JP2001278806A - Colistin sulfate stabilized preparation - Google Patents
Colistin sulfate stabilized preparationInfo
- Publication number
- JP2001278806A JP2001278806A JP2000097420A JP2000097420A JP2001278806A JP 2001278806 A JP2001278806 A JP 2001278806A JP 2000097420 A JP2000097420 A JP 2000097420A JP 2000097420 A JP2000097420 A JP 2000097420A JP 2001278806 A JP2001278806 A JP 2001278806A
- Authority
- JP
- Japan
- Prior art keywords
- colistin sulfate
- colistin
- producing
- starch
- preparation
- 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.)
- Pending
Links
Landscapes
- Feed For Specific Animals (AREA)
- Fodder In General (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、硫酸コリスチンお
よびデンプン類とを用いる硫酸コリスチン製剤の製造法
に関する。TECHNICAL FIELD The present invention relates to a method for producing a colistin sulfate preparation using colistin sulfate and starches.
【０００２】[0002]
【従来の技術】硫酸コリスチンは家畜や家禽の発育促
進、飼料効率の改善を目的に飼料添加物として広く使用
されている。しかし、プレミックスや飼料に配合するこ
とにより硫酸コリスチンが不活化されることが明らかに
なり、製剤技術の改良による安定化が種々試みられてい
る。飼料添加物の硫酸コリスチン製剤を製造するために
用いられる賦形物質としては、トウモロコシデンプン、
コムギデンプン、デンプン、変性食用デンプン、α―デ
ンプン、デキストリン、小麦粉、とうもろこし粉、大豆
粉、米粉、ふすま、米ぬか油かす、もみがら粉末、ダイ
ズミール、トルラ酵母、乳糖、二酸化珪素、結晶性セル
ロース、ゼラチン、パラフィン、植物性のガム物質、各
種セルロース類などがあげられ、具体的な製法として
は、（ｉ）硫酸コリスチンに希釈剤を加えて前造粒した
顆粒の表面に、保護剤を被覆する方法（特開平５−３７
５９）、（ii）硫酸コリスチンをモミガラ焼成剤に混合
する方法または珪藻土に含有させる方法（特開平５−１
６８４２１）、（iii）硫酸コリスチンの水溶液にデン
プンを混合し、加熱、α化し、またはα化デンプンを混
合し、賦形剤として更にデンプンを加え、練合、造粒、
乾燥、粉砕、篩過することにより安定化製剤を製造する
方法（特開平６−１８９６９１）等がある。BACKGROUND OF THE INVENTION Colistin sulfate is widely used as a feed additive for the purpose of promoting the growth of livestock and poultry and improving feed efficiency. However, it has been revealed that colistin sulfate is inactivated by blending it in a premix or feed, and various attempts have been made to stabilize colistin sulfate by improving formulation techniques. Maize starch, as excipients used for producing colistin sulfate preparations of feed additives,
Wheat starch, starch, modified edible starch, α-starch, dextrin, wheat flour, corn flour, soy flour, rice flour, bran, rice bran oil cake, rice bran powder, soybean meal, tolula yeast, lactose, silicon dioxide, crystalline cellulose, gelatin , Paraffin, vegetable gums, and various celluloses. Specific examples of the production method include (i) a method of adding a diluent to colistin sulfate and coating the surface of granules pre-granulated with a protective agent. (JP-A-5-37
59) and (ii) a method of mixing colistin sulfate in a burning husk or a method of including it in diatomaceous earth (Japanese Patent Laid-Open No. 5-1)
68421), (iii) mixing starch in an aqueous solution of colistin sulfate, heating, pregelatinizing or mixing pregelatinized starch, further adding starch as an excipient, kneading, granulating,
There is a method of producing a stabilized preparation by drying, pulverizing and sieving (JP-A-6-189691).
【０００３】[0003]
【発明が解決しようとする課題】これらの方法はいずれ
も、製造工程は複雑であり、経済性に優れた製造法であ
るとは言い難かった。本発明の目的は、従来の製剤に比
較して製造工程の簡略化とともにコリスチンの十分な安
定性が保証される硫酸コリスチン安定化製剤およびその
製造法を提供することにある。However, all of these methods have complicated production steps and cannot be said to be economical. An object of the present invention is to provide a stabilized colistin sulfate preparation which simplifies the production process and ensures sufficient stability of colistin as compared with conventional preparations, and a method for producing the same.
