JPS63243030A - Sustained release cephradine pharmaceutical - Google Patents
Sustained release cephradine pharmaceuticalInfo
- Publication number
- JPS63243030A JPS63243030A JP7678487A JP7678487A JPS63243030A JP S63243030 A JPS63243030 A JP S63243030A JP 7678487 A JP7678487 A JP 7678487A JP 7678487 A JP7678487 A JP 7678487A JP S63243030 A JPS63243030 A JP S63243030A
- Authority
- JP
- Japan
- Prior art keywords
- preparation
- cefrazine
- coated
- sustained
- release
- 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.)
- Granted
Links
- 238000013268 sustained release Methods 0.000 title claims abstract description 33
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 33
- 229960002588 cefradine Drugs 0.000 title abstract description 20
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 title abstract description 20
- 239000008187 granular material Substances 0.000 claims abstract description 55
- 239000000203 mixture Substances 0.000 claims abstract description 28
- 239000011324 bead Substances 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 15
- 239000012188 paraffin wax Substances 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 65
- 239000011248 coating agent Substances 0.000 claims description 23
- 238000000576 coating method Methods 0.000 claims description 19
- 238000009472 formulation Methods 0.000 claims description 9
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 7
- 239000000194 fatty acid Substances 0.000 claims description 7
- 229930195729 fatty acid Natural products 0.000 claims description 7
- 239000007931 coated granule Substances 0.000 claims description 6
- -1 fatty acid esters Chemical class 0.000 claims description 6
- 239000003094 microcapsule Substances 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000002702 enteric coating Substances 0.000 claims description 3
- 238000009505 enteric coating Methods 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 239000011159 matrix material Substances 0.000 claims description 3
- 229910052751 metal Chemical class 0.000 claims description 3
- 239000002184 metal Chemical class 0.000 claims description 3
- 229920003176 water-insoluble polymer Polymers 0.000 claims description 3
- 239000010419 fine particle Substances 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 9
- 239000000843 powder Substances 0.000 abstract description 4
- 239000000725 suspension Substances 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 2
- 230000000996 additive effect Effects 0.000 abstract description 2
- 229920000642 polymer Polymers 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 abstract description 2
- 230000003111 delayed effect Effects 0.000 abstract 3
- 230000036765 blood level Effects 0.000 abstract 1
- 230000002542 deteriorative effect Effects 0.000 abstract 1
- 239000004503 fine granule Substances 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 239000008280 blood Substances 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- 229920002678 cellulose Polymers 0.000 description 9
- 239000001913 cellulose Substances 0.000 description 9
- 239000001856 Ethyl cellulose Substances 0.000 description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 235000019325 ethyl cellulose Nutrition 0.000 description 6
- 229920001249 ethyl cellulose Polymers 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000001993 wax Substances 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 240000008042 Zea mays Species 0.000 description 3
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 3
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 235000005822 corn Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- UTKBLLDLHPDWDU-ODZAUARKSA-N acetic acid;(z)-but-2-enedioic acid Chemical compound CC(O)=O.OC(=O)\C=C/C(O)=O UTKBLLDLHPDWDU-ODZAUARKSA-N 0.000 description 2
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 238000004088 simulation Methods 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 108700042658 GAP-43 Proteins 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127249 oral antibiotic Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】 〔産業上の利用分野〕 本発明は、特効性セフラジン製剤に関する。[Detailed description of the invention] [Industrial application field] The present invention relates to specific cefrazine formulations.
セフラジンは、経口用の合成セファロス−リン系抗生物
質であり１種々の感染症に繁用されている。しかし、現
在のセフラジン製剤は１日４回すなわち６時間毎の服用
が必要であり、夜間あるいは日中（昼食時）服用するこ
とになるため５服用が困難であったり１服用忘れが多く
セフラジンの効力を最大限に発揮できない欠点があった
。かかる現状において、患者の生活リズムにあった服用
間隔すなわち１日２回、１２時間間隔で服用できる持効
性セフラジン製剤が要望されていた。Cefrazine is an oral synthetic cephalothrin antibiotic that is frequently used for a variety of infectious diseases. However, current cefrazine preparations need to be taken four times a day, that is, every 6 hours, and because they are taken at night or during the day (at lunch), it is difficult to take 5 doses, and patients often forget to take 1 dose. There was a drawback that it was not able to maximize its effectiveness. Under these circumstances, there has been a need for a long-acting cefrazine preparation that can be taken at intervals of 12 hours, twice a day, in accordance with the patient's daily rhythm.
また、従来持効性を目的とした経口用抗生物質製剤は速
溶性製剤と腸溶性製剤を混合したものが多く、速溶性の
吸収速度あるいは消失速度が速いセフラジンのような抗
生物質では、速溶性製剤から得られる血中濃度ピークと
、腸溶性製剤から得られるピークとの間で。In addition, conventional oral antibiotic preparations aimed at long-acting effects are often a mixture of fast-dissolving preparations and enteric-coated preparations, and for antibiotics such as cefrazine, which have a fast-dissolving absorption rate or a fast elimination rate, between the blood concentration peak obtained from the formulation and the peak obtained from the enteric-coated formulation.
