JP4643922B2 - Granules containing pantethine - Google Patents
Granules containing pantethine Download PDFInfo
- Publication number
- JP4643922B2 JP4643922B2 JP2004096257A JP2004096257A JP4643922B2 JP 4643922 B2 JP4643922 B2 JP 4643922B2 JP 2004096257 A JP2004096257 A JP 2004096257A JP 2004096257 A JP2004096257 A JP 2004096257A JP 4643922 B2 JP4643922 B2 JP 4643922B2
- Authority
- JP
- Japan
- Prior art keywords
- pantethine
- granular material
- calcium silicate
- granule
- porous calcium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- DJWYOLJPSHDSAL-UHFFFAOYSA-N Pantethine Natural products OCC(C)(C)C(O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)C(O)C(C)(C)CO DJWYOLJPSHDSAL-UHFFFAOYSA-N 0.000 title claims description 80
- 229960000903 pantethine Drugs 0.000 title claims description 80
- 235000008975 pantethine Nutrition 0.000 title claims description 80
- 239000011581 pantethine Substances 0.000 title claims description 80
- DJWYOLJPSHDSAL-ROUUACIJSA-N pantethine Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSSCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO DJWYOLJPSHDSAL-ROUUACIJSA-N 0.000 title claims description 80
- 239000008187 granular material Substances 0.000 title claims description 76
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 40
- 239000000378 calcium silicate Substances 0.000 claims description 37
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 37
- 239000002245 particle Substances 0.000 claims description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000000843 powder Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 12
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- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 4
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010010774 Constipation Diseases 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 2
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Description
本発明は、パンテチンを含有する粒状物およびその粒状物を含む固形製剤に関する。 The present invention relates to a granule containing pantethine and a solid preparation containing the granule.
パンテチンは、(1)パントテン酸欠乏症の予防および治療、(2)消耗性疾患、甲状腺機能亢進症、妊産婦、授乳婦などのパントテン酸の需要が増大し、食事からの摂取が不十分な際の補給、(3)高脂血症、弛緩性便秘、ストレプトマイシンおよびカナマイシンによる副作用の予防および治療、急・慢性湿疹、血液疾患の血小板数および出血傾向の改善のうち、パントテン酸の欠乏または代謝障害が関与すると推定される場合などに1日あたり30〜600mg(内服の場合)で用いられる有用な薬物である。 Pantethine is (1) prevention and treatment of pantothenic acid deficiency, (2) consumable diseases, hyperthyroidism, maternal and lactating women, and the demand for pantothenic acid is increased, resulting in insufficient intake from the diet Supplementation, (3) hyperlipidemia, flaccid constipation, prevention and treatment of side effects caused by streptomycin and kanamycin, acute / chronic eczema, improvement in platelet count and bleeding tendency in blood disorders, pantothenic acid deficiency or metabolic disorder It is a useful drug used at 30 to 600 mg (in the case of internal use) per day when it is estimated to be involved.
パンテチンは常温で無水状態であれば無定形粉末であるが、吸湿性が高いため、粉末状態を保つことができず、飴状となる。このため、パンテチンは粘性の液体として提供され、日本薬局方におけるパンテチンは、80%のパンテチンを含む水溶液で、無色〜微黄色澄明の粘性の液である。このものは、遮光して、10℃以下で保存する必要があり、必ずしも保存安定性がよいものではない。
すなわち、日本薬局方のパンテチンは、高粘性の液体であるため、取り扱いにくく、また保存安定性の点で問題がある。
Panthetin is an amorphous powder if it is in an anhydrous state at room temperature. However, since it has high hygroscopicity, the powder state cannot be maintained and is in the form of a bowl. For this reason, pantethine is provided as a viscous liquid, and panthetin in the Japanese Pharmacopoeia is an aqueous solution containing 80% pantethine and is a colorless to slightly yellow clear viscous liquid. This product needs to be stored at 10 ° C. or less while being shielded from light, and does not necessarily have good storage stability.
That is, the Japanese Pharmacopoeia pantethine is a highly viscous liquid, so it is difficult to handle and has problems in terms of storage stability.
薬物の固形製剤化においては、一般に薬物を粉末状態とすることが望ましく、パンテチンの粉末化技術については、種々検討されている。例えば、少量の共晶点の高いアミノ酸または糖類(グリシン、α−アラニン、乳糖、マンニット、デキストラン)の存在下、パンテチンを凍結乾燥する方法(特許文献1)やパンテチン水溶液を凍結し、この凍結物を粉砕した後、凍結乾燥する方法(特許文献2)が知られている。
この他、80%パンテチン水溶液を用い、多量の糖類、デンプン類、セルロース類等の賦形剤と共に混合し、乾燥して、散剤、細粒剤、顆粒剤、錠剤、カプセル剤等とするなどの試みがなされている。
In making a drug into a solid preparation, it is generally desirable to make the drug in a powder state, and various techniques for powdering pantethine have been studied. For example, a method of freeze-drying pantethine (Patent Document 1) or a pantethine aqueous solution in the presence of a small amount of an amino acid or saccharide having a high eutectic point (glycine, α-alanine, lactose, mannitol, dextran) or freezing pantethine solution. A method (Patent Document 2) is known in which a product is pulverized and then freeze-dried.
In addition, 80% pantethine aqueous solution is used, mixed with a large amount of excipients such as sugars, starches, celluloses, etc., and dried to form powders, fine granules, granules, tablets, capsules, etc. Attempts have been made.
本発明は、上述のような煩雑な凍結乾燥などの操作を必要とせずに製造でき、また、流動性が良く、取り扱いに優れた粒子径を有し、かつ、保存安定性が優れたパンテチンを含む粒状物を提供するものである。 The present invention provides a pantethine that can be produced without the need for complicated operations such as lyophilization as described above, has good fluidity, has a particle size excellent in handling, and has excellent storage stability. The granular material containing is provided.
