JPS63295507A - Production of stabilized pharmaceutical preparation - Google Patents
Production of stabilized pharmaceutical preparationInfo
- Publication number
- JPS63295507A JPS63295507A JP62129467A JP12946787A JPS63295507A JP S63295507 A JPS63295507 A JP S63295507A JP 62129467 A JP62129467 A JP 62129467A JP 12946787 A JP12946787 A JP 12946787A JP S63295507 A JPS63295507 A JP S63295507A
- Authority
- JP
- Japan
- Prior art keywords
- reduced pressure
- under
- particles
- drug
- oil
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 title abstract 3
- 239000003814 drug Substances 0.000 claims abstract description 17
- 229940079593 drug Drugs 0.000 claims abstract description 17
- 239000011230 binding agent Substances 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 10
- 239000011248 coating agent Substances 0.000 claims abstract description 9
- 238000000576 coating method Methods 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims abstract description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 9
- 239000003921 oil Substances 0.000 claims abstract description 8
- 235000019198 oils Nutrition 0.000 claims abstract description 8
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 7
- 239000008158 vegetable oil Substances 0.000 claims abstract description 7
- 238000005507 spraying Methods 0.000 claims abstract description 6
- 238000001035 drying Methods 0.000 claims abstract description 5
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 9
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 150000004667 medium chain fatty acids Chemical class 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 2
- MYGVPKMVGSXPCQ-JEDNCBNOSA-N Methylmethionine sulfonium salt Chemical compound [Cl-].C[S+](C)CC[C@H](N)C(O)=O MYGVPKMVGSXPCQ-JEDNCBNOSA-N 0.000 abstract description 11
- 239000000203 mixture Substances 0.000 abstract description 9
- 238000003860 storage Methods 0.000 abstract description 9
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 2
- 239000000194 fatty acid Substances 0.000 abstract description 2
- 229930195729 fatty acid Natural products 0.000 abstract description 2
- 150000004665 fatty acids Chemical class 0.000 abstract description 2
- -1 grinding Substances 0.000 abstract description 2
- 238000000227 grinding Methods 0.000 abstract description 2
- 238000000354 decomposition reaction Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 5
- 239000011812 mixed powder Substances 0.000 description 5
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 4
- 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 4
- 229920001249 ethyl cellulose Polymers 0.000 description 4
- 235000019325 ethyl cellulose Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- YMEBNAABDXLAJE-GPAWKIAZSA-N [(e)-4-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-3-[[(e)-2-[(4-amino-2-methylpyrimidin-5-yl)methyl-formylamino]-5-butanoyloxypent-2-en-3-yl]disulfanyl]pent-3-enyl] butanoate Chemical compound C=1N=C(C)N=C(N)C=1CN(C=O)C(\C)=C(/CCOC(=O)CCC)SS\C(CCOC(=O)CCC)=C(/C)N(C=O)CC1=CN=C(C)N=C1N YMEBNAABDXLAJE-GPAWKIAZSA-N 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 239000003549 soybean oil Substances 0.000 description 3
- 235000012424 soybean oil Nutrition 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 229960002061 ergocalciferol Drugs 0.000 description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 235000001892 vitamin D2 Nutrition 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- XDLNRRRJZOJTRW-UHFFFAOYSA-N thiohypochlorous acid Chemical compound ClS XDLNRRRJZOJTRW-UHFFFAOYSA-N 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は安定化製剤の製造方法に関し、更に詳しくは保
存中に吸湿して分解を起し易い不安定な薬物の安定化製
剤の製造方法に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing a stabilized drug, and more specifically, a method for producing a stabilized drug that is susceptible to moisture absorption and decomposition during storage. Regarding.
（従来の技術）
常用されている薬物の中には保存中に吸湿して分解を起
しやすい不安定な薬物が多数存在する。(Prior Art) Among commonly used drugs, there are many unstable drugs that tend to absorb moisture and decompose during storage.
たとえば、メチルメチオニンスルホニウムクロライドは
極めて吸湿性が強く、吸湿すると分解を起して不快臭を
有するジメチルサルファイドを発生する。For example, methylmethionine sulfonium chloride is extremely hygroscopic, and when it absorbs moisture, it decomposes and generates dimethyl sulfide, which has an unpleasant odor.
メチルメチオニンスルホニウムクロライドを常用の賦形
剤や結合剤を用いて通常の製法で経口製剤に調製した場
合にはその保存中に起る分解を防止することができない
。When methylmethionine sulfonium chloride is prepared into oral preparations by conventional methods using conventional excipients and binders, it is impossible to prevent decomposition during storage.