【０００４】[0004]
【課題を解決するための手段】従来の製剤に比較して十
分な飼料中での安定性を維持し、かつ製造工程の簡略化
を目指して鋭意検討した結果、デンプンをα化する工程
や高価なα化デンプンを添加することなく、また保護剤
で被覆することなしに製剤できる製造法を確立した。さ
らに、従来の飼料添加物用コリスチン製剤では、造粒
後、コリスチンを所定濃度に調整するために、米ぬか油
かす、トウモロコシデンプン、トルラ酵母、二酸化珪
素、結晶性セルロースなどの希釈剤を添加して各種濃度
の硫酸コリスチン製剤を製造していたが、本発明は、こ
の工程が不要となり、所定濃度の硫酸コリスチン製剤を
直接に製造することが可能となった。すなわち、本発明
は、硫酸コリスチンおよびデンプン類とを混合し、次い
でその混合物に水を添加し、造粒することを特徴とする
硫酸コリスチン製剤の製造法及び、その製造法にて製造
された硫酸コリスチン製剤を提供する。Means for Solving the Problems As a result of intensive studies aimed at maintaining sufficient stability in feed compared to conventional preparations and simplifying the production process, it has been found that the process of converting starch into α-form and expensive We have established a production method that can be formulated without adding any pregelatinized starch and without coating with a protective agent. In addition, in the conventional feed additive colistin preparation, after granulation, in order to adjust the colistin to a predetermined concentration, rice bran oil cake, corn starch, torula yeast, silicon dioxide, a diluent such as crystalline cellulose is added. Although colistin sulfate preparations of various concentrations have been produced, the present invention eliminates this step and makes it possible to directly produce colistin sulfate preparations of a predetermined concentration. That is, the present invention provides a method for producing a colistin sulfate preparation, which comprises mixing colistin sulfate and starches, then adding water to the mixture, and granulating the mixture, and sulfuric acid produced by the production method. A colistin preparation is provided.
【０００５】[0005]
【発明の実施の形態】以下に、本発明を詳しく説明す
る。本発明の硫酸コリスチン製剤の製造法において用い
られるデンプン類としては、トウモロコシデンプン、コ
ムギデンプン、変性食用デンプンがあげられ、好ましく
はトウモロコシデンプンがあげられる。硫酸コリスチン
とデンプン類とを混合する際には、硫酸コリスチンおよ
びデンプン類とを１：１〜３０の重量比にて混合し、次
いで、硫酸コリスチンおよびデンプン類との混合物の１
０〜４０Ｖ／Ｗ％となるように水を添加し造粒すること
により所定の濃度のコリスチン製剤を製造することがで
きる。水の添加は滴下ないしは噴霧などの添加方法があ
り、好ましくは噴霧添加する方法である。造粒機とし
て、造粒の機能に混合、練合および整粒の機能を兼ね備
えた混合造粒機や高速撹拌型混合造粒機などを用いるこ
とができる。造粒時の温度はデンプン類がα化する温度
に上げる必要はなく、例えばトウモロコシデンプンを用
いる場合には、７０℃以下に設定することにより、本発
明を実施でき、その温度範囲は３０ないし７０℃が好ま
しい。本製造法では、硫酸コリスチンとデンプン類の量
比を１：１〜３０の重量比の範囲内で適宜、変えること
により、所望濃度のコリスチン製剤を製造することがで
きる。BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail. Examples of the starch used in the method for producing the colistin sulfate preparation of the present invention include corn starch, wheat starch, and modified edible starch, and preferably corn starch. When colistin sulfate and starch are mixed, colistin sulfate and starch are mixed at a weight ratio of 1: 1 to 30. Then, one of the mixture of colistin sulfate and starch is mixed.