すなわち、本発明は、以下のものに関する。
(1)実質的にパンテチンおよび多孔性ケイ酸カルシウムからなる粒状物。
(2)パンテチン1重量部に対する多孔性ケイ酸カルシウムの量が0.1〜9重量部である上記(1)記載の粒状物。
(3)パンテチンの含有量が粒状物に対して、10〜90W/W%含有するものである上記(1)または(2)に記載の粒状物。
(4)多孔性ケイ酸カルシウムが以下の性質を有するものである上記(1)〜(3)のいずれか1つに記載の粒状物。
化学式:2CaO・3SiO2・mSiO2・nH2O(1<m<2、2<n<3)
平均粒子径:20〜30μm
見掛け比重:0.08〜0.12g/mL
吸油量:4〜6mL/g
(5)体積基準平均粒子径が20〜500μmである上記(1)〜(4)のいずれか1つに記載の粒状物。
(6)水分活性値(AW)が0.5以下である上記(1)〜(5)のいずれか1つに記載の粒状物。
(7)上記(1)〜(6)のいずれか1つに記載の粒状物を含む固形製剤。
(8)剤形が、散剤、細粒剤、顆粒剤、錠剤またはカプセル剤である上記(7)記載の固形製剤。
That is, the present invention relates to the following.
(1) A granular material substantially composed of pantethine and porous calcium silicate.
(2) The granular material according to the above (1), wherein the amount of porous calcium silicate with respect to 1 part by weight of pantethine is 0.1 to 9 parts by weight.
(3) The granular material according to (1) or (2) above, wherein the content of pantethine is 10 to 90 W / W% of the granular material.
(4) The granular material according to any one of (1) to (3), wherein the porous calcium silicate has the following properties.
Chemical formula: 2CaO.3SiO 2 .mSiO 2 .nH 2 O (1 <m <2, 2 <n <3)
Average particle size: 20-30 μm
Apparent specific gravity: 0.08 to 0.12 g / mL
Oil absorption: 4-6mL / g
(5) The granular material according to any one of (1) to (4), wherein the volume-based average particle diameter is 20 to 500 μm.
(6) The granular material according to any one of (1) to (5), wherein the water activity value (AW) is 0.5 or less.
(7) A solid preparation containing the granular material according to any one of (1) to (6) above.
(8) The solid preparation according to the above (7), wherein the dosage form is a powder, a fine granule, a granule, a tablet or a capsule.
本発明によれば、煩雑な操作を必要とせずに製造でき、また、流動性に優れ、取り扱いに優れた粒子径を有し、保存安定性が優れたパンテチンを含む粒状物を提供することができる。さらに、この粒状物を用いれば、小型化した服用し易い高含量のパンテチンを含む固形製剤を提供することができる。 According to the present invention, it is possible to provide a granular material containing pantethine that can be produced without requiring a complicated operation, has excellent fluidity, has a particle size excellent in handling, and has excellent storage stability. it can. Furthermore, if this granular material is used, it is possible to provide a solid preparation containing a high content of pantethine that is easily reduced in size.
パンテチンは、一般に液体として入手できるものであり、本発明のパンテチンを含有する粒状物を製造する方法としては、多孔性ケイ酸カルシウムにパンテチンを適当な濃度の溶液として加え、撹拌し、パンテチンを多孔性ケイ酸カルシウムに吸着させた後、乾燥させる方法を挙げることができる。 Pantethine is generally available as a liquid. As a method for producing a granule containing pantethine according to the present invention, pantethine is added to porous calcium silicate as a solution having an appropriate concentration, stirred, and the pantethine is made porous. The method of making it dry after making it adsorb | suck to the property calcium silicate can be mentioned.
具体的には、日本薬局方に記載されている80w/w%のパンテチン水溶液をそのまま、または適当量の水、エタノールまたは含水エタノールを用いて適当な濃度に希釈した溶液を、流動層造粒乾燥機、転動流動層造粒機または撹拌造粒機等の造粒機内で、多孔性ケイ酸カルシウムに噴霧または滴下して造粒した後、乾燥することにより、本発明のパンテチンを含む粒状物を製することができる。
また、多孔性ケイ酸カルシウムの一部を80w/w%のパンテチン水溶液または適当量の水、エタノール、含水エタノールを用いて適当な濃度に希釈した溶液中に分散させた後、この分散液を造粒機内で多孔性ケイ酸カルシウムの残余に噴霧または添加して造粒した後、乾燥することによっても、本発明のパンテチンを含む造粒物を製することができる。
さらに、多孔性ケイ酸カルシウムの全部を80w/w%のパンテチン水溶液または適当量の水、エタノール、含水エタノールを用いて適当な濃度に希釈した溶液中に分散させた後、この分散液を噴霧乾燥機内に噴霧し造粒した後、乾燥することによっても、本発明のパンテチンを含む造粒物を製することができる。
パンテチンは吸湿性が高いため、造粒物の水分含量を減らすことが好ましく、具体的には3.0%以下とすることが好ましく、2.0%以下とすることがさらに好ましく、1.5%以下とすることがより好ましい。水分活性値(AW)としては、0.5以下とすることが好ましく、0.3以下とすることがさらに好ましく、0.05〜0.2とすることがより好ましい。
Specifically, a solution obtained by diluting an 80 w / w% pantethine aqueous solution described in the Japanese Pharmacopoeia as it is or using an appropriate amount of water, ethanol or hydrous ethanol to an appropriate concentration is fluidized bed granulated and dried. Granules containing the pantethine of the present invention by granulating by spraying or dripping onto porous calcium silicate in a granulator such as a pulverizer, a rolling fluidized bed granulator or a stirring granulator Can be manufactured.
A part of the porous calcium silicate is dispersed in an 80 w / w% pantethine aqueous solution or a solution diluted to an appropriate concentration with an appropriate amount of water, ethanol or hydrous ethanol, and then this dispersion is prepared. The granulated product containing the pantethine of the present invention can also be produced by spraying or adding to the remainder of the porous calcium silicate in the granulator and granulating, followed by drying.
Further, the entire porous calcium silicate was dispersed in an 80 w / w% pantethine aqueous solution or a solution diluted to an appropriate concentration using an appropriate amount of water, ethanol, or hydrous ethanol, and then the dispersion was spray-dried. A granulated product containing the pantethine of the present invention can also be produced by spraying and granulating in the machine and then drying.
Since pantethine has high hygroscopicity, it is preferable to reduce the water content of the granulated product, specifically 3.0% or less, more preferably 2.0% or less, % Or less is more preferable. The water activity value (AW) is preferably 0.5 or less, more preferably 0.3 or less, and even more preferably 0.05 to 0.2.
