られた錠剤の摩損や端欠けが少なく形状保持安定性の優れた錠剤が得られることが判った。この形状保持安定性の効果は、特定形状によることばかりでなく、2種類の崩壊剤と結合剤の組合せによることも寄与しているものと考えられる。
(1)該酸化マグネシウム粒子は、レーザー回折散乱法で測定された平均2次粒子径が1~7μmであること、
(2)該酸化マグネシウム粒子の含有割合が88~92重量%であること、
(3)結合剤としての結晶セルロースの含有割合が4~6重量%であるこ
と、
(4)崩壊剤-Iとしてのクロスカルメロースナトリウムの含有割合が1.2~1.8重量%であること、
(5)崩壊剤-IIとしての不溶性ポリビニルピロリドンの含有割合が1.5~2.8重量%であること、
(6)滑沢剤がステアリン酸カルシウムであること、
(7)円柱板状の上下水平面にドーム型形状を有し、その上下水平面におけるドーム型形状は、円柱板状の中心線の直角断面形状において、下記(a)、(b)および(c)の要件、
(a)隅角角度が25~45゜
(b)隅角水平距離が0.30~1.0mm
(c)カップ深さが0.6~1.2mm
を満足すること、
(8)前記直角断面形状において(a)隅角角度が28~40゜であるこ
と、
(9)前記直角断面形状において、(b)隅角水平距離が0.35~0.85mmであること、
(10)前記直角断面形状において(c)カップ深さが0.65~1.1mmであること、
(11)前記直角断面形状における水平面の長さ(直径)が7~11mmであること、
また、本発明によれば、(1)レーザー回折散乱法で測定された平均2次粒子径が0.5~10μmの酸化マグネシウム粒子、結合剤としての結晶セルロース、崩壊剤-Iとしてのクロスカルメロースナトリウムおよび滑沢剤を混合して乾式造粒して酸化マグネシウム顆粒物を作り、
(2)次いでこの酸化マグネシウム顆粒物に、結合剤としての結晶セルロース、崩壊剤-IIとしての不溶性ポリビニルピロリドンおよび滑沢剤を配合し、そして
(3)得られた顆粒物を打錠することを特徴とする酸化マグネシウム粒子を主成分とする制酸・緩下用錠剤の製造方法が提供される。
前記酸化マグネシウム顆粒物は平均粒径が250~550μmであることが好ましい。
この滑沢剤としては、例えばステアリン酸およびその塩(Na,Mg,Ca塩)等がある。好ましくはステアリン酸塩、特にステアリン酸カルシウムおよびステアリン酸マグネシウムであるが、最も有効なものは、ステアリン酸カルシウムである。これら滑沢剤は、多すぎると崩壊遅延となり、少なすぎると杵、臼に付着する。従って、滑沢剤の添加量は0.5~2重量%が好ましく、さらに好ましくは、0.8~1.5重量%である。
(1)レーザー回折散乱法で測定された平均2次粒子径が0.5~10μmの酸化マグネシウム粒子、結合剤としての結晶セルロース、崩壊剤-Iとしてのクロスカルメロースナトリウムおよび滑沢剤を混合して乾式造粒して酸化マグネシウム顆粒物を作り、
(2)次いでこの酸化マグネシウム顆粒物に、結合剤としての結晶セルロース、崩壊剤-IIとしての不溶性ポリビニルピロリドンおよび滑沢剤を配合し、そして
(3)得られた顆粒物を打錠することを特徴とする酸化マグネシウム粒子を主成分とする制酸・緩下用錠剤の製造方法。
(a)隅角角度が25~45゜、好ましくは28~40°
(b)隅角水平距離が0.30~1.0mm、好ましくは0.35~0.