血中濃度がＭＩＣ（最小発育阻止濃度）以下になり、持
効性製剤とするのは困難であった。The blood concentration was below the MIC (minimum inhibitory concentration), making it difficult to create a sustained-acting formulation.
更に、本薬物のように吸収部位が小腸上部に限られてい
るものは、腸溶性製剤を用いず、不溶性の徐放化剤を使
用した遅溶性製剤単独で持効性にすると、長時間一定の
血中濃度を維持できないか、あるいは有効血中濃度に到
達する時間が遅く、また生物学的利用能を低下させる欠
点があった。Furthermore, for drugs like this drug whose absorption site is limited to the upper small intestine, it is possible to maintain a sustained effect over a long period of time by using a slow-dissolving formulation alone using an insoluble sustained-release agent without using an enteric-coated formulation. They have the disadvantage that they are unable to maintain a blood concentration of or take a long time to reach an effective blood concentration, and that their bioavailability is reduced.
かかる現状において２本発明者らは鋭意研究を行なった
結果、徐放化剤全含有した遅溶性セフラジン製剤と腸溶
性セフラジン製剤を組合せることによシ、生物学的利用
能を低下させずに、セフラジンの血中濃度一時間推移を
調節できることを見い出し、本発明を完成するに至った
。Under these circumstances, the present inventors conducted extensive research and found that by combining a slow-dissolving cefrazine preparation containing all sustained-release agents with an enteric-coated cefrazine preparation, it was possible to obtain a drug without reducing bioavailability. They discovered that it is possible to control the hourly change in blood concentration of cefrazine, and have completed the present invention.
すなわち、本発明は遅溶性セフラジン製剤と腸溶性セフ
ラジン製剤とを組合せたことを特徴とする持効性セフラ
ジン製剤を提供するものである。That is, the present invention provides a sustained-release cefrazine preparation characterized by a combination of a slow-dissolving cefrazine preparation and an enteric-coated cefrazine preparation.
本発明で用いる遅溶性セフラジン製剤は、予めセフラジ
ンを含有した製剤用粉末に、徐放化剤を固形、溶液ある
いは懸濁液の状態で添加し、常法により細粒剤、顆粒剤
、ビーズとすることによシ、または、常法によシ得られ
たセフ２シンを含有する散剤、細粒剤、顆粒剤、ビーズ
を徐放化剤を用いマイクロカプセル化、湿式あるいは乾
式で被覆することによ如製造され、更に必要に応じて適
当な結合剤、滑沢剤、崩壊剤、賦形剤などを使用するこ
とができる。The slow-dissolving cefrazine preparation used in the present invention is prepared by adding a sustained release agent in the form of a solid, solution, or suspension to a pharmaceutical powder containing cefrazine in advance, and then forming it into fine granules, granules, or beads by a conventional method. or microencapsulation, wet or dry coating of powders, fine granules, granules, beads containing cef2cin obtained by conventional methods using a sustained release agent. If necessary, suitable binders, lubricants, disintegrants, excipients, etc. can be used.
遅溶性セフラジン実刑の製造に用いる徐放化剤としては
非水溶性高分子、・９ラフインワツクス、 高級アルコ
ール、脂肪酸エステル。The sustained release agents used in the production of slow-soluble cefradine include water-insoluble polymers, 9 rough-in wax, higher alcohols, and fatty acid esters.
高級脂肪酸あるいはそれらの金属塩があり。Contains higher fatty acids or their metal salts.
特に限定されないが、好ましい具体例としては、非水溶
性高分子としてエチルセルロース、アミノアルキルメタ
アクリレ−トコ昶すマー。Although not particularly limited, preferred specific examples include ethyl cellulose and aminoalkyl methacrylate polymers as water-insoluble polymers.
ポリ酢酸ビニル、フタル酸セルロースアセテート、マレ
イン酸セルロースアセテート、ヒドロキシゾロビルメチ
ルセルロースフタレート、カルボキシメチルエチルセル
ロース、スチレン・マレイン酸コ？リマー、メタアクリ
ル酸コポリマー％ぼりエチレン、？り塩化ビニル力、ノ
ＱラフイワツクスとしてノＱラフイン、マイクロクリス
タリンワックスが、高級アルコールトシテステアリルア
ルコール、セタノールが、脂肪酸エステルとしてグリセ
リン脂肪酸エステル、硬化油、グイロウ、ミツロウ。Polyvinyl acetate, cellulose phthalate acetate, cellulose maleate acetate, hydroxyzolobyl methylcellulose phthalate, carboxymethylethylcellulose, styrene/maleic acid co? Rimmer, methacrylic acid copolymer% ethylene, ? Polyvinyl chloride strength, NOQ rough wax, NOQ rough wax, microcrystalline wax, higher alcohols, stearyl alcohol, cetanol, fatty acid esters include glycerin fatty acid ester, hydrogenated oil, wax wax, and beeswax.