By adding water and granulating so as to be 0 to 40 V / W%, a colistin preparation having a predetermined concentration can be produced. Water is added by dropping or spraying, preferably by spraying. As the granulator, a mixing granulator having a function of mixing, kneading and sizing in addition to a function of granulation, a high-speed stirring type mixing granulator, or the like can be used. It is not necessary to raise the temperature at the time of granulation to the temperature at which the starch is turned into α. For example, when corn starch is used, the temperature can be set to 70 ° C. or less, and the present invention can be carried out. C is preferred. In the present production method, a colistin preparation having a desired concentration can be produced by appropriately changing the amount ratio of colistin sulfate to starch within a range of 1: 1 to 30 by weight.
【０００６】以下、実施例を挙げて本発明を説明する
が、本発明はこれにより制限されるものではない。Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited thereto.
【０００７】[0007]
【実施例】〔実施例１〕高速撹拌型混合造粒機（パウレ
ックス社製、FMVG600）に硫酸コリスチン（科研製薬
製）４．５５kgおよびトウモロコシデンプン（ホーネン
製コーンスターチ）９５．４５kgを加えて混合する。次
に水１６ｌを噴霧しながら、ジャケット温度７０℃で２
５分間造粒したのち、流動層乾燥機で乾燥（排風温度６
０℃で終了）する。次に破砕、篩別し、粒子径１５０〜
８４０μm画分を採取し、硫酸コリスチン製剤を得た。 〔実施例２〕高速撹拌型混合造粒機に硫酸コリスチン１
１．４５kgおよびトウモロコシデンプン８８．５５kgを
加えて混合する。次に水１８ｌを噴霧しながら、ジャケ
ット温度７０℃で２５分間造粒したのち、流動層乾燥機
で乾燥する。次に破砕、篩別し、粒子径１５０〜８４０
μｍ画分を採取し、硫酸コリスチン製剤を得た。 〔実施例３〕高速撹拌型混合造粒機に硫酸コリスチン１
７．２５kgおよびトウモロコシデンプン８２．７５kgを
加えて混合する。次に水１９ｌを噴霧しながら、ジャケ
ット温度７０℃で２５分間造粒したのち、流動層乾燥機
で乾燥する。次に破砕、篩別し、粒子径１５０〜８４０
μｍ画分を採取し、硫酸コリスチン製剤を得た。 〔実施例４〕高速撹拌型混合造粒機に硫酸コリスチン１
８．３５kgおよびトウモロコシデンプン８１．６５kgを
加えて混合する。次に水２５ｌを噴霧しながら、ジャケ
ット温度６０℃で３０分間造粒したのち、流動層乾燥機
で乾燥する。次に破砕、篩別し、粒子径１５０〜８４０
μｍ画分を採取し、硫酸コリスチン製剤を得た。 〔実施例５〕高速撹拌型混合造粒機に硫酸コリスチン１
７．２５kgおよびトウモロコシデンプン８２．７５kgを
加えて混合する。次に水２９ｌを噴霧しながらジャケッ
ト温度３０℃で３０分間造粒し、流動層乾燥機で乾燥す
る。次に破砕、篩別し、粒子径１５０〜８４０μｍ画分
を採取し、硫酸コリスチン製剤を得た。 〔実施例６〕高速撹拌型混合造粒機に硫酸コリスチンを
１４．４kgおよびトウモロコシデンプン８５．６kgを加
えて混合する。次に水１４ｌを噴霧しながらジャケット
温度４０℃で３５分間造粒し、流動層乾燥機で乾燥す
る。次に破砕、篩別し、粒子径１５０〜８４０μｍ画分
を採取し、硫酸コリスチン製剤を得た。 〔実施例７〕高速撹拌型混合造粒機に硫酸コリスチンを
３４．２kgおよびトウモロコシデンプン６５．８kgを加
えて混合する。次に水２３ｌを噴霧しながらジャケット
温度４０℃で３０分間造粒し、流動層乾燥機で乾燥す
る。次に破砕、篩別し、粒子径１５０〜８４０μm画分
を採取し、硫酸コリスチン製剤を得た。EXAMPLES Example 1 4.55 kg of colistin sulfate (manufactured by Kaken Pharmaceutical Co., Ltd.) and 95.45 kg of corn starch (corn starch manufactured by Honen) were added to a high-speed stirring-type mixing granulator (manufactured by Pourex, FMVG600) and mixed. I do. Next, while spraying 16 liters of water, a jacket temperature of 70 ° C.