得られた粒状物は、適当な目開きを有する篩いを用いて篩過し、分級することにより、所望の粒子径の粒状物(散剤、細粒剤、顆粒剤)とすることができる。粒状物の粒子径をコントロールする方法としては、例えば、流動層造粒乾燥機を用いて粒状物を製する場合では、噴霧ノズルの口径、噴霧液速度、噴霧空気圧を適宜検討することによって、所望の粒子径の粒状物を得ることができる。また、転動流動層造粒機、撹拌造粒機を用いて粒状物を製する場合では、注入液量、撹拌強度、撹拌時間を適宜検討することによって、所望の粒子径の粒状物を得ることができる。
上述のように粒子径をコントールすることにより、取り扱いに優れた体積基準平均粒子径、より具体的には20〜500μmを有するパンテチン含有粒状物を容易に得ることができる。
The obtained granular material can be made into a granular material (a powder, a fine granule, a granule) of a desired particle diameter by sieving and classifying using a sieve having an appropriate opening. As a method for controlling the particle size of the granular material, for example, in the case of producing the granular material using a fluidized bed granulator / dryer, it is desirable to appropriately examine the diameter of the spray nozzle, the spray liquid speed, and the spray air pressure. A granular material having a particle size of can be obtained. In the case of producing a granular material using a rolling fluidized bed granulator or a stirring granulator, a granular material having a desired particle diameter is obtained by appropriately examining the amount of the injected liquid, the stirring strength, and the stirring time. be able to.
By controlling the particle diameter as described above, a panthetin-containing granular material having a volume-based average particle diameter excellent in handling, more specifically 20 to 500 μm, can be easily obtained.
本発明においては、本発明の粒状物中の多孔性ケイ酸カルシウムの含有量がパンテチン1重量部に対して0.1〜9重量部含むものが好ましく、0.1〜1重量部含むものがさらに好ましく、0.15〜0.45重量部で含むものがより好ましく、0.2〜0.3重量部含むものが特に好ましい。 In the present invention, the porous calcium silicate content in the granular material of the present invention is preferably 0.1 to 9 parts by weight, preferably 0.1 to 1 part by weight per 1 part by weight of pantethine. More preferably, 0.15 to 0.45 parts by weight is more preferable, and 0.2 to 0.3 parts by weight is particularly preferable.
本発明の粒状物においては、パンテチンの含有量が10〜90w/w%含むものが好ましく、50〜90w/w%含むものがさらに好ましく、70〜90w/w%含むものがより好ましく、75〜85w/w%含むものが特に好ましい。 In the granular material of the present invention, the content of pantethine is preferably 10 to 90 w / w%, more preferably 50 to 90 w / w%, more preferably 70 to 90 w / w%, more preferably 75 to Those containing 85 w / w% are particularly preferred.
パンテチンを服用(投与)するに際して、粒状物中のパンテチンの含有量が高いほど、パンテチンを含有する粒状物またはこの粒状物を含有する固形製剤の投与量を少なくすることができるので、好ましい。また、本発明の粒状物を用いて、錠剤、カプセル剤、顆粒剤、細粒剤、散剤などの固形製剤を製造する場合に、固形製剤を小型化することができ、服用し易くなることから、コンプライアンスを確保する上でも有利である。 When taking (administering) pantethine, the higher the content of pantethine in the granular material, the more preferable it is because the dosage of the granular material containing pantethine or the solid preparation containing this granular material can be reduced. In addition, when a solid preparation such as a tablet, capsule, granule, fine granule, powder, etc. is produced using the granular material of the present invention, the solid preparation can be reduced in size and easily taken. This is also advantageous in ensuring compliance.
本発明にかかる多孔性ケイ酸カルシウムとしては、エーザイ株式会社より商品名「フローライトRE」として市販されている、下記の化学式と物性を有する特殊ケイ酸カルシウムが好ましい。
化学式:2CaO・3SiO2・mSiO2・nH2O(1<m<2、2<n<3)
性状:白色〜淡黄色微粉末、無臭
平均粒子径:20〜30μm
見掛け比重:0.08〜0.12g/mL
吸油量:4〜6mL/g
一般に市販されているケイ酸カルシウムとの相違点は、バラの花ような花弁状結晶構造を有する特殊ケイ酸カルシウムの粉末であり、多孔性(平均細孔径:0.1〜0.2μm、比表面積:100〜130m2/g)のため、吸油能が大きい点である。
The porous calcium silicate according to the present invention is preferably a special calcium silicate having the following chemical formula and physical properties commercially available from Eisai Co., Ltd. under the trade name “FLORITE RE”.
Chemical formula: 2CaO.3SiO 2 .mSiO 2 .nH 2 O (1 <m <2, 2 <n <3)
Properties: White to pale yellow fine powder, odorless Average particle size: 20 to 30 μm
Apparent specific gravity: 0.08 to 0.12 g / mL
Oil absorption: 4-6mL / g
The difference from the commercially available calcium silicate is a powder of special calcium silicate having a petal-like crystal structure like a rose flower, which is porous (average pore diameter: 0.1 to 0.2 μm, ratio) Surface area: 100 to 130 m 2 / g), the oil absorption capacity is high.
本発明の粒状物は、固形製剤として有用なものであり、このまま製剤(散剤、細粒剤、顆粒剤)としても良いが、所望により、種々の製剤添加物を用い、公知の製剤化技術に従って、錠剤、カプセル剤、顆粒剤、細粒剤、散剤等に固形製剤化しても良い。 The granular material of the present invention is useful as a solid preparation, and may be used as it is as a preparation (powder, fine granule, granule). If desired, various preparation additives may be used according to known preparation techniques. , Tablets, capsules, granules, fine granules, powders, etc.