モクロウが、高級脂肪酸あるいはそれらの塩としてステ
アリン酸、ノｑルミチン酸、ミリスチン酸あるいはそれ
らのナトリウム、カルシウム、マグネシウム等の金属塩
等が挙げられる。これら徐放化剤はマトリックス形成剤
。Examples of higher fatty acids and their salts include stearic acid, normitic acid, myristic acid, and their metal salts such as sodium, calcium, and magnesium. These sustained release agents are matrix forming agents.
あるいは被膜化剤として使用し、各々単独で用いてもよ
いが、２種以上を組合せて使用することもできる。Alternatively, they may be used as a coating agent, and each may be used alone, but two or more types can also be used in combination.
徐放化剤の配合量は遅溶性セフラジン製剤の製法や剤型
によっても異なるが、マトリックス形成剤として用いる
場合は５〜７０重量％（以下単に％で示す）、好ましく
は１０〜 Ｂ −
５０％であシ、被膜化剤として使用する場合は２〜４０
％、％に、２〜３０％であることが好ましい。The blending amount of the sustained release agent varies depending on the manufacturing method and dosage form of the slow-soluble cefrazine preparation, but when used as a matrix forming agent, it is 5 to 70% by weight (hereinafter simply expressed as %), preferably 10 to B-50%. Ash, 2 to 40 when used as a coating agent
%, preferably 2 to 30%.
また、本発明で用いる腸溶性セフラジン製剤を調製する
には、セフラジンをそのまま力へあるいは適当な添加剤
を適量セフラジンに加えた後、公知の方法によりマイク
ロカプセルとするか、また常法により得られたセフラジ
ンを含有する細粒剤、！ｌ！ｊｉ粒剤、ビーズに上記の
腸溶性物質で被覆することによシ製造することができ、
更に必要に応じて適当な可塑剤。In addition, in order to prepare the enteric-coated cefrazine preparation used in the present invention, cefrazine can be prepared as is, or after adding an appropriate amount of an appropriate additive to cefrazine, it can be made into microcapsules by a known method, or it can be prepared by a conventional method. Fine granules containing cefrazine,! l! ji granules, which can be produced by coating beads with the above enteric substance;
Furthermore, a suitable plasticizer as required.
溶解速度調節剤、滑沢剤等を加えることができる。Dissolution rate regulators, lubricants, etc. can be added.
この腸溶性セフラジン製剤は、セフラジンの吸収部位が
小腸上部に限られているため、ｐＨ５．０〜７．０．更
に好ましくはｐＨａ５〜ａ５の範囲内でセフラジンを完
全に放出することが必要であり、この目的のため用いる
ことのできる腸溶性被膜としては５例えばフタル酸セル
ロースアセテート、マレイン酸セルロースアセテート、
ヒドロキシノロビルメチルセルロースフタレート、カル
ボキシメチルエチルセルロース、スチレン伊マレイン酸
コポリマー、メタアクリル酸コ？リマー等が挙げられる
。This enteric-coated cefrazine preparation has a pH of 5.0 to 7.0 because the absorption site of cefrazine is limited to the upper small intestine. More preferably, it is necessary to completely release cefrazine within the pH range of 5 to a5, and examples of enteric coatings that can be used for this purpose include cellulose phthalate acetate, cellulose maleate acetate,
Hydroxynorobyl methylcellulose phthalate, carboxymethylethylcellulose, styrene-malate copolymer, methacrylic acid copolymer? Examples include Rimmer et al.
腸溶性被膜の量は剤型によっても異なシ。The amount of enteric coating varies depending on the dosage form.
通常１０〜７５％の範囲にあるが、腸溶性被膜を形成す
ることが目的のため、特にその量を制限するものではな
い。The amount is usually in the range of 10 to 75%, but since the purpose is to form an enteric coat, the amount is not particularly limited.
本発明の持効性セフラジン製剤は、上記の方法によシ得
られた遅溶性セフラジン製剤と腸溶性セフラジン製剤を
混合した混合製剤か、あるいは腸溶性セフラジンを遅溶
性セフラジン製剤で被覆した単一製剤として得られる。The sustained-release cefrazine preparation of the present invention is either a mixed preparation of the slow-dissolving cefrazine preparation obtained by the above method and an enteric-coated cefrazine preparation, or a single preparation of enteric-coated cefrazine coated with a slow-dissolving cefrazine preparation. obtained as.
遅溶性セフラジン製剤と腸溶性セフラジン製剤中に含有
するセフラジンの力価換算重量比は、使用する遅溶性セ
フラジン製剤の性質によっても異なるが、一般には３ニ
ア〜５：５の範囲にあることが好ましい。The potency-based weight ratio of cefrazine contained in a slow-dissolving cefrazine preparation and an enteric-coated cefrazine preparation varies depending on the properties of the slow-dissolving cefrazine preparation used, but is generally preferably in the range of 3 to 5:5. .