85mm
(c)カップ深さが0.6~1.2mm、好ましくは0.65~1.1
mm
を満足する制酸・緩下用錠剤が提供される(以下この錠剤を“錠剤A”と称することがある)。
図1は、錠剤Aの円柱形状における中心線1に沿って垂直方向の断面構造を示すものである。図1に示すように、錠剤Aの中心線に沿って垂直方向の断面構造(以下単に“断面形状”ということがある)は、中心線1を中心軸として左右が対象であり、また円柱板状は、上部水平面2-a、下部水平面2-b、周囲側面3-aおよび周囲側面3-bの4つの辺から形成される4辺形を基本骨格とし、この基本骨格の上部水平面2-a上にドーム型形状および下部水平面2-b上にもドーム型形状を有している。この上部水平面上のドーム型形状と下部水平面上のドーム型形状は上下方向で対象に同じ形状を有している。
(a)円柱板状に基づく4辺形の基本骨格を有すること、
(基本骨格部分は丸い板状形状である)
(b)その上部水平面2-aの両端部からドーム型形状の直線状の辺8がなす水平面から角度θ(“隅角角度”という)が25~45°であること、
(c)前記隅角角度の直線状の辺8の長さを、上部水平面に投影した距離9(“隅角水平距離”という)が0.35~0.85mmであること、
(d)上部水平面からのドーム型形状の頂点までの中心線の長さ7(“カップ深さ”という)が0.65~1.1mmであること、
(e)中心線1を中心軸として左右対象であり、また上部水平面上と下部水平面上におけるドーム型形状は上下対象の形をしていること、
さらに本発明の錠剤は断面形状において、上ドーム水平面4-a上に形成されるドーム型形状は、単一の曲率R(“曲率R”という)を有する円形の一部であることが望ましく、その曲率Rの径(半径)は、7~25mm、好ましくは8~22mmであるのが有利である。
そのうち、隅角角度θが25~45°、好ましくは28~40°、特に好ましくは29~33°であり、この隅角角度を形成する水平面端部からの辺8が直線状であり、その直線状の長さが一定の長さであることが肝要である。
実施例および比較例において、錠剤の(a)硬度、(b)崩壊時間、(c)摩損度、(d)錠剤厚み、(e)顆粒の粒度分布、(f)顆粒の平均粒子径、(g)顆粒のかさ密度は以下に記載する測定法によって測定された値を意味する。
(a)硬度
錠剤硬度計 DC-50(岡田精工(株))を用いて、錠剤硬度を測定し
た。
(b)崩壊時間
「第15局改正日局試験法、一般試験法・崩壊試験法に準拠し、試験
液は水を用いた。
(c)摩損度
全質量が6.5gにできるだけ近い量に相当する錠剤を試験試料とし、
100回転(24~26回転/分)後、摩損度(初期質量に対する減少質量
の百分率)を算出した。
「第15局改正日局試験法、参考情報・錠剤の摩損度試験法」に準拠。
摩損度=((摩損前の錠剤初期質量(g)-摩損後の錠剤質量(g))×100
摩損前の錠剤初期質量(g)
(d)錠剤厚み
シックネスゲージ(新潟精機)を用いて、錠剤厚みを測定した。
(e)顆粒の粒度分布
電磁振動ふるい装置:エンデコッツ製オクタゴン
使用ふるい:850、710、500、355、180、150、106μm
試験条件:振動強度5、篩時間5分
試料約100gをふるい及び受器を重ね合わせた容器の上段のふるいに
いれ、上ぶたをした後、装置にセットする。上記の条件で試験した
後、各々のふるい及び受器の残留物の重量を量る(0.01g単位ま
で)。
(f)顆粒の平均粒子径D50
上記粒度分布の大きい粒子から積算し50重量%積算値の粒径とし
た。
(g)顆粒のかさ密度
試料をJIS K5101 見掛け比容静置法で使用する容量100mlの容器
に標準ふるい16メッシュ(目開き1.0mm)を施し、容器が山盛りに
なるまで入れる。
直線にへらで山盛りを削り取る。
受器の内容物の質量を0.01gの単位まで量る。
かさ密度(g/ml)=F/100 F:受器内の試料の質量、100:受器
の容量(ml)
表1、表2、表3の処方例に従い、下記の製造法で実施した。
なお、330mg製剤及び250mg製剤においては、基本的には500mg製剤とほぼ同一比例処方である。
実施例および比較例において使用された試剤の商品名(または商標名)および入手先は下記のとおりである。
(a)酸化マグネシウム粒子:“酸化マグネシウムT”
(協和化学工業(株)社製)
(b)結晶セルロース-I:“VIVAPUR 101 Premium”
(JRS Pharma Gmbh&Co.,Kg.,社製)
(c)結晶セルロース-II: “セオラスKG-1000”
(旭化成ケミカルズ(株)社製)
(d)トウモロコシデンプン: “精製乾燥殺菌コーンスターチ”
(松谷化学工業(株)社製)
(e)クロスカルメロ-スナトリウム: “キッコレートND-2HS”
(ニチリン化学工業(株)社製)