（発明が解決しようとする問題点）
この現象はメチルメチオニンスルホニウムクロライドに
のみ起る現象ではなく、ジアノコバラミン、エルゴカル
シフェロールなどの吸湿して分解を起し易い薬物にはよ
く見られる現象である。(Problem to be solved by the invention) This phenomenon does not only occur with methylmethionine sulfonium chloride, but is often seen with drugs that absorb moisture and easily decompose, such as dianocobalamin and ergocalciferol. be.
本発明の目的は、これら吸湿して分解を起し易い薬物に
特殊な吸湿防止コーティングを施すことにより安定化製
剤を製造する方法を提供することにある。An object of the present invention is to provide a method for producing stabilized preparations by applying a special anti-moisture coating to these drugs that tend to absorb moisture and cause decomposition.
本発明者らは、前記問題点を解決すべく研究した結果、
これら不安定な薬物を硬化油と粉砕混合後、減圧下でこ
れらの粒子に植物油のコーティングを施し、賦形剤と結
合剤を用いて造粒、乾燥することによ多安定化製剤を製
造することに成功し、本発明を完成した。As a result of research to solve the above problems, the present inventors found that
After grinding and mixing these unstable drugs with hydrogenated oil, these particles are coated with vegetable oil under reduced pressure, granulated using excipients and binders, and dried to produce multi-stabilized formulations. They were very successful and completed the present invention.
本発明の方法は、不安定な薬物を硬化油と混合。The method of the invention involves mixing unstable drugs with hydrogenated oils.
粉砕後、減圧下に、
ａ）この混合粒子に植物油または中鎖脂肪酸トリグリセ
リドをスプレー・コーティングし、ｂ）これに賦形剤を
添加し、混合しながら結合剤溶液をスプレーしてコーテ
ィングと造粒を行ない、
Ｃ）最後にこの造粒物を乾燥すること
を特徴とする安定化製剤の製造方法である。After pulverization, under reduced pressure, a) spray-coat the mixed particles with vegetable oil or medium-chain fatty acid triglyceride, b) add excipients to this, and spray a binder solution while mixing to coat and granulate. C) Finally, this granulated product is dried.
本発明において、不安定な薬物とは、吸湿して分解を起
しやすい薬物、たとえば、メチルメチオニンスルホニウ
ムクロライド、ジアノコバラミン。In the present invention, unstable drugs are drugs that tend to absorb moisture and cause decomposition, such as methylmethionine sulfonium chloride and dianocobalamin.
エルゴカルシフェロール、ビスイブチアミン、酢酸レチ
ノールなどである。These include ergocalciferol, bisbutiamine, and retinol acetate.
硬化油とは、綿実油、大豆油、ヒマシ油又は魚油などを
原料にして水素添加を行ない、日本薬局方の基準に合致
するものであり、たとえばラブリワックス１０１〔商品
名、用研ファインケミカル■製〕などである。Hydrogenated oil is hydrogenated oil made from raw materials such as cottonseed oil, soybean oil, castor oil, or fish oil, and meets the standards of the Japanese Pharmacopoeia. For example, Loveliwax 101 [trade name, manufactured by Yoken Fine Chemicals] etc.
植物油とは、けん化価１８０〜２００程度の、食用とな
し得る植物油をいい、たとえば日本薬局方の基準に合致
する大豆油、落花生油、オリブ油。Vegetable oil refers to edible vegetable oil with a saponification value of about 180 to 200, such as soybean oil, peanut oil, and olive oil that meet the standards of the Japanese Pharmacopoeia.
トウモロコシ油などが好ましい。Corn oil and the like are preferred.
中鎖脂肪酸トリグリセリドとは、炭素原子数が６〜１２
の脂肪酸のトリグリセリドをいい、たとえばパナセート
〔商品名９日本油脂■製）、ＯＤＯ〔商品名１日清製油
■製〕、ココナート〔商品名。Medium-chain fatty acid triglycerides have 6 to 12 carbon atoms.
It refers to triglycerides of fatty acids, such as Panacet [product name 9 manufactured by Nisshin Oil Co., Ltd.], ODO [product name 1 manufactured by Nisshin Oil Co., Ltd.], and Coconato [product name].
日量化学工業■製〕、ミグリオール〔商品名２日量化学
工業■製〕などとして入手できる。It is available as Miglyol (trade name: manufactured by Nichiryo Kagaku Kogyo ■), Miglyol (trade name: manufactured by Nichiryo Kagaku Kogyo ■), etc.