また、該持効性セフラジン製剤の剤型は特に制限されな
いが、単一製剤の場合は、顆粒剤またはビーズとするか
、あるいはカプセル剤、錠剤とすることができる。また
混合製剤の場合は、予め、あるｂは必要に応じて散剤、
細粒剤、顆粒剤、ビーズ、カシセル剤あるいは錠剤とす
ることができる。更に遅溶性セフラジン製剤を別層に配
した多層錠、有核錠とすることができる。Further, the dosage form of the sustained-release cefrazine preparation is not particularly limited, but in the case of a single preparation, it may be in the form of granules or beads, or in the form of capsules or tablets. In addition, in the case of a mixed preparation, some b may be added as a powder or as needed.
It can be in the form of fine granules, granules, beads, cassettes or tablets. Furthermore, it can be made into a multilayer tablet or dry-coated tablet in which a slow-soluble cefrazine preparation is arranged in a separate layer.
かくして得られた本発明の特効性セフラジン製剤は、生
物学的利用能の低下もみられず。The specifically effective cefradine preparation of the present invention thus obtained showed no decrease in bioavailability.
長時間一定した血中濃度が得られ、従来製剤よシ少ない
１日２回服用で従来製剤と同等の効果を期待できるもの
であった。このことよシ、該持効性セ７ラゾン製剤は患
者の生活リズムにあった服用が可能となシ、従来製剤に
有りがちでめった服用忘れによる臨床効果の減温を回避
できるため、セフラジンによる治療効果をよシ高めるこ
とが可能となった。A constant blood concentration was obtained over a long period of time, and the same effects as conventional formulations could be expected with twice-daily administration, which is less than conventional formulations. For this reason, the long-acting cephrazone preparation can be taken in accordance with the patient's daily rhythm, and it can avoid the decrease in clinical efficacy due to the frequent forgetting of doses, which is common with conventional preparations. It has become possible to further enhance the therapeutic effect.
次に実施例を挙げ１本発明を説明する。 Next, the present invention will be explained with reference to examples.
実施例１
裸顆粒人の製造：
セフラジン１フ２１６ｆ、乳糖６１４４ｆ及び精製白糖
４８０ ｆ！の混合米に１０％ヒドロキシゾロビルセル
ロース溶液６４０ｆを加えて練合する。この練合物を円
筒型造粒機音用いて造粒し、次いで５５℃、２時間乾燥
する。Example 1 Manufacture of naked granules: Cefrazine 1f 216f, lactose 6144f and refined white sugar 480f! Add 640f of 10% hydroxyzorobyl cellulose solution to the mixed rice and knead. This kneaded product is granulated using a cylindrical granulator and then dried at 55° C. for 2 hours.
この乾燥顆粒の１６メツシユを通過し３０メツシユを通
過しないものを裸顆粒ムとする。The dry granules that pass through 16 meshes but do not pass through 30 meshes are defined as bare granules.
なお、この裸顆粒人の組成は次の通りである。The composition of this naked granule is as follows.
組成 ％
セフラジン ５９．８乳糖
２Ｌ３
精製白糖 １ａ７ヒドロキ
シノロピルセルロース ２２合 計
１０αＯ実施例２
裸顆粒Ｂの製造：
セ７ラン７１１８ａ６ ｔ ｈ乳糖５９４ｆ及び精製白
糖２６８４ ｆの混合床に１０％ヒドロキシゾロピルセ
ルロース溶液４４０ｆを加えて練合し、以下実施例１の
方法に従い裸顆粒Ｂｆ製する。この裸顆粒Ｂの組成は次
の通りである。Composition % Cefrazine 59.8 Lactose
2L3 Refined white sugar 1a7 hydroxynolopyl cellulose 22 total
10αO Example 2 Manufacture of naked granules B: 10% hydroxyzolopyl cellulose solution 440f was added to a mixed bed of 594f of Se7lan 7118a6t lactose and 2684f of refined white sugar and kneaded, and then the bare granules were prepared according to the method of Example 1. Granules Bf are made. The composition of this naked granule B is as follows.
組成 ％
七７ラゾン ５ａ７乳糖
２８４
精製白糖 １２８ヒドロキシゾ
ロビルセルロース ２１合計 １０
０．０
実施例３
遅溶性顆粒Ｓ−１の製造：
実施例１で製した裸顆粒Ａ ５００ｆを流動層コーテ
ィング装置に入れ、下記組成のコーテイング液１０００
Ｆを常法に従ってスプレーコーティングを行ない遅溶性
顆粒Ｓ−１を製する。このものの被覆量は裸顆粒重量に
対して約４％であった。Composition % 77razon 5a7 lactose
284 Refined white sugar 128 Hydroxyzorobyl cellulose 21 Total 10
0.0 Example 3 Manufacture of slow-dissolving granules S-1: 500f of bare granules A produced in Example 1 were placed in a fluidized bed coating device, and 1000 g of coating liquid having the following composition was added.
F is spray coated according to a conventional method to prepare slow-dissolving granules S-1. The coating amount of this material was about 4% based on the weight of the bare granules.