(f)ステアリン酸カルシウム: “ステアリン酸カルシウム 植物性”
(太平化学産業(株)社製)
(g)不溶性ポリビニルピロリドン(クロスポビドン):
“Kollidon CL”(BASF JAPAN社製)
なお表1~表3中、“内部添加剤”は顆粒剤を調製する場合に使用された試剤を意味し、“外部添加剤”は一旦得られた顆粒剤(本整粒顆粒)にさらに配合された試剤を意味する。
平均2次粒子径が6.50μmの酸化マグネシウム粒子17.17kg、結晶セルロース-I 0.33kg、高成形性の結晶セルロース-II 0.33kg、クロスカルメロースナトリウム 0.27kg、ステアリン酸カルシウム0.07kgをコンテナ型混合機にて混合後、ロール成形型乾式造粒機にてロール圧力5MPaで造粒した成形物をオシレーター式粉砕機にて顆粒を製した。本整粒顆粒18.17kgとステアリン酸カルシウム0.17kgをコンテナ型混合機にて混合後、さらに外部添加剤のクロスポビドン 0.50kg、結晶セルロース-II 0.17kgをコンテナ型混合機にて混合し製錠顆粒とした(表4参照)。但し、330mg製剤は、外部添加剤の結晶セルロース-II 0.16kgとする。その製錠顆粒物性を表5、6、7に示す。
平均2次粒子径が6.50μmの酸化マグネシウム粒子17.17kg、結晶セルロース-I 0.17kg、結晶セルロース-II 0.50kg、クロスカルメロースナトリウム0.27kg、ステアリン酸カルシウム0.07kgをコンテナ型混合機にて混合後、ロール成形型乾式造粒機にてロール圧力5MPaで造粒した成形物をオシレーター式粉砕機にて顆粒を製した。本整粒顆粒18.17kgとステアリン酸カルシウム0.17kgをコンテナ型混合機にて混合後、さらに外部添加剤クロスポビドン0.50kg、結晶セルロース-II 0.17kgをコンテナ型混合機にて混合し製錠顆粒とした(表4参照)。但し、330mg製剤は、外部添加剤の結晶セルロース-II 0.16kgとする。その製錠顆粒物性を表5、6、7に示す。
平均2次粒子径が6.50μmの酸化マグネシウム粒子17.17kg、結晶セルロース-I 1.19kg、クロスカルメロースナトリウム0.59kgをコンテナ型混合機にて混合後、ロール成形型乾式造粒機にてロール圧力5MPaで造粒した成形物をオシレーター式粉砕機にて顆粒を製した。本整粒顆粒19.15kgとステアリン酸カルシウム0.20kgをコンテナ型混合機にて混合し製錠顆粒とした(表4参照)。その製錠顆粒物性を表5に示す。
平均2次粒子径が6.50μmの酸化マグネシウム粒子17.17kg、結晶セルロース-I 1.20kg、トウモロコシデンプン0.36kg、クロスカルメロースナトリウム0.59kgをコンテナ型混合機にて混合後、ロール成形型乾式造粒機にてロール圧力5MPaで造粒した成形物をオシレーター式粉砕機にて顆粒を製した。本整粒顆粒19.3kgとステアリン酸カルシウム0.21kgをコンテナ型混合機にて混合し製錠顆粒とした(表4参照)。その製錠顆粒の顆粒物性を表6に示す。
平均2次粒子径が6.50μmの酸化マグネシウム粒子17.17kg、結晶セルロース-I 1.24kg、トウモロコシデンプン0.34kg、クロスカルメロースナトリウム 0.62kgをコンテナ型混合機にて混合後、ロール成形型乾式造粒機にてロール圧力5MPaで造粒した成形物をオシレーター式粉砕機にて顆粒を製した。本整粒顆粒19.37kgとステアリン酸カルシウム0.21kgをコンテナ型混合機にて混合し製錠顆粒とした(表4参照)。その製錠顆粒物性を表7に示す。
実施例1、2で製した顆粒を用い、直径10.5mm、エッジ摩損抑制に有効な隅角単R杵(隅角角度30°、隅角水平距離0.8mm、カップ深さ0.94mm、R20°)を24本装着したロータリー打錠機にて、打錠圧力15~16KNで製錠し、1錠当たり重量570mg、厚み5.1mmの酸化マグネシウム錠剤を得た。
一方、比較例3で製した顆粒を用い、単R杵(直径10.5mm、カップ深さ0.78mm、R17.5)を用い、580mg/錠、厚み5.1mmの酸化マグネシウム錠剤を得た(比較例3)。ここで“単R”とは隅角角度および隅角水平距離を有しない形状を意味する。その錠剤物性値を表8に示す。
実施例3、4で製した顆粒を用い、直径9.0mm、エッジ摩損抑制に有効な隅角単R杵(隅角角度30°、隅角水平距離0.68mm、カップ深さ0.87mm、R14.7)を24本装着したロータリー打錠機にて、打錠圧力9~10KNで製錠し、1錠当たり重量376mg、厚み4.7mmの酸化マグネシウム錠剤を得た。
一方、比較例2で製した顆粒を用い、単R杵(直径9.0mm、カップ深さ0.77mm、R13mm)を用い、375mg/錠、厚み4.7mmの酸化マグネシウム錠剤を得た(比較例5)。その錠剤物性値を表9に示す。