前記製剤添加物としては、例えば、賦形剤、崩壊剤、結合剤、滑沢剤等を挙げることができる。
賦形剤としては、結晶セルロース、粉末セルロース、トウモロコシデンプン、バレイショデンプン、軽質無水ケイ酸、含水二酸化ケイ素、二酸化ケイ素、沈降炭酸カルシウム、無水リン酸水素カルシウム、酸化マグネシウム、乳酸カルシウム、ケイ酸カルシウム、メタケイ酸アルミン酸マグネシウム、合成ヒドロタルサイト、合成ケイ酸アルミニウム、乳糖、白糖、D−マンニトール、ブドウ糖、果糖等を挙げることができる。
崩壊剤としては、例えば、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、低置換度ヒドロキシプロピルセルロース、クロスポビドン、アルギン酸、部分アルファー化デンプン、ベントナイト等を挙げることができる。
結合剤としては、例えば、メチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニールアルコール、ポビドン、マクロゴール、アラビアゴム、アルギン酸ナトリウム、カルボキシビニールポリマー、ゼラチン、デキストリン、ペクチン、ポリアクリル酸ナトリウム、プルラン等を挙げることができる。
滑沢剤としては、例えば、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、ショ糖脂肪酸エステル、グリセリン脂肪酸エステル、ポリエチレングリコール、硬化油等を挙げることができる。これら製剤添加物は、1種又は2種以上を組み合わせて用いても良い。
Examples of the formulation additive include an excipient, a disintegrant, a binder, and a lubricant.
Excipients include crystalline cellulose, powdered cellulose, corn starch, potato starch, light anhydrous silicic acid, hydrous silicon dioxide, silicon dioxide, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium oxide, calcium lactate, calcium silicate, Examples thereof include magnesium aluminate metasilicate, synthetic hydrotalcite, synthetic aluminum silicate, lactose, sucrose, D-mannitol, glucose, fructose and the like.
Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropylcellulose, crospovidone, alginic acid, partially pregelatinized starch, and bentonite.
Examples of the binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, povidone, macrogol, gum arabic, sodium alginate, carboxyvinyl polymer, gelatin, dextrin, pectin, sodium polyacrylate, pullulan and the like. Can be mentioned.
Examples of the lubricant include magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, glycerin fatty acid ester, polyethylene glycol, and hardened oil. These formulation additives may be used alone or in combination of two or more.
本発明の粒状物は、パンテチンのみを有効成分として含有する単味製剤として用いても良いが、所望により、さらに他の薬効成分を加えても良い。
薬効成分としては、特に制限はなく、用途に応じて添加することができ、また、粉末状、結晶状、油状、液状など何れの形状のものでも用いることができる。薬効成分としては、例えば、ビタミン剤、抗ヒスタミン剤、鎮咳薬、解熱鎮痛薬、交感神経興奮薬、中枢神経興奮薬、抗炎症薬、局所麻酔薬、殺菌剤、制酸剤、健胃剤、消化剤、胃粘膜修復剤、鎮痛鎮痙薬、生薬成分、便秘治療剤、向精神薬、H2受容体拮抗剤、潰瘍治療剤、抗生物質、抗菌剤、降圧剤等を挙げることができる。
また、薬効成分のかわりに嗜好成分、健康食品成分、栄養補助食品成分なども用いることができる。
The granular material of the present invention may be used as a simple preparation containing only pantethine as an active ingredient, but may further contain other medicinal ingredients as desired.
There is no restriction | limiting in particular as a medicinal ingredient, According to a use, it can add and can use what kind of shapes, such as a powder form, a crystalline form, oily, and a liquid form. Examples of medicinal ingredients include vitamins, antihistamines, antitussives, antipyretic analgesics, sympathomimetic drugs, central nervous stimulants, anti-inflammatory drugs, local anesthetics, bactericides, antacids, gastric agents, digestives, stomach Examples include mucosal repair agents, analgesics and antispasmodics, crude drug components, constipation treatment agents, psychotropic drugs, H 2 receptor antagonists, ulcer treatment agents, antibiotics, antibacterial agents, antihypertensive agents and the like.
Moreover, a preference ingredient, a health food ingredient, a dietary supplement ingredient, etc. can be used instead of a medicinal ingredient.
以下に、実施例および試験例を挙げて本発明を説明するが、本発明はこれらのみに限定されるべきものではない。 Hereinafter, the present invention will be described with reference to Examples and Test Examples, but the present invention should not be limited to these.
試験例1 50w/w%パンテチン水溶液の吸着量の検討
表1の成分、3〜10gを精密に量り、これを乳鉢に入れ、粒状物の場合は、乳棒で粉砕し、試料とした。一方、日局パンテチン(80w/w%)液62.5gを量り、水を加えて混和し100gとして、50w/w%パンテチン水溶液を調製した。
試料に、50w/w%パンテチン水溶液をビュレット(最小目盛0.1mLの25mLビュレット)を用いて、試料上に少しずつ注ぎ、軽く練合した。乳棒や乳鉢の側壁に付着した試料は、スパチュラで掻き落とし試料に混練した。
試料が50w/w%パンテチン水溶液を吸水し、パサパサ状態(空気が液体の間に閉じ込められて不連続に存在する状態。)からネバネバ状態(空気の容積がなくなって最も締まった状態であり、更に滴下を続けたとき急激に軟化する状態。)となった点を終点とした。
終点に近くなったら数滴ずつ加え、これらの操作を10〜15分で終わるようにし、50w/w%パンテチン水溶液の滴下量を読み、次式によって50w/w%パンテチン水溶液の吸着量を算出した。
50w/w%パンテチン水溶液の吸着量(mL/g)=滴下量(mL)/試料量(g)
Test Example 1 Examination of Adsorption Amount of 50 w / w% Pantethine Aqueous Solution 3 to 10 g of the components in Table 1 were accurately weighed and placed in a mortar. On the other hand, 62.5 g of JP pantethine (80 w / w%) solution was weighed and mixed with water to make 100 g to prepare a 50 w / w% pantethine aqueous solution.
A 50 w / w% pantethine aqueous solution was poured into the sample little by little on the sample using a burette (minimum scale 0.1 mL 25 mL burette) and lightly kneaded. The sample adhered to the side wall of the pestle or mortar was scraped off with a spatula and kneaded into the sample.
The sample absorbs a 50 w / w% pantethine aqueous solution, and is in the tightest state from the papasa state (the state where air is trapped between the liquids and discontinuously exists) to the sticky state (the volume of air is lost, and The point where the dripping continued to soften rapidly) was taken as the end point.
A few drops were added when the end point was approached, and these operations were completed in 10 to 15 minutes. The amount of 50 w / w% pantethine aqueous solution added was read, and the amount adsorbed by the 50 w / w% pantethine aqueous solution was calculated using the following equation. .