組成 ％
エチルセルロース ２０エタノール
９ａＯ合 計
１０００実施例４
遅溶性顆粒Ｓ−２の製造：
実施例１で製した裸顆粒Ａ ５００？及び実施例３で
製したコーテイング液２５０Ｏｒを用い、以下実施例３
の方法に従ってスプレーコーティングを行ない遅溶性顆
粒Ｓ−２を得た。このものの被覆量は裸顆粒重量に対し
約１０％であった。Composition % Ethyl cellulose 20 ethanol
9aO total
1000 Example 4 Production of slow-dissolving granules S-2: Naked granules A produced in Example 1 500? Using the coating liquid 250 Or produced in Example 3, Example 3 is as follows.
Spray coating was carried out according to the method described in 2007 to obtain slow-dissolving granules S-2. The coating amount of this product was about 10% based on the weight of the bare granules.
実施例５
遅溶性セフラジン顆粒Ｓ−３の製造：
セフラジン５２８ｆ、ステアリルアルコール１５０ｆ、
エチルセルロース５０ｆ及び乳糖１７２ ｆの混合床に
１０％エチルセルロース溶液１０００ Ｐｉ加え練合す
る。この練合物を円筒型造粒機を用いて造粒し１次いで
５０℃％３時間乾燥する。この乾燥顆粒の１６メツシユ
を通過し、３０メツシユを通過しないものを遅溶性セフ
ラジン顆粒Ｓ−３とする。なお、との遅溶性セフラジン
顆粒Ｓ−３の組成は次の通シである。Example 5 Production of slow-soluble cefrazine granules S-3: cefrazine 528f, stearyl alcohol 150f,
1000 Pi of a 10% ethyl cellulose solution was added to a mixed bed of 50 f of ethyl cellulose and 172 f of lactose and kneaded. This kneaded product is granulated using a cylindrical granulator and then dried at 50°C for 3 hours. The dried granules that passed through 16 meshes but did not pass through 30 meshes were designated slow-soluble cefrazine granules S-3. The composition of slow-soluble cefradine granules S-3 is as follows.
組成 ％
セフラジン ５２８ステ
アリルアルコール ＩＦ５．．０エチ
ルセルロース １ａＯ合計
１０００
実施例６
腸溶性顆粒子−１の製造：
実施例２で製した裸顆粒Ｂ ５００１を流動層コーテ
ィング装置に入れ、下記組成のコーテイング液２７７７
８ ｆｆ常法に従ってスゾレーコーティングを行ない腸
溶性顆粒Ｉ−１を製する。このものの被膜量は裸顆粒重
量に対し約４０％であった。Composition % Cefrazine 528 Stearyl Alcohol IF5. ．． 0 Ethylcellulose 1aO total
1000 Example 6 Production of enteric-coated granules-1: The bare granules B 5001 produced in Example 2 were placed in a fluidized bed coating device, and a coating liquid 2777 having the following composition was added.
8 ff Ssollet coating is performed according to a conventional method to prepare enteric-coated granules I-1. The coating amount of this product was approximately 40% of the weight of the bare granules.
組成 ％
メタアクリル酸コ？リマーＬ ａ５マクロ
ゴール ６０００ α５タルク
０２精製水
ａ８イソゾロビルアルコール
ＳａＯ合計 １０００
実施例７
持効性セフラジン顆粒Ｒ−１の製造：
実施例３で製した遅溶性セフラジン顆粒Ｓ−１と、実施
例６で製した腸溶性セフラジン顆粒Ｉ−１をそれぞれ力
価換算重量比が４：６になるように混合し持効性セフラ
ジン顆粒Ｒ−１を製した。Composition % Methacrylic acid co? Rimmer L a5 macrogol 6000 α5 talc
02 Purified water
a8 isozorobyl alcohol
SaO total 1000 Example 7 Production of sustained-release cefrazine granules R-1: Slow-dissolving cefrazine granules S-1 produced in Example 3 and enteric-coated cefrazine granules I-1 produced in Example 6 were converted into titer, respectively. They were mixed at a weight ratio of 4:6 to produce sustained-release cefrazine granules R-1.
実施例８
持効性セフラジン顆粒Ｒ−２の製造：
実施例５で製した遅溶性セフラジン顆粒Ｓ−３と、実施
例６で製した腸溶性セフラジン顆粒Ｉ−１’ｉそれぞれ
力価換算重量比が４二〇になるように混合し持効性セフ
ラジン顆粒Ｒ−２を製した。Example 8 Production of sustained-release cefrazine granules R-2: Weight ratio of slow-dissolving cefrazine granules S-3 produced in Example 5 and enteric-coated cefrazine granules I-1'i produced in Example 6 in terms of potency, respectively The ingredients were mixed so that the amount of cefrazine was 420, and sustained-release cefrazine granules R-2 were prepared.
実施例９
遅溶性マイクロカプセルｓ −４ノｊｌ造：セフラゾン
ａ４Ｆを９％エチルセルロースゾクロロメタン溶液Ｌｏ
ｏｍ中に分散させた懸濁液にｎ−ヘキサン３００ｄを加
え、相分離を起こさせた後、上澄液を除去する。次にｎ
−ヘキサン３００ｉｄでカッセルの洗浄と壁膜の硬化を
行ない、減圧乾燥によシ遅溶性マイクロカプセルＳ−４
を得た。Example 9 Slow-dissolving microcapsule s-4 nojl construction: Cefrazone a4F was added to a 9% ethylcellulose chloromethane solution Lo
After adding 300 d of n-hexane to the suspension dispersed in om to cause phase separation, the supernatant liquid is removed. Then n
- Clean the cassette with 300 id hexane and harden the wall film, then dry under reduced pressure. Slowly soluble microcapsule S-4
I got it.