減圧とは、１０〜１５０トル（ｔｏｒｒ）程度の減圧、
好ましくは１０〜１００トル程度の減圧をいう。Depressurization is a decompression of about 10 to 150 torr,
Preferably, the reduced pressure is about 10 to 100 torr.
賦形剤としては、低置換度ヒドロキシプロピルセルロー
ス、マンニトール、テンプン、炭酸カルシウム、カオリ
ン、リン酸カルシウムなどを１程または２種以上用いる
ことができる。As excipients, one or more of low-substituted hydroxypropylcellulose, mannitol, starch, calcium carbonate, kaolin, calcium phosphate, etc. can be used.
結合剤としては、エチルセルロース、ヒドロキシプロピ
ルセルロースなどの有機溶媒による溶液、好ましくはエ
タノール溶液を用いる。As the binder, a solution of organic solvent such as ethyl cellulose or hydroxypropyl cellulose, preferably an ethanol solution, is used.
生薬が水の存在を嫌うことから、賦形剤や結合剤はなる
べく水を含まないものか、水を含んでも極く微量のもの
を用いる。Since herbal medicines dislike the presence of water, excipients and binders should either contain as little water as possible, or contain only a very small amount of water.
この他必要に応じて矯味剤１着色剤、保存剤などを用い
ることができる。In addition, a flavoring agent 1, a coloring agent, a preservative, etc. can be used as necessary.
本発明のコーティング、造粒、乾燥の工程は、減圧下に
各工程毎にバッチ方式で行なっても差支えないが、攪拌
装置、加温装置、スプレー装置および減圧装置を備えた
造粒機を用いてこれらの工程を一貫作業で行なうことが
効率的で好ましい。The coating, granulation, and drying steps of the present invention may be performed in a batch manner under reduced pressure for each step, but a granulator equipped with a stirring device, a heating device, a spray device, and a decompression device is used. It is efficient and preferable to carry out these steps in an integrated operation.
この上うな造粒機としては、万能混合攪拌機〔三英製作
所■製〕、パン型の真空造粒コーテイング機であるＶＧ
ココ−−〔菊水製作所■〕２球型で全体の揺動が可能な
スフエリツク・グラニユレータ−〔富士産業■製〕など
がある。In addition, the eel granulator includes a universal mixing stirrer [manufactured by Sanei Manufacturing Co., Ltd.] and a pan-shaped vacuum granulation coating machine called VG.
Coco (Kikusui Seisakusho ■) and Spheric Granulator (manufactured by Fuji Sangyo ■), which has two spheres and can swing as a whole, are examples.
本発明の製造方法は次のようにして行なう。The manufacturing method of the present invention is carried out as follows.
まず、不安定な薬物をその１〜３倍量の硬化油と混合し
、粉砕する。First, the unstable drug is mixed with 1 to 3 times the amount of hydrogenated oil and ground.
次いで、この混合粉末を前記の性能を備えた造粒機に投
入し、１０〜１５０トル程度の減圧下５０〜６０℃で攪
拌混合しながら前記混合粉末の九量程度の植物油または
中鎖脂肪酸トリグリセリドをこれにスプレーしてコーテ
ィングを施す。Next, this mixed powder is put into a granulator equipped with the above-mentioned performance, and while stirring and mixing at a reduced pressure of about 10 to 150 Torr and at 50 to 60°C, about 90% of the mixed powder is mixed with vegetable oil or medium chain fatty acid triglyceride. Spray on this to apply a coating.
このコーティング粉末にその１〜３倍量の賦形剤を加え
、１０〜１００トルの減圧下で均一に混合する。Add 1 to 3 times the amount of excipient to this coating powder and mix uniformly under reduced pressure of 10 to 100 torr.
この混合粉末を攪拌混合しながら、４５〜５５℃、１０
０〜１５０トルの減圧下、５〜８％程度の結合剤溶液を
スプレーしてコーティングと造粒を行ない、次いで４５
〜５５℃、１０〜１００トルの減圧下で乾燥し、安定化
製剤を調製する。This mixed powder was stirred and mixed at 45-55℃ for 10 minutes.
Coating and granulation are carried out by spraying a binder solution of about 5 to 8% under reduced pressure of 0 to 150 Torr, and then
A stabilized formulation is prepared by drying at ~55° C. under a vacuum of 10-100 torr.
（発明の効果）
本発明の方法により、吸湿して分解を起し易い薬物の安
定化製剤を大量かつ安価に提供することができる。(Effects of the Invention) According to the method of the present invention, stabilized preparations of drugs that tend to absorb moisture and cause decomposition can be provided in large quantities and at low cost.