Adsorption amount of 50 w / w% pantethine aqueous solution (mL / g) = Drip amount (mL) / Sample amount (g)
表1 50w/w%パンテチン水溶液の吸着量
Table 1 Adsorption of 50 w / w% pantethine aqueous solution
表1から明らかなように、50w/w%パンテチン水溶液の吸着量は、多孔性ケイ酸カルシウムが顕著に大きく5.37mL/gであった。また、一般に市販されているケイ酸カルシウムは0.75〜1.26mL/gと少なく、明らかに多孔性ケイ酸カルシウムとは異なることが分かった。 As is clear from Table 1, the amount of adsorption of the 50 w / w% pantethine aqueous solution was 5.37 mL / g, which was significantly larger for porous calcium silicate. Moreover, it was found that the commercially available calcium silicate is as low as 0.75 to 1.26 mL / g, which is clearly different from porous calcium silicate.
実施例1 パンテチン含有粒状物の製造
パンテチン80w/w%液600g(パンテチンとして480g)を量り、精製水を加えて混和し、全量を960gとして、パンテチン50w/w%液を調製し、噴霧液とした。
多孔性ケイ酸カルシウム(エーザイ株式会社製、フローライトRE)120gを流動層造粒乾燥機(フロイント産業製、フローコーターFLO−1型)に入れ、吸気温度80℃で5分間混合した後、噴霧液を用いてスプレー圧2kg/cm2、スプレー液速度20mL/minで造粒を行った。噴霧終了後、得られた粒状物の水分が2%以下(メトラー水分計、80℃、1d/30sec、2g)になるまで乾燥し、パンテチンを約80w/w%含有する粒状物を得た。
Example 1 Production of Panthetine-Containing Granules Weigh 600 g of pantethine 80 w / w% solution (480 g as pantethine), add purified water and mix to make a total amount of 960 g, prepare a pantethine 50 w / w% solution, did.
120 g of porous calcium silicate (Florite RE, manufactured by Eisai Co., Ltd.) is placed in a fluidized bed granulator / dryer (Freund Sangyo, Flow Coater FLO-1 type), mixed at an intake air temperature of 80 ° C. for 5 minutes, and then sprayed. Granulation was performed using the liquid at a spray pressure of 2 kg / cm 2 and a spray liquid speed of 20 mL / min. After the spraying was completed, the obtained granular material was dried until the water content became 2% or less (Mettler moisture meter, 80 ° C., 1 d / 30 sec, 2 g) to obtain a granular material containing about 80 w / w% of pantethine.
実施例2 パンテチン含有粒状物の製造
パンテチン80w/w%液600g(パンテチンとして480g)を量り、精製水を加えて混和し、全量を960gとして、パンテチン50w/w%液を調製した。この液に多孔性ケイ酸カルシウム(エーザイ株式会社製、フローライトRE)48g(パンテチンとして480gに対して多孔性ケイ酸カルシウムが10w/w%相当)を加えて分散させ、さらに、100mesh篩で篩過し、噴霧液とした。
多孔性ケイ酸カルシウム(エーザイ株式会社製、フローライトRE)472gを流動層造粒乾燥機(フロイント産業製、フローコーターFLO−1型)に入れ、吸気温度80℃で5分間混合した後、噴霧液を用いてスプレー圧2kg/cm2、スプレー液速度20mL/minで造粒を行った。噴霧終了後、得られた粒状物の水分が2%以下(メトラー水分計、80℃、1d/30sec、2g)になるまで乾燥し、パンテチンを約80w/w%含有する粒状物を得た。
Example 2 Production of Panthetin-Containing Granules A pantethine 80 w / w% solution 600 g (480 g as pantethine) was weighed and mixed with purified water to prepare a pantethine 50 w / w% solution with a total amount of 960 g. To this solution, 48 g of porous calcium silicate (Esai Co., Ltd., Fluorite RE) 48 g (corresponding to 10% w / w of porous calcium silicate with respect to 480 g as pantethine) is added and dispersed, and further sieved with a 100 mesh sieve. A spray solution was obtained.
472 g of porous calcium silicate (Eisai Co., Ltd., Fluorite RE) was placed in a fluidized bed granulator / dryer (Freund Sangyo, Flow Coater FLO-1 type), mixed at an intake air temperature of 80 ° C. for 5 minutes, and then sprayed. Granulation was performed using the liquid at a spray pressure of 2 kg / cm 2 and a spray liquid speed of 20 mL / min. After the spraying was completed, the obtained granular material was dried until the water content became 2% or less (Mettler moisture meter, 80 ° C., 1 d / 30 sec, 2 g) to obtain a granular material containing about 80 w / w% of pantethine.
実施例3 パンテチン含有粒状物の製造
パンテチン80w/w%液600g(パンテチンとして480g)を量り、精製水を加えて混和し、全量を960gとして、パンテチン50w/w%液を調製した。この液に多孔性ケイ酸カルシウム(エーザイ株式会社製、フローライトRE)472g(パンテチンとして480gに対して多孔性ケイ酸カルシウムが15w/w%相当)を加えて分散させ、さらに、100mesh篩で篩過し、噴霧液とした。
多孔性ケイ酸カルシウム(エーザイ株式会社製、フローライトRE)448gを流動層造粒乾燥機(フロイント産業製、フローコーターFLO−1型)に入れ、吸気温度80℃で5分間混合した後、噴霧液を用いてスプレー圧2kg/cm2、スプレー液速度20mL/minで造粒を行った。噴霧終了後、得られた粒状物の水分が2%以下(メトラー水分計、80℃、1d/30sec、2g)になるまで乾燥し、パンテチンを約80w/w%含有する粒状物を得た。
Example 3 Production of Panthetin-Containing Granules A pantethine 80 w / w% solution 600 g (480 g as pantethine) was weighed and purified water was added and mixed to prepare a pantethine 50 w / w% solution with a total amount of 960 g. To this solution, 472 g of porous calcium silicate (Fluorite RE, manufactured by Eisai Co., Ltd.) is added and dispersed with 480 g of pantethine (corresponding to 15 w / w% of porous calcium silicate), and further sieved with a 100 mesh sieve. A spray solution was obtained.
448 g of porous calcium silicate (Florite RE, manufactured by Eisai Co., Ltd.) was placed in a fluidized bed granulator / dryer (Freund Sangyo, Flow Coater FLO-1 type), mixed at an intake air temperature of 80 ° C. for 5 minutes, and then sprayed. Granulation was performed using the liquid at a spray pressure of 2 kg / cm 2 and a spray liquid speed of 20 mL / min. After the spraying was completed, the obtained granular material was dried until the water content became 2% or less (Mettler moisture meter, 80 ° C., 1 d / 30 sec, 2 g) to obtain a granular material containing about 80 w / w% of pantethine.