実施例１０
裸ビーズＣの製造：
セフラジン５３Ｅ１３ｆ、 トウモロコシデンゾン６
１．８ ｆの混合米及びノン／Ｑレル４００ｆを遠心流
動型コーティング造粒機を用いて造粒し５次いで５５℃
、２時間乾燥した。この乾燥ビーズの１６メツシユを通
過し、 ３０メツシユを通過しないものを裸ビーズＣと
する。なお、この裸ビーズＣの組成は次の通シである。Example 10 Production of bare beads C: Cefrazine 53E13f, Corn Denzone 6
1.8 f mixed rice and non/Qrel 400 f were granulated using a centrifugal fluid coating granulator, and then heated to 55°C.
, dried for 2 hours. The dried beads that pass through 16 meshes but do not pass through 30 meshes are designated as bare beads C. The composition of the bare beads C is as follows.
組成 ％
セフラジン ５３８２−２〇−
トウモロコシデンゾン ａ１８ノンノＱ
レル ４ＱＯ合計
１０α０
実施例１１
腸溶性ビーズＩ−２の製造：
実施例１０で製した裸ビーズＣ５００ｆを流動層コーテ
ィング装置に入れ、下記組成のコーテイング液１０００
Ｆを常法に従ってスプレーコーティングを行ない、腸溶
性ビーズＩ−２を製する。このものの被覆量は裸ビーズ
重量に対して約４％であった。Composition % Cefrazine 5382-2〇- Corn Denzon a18 NonnoQ
Rel 4QO total
10α0 Example 11 Production of enteric beads I-2: The bare beads C500f produced in Example 10 were placed in a fluidized bed coating device, and a coating liquid of the following composition was added to the coating solution.
Enteric beads I-2 are prepared by spray coating F in a conventional manner. The coverage of this product was about 4% based on the weight of the bare beads.
組成 ％
カルボキシメチルエチルセルロース ２０エタノー
ル
９ａＯ合計 １０００
実施例１２
持効性セフラジンビーズＲ−３の製造：実施例１１で製
した腸溶性ビーズｌ−２５００ｆ及びセフラジン１７９
．４Ｆとトウモロコシデンゾン２０６１の混合物を遠心
流動型コーティング造粒機を用いて造粒し、次いで５５
℃、２時間乾燥した。更に得られた乾燥ビーズ５００ｆ
’ｉ流動層コーティング装置に入れ、下記組成のコーテ
イング液５００ｆを常法に従ってスプレーコーティング
を行ない、特効性セフラジンビーズＲ−３を製した。Composition % Carboxymethylethyl cellulose 20 ethanol
9aO total 1000 Example 12 Production of sustained-release cefrazine beads R-3: Enteric-coated beads l-2500f produced in Example 11 and cefrazine 179
．． A mixture of 4F and Corn Denzone 2061 was granulated using a centrifugal fluid coating granulator, and then 55
It was dried at ℃ for 2 hours. Further obtained dry beads 500f
The beads were placed in a fluidized bed coating apparatus and spray coated with 500f of a coating solution having the following composition according to a conventional method to produce specific cefradine beads R-3.
組成 ％
サラシミツロウ ａＯメルク
ａＯイソゾロビルアルコール
１９．０塩化メチレン
７ ａ Ｏ合計 １０００
実施例１３
試験１：
実施例１，３．４及び６で製した顆粒人をセフラジン２
５０１Ｒ９力価、Ｓ−４，Ｓ−２及びＩ−１をそれぞれ
６００′ＩＩｇ力価健康成人に食後投与し、セフラジン
の血中濃度を測定した。結果を第１図に示した。Composition % White beeswax aO Merck
aO isozorobyl alcohol
19.0 Methylene chloride
7 aO total 1000 Example 13 Test 1: The granules prepared in Examples 1, 3.4 and 6 were treated with cefrazine 2.
501R9 titer, S-4, S-2 and I-1 were each administered to healthy adults with a 600'IIg titer after meals, and the blood concentration of cefrazine was measured. The results are shown in Figure 1.
実施例１４
試験２：
試験１の結果を基にＩＭｈ溶性セ７ラゾン顆粒Ｉ−１と
、裸顆粒Ａあるいは遅溶性顆粒Ｓ−１またはＳ−２を組
合せた場合の最適混合比率の推定を行なった。得られた
最適混合比率での血中濃度一時間推移曲線のシミュレー
ション曲線を第２図に示した。第２図から明らかなよう
に、腸溶性セフラジン顆粒と遅溶性セフラジン顆粒５−
１ｉるいはＳ−２を組合せることによ＃）、裸顆粒人を
用いた場合に見られるような血中濃度の谷は消失し、良
好な持効性を示すことがわかった。Example 14 Test 2: Based on the results of Test 1, the optimal mixing ratio was estimated when IMh-soluble se7lazone granules I-1 were combined with bare granules A or slow-soluble granules S-1 or S-2. Ta. FIG. 2 shows a simulation curve of an hourly blood concentration curve at the obtained optimal mixing ratio. As is clear from Figure 2, enteric-coated cefrazine granules and slow-dissolving cefrazine granules 5-
It was found that by combining 1i or S-2), the trough in blood concentration that was seen when naked granules were used disappeared, and good sustained efficacy was exhibited.