実施例5、6で製した顆粒を用い、直径8.0mm、エッジ摩損抑制に有効な隅角単R杵(隅角角度30°、隅角水平距離0.61mm、カップ深さ0.78mm、R12.8)を24本装着したロータリー打錠機にて、打錠圧力9~10KNで製錠し、1錠当たり重量285mg、厚み4.4mの酸化マグネシウム錠剤を得た。
一方、比較例3で製した顆粒を用い、単R杵(直径8.0mm、カップ深さ0.65mm、R12)を用い、285mg/錠、厚み4.4mmの酸化マグネシウム錠剤を得た(比較例6)。その錠剤物性値を表10に示す。
製剤処方及び錠剤形状杵剤形(単Rと隅角単R)の組合せと錠剤物性(錠剤硬度及び摩損度)の関係を表11~13に示す。その結果、250mg製剤、330mg製剤、500mg製剤ともに、本発明の錠剤形状のものは摩損度の低減となり、優位性が確認された。また杵剤形を隅角単R杵に変更することで大幅な摩損度の低減となった。
実施例7、8および比較例4の錠剤を用い、安定性評価を実施した。試験は加速経時条件下(40℃-RH75%)、裸錠における崩壊時間の遅延抑制状況を測定した。その結果を表14に示す。
机上80cmの高さから、錠剤入りボトルを垂直に落下させ、錠剤の割れ欠けを調べた。その結果を、表15に示す。その結果、本発明の錠剤は、大幅に錠剤の割れ欠けの発現が抑制された。
Claims (15)
- 酸化マグネシウム粒子を主成分とする錠剤であって、該錠剤は(a)該酸化マグネシウム粒子は、レーザー回折散乱法で測定された平均2次粒子径が0.5~10μmであり、(b)該酸化マグネシウム粒子の含有割合が85~96重量%であり、(c)結合剤としての結晶セルロースの含有割合が2~8重量%であり、(d)崩壊剤-Iとしてクロスカルメロースナトリウムの含有割合が0.8~2.5重量%であり、(e)崩壊剤-IIとして不溶性ポリビニルピロリドンの含有割合が1~3.5重量%であり、かつ(f)滑沢剤の含有割合が0.5~2重量%であることを特徴とする制酸・緩下用錠剤。
- 該酸化マグネシウム粒子は、レーザー回折散乱法で測定された平均2次粒子径が1~7μmである請求項1記載の制酸・緩下用錠剤。
- 該酸化マグネシウム粒子の含有割合が88~92重量%である請求項1記載の制酸・緩下用錠剤。
- 結合剤としての結晶セルロースの含有割合が4~6重量%である請求項1記載の制酸・緩下用錠剤。
- 崩壊剤-Iとしてのクロスカルメロースナトリウムの含有割合が1.2~1.8重量%である請求項1記載の制酸・緩下用錠剤。
- 崩壊剤-IIとしての不溶性ポリビニルピロリドンの含有割合が1.5~2.8重量%である請求項1記載の制酸・緩下用錠剤。
- 滑沢剤がステアリン酸カルシウムである請求項1記載の制酸・緩下用錠剤。
- 円柱板状の上下水平面にドーム型形状を有し、その上下水平面におけるドーム型形状は、円柱板状の中心線の直角断面形状において、下記(a)、(b)および(c)の要件、
(a)隅角角度が25~45゜
(b)隅角水平距離が0.30~1.0mm
(c)カップ深さが0.6~1.2mm
を満足する請求項1記載の制酸・緩下用錠剤。 - (a)隅角角度が28~40゜である請求項8記載の制酸・緩下用錠剤。
- (b)隅角水平距離が0.35~0.85mmである請求項8記載の制酸・緩下用錠剤。
- (c)カップ深さが0.65~1.1mmである請求項8記載の制酸・緩下用錠剤。
- 直角断面形状における水平面の長さ(直径)が7~11mmである請求項8記載の制酸・緩下用錠剤。
- (1)レーザー回折散乱法で測定された平均2次粒子径が0.5~10μmの酸化マグネシウム粒子、結合剤としての結晶セルロース、崩壊剤-Iとしてのクロスカルメロースナトリウムおよび滑沢剤を混合して乾式造粒して酸化マグネシウム顆粒物を作り、
(2)次いでこの酸化マグネシウム顆粒物に、結合剤としての結晶セルロース、崩壊剤-IIとしての不溶性ポリビニルピロリドンおよび滑沢剤を配合し、そして
(3)得られた顆粒物を打錠することを特徴とする酸化マグネシウム粒子を主成分とする制酸・緩下用錠剤の製造方法。 - 酸化マグネシウム顆粒物は平均粒径が250~550μmである請求項13記載の制酸・緩下用錠剤の製造方法。
- 請求項1または請求項13記載の錠剤の制酸または緩下への使用。
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JP2011530796A JP5696050B2 (ja) | 2009-09-08 | 2010-08-20 | 制酸・緩下用錠剤 |
US13/393,713 US20120156293A1 (en) | 2009-09-08 | 2010-08-20 | Antacid and laxative tablet |