（実 施 例）
以下、実施例および試験例を挙げて本発明を具体的に説
明する。(Examples) Hereinafter, the present invention will be specifically explained with reference to Examples and Test Examples.
実施例 １
メチオニンスルホニウムクロライド１５０部とラブリワ
ックス１０１ ３００部を混合機で混合後粉砕機で粉砕
した。Example 1 150 parts of methionine sulfonium chloride and 300 parts of Lovely Wax 101 were mixed in a mixer and then ground in a grinder.
次にこの混合粉末をスフエリツクグラニユレータ−に投
入し、攪拌混合しながら１００トルの減圧下、５０℃で
大豆油４０部をスプレーしてこの混合粉末にコーティン
グを施した。Next, this mixed powder was put into a spherical granulator, and while stirring and mixing, 40 parts of soybean oil was sprayed at 50° C. under a reduced pressure of 100 torr to coat the mixed powder.
このコーティング粉末に低置換度ヒドロキシプロピルセ
ルロース３００部、マンニトール６６０部、ヒドロキシ
グロビルセルロースｓ ｏ 部ヲ加え、５０トルの減圧
下５５℃で均一に混合した。To this coating powder were added 300 parts of low-substituted hydroxypropyl cellulose, 660 parts of mannitol, and 2 parts of hydroxyglobil cellulose, and the mixture was uniformly mixed at 55° C. under a reduced pressure of 50 torr.
この混合、攪拌を続けながら、１００トルの減圧下、５
５℃で別に調製しておいた結合剤溶液（エタノール８０
０部にエチルセルロース６０部を溶解させた溶液）をこ
の混合物にスプレーしてコーティングと造粒を行なった
後、更に１０トルの減圧下、５５℃で乾燥を行ない、最
後に５０℃で乾燥して顆粒状のメチルメチオニンスルホ
ニウムクロライドの安定化製剤を得た。While continuing this mixing and stirring, under a reduced pressure of 100 torr,
Separately prepared binder solution (ethanol 80
The mixture was coated and granulated by spraying a solution of 60 parts of ethyl cellulose in 0 parts of ethyl cellulose, followed by further drying at 55°C under a vacuum of 10 torr, and finally at 50°C. A stabilized formulation of granular methylmethionine sulfonium chloride was obtained.
実施例 ２
ジアノコバラミン ０．０６部ラうリワックス
１０１ １００ 部オリプ油 １０
部
マンニトール ２００ 部
計 ３２０．０６部
実施例１に準じて上記処方のジアノコバラミン安定化製
剤を得た。Example 2 Dianocobalamin 0.06 parts Lauriwax 101 100 parts Olive oil 10
part mannitol 200 parts total 320.06 parts A dianocobalamin stabilized preparation having the above formulation was obtained according to Example 1.
実施例 ３
ビスイブチアミン ２５部
ラブリワックス１０１ ５０部
パナセート １０部
マンニトール ７５部
エチルセルロース １０部
１７０部
実施例１に準じて上記処方のビスイブチアミンの安定化
製剤を得た。Example 3 Bisbutiamine 25 parts Loveriwax 101 50 parts Panasate 10 parts Mannitol 75 parts Ethylcellulose 10 parts 170 parts A stabilized preparation of bisbutiamine having the above formulation was obtained according to Example 1.
試験例 １
メチルメチオニンスルホニウムクロライド５２をそれぞ
れ後記５条件のデシケータ−にオープン状態で６日間保
存し、吸湿による重量の増加を測定した。Test Example 1 Methylmethionine sulfonium chloride 52 was stored in an open state in a desiccator under the following conditions for 6 days, and the increase in weight due to moisture absorption was measured.
その後、各試料を密栓容器にいれて４０℃１週間保存後
と同５０℃１週間保存後のメチルメチオニンスルホニウ
ムクロライドの残存量を測定した。Thereafter, each sample was placed in a sealed container and the remaining amount of methylmethionine sulfonium chloride was measured after storage at 40°C for one week and after storage at 50°C for one week.
その結果を第１表に示す。The results are shown in Table 1.
第 １ 表
試験例 ２
実施例１で得た製剤を試料とし、実施例１の処方から２
ブリワツクス１０１を抜いた処方のものを実施例１に準
じて調製したものをコントロールとした。Table 1 Test Example 2 The preparation obtained in Example 1 was used as a sample, and 2
A control was prepared according to Example 1 except that Briwax 101 was omitted.