After granulation for 5 minutes, drying with fluidized bed dryer (exhaust air temperature 6
(End at 0 ° C). Next, crushing and sieving, particle size of 150 ~
The 840 μm fraction was collected to obtain a colistin sulfate preparation. Example 2 Colistin sulfate 1 was added to a high-speed stirring type mixing granulator.
1.45 kg and 88.55 kg of corn starch are added and mixed. Next, while spraying 18 l of water, the mixture is granulated at a jacket temperature of 70 ° C. for 25 minutes, and then dried by a fluidized bed drier. Next, it is crushed and sieved to obtain a particle size of 150 to 840.
The μm fraction was collected to obtain a colistin sulfate preparation. [Example 3] Colistin sulfate 1 was added to a high-speed stirring type mixing granulator.
Add 7.25 kg and 82.75 kg corn starch and mix. Next, while spraying 19 l of water, the mixture is granulated at a jacket temperature of 70 ° C. for 25 minutes, and then dried by a fluidized bed drier. Next, it is crushed and sieved to obtain a particle size of 150 to 840.
The μm fraction was collected to obtain a colistin sulfate preparation. Example 4 Colistin sulfate 1 was added to a high-speed stirring type mixing granulator.
Add 8.35 kg and 81.65 kg corn starch and mix. Next, while spraying 25 l of water, the mixture is granulated at a jacket temperature of 60 ° C. for 30 minutes, and then dried by a fluidized bed drier. Next, it is crushed and sieved to obtain a particle size of 150 to 840.
The μm fraction was collected to obtain a colistin sulfate preparation. [Example 5] Colistin sulfate 1 was added to a high-speed stirring type mixing granulator.
Add 7.25 kg and 82.75 kg corn starch and mix. Next, while spraying 29 l of water, the mixture is granulated at a jacket temperature of 30 ° C. for 30 minutes, and dried by a fluidized bed drier. Next, the mixture was crushed and sieved, and a fraction having a particle size of 150 to 840 μm was collected to obtain a colistin sulfate preparation. Example 6 14.4 kg of colistin sulfate and 85.6 kg of corn starch were added to a high-speed stirring type mixing granulator and mixed. Next, while spraying 14 l of water, the mixture is granulated at a jacket temperature of 40 ° C. for 35 minutes, and dried by a fluidized bed drier. Next, the mixture was crushed and sieved, and a fraction having a particle size of 150 to 840 μm was collected to obtain a colistin sulfate preparation. Example 7 34.2 kg of colistin sulfate and 65.8 kg of corn starch were added to a high-speed stirring type mixing granulator and mixed. Next, the mixture is granulated at a jacket temperature of 40 ° C. for 30 minutes while spraying 23 l of water, and dried by a fluidized bed drier. Next, the mixture was crushed and sieved, and a fraction having a particle size of 150 to 840 μm was collected to obtain a colistin sulfate preparation.
【０００８】〔試験例１〕製剤の安定性試験 実施例１ないし７で得られた硫酸コリスチン製剤を、そ
れぞれポリエチレン袋に２００g入れヒートシーラーで
溶着する。さらに三層クラフト袋に入れてテープで封印
する。封印された試料を４０℃、湿度７５％の条件下で
保管し、開始時、１週間、２週間、３週間、４週間後の
コリスチン力価を生物検定法により測定し、開始時力価
を１００％として、硫酸コリスチンの残存率を経時的に
調べる。抽出法は日本抗生物質医薬品基準（以下 公定
法）に準拠して実施し、各検体の測定データ数値６個の
平均をもって判定データとした。なお対照として明治製
菓(株)製(コリスチン１０％Ｇ「明治」)および旭化成
(株)製(旭化成コリスチン−１００Ｐ)の１０％硫酸コリ
スチン製剤を用い、それぞれ比較例１、比較例２とし
た。得られた結果を表１に示す。Test Example 1 Stability Test of Formulation 200 g of the colistin sulfate preparation obtained in Examples 1 to 7 was put in a polyethylene bag and welded with a heat sealer. Then put in a three-layer kraft bag and seal with tape. The sealed sample was stored under the conditions of 40 ° C. and 75% humidity, and the colistin titer was measured by a bioassay at the start, 1 week, 2 weeks, 3 weeks, and 4 weeks later. The residual rate of colistin sulfate is examined over time as 100%. The extraction method was carried out in accordance with the Japanese Standards for Antibiotics and Pharmaceuticals (hereinafter referred to as the official method), and the average of six measured data values of each sample was used as judgment data. For comparison, Meiji Seika Co., Ltd. (Coristin 10% G "Meiji") and Asahi Kasei
Comparative Examples 1 and 2 were prepared using 10% colistin sulfate preparations (Asahi Kasei Colistin-100P) manufactured by K.K. Table 1 shows the obtained results.