実施例１５
試験３：
実施例６で製した持効性セフラジン顆粒Ｒ−１をセフラ
ジン５００■力価相当蓋健康成人に投与し、セフラジン
の血中濃度全測定した。第３図に示したように１本発明
の持効性セフラジン顆粒は持効性製剤として優れた血中
濃度一時間推移曲線を示していた○Example 15 Test 3: The sustained-release cefrazine granules R-1 prepared in Example 6 were administered to healthy adults with a cefrazine titer of 500 µm, and the total blood concentration of cefrazine was measured. As shown in Figure 3, the long-acting cefradine granules of the present invention showed an excellent one-hour blood concentration curve as a long-acting preparation.○
第１図はセフラジンの裸顆粒Ａ％遅溶性セフラゾンｌｉ
ｔ粒Ｓ−１，Ｓ−２及び腸溶性セフラジン顆粒１−１全
それぞれ単独で投与したときの血中濃度一時間推移曲線
を示す図面である。
第２図はセフラジンの腸溶性顆粒１−１と。
裸顆粒人おるいは遅溶性顆粒Ｓ−１またＨｓ−２を組合
せて投与した場合の最適混合比率における血中濃度一時
間推移曲線（シミュレーション）を示す図面である。
第３図は持効性セフラジン顆粒Ｒ−１−と従来製剤の血
中濃度一時間推移曲線を示す図面である。
以上Figure 1 shows naked granules of cefrazine A% slow-soluble cefrazone li
FIG. 2 is a drawing showing one-hour time course curves of blood concentrations when T-grains S-1, S-2 and enteric-coated cefrazine granules 1-1 were each administered alone. Figure 2 shows enteric-coated granules of cefradine 1-1. FIG. 2 is a diagram showing a one-hour change curve (simulation) of blood concentration at an optimal mixing ratio when naked granules or slow-soluble granules S-1 or Hs-2 are administered in combination. FIG. 3 is a diagram showing one-hour blood concentration time course curves of sustained-release cefradine granules R-1- and conventional preparations. that's all
Claims (1)
合せたことを特徴とする持効性セフラジン製剤。 ２、遅溶性セフラジン製剤と腸溶性セフラジン製剤とを
、それらのセフラジン力価換算全量比が３：７〜５：５
となるよう組合せたものである特許請求の範囲第１項記
載の持効性セフラジン製剤。 ３、遅溶性セフラジン製剤が非水溶性高分子、パラフィ
ンワックス、高級アルコール、脂肪酸エステル、高級脂
肪酸、あるいはそれらのの金属塩から選ばれる１種以上
の徐放化剤を含有することを特徴とする特許請求の範囲
第１項または第２項記載の持効性セフラジン製剤。 ４、遅溶性セフラジン製剤の徐放化剤がマトリックス形
成剤であり、これを該製剤全重量に対し５〜７０重量％
配合したことを特徴とする特許請求の範囲第３項記載の
持効性セフラジン製剤。 ５、遅溶性セフラジン製剤の徐放化剤が被膜化剤であり
、該製剤全重量の２〜４０重量％の該被膜化剤で被覆し
たことを特徴とする特許請求の範囲第３項記載の持効性
セフラジン製剤。 ６、遅溶性製剤が細粒、顆粒またはビーズである特許請
求の範囲第１〜４項のいずれかの項記載の持効性セフラ
ジン製剤。 ７、遅溶性製剤がマイクロカプセル、被覆細粒、被覆顆
粒または被覆ビーズである特許請求の範囲第１〜３項ま
たは第５項のいずれかの項記載の持効性セフラジン製剤
。 ８、腸溶性製剤がｐＨ５．０〜７．０の範囲内で溶解す
る被膜で被覆したものである特許請求の範囲第１項また
は第２項記載の持効性セフラジン製剤。 ９、腸溶性製剤が腸溶性被膜を腸溶部裸製剤に被覆して
得られたものである特許請求の範囲第８項記載の持効性
セフラジン製剤。 １０、腸溶性製剤がマイクロカプセル、被覆細粒、被覆
顆粒または被覆ビーズである特許請求の範囲第１項、第
２項、第８項または第９項のいずれかの項記載の持効性
セフラジン製剤。 １１、腸溶性製剤を遅溶性製剤で被覆して成る単一製剤
である特許請求の範囲第１〜１０項のいずれかの項記載
の持効性セフラジン製剤。 １２、遅溶性製剤と腸溶性製剤とを混合して成る混合製
剤である特許請求の範囲第１〜１０項のいずれかの項記
載の持効性セフラジン製剤。[Scope of Claims] 1. A sustained-release cefrazine preparation, which is characterized by a combination of a slow-dissolving cefrazine preparation and an enteric-coated cefrazine preparation. 2. The slow-dissolving cefrazine preparation and the enteric-coated cefrazine preparation have a total ratio of 3:7 to 5:5 in terms of cefrazine potency.