EP10815256.2A EP2476423A4 (en) | 2009-09-08 | 2010-08-20 | TABLET ANTIACIDE AND LAXATIVE |
CN201080040020.1A CN102481315B (zh) | 2009-09-08 | 2010-08-20 | 抗酸缓泻用片剂 |
MX2012002789A MX2012002789A (es) | 2009-09-08 | 2010-08-20 | Tableta antiacida y laxante. |
CA2772750A CA2772750A1 (en) | 2009-09-08 | 2010-08-20 | Antacid and laxative tablet |
RU2012113740/15A RU2501561C1 (ru) | 2009-09-08 | 2010-08-20 | Антацидная и слабительная таблетка |
BR112012005163A BR112012005163A2 (pt) | 2009-09-08 | 2010-08-20 | comprimido antiácido e laxante compreendendo partículas de óxido de magnésio, processo para produzir um comprimido antiácido e laxante, e, uso do comprimido |
AU2010293637A AU2010293637B2 (en) | 2009-09-08 | 2010-08-20 | Antacid and laxative tablet |
HK12112239.2A HK1171381A1 (en) | 2009-09-08 | 2012-11-28 | Antacid and laxative tablet |
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US (1) | US20120156293A1 (ja) |
EP (1) | EP2476423A4 (ja) |
JP (1) | JP5696050B2 (ja) |
KR (1) | KR101560438B1 (ja) |
CN (1) | CN102481315B (ja) |
AU (1) | AU2010293637B2 (ja) |
BR (1) | BR112012005163A2 (ja) |
CA (1) | CA2772750A1 (ja) |
HK (1) | HK1171381A1 (ja) |
MX (1) | MX2012002789A (ja) |
RU (1) | RU2501561C1 (ja) |
TW (1) | TWI466689B (ja) |
WO (1) | WO2011030659A1 (ja) |
Cited By (4)
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WO2016175042A1 (ja) * | 2015-04-30 | 2016-11-03 | 協和化学工業株式会社 | マグネシウム化合物を有効成分として含有する医薬製剤 |
US10004763B2 (en) | 2014-02-25 | 2018-06-26 | Konoshima Chemical Co., Ltd. | Magnesium oxide granules for pharmaceutical applications or for use as food additives |
WO2020101016A1 (ja) | 2018-11-16 | 2020-05-22 | 協和化学工業株式会社 | 緩下用錠剤 |
JP7340572B2 (ja) | 2021-08-20 | 2023-09-07 | セトラスホールディングス株式会社 | 酸化マグネシウム錠剤 |
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EP2422771A4 (en) * | 2009-04-22 | 2014-02-19 | Kyowa Chem Ind Co Ltd | TABLET AND PILONS FOR THIS |
CN107137233B (zh) * | 2017-04-20 | 2022-09-13 | 扬州大学 | 一种具有鸡尾酒疗效口服药片的加工方法 |
DE102019213938A1 (de) * | 2019-09-12 | 2021-03-18 | Fim Biotech Gmbh | Poröses Magnesiumoxidcarbonat zur Verwendung als Mittel zur Bindung von Phosphaten im Dünndarm mit dem Ziel der Reduzierung von nichtübertragbaren Krankheiten |