【０００９】[0009]
【表１】 [Table 1]
【００１０】表１から、本発明の硫酸コリスチン製剤
は、いずれも、市販品と同等の加速安定性を示した。造
粒時の温度や添加する水の量を変えて製造しても、得ら
れた製剤の加速安定性に全く差が認められなかった。[0010] From Table 1, all of the colistin sulfate preparations of the present invention showed accelerated stability equivalent to that of a commercially available product. Even if the temperature was changed during granulation or the amount of water added was changed, no difference was observed in the accelerated stability of the obtained preparation.
【００１１】〔試験例２〕製剤の長期安定性試験 実施例１ないし７で得られた硫酸コリスチン製剤を、そ
れぞれポリエチレン袋に２００ｇ入れヒートシーラーで
溶着する。さらに三層クラフト袋に入れてテープで封印
する。封印された試料は室温下で保管し、開始時、１カ
月、３カ月、６カ月、１年後のコリスチン力価を生物検
定法により測定し、開始時の力価を１００％として、硫
酸コリスチンの残存率を経時的に調べる。抽出法は公定
法に準拠して実施し、各検体の測定データ数値６個の平
均をもって判定データとした。得られた結果を表２に示
す。[Test Example 2] Long-term stability test of the preparations The colistin sulfate preparations obtained in Examples 1 to 7 were each placed in a polyethylene bag in an amount of 200 g and welded with a heat sealer. Then put in a three-layer kraft bag and seal with tape. The sealed sample is stored at room temperature, and the colistin titer at the start, 1 month, 3 months, 6 months, and 1 year later is measured by a bioassay method. Is checked over time. The extraction method was performed in accordance with the official method, and the average of six measured data values of each sample was used as judgment data. Table 2 shows the obtained results.
【００１２】[0012]
【表２】 [Table 2]
【００１３】表２から、本発明の硫酸コリスチン製剤は
いずれも、長期間の室温での安定性を示した。造粒時の
温度や添加する水の量を変えて製造しても、得られた製
剤の安定性に全く差が認められなかった。From Table 2, all the colistin sulfate formulations of the present invention exhibited long-term stability at room temperature. Even when the temperature was changed during granulation or the amount of water to be added was changed, no difference was observed in the stability of the obtained preparation.
【００１４】〔試験例３〕製剤の物理性状 実施例５で得られた硫酸コリスチン製剤の物性を調べる
ため、飛散度、嵩比重および安息角を測定した。 １．飛散度 高さ２５０cm、内径１０cmの管上部より試料１ｇを投入
して、３秒間に管下部のビーカーに落下した物の試験１
０回の平均重量（Ａｇ）を測定して、（１−Ａ）gを浮
遊重量とし、その百分率を飛散度とした。 ２．嵩比重 １）粗充填嵩比重 ５０mlのガラスシリンダー（Ｂｇ）より５cmの高さに口
先内径１２mmのガラスロートを置き、試料５０ｇをゆっ
くりとガラスロート面に落としてガラスシリンダーに満
たす。ただちにスライドガラスを用いて余剰分をすり落
として秤量し、重量（Ａｇ）を求める。なお、試験は２
回行った。 粗充填嵩比重＝Ａｇ―Ｂｇ／５０ml ２）密充填嵩比重 粗充填嵩比重測定後のガラスシリンダーを２００回タッ
ピングし、その容積（Ｃml）を求めて、密充填嵩比重を
測定する。 密充填嵩比重＝（Ａｇ―Ｂｇ）／Ｃml ３．安息角 コニシFK型安息角測定器（(株)小西製作所製）を用い
て、試料５０gを使い測定した。なお、試験は２回行っ
た。 測定器条件 振動目盛り ３０ 試料添加速度目盛
り ４０ 試料落下高さ １１cmTest Example 3 Physical Properties of Preparation In order to examine the physical properties of the colistin sulfate preparation obtained in Example 5, the degree of scattering, bulk specific gravity and angle of repose were measured. 1. Dispersion test 1g of a sample was placed from the upper part of a tube having a height of 250cm and an inner diameter of 10cm, and dropped into a beaker under the tube in 3 seconds.