The sustained-release cefrazine preparation according to claim 1, which is a combination of cefrazine and cefrazine. 3. The slow-soluble cefrazine preparation is characterized by containing one or more sustained release agents selected from water-insoluble polymers, paraffin wax, higher alcohols, fatty acid esters, higher fatty acids, or metal salts thereof. A sustained-release cefrazine preparation according to claim 1 or 2. 4. The sustained release agent of the slow-soluble cefrazine preparation is a matrix forming agent, which is used in an amount of 5 to 70% by weight based on the total weight of the preparation.
The sustained-release cefrazine preparation according to claim 3, characterized in that it is blended with cefrazine. 5. The sustained release agent of the slow-soluble cefrazine preparation is a coating agent, and the preparation is coated with the coating agent in an amount of 2 to 40% by weight of the total weight of the preparation. Long-acting cefrazine preparation. 6. The sustained-release cefrazine preparation according to any one of claims 1 to 4, wherein the slow-dissolving preparation is fine particles, granules, or beads. 7. The sustained-release cefrazine preparation according to any one of claims 1 to 3 or 5, wherein the slow-dissolving preparation is a microcapsule, coated granules, coated granules, or coated beads. 8. The sustained-release cefrazine preparation according to claim 1 or 2, wherein the enteric-coated preparation is coated with a film that dissolves within the pH range of 5.0 to 7.0. 9. The sustained-release cefrazine preparation according to claim 8, wherein the enteric-coated preparation is obtained by coating a bare enteric-coated preparation with an enteric coating. 10. The sustained-release cefrazine according to any one of claims 1, 2, 8, or 9, wherein the enteric-coated preparation is a microcapsule, coated granule, coated granule, or coated bead. formulation. 11. The sustained-release cefrazine preparation according to any one of claims 1 to 10, which is a single preparation comprising an enteric-coated preparation coated with a slow-dissolving preparation. 12. The sustained-release cefrazine preparation according to any one of claims 1 to 10, which is a mixed preparation comprising a slow-dissolving preparation and an enteric-coated preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62076784A JP2528652B2 (en) | 1987-03-30 | 1987-03-30 | Long-acting cefradine formulation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62076784A JP2528652B2 (en) | 1987-03-30 | 1987-03-30 | Long-acting cefradine formulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63243030A true JPS63243030A (en) | 1988-10-07 |
| JP2528652B2 JP2528652B2 (en) | 1996-08-28 |
Family
ID=13615228
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62076784A Expired - Lifetime JP2528652B2 (en) | 1987-03-30 | 1987-03-30 | Long-acting cefradine formulation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2528652B2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002064120A1 (en) * | 2001-02-13 | 2002-08-22 | Taisho Pharmaceutical Co., Ltd. | Gel preparations for internal use |
| JP2004528272A (en) * | 2000-10-13 | 2004-09-16 | アドバンシス ファーマスーティカルス | Extended release erythromycin derivatives |
| WO2006080481A1 (en) * | 2005-01-31 | 2006-08-03 | Kyorin Pharmaceutical Co., Ltd. | Multiple unit oral sustained release preparation and process for production of the same |
| JP2007510656A (en) | 2003-11-04 | 2007-04-26 | スパーナス ファーマシューティカルズ インコーポレイテッド | Trospium once a day dosage form |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61137813A (en) * | 1984-12-07 | 1986-06-25 | Sawai Seiyaku Kk | Long acting cephradine pharmaceutical preparation |
-
1987
- 1987-03-30 JP JP62076784A patent/JP2528652B2/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61137813A (en) * | 1984-12-07 | 1986-06-25 | Sawai Seiyaku Kk | Long acting cephradine pharmaceutical preparation |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004528272A (en) * | 2000-10-13 | 2004-09-16 | アドバンシス ファーマスーティカルス | Extended release erythromycin derivatives |
| WO2002064120A1 (en) * | 2001-02-13 | 2002-08-22 | Taisho Pharmaceutical Co., Ltd. | Gel preparations for internal use |
| JP2007510656A (en) | 2003-11-04 | 2007-04-26 | スパーナス ファーマシューティカルズ インコーポレイテッド | Trospium once a day dosage form |
| JP2012144577A (en) * | 2003-11-04 | 2012-08-02 | Supernus Pharmaceuticals Inc | Once-a-day dosage form of trospium |
| WO2006080481A1 (en) * | 2005-01-31 | 2006-08-03 | Kyorin Pharmaceutical Co., Ltd. | Multiple unit oral sustained release preparation and process for production of the same |
| JPWO2006080481A1 (en) * | 2005-01-31 | 2008-06-19 | 杏林製薬株式会社 | Multiple unit type oral sustained-release preparation and method for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2528652B2 (en) | 1996-08-28 |
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