KR102588239B1 (ko) * | 2021-12-22 | 2023-10-12 | 알고케어 주식회사 | 기둥 형상의 제형을 제공하는 디스펜서 |
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- 2010-08-20 MX MX2012002789A patent/MX2012002789A/es not_active Application Discontinuation
- 2010-08-20 RU RU2012113740/15A patent/RU2501561C1/ru not_active IP Right Cessation
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- 2010-08-20 EP EP10815256.2A patent/EP2476423A4/en not_active Withdrawn
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US10004763B2 (en) | 2014-02-25 | 2018-06-26 | Konoshima Chemical Co., Ltd. | Magnesium oxide granules for pharmaceutical applications or for use as food additives |
WO2016175042A1 (ja) * | 2015-04-30 | 2016-11-03 | 協和化学工業株式会社 | マグネシウム化合物を有効成分として含有する医薬製剤 |
WO2020101016A1 (ja) | 2018-11-16 | 2020-05-22 | 協和化学工業株式会社 | 緩下用錠剤 |
KR20210076066A (ko) | 2018-11-16 | 2021-06-23 | 교와 가가꾸고교 가부시키가이샤 | 완하용 정제 |
JPWO2020101016A1 (ja) * | 2018-11-16 | 2021-09-02 | 協和化学工業株式会社 | 緩下用錠剤 |
JP2022105754A (ja) * | 2018-11-16 | 2022-07-14 | 協和化学工業株式会社 | 緩下用錠剤 |
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JP7360503B2 (ja) | 2018-11-16 | 2023-10-12 | セトラスホールディングス株式会社 | 緩下用錠剤 |
JP7340572B2 (ja) | 2021-08-20 | 2023-09-07 | セトラスホールディングス株式会社 | 酸化マグネシウム錠剤 |
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CA2772750A1 (en) | 2011-03-17 |
KR101560438B1 (ko) | 2015-10-14 |
JP5696050B2 (ja) | 2015-04-08 |
JPWO2011030659A1 (ja) | 2013-02-07 |
RU2501561C1 (ru) | 2013-12-20 |
TW201109042A (en) | 2011-03-16 |
RU2012113740A (ru) | 2013-10-20 |
KR20120064071A (ko) | 2012-06-18 |
EP2476423A1 (en) | 2012-07-18 |
TWI466689B (zh) | 2015-01-01 |
BR112012005163A2 (pt) | 2016-05-03 |
HK1171381A1 (en) | 2013-03-28 |
AU2010293637B2 (en) | 2015-12-03 |
US20120156293A1 (en) | 2012-06-21 |
EP2476423A4 (en) | 2014-02-19 |
MX2012002789A (es) | 2012-06-01 |
AU2010293637A1 (en) | 2012-03-22 |
CN102481315B (zh) | 2014-11-19 |
CN102481315A (zh) | 2012-05-30 |
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