試験例2 粒状物の物性
実施例1〜3で得られた粒状物について、以下の試験を行った。結果を表2に示した。
(1)性状
外観を肉眼で評価した。
(2)見掛け比容積
見掛比容積減少度測定器(小西医療器株式会社、RHK型)を用いて、疎比容積(mL/g)および密比容積(mL/g)を測定した。
(3)粒度分布
目開きの異なる篩を用い、ロータップシェーカー(株式会社特寿工作所、T−ST型)で粒度分布を測定した。
(4)体積基準平均粒子径
レーザ回折式粒度分布測定装置HELOS&RODOS(株式会社日本レーザー)を用いて、体積基準平均粒子径を測定した。
(5)安息角
パウダーテスター(ホソカワミクロン株式会社、E型)を用いて、安息角(°)を測定した。
(6)流出最小オリフィス径
流出速度及び流出最小オリフィス径測定装器(小西医療器株式会社)を用いて、流出最小オリフィス径(mmΦ)を測定した。
(7)水分
メトラー水分計(Mettler LP−16型、80℃、1d/30sec、2g)を用いて、水分(%)を測定した。
(8)水分活性値
ロトロニック水分活性測定装置(グンゼ産業株式会社、BT−RS1型)を用いて水分活性値(AW)を測定した。
Test Example 2 Physical Properties of Granular Material The following tests were performed on the granular materials obtained in Examples 1 to 3. The results are shown in Table 2.
(1) Properties The appearance was evaluated with the naked eye.
(2) Apparent specific volume The apparent specific volume (mL / g) and the dense specific volume (mL / g) were measured using an apparent specific volume decrease measuring device (Konishi Medical Instrument Co., Ltd., RHK type).
(3) Particle size distribution The particle size distribution was measured with a low-tap shaker (Tokuju Kogyo Co., Ltd., T-ST type) using sieves with different openings.
(4) Volume-based average particle diameter The volume-based average particle diameter was measured using a laser diffraction particle size distribution measuring device HELOS & RODOS (Japan Laser Co., Ltd.).
(5) Angle of repose The angle of repose (°) was measured using a powder tester (Hosokawa Micron Corporation, E type).
(6) Outflow minimum orifice diameter The outflow minimum orifice diameter (mmΦ) was measured using an outflow speed and outflow minimum orifice diameter measuring device (Konishi Medical Instrument Co., Ltd.).
(7) Moisture Moisture (%) was measured using a Mettler moisture meter (Mettler LP-16 type, 80 ° C., 1 d / 30 sec, 2 g).
(8) Water activity value Water activity value (AW) was measured using a Rotronic water activity measuring device (Gunze Sangyo Co., Ltd., BT-RS1 type).
表2 粒状物の物性
Table 2 Physical properties of granular materials
表2から明らかなように、実施例1〜3で得られた粒状物は、流出最小オリフィス径(mmΦ)が最小の3.15mmΦであり、良好な流動性を示した。中でも、実施例1及び3で得られた粒状物は、200mesh(目開き:74μm)以下の微粉が少なく、また、安息角も36°と小さく、優れた流動性を示した。 As is clear from Table 2, the granular materials obtained in Examples 1 to 3 had a minimum flow-out minimum orifice diameter (mmΦ) of 3.15 mmΦ, and exhibited good fluidity. Among them, the granular materials obtained in Examples 1 and 3 had few fine powders of 200 mesh (aperture: 74 μm) or less, and the repose angle was as small as 36 °, and showed excellent fluidity.
試験例3 粒状物の安定性
パンテチン含有粒状物の経時安定性を評価するために、実施例1および3で得られた粒状物並びにパンテチン80w/w%液を用いて、40℃、50℃、60℃で保存し、液体クロマトグラフ法により、パンテチン含量を測定した。結果を表3に示した。
操作条件
検出器 :紫外吸光光度計(測定波長;220nm)
カラム :内径4.6mm、長さ15cmのステンレス管に5μmの液体クロマトグラフ用オクタデシルシリル化シリカゲルを充填する。
カラム温度 :40℃付近の一定温度
移動相 :pH3.5の0.05mol/Lリン酸二水素カリウム溶液/アセトニトリル混液(6:1)
流量 :パンテチンの保持時間が約13分になるように調整する。
Test Example 3 Stability of Granules In order to evaluate the temporal stability of the panthetin-containing granule, the granule obtained in Examples 1 and 3 and the pantethine 80 w / w% solution were used. The panthetin content was measured by liquid chromatography after storage at 60 ° C. The results are shown in Table 3.
Operating conditions Detector: Ultraviolet absorptiometer (measurement wavelength: 220 nm)
Column: A stainless tube having an inner diameter of 4.6 mm and a length of 15 cm is packed with 5 μm of octadecylsilylated silica gel for liquid chromatography.
Column temperature: constant temperature around 40 ° C. Mobile phase: 0.05 mol / L potassium dihydrogen phosphate solution / acetonitrile mixture (6: 1) at pH 3.5
Flow rate: Adjust so that the retention time of pantethine is about 13 minutes.
表3 粒状物の安定性(パンテチン含量)
Table 3 Stability of granules (pantethine content)
表3から明らかなように、80w/w%パンテチン液に比較して、実施例1および実施例3で得られた粒状物は、パンテチンの安定性が顕著に優れていた。一般に、50℃、2ケ月の苛酷試験は室温で3年に相当し、60℃、1ケ月の苛酷試験は室温で4〜5年に相当することから、本発明のパンテチン含有粒状物は室温で3年以上の品質保証が十分可能であることがわかった。 As apparent from Table 3, the stability of pantethine was remarkably excellent in the granular materials obtained in Example 1 and Example 3 as compared with the 80 w / w% pantethine solution. In general, a severe test at 50 ° C. for 2 months corresponds to 3 years at room temperature, and a severe test at 60 ° C. for 1 month corresponds to 4 to 5 years at room temperature. It was found that quality assurance for 3 years or more is sufficiently possible.