試料とコントロールとを、それぞれ密栓容器にいれ、５
０℃で１ケ月保存後のメチルメチオニンスルホニウムク
ロライドの残存量を測定した。Place the sample and control in a sealed container, and
The remaining amount of methylmethionine sulfonium chloride after storage at 0°C for one month was measured.
その結果を第２表に示す。The results are shown in Table 2.
試験例 ３
実施例１で得た製剤１２をアルミパックに封入し、相対
湿度７５％、４０℃で６ケ月保存後の状態を調べ、メチ
ルメチオニンスルホニウムクロライドの残存量を測定し
た。Test Example 3 Preparation 12 obtained in Example 1 was sealed in an aluminum pack, and after storage for 6 months at 75% relative humidity and 40° C., the condition was examined and the remaining amount of methylmethionine sulfonium chloride was measured.
製剤の外観には変化がなく、分解臭もなかった。There was no change in the appearance of the preparation and there was no decomposition odor.
メチルメチオニンスルホニウムクロライドの残存量は９
９５％であった。The remaining amount of methylmethionine sulfonium chloride is 9
It was 95%.
Claims (1)
リドをスプレー・コーティングし、 ｂ）これに賦形剤を添加し、混合しながら結合剤溶液を
スプレーしてコーティングと造粒を行ない、ｃ）最後に
この造粒物を乾燥すること を特徴とする安定化製剤の製造方法。[Claims] 1) After mixing the unstable drug with hydrogenated oil and pulverizing it, under reduced pressure, a) spray coating the mixed particles with vegetable oil or medium chain fatty acid triglyceride, and b) adding excipients to the mixed particles. A method for producing a stabilized preparation, characterized in that: c) coating and granulation are carried out by spraying a binder solution while mixing, and finally drying the granulation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62129467A JP2515802B2 (en) | 1987-05-26 | 1987-05-26 | Stabilized formulation manufacturing method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62129467A JP2515802B2 (en) | 1987-05-26 | 1987-05-26 | Stabilized formulation manufacturing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63295507A true JPS63295507A (en) | 1988-12-01 |
| JP2515802B2 JP2515802B2 (en) | 1996-07-10 |
Family
ID=15010213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP62129467A Expired - Lifetime JP2515802B2 (en) | 1987-05-26 | 1987-05-26 | Stabilized formulation manufacturing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2515802B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007508292A (en) * | 2003-10-10 | 2007-04-05 | エティファルム | Release-sustained microgranule containing ginkgo biloba extract and method for producing such granule |
| KR100966219B1 (en) * | 2002-04-16 | 2010-06-25 | 코와 가부시키가이샤 | Method For Producing Pharmaceutical Preparation Containing Methylmethioninesulfonium Chloride |
| JP2016037537A (en) * | 2014-08-06 | 2016-03-22 | 長谷川香料株式会社 | Powdery or granular composition and manufacturing method therefor |
| JP2018023309A (en) * | 2016-08-09 | 2018-02-15 | ミヨシ油脂株式会社 | Oil and fat composition and oil and fat-containing food material using the same, drink and food product and method for producing the same |
| WO2020090968A1 (en) * | 2018-10-31 | 2020-05-07 | 富士フイルム株式会社 | Granule containing anti-tumor agent |
-
1987
- 1987-05-26 JP JP62129467A patent/JP2515802B2/en not_active Expired - Lifetime
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100966219B1 (en) * | 2002-04-16 | 2010-06-25 | 코와 가부시키가이샤 | Method For Producing Pharmaceutical Preparation Containing Methylmethioninesulfonium Chloride |
| JP2007508292A (en) * | 2003-10-10 | 2007-04-05 | エティファルム | Release-sustained microgranule containing ginkgo biloba extract and method for producing such granule |
| JP2016037537A (en) * | 2014-08-06 | 2016-03-22 | 長谷川香料株式会社 | Powdery or granular composition and manufacturing method therefor |
| JP2018023309A (en) * | 2016-08-09 | 2018-02-15 | ミヨシ油脂株式会社 | Oil and fat composition and oil and fat-containing food material using the same, drink and food product and method for producing the same |
| WO2020090968A1 (en) * | 2018-10-31 | 2020-05-07 | 富士フイルム株式会社 | Granule containing anti-tumor agent |
| CN112996515A (en) * | 2018-10-31 | 2021-06-18 | 富士胶片株式会社 | Granulated substance containing antitumor agent |
| JPWO2020090968A1 (en) * | 2018-10-31 | 2021-09-16 | 富士フイルム株式会社 | Granulation containing antitumor agent |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2515802B2 (en) | 1996-07-10 |
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