実施例4 錠剤
実施例1の製造方法に準じて、パンテチンと多孔性ケイ酸カルシウムの粒状物を製し、常法により以下の組成(1日量として3錠、錠径:約10mmΦ)の糖衣錠を製造した。
パンテチン 60mg
(日局パンテチンとして 75mg)
硝酸チアミン 6mg
リボフラビン 12mg
塩酸ピリドキシン 50mg
L−アスコルビン酸ナトリウム 150mg
酢酸d−α−トコフェロール 10mg
ニコチン酸アミド 40mg
多孔性ケイ酸カルシウム 31mg
結晶セルロース 60mg
トウモロコシデンプン 59mg
ヒドロキシプロピルセルロース 9mg
カルメロースカルシウム 15mg
ステアリン酸マグネシウム 5.5mg
ヒドロキシプロピルメチルセルロース 22.5mg
マクロゴール6000 3.75mg
精製白糖 590mg
アラビアゴム 12mg
ゼラチン 4mg
沈降炭酸カルシウム 107mg
タルク 120mg
カルナウバロウ 微量
Example 4 Tablet According to the production method of Example 1, a granulated product of pantethine and porous calcium silicate is produced, and a sugar-coated tablet having the following composition (3 tablets as a daily dose, tablet diameter: about 10 mmΦ) by a conventional method Manufactured.
Pantethine 60mg
(75 mg as JP pantethine)
Thiamine nitrate 6mg
Riboflavin 12mg
Pyridoxine hydrochloride 50mg
L-sodium ascorbate 150mg
10 mg of d-α-tocopherol acetate
Nicotinamide 40mg
Porous calcium silicate 31mg
Crystalline cellulose 60mg
Corn starch 59mg
Hydroxypropylcellulose 9mg
Carmellose calcium 15mg
Magnesium stearate 5.5mg
Hydroxypropyl methylcellulose 22.5mg
Macrogol 6000 3.75mg
Purified white sugar 590mg
Arabic gum 12mg
Gelatin 4mg
Precipitated calcium carbonate 107mg
Talc 120mg
Carnauba wax
実施例5 錠剤
実施例3の製造方法に準じて、パンテチンと多孔性ケイ酸カルシウムの粒状物を製し、常法により以下の組成(1日量として3錠、錠径:約10mmΦ)の糖衣錠を製造した。
パンテチン 60mg
(日局パンテチンとして 75mg)
塩酸フルスルチアミン 100mg
塩酸ピリドキシン 100mg
シアノコバラミン 1.5mg
コハク酸トコフェロール 100mg
多孔性ケイ酸カルシウム 15mg
乳糖 65mg
結晶セルロース 38mg
カルメロースカルシウム 70mg
ヒドロキシプロピルセルロース 4mg
ステアリン酸マグネシウム 5mg
ヒドロキシプロピルメチルセルロース 6mg
マクロゴール6000 4mg
精製白糖 530mg
アラビアゴム末 11mg
沈降炭酸カルシウム 96mg
タルク 108mg
カルナウバロウ 微量
Example 5 Tablet According to the production method of Example 3, a granulated product of pantethine and porous calcium silicate was produced, and a sugar-coated tablet having the following composition (3 tablets as a daily dose, tablet diameter: about 10 mmΦ) by a conventional method Manufactured.
Pantethine 60mg
(75 mg as JP pantethine)
Fursultiamine hydrochloride 100mg
Pyridoxine hydrochloride 100mg
Cyanocobalamin 1.5mg
Tocopherol succinate 100mg
Porous calcium silicate 15mg
Lactose 65mg
Crystalline cellulose 38mg
Carmellose calcium 70mg
Hydroxypropylcellulose 4mg
Magnesium stearate 5mg
Hydroxypropyl methylcellulose 6mg
Macrogol 6000 4mg
Purified white sugar 530mg
Arabic gum powder 11mg
Precipitated calcium carbonate 96mg
Talc 108mg
Carnauba wax
実施例6 錠剤
実施例1の製造方法に準じて、パンテチンと多孔性ケイ酸カルシウムの粒状物を製し、常法(2顆粒法)により、以下の組成(1日量として6錠、錠径:約8mmΦ)のフイルムコーティング錠を製造した。
A顆粒:
パンテチン 90mg
(日局パンテチンとして 112.5mg)
塩酸ピリドキシン 6mg
リボフラビン 5mg
多孔性ケイ酸カルシウム 22.5mg
結晶セルロース 50mg
トウモロコシデンプン 46.5mg
低置換度ヒドロキシプロピルセルロース 25mg
ヒドロキシプロピルセルロース 10mg
ステアリン酸マグネシウム 5mg
B顆粒:
アスコルビン酸 600mg
L−システイン 240mg
リボフラビン 7mg
結晶セルロース 76mg
トウモロコシデンプン 8.4mg
低置換度ヒドロキシプロピルセルロース 38mg
ヒドロキシプロピルセルロース 23mg
ステアリン酸マグネシウム 7.6mg
フイルムコーティング:
ヒドロキシプロピルメチルセルロース2910 60mg
マクロゴール6000 12mg
タルク 10mg
酸化チタン 18mg
Example 6 Tablet According to the production method of Example 1, a granule of pantethine and porous calcium silicate was produced, and the following composition (6 tablets as a daily dose, tablet diameter) by a conventional method (2 granule method) : About 8 mmΦ).
A granule:
Pantethine 90mg
(112.5 mg as JP pantethine)
Pyridoxine hydrochloride 6mg
Riboflavin 5mg
Porous calcium silicate 22.5mg
Crystalline cellulose 50mg
Corn starch 46.5mg
Low substituted hydroxypropylcellulose 25mg
Hydroxypropylcellulose 10mg
Magnesium stearate 5mg
B granule:
Ascorbic acid 600mg
L-cysteine 240mg
Riboflavin 7mg
Crystalline cellulose 76mg
Corn starch 8.4mg
Low substituted hydroxypropylcellulose 38mg
Hydroxypropylcellulose 23mg
Magnesium stearate 7.6mg
Film coating:
Hydroxypropyl methylcellulose 2910 60mg
Macrogol 6000 12mg
Talc 10mg
Titanium oxide 18mg
実施例7 カプセル剤
実施例3の製造方法に準じて、パンテチンと多孔性ケイ酸カルシウムの粒状物を製し、常法(2顆粒法)により、以下の組成(1日量として4カプセル、大きさ:2号の硬カプセル)のカプセル剤を製造した。
A顆粒:
パンテチン 90mg
(日局パンテチンとして 112.5mg)
酢酸d−α−トコフェロール 100mg
多孔性ケイ酸カルシウム 70mg
結晶セルロース 80mg
トウモロコシデンプン 20mg
ステアリン酸マグネシウム 4mg
B顆粒:
乾燥コウジンエキス 350mg
(日局コウジンとして 1000mg)
多孔性ケイ酸カルシウム 80mg
カルメロースカルシウム 20mg
ヒドロキシプロピルセルロース 20mg
結晶セルロース 80mg
ステアリン酸マグネシウム 6mg
Example 7 Capsule In accordance with the production method of Example 3, a granule of pantethine and porous calcium silicate was prepared, and the following composition (4 capsules as a daily dose, large size) by a conventional method (2 granule method) Sa: No. 2 hard capsule).
A granule:
Pantethine 90mg
(112.5 mg as JP pantethine)
100 mg of d-α-tocopherol acetate
Porous calcium silicate 70mg
Crystalline cellulose 80mg
Corn starch 20mg
Magnesium stearate 4mg
B granule:
Dried Koujin extract 350mg
(1000mg as JP Koji)
Porous calcium silicate 80mg
Carmellose calcium 20mg
Hydroxypropylcellulose 20mg
Crystalline cellulose 80mg
Magnesium stearate 6mg
本発明の粒状物は、煩雑な操作を必要とせずに製造でき、また、流動性に優れ、取り扱いに優れた粒子径を有し、保存安定性が優れたパンテチンを含むものである。この粒状物を用いれば、小型化した服用し易い高含量のパンテチンを含む固形製剤を提供することができる。
The granular material of the present invention contains pantethine that can be produced without the need for complicated operations, has excellent fluidity, has a particle size excellent in handling, and has excellent storage stability. If this granular material is used, it is possible to provide a solid preparation containing a small amount of pantethine that is easily reduced in size.
Claims (7)
化学式:2CaO・3SiO2・mSiO2・nH2O(1<m<2、2<n<3)
平均粒子径:20〜30μm
見掛け比重:0.08〜0.12g/mL
吸油量:4〜6mL/g The granular material according to any one of claims 1 to 2, wherein the porous calcium silicate has the following properties.
Chemical formula: 2CaO.3SiO 2 .mSiO 2 .nH 2 O (1 <m <2, 2 <n <3)
Average particle size: 20-30 μm
Apparent specific gravity: 0.08 to 0.12 g / mL
Oil absorption: 4-6mL / g
The solid preparation according to claim 6, wherein the dosage form is a powder, a fine granule, a granule, a tablet or a capsule.
Priority Applications (1)
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JP2004096257A JP4643922B2 (en) | 2004-03-29 | 2004-03-29 | Granules containing pantethine |
Applications Claiming Priority (1)
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JP2004096257A JP4643922B2 (en) | 2004-03-29 | 2004-03-29 | Granules containing pantethine |
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JP4643922B2 true JP4643922B2 (en) | 2011-03-02 |
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Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2006045218A (en) * | 2004-07-08 | 2006-02-16 | Ono Pharmaceut Co Ltd | Medicinal composition for oral administration |
JPWO2007097333A1 (en) * | 2006-02-20 | 2009-07-16 | アサヒビール株式会社 | Granules, tablets and methods for producing them |
JP4970546B2 (en) * | 2007-10-03 | 2012-07-11 | アサヒグループホールディングス株式会社 | Granules, tablets and methods for producing them |
JP4889048B2 (en) * | 2008-03-10 | 2012-02-29 | 株式会社アマミファッション研究所 | Shochu distillation residue liquid dried product and its production method |
JP2010280601A (en) * | 2009-06-04 | 2010-12-16 | Suntory Holdings Ltd | Tablet highly containing xylo-oligosaccharide |
JP5585920B2 (en) * | 2010-12-27 | 2014-09-10 | 富田製薬株式会社 | Particulate preparation |
JP5947041B2 (en) * | 2011-01-07 | 2016-07-06 | 第一三共ヘルスケア株式会社 | Safe IL-17 production inhibitor |
JP7353103B2 (en) * | 2019-08-23 | 2023-09-29 | アサヒグループ食品株式会社 | Nutritional supplement composition and method for producing the same, method for suppressing unpleasant odor of a nutritional supplement composition, and composition for suppressing unpleasant odor of a nutritional supplement composition |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5328117A (en) * | 1976-08-25 | 1978-03-16 | Sogo Yatsuko Kk | Freezeedryymethod of panthethine |
JPS5538344A (en) * | 1978-09-12 | 1980-03-17 | Dai Ichi Seiyaku Co Ltd | Manufacturing of pantethine powder |
JPS5581855A (en) * | 1978-12-14 | 1980-06-20 | Dai Ichi Seiyaku Co Ltd | Adduct of pantethine with metal salt |
JP2000191524A (en) * | 1998-12-25 | 2000-07-11 | Pasuteru:Kk | Composition for improving constipation |
JP2002265357A (en) * | 2001-03-12 | 2002-09-18 | Lion Corp | Composition for use in ophthalmology |
JP2003095980A (en) * | 2001-09-21 | 2003-04-03 | Nippon Shinyaku Co Ltd | Composition containing deliquescent substance |
-
2004
- 2004-03-29 JP JP2004096257A patent/JP4643922B2/en not_active Expired - Lifetime
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5328117A (en) * | 1976-08-25 | 1978-03-16 | Sogo Yatsuko Kk | Freezeedryymethod of panthethine |
JPS5538344A (en) * | 1978-09-12 | 1980-03-17 | Dai Ichi Seiyaku Co Ltd | Manufacturing of pantethine powder |
JPS5581855A (en) * | 1978-12-14 | 1980-06-20 | Dai Ichi Seiyaku Co Ltd | Adduct of pantethine with metal salt |
JP2000191524A (en) * | 1998-12-25 | 2000-07-11 | Pasuteru:Kk | Composition for improving constipation |
JP2002265357A (en) * | 2001-03-12 | 2002-09-18 | Lion Corp | Composition for use in ophthalmology |
JP2003095980A (en) * | 2001-09-21 | 2003-04-03 | Nippon Shinyaku Co Ltd | Composition containing deliquescent substance |
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