The average weight (Ag) of 0 times was measured, (1-A) g was taken as the suspended weight, and the percentage was taken as the flying degree. 2. Bulk Specific Gravity 1) Roughly Filled Bulk Specific Gravity A glass funnel having an inner diameter of a mouth of 12 mm is placed at a height of 5 cm from a 50 ml glass cylinder (Bg), and 50 g of a sample is slowly dropped on the glass funnel to fill the glass cylinder. Immediately, the excess is scraped off using a slide glass, weighed, and the weight (Ag) is determined. In addition, the test is 2
I went there. Roughly-filled bulk specific gravity = Ag-Bg / 50 ml 2) Closely-packed bulk specific gravity The glass cylinder after rough-filled bulk specific gravity measurement is tapped 200 times, and its volume (Cml) is determined to measure densely-filled bulk specific gravity. 2. Closely packed bulk specific gravity = (Ag-Bg) / Cml Angle of repose Using a Konishi FK type angle of repose measuring instrument (manufactured by Konishi Seisakusho), measurement was performed using 50 g of the sample. The test was performed twice. Measuring instrument condition Vibration scale 30 Sample addition speed scale 40 Sample drop height 11cm
【００１５】 得られた結果から、流動性が良好で、粉塵として飛散す
ることなく、取り扱い者に対しても安全性の高い製剤で
あることが判る。[0015] From the results obtained, it can be seen that the formulation has good flowability, does not scatter as dust, and is highly safe for the handler.
【００１６】〔実施例８及び９〕鶏用プレミックスの調
製 実施例３および５で得られた硫酸コリスチン製剤２５g
を鶏プレミックス（グルフィードミックス−P、科学飼
料研究所製）９７５gに混合し、硫酸コリスチン含有鶏
用プレミックスを調製し、それぞれ実施例８及び９とし
た。対照として明治製菓製及び、旭化成製製剤を用いて
同様にプレミックスを調製し、それぞれ比較例３、比較
例４とした。[Examples 8 and 9] Preparation of chicken premix 25 g of colistin sulfate preparation obtained in Examples 3 and 5
Was mixed with 975 g of chicken premix (Guru Feed Mix-P, manufactured by Kagaku Kenkyu Kenkyusho) to prepare a colistin sulfate-containing chicken premix, which was used in Examples 8 and 9, respectively. As controls, premixes were prepared in the same manner by using formulations manufactured by Meiji Seika and Asahi Kasei.
【００１７】〔試験例４〕製剤の安定性試験 前記で得られた鶏用プレミックスをそれぞれポリエチレ
ン袋に２００g入れヒートシーラーにて溶着する。更に
三層クラフト袋に収めテープにて封印する。封印された
試料を４０℃、湿度７５%の条件下で保管し、開始時、
１週間、２週間、３週間、４週間後のコリスチン力価を
生物検定法により測定し、開始時の力価を１００％とし
て、硫酸コリスチンの残存率を経時的に調べる。抽出法
は公定法に準拠して実施し、各検体の測定データ数値６
個の平均をもって判定データとした。得られた結果を表
３に示す。Test Example 4 Stability Test of Formulation Each of the chicken premixes obtained above was put in a polyethylene bag in an amount of 200 g and welded with a heat sealer. Furthermore, it is stored in a three-layer craft bag and sealed with tape. Store the sealed sample under the condition of 40 ° C and 75% humidity.
After 1 week, 2 weeks, 3 weeks, and 4 weeks, the colistin titer is measured by a bioassay, and the residual ratio of colistin sulfate is determined over time with the initial titer being 100%. The extraction method was carried out in accordance with the official method.
The average was used as the judgment data. Table 3 shows the obtained results.
【００１８】[0018]
【表３】 [Table 3]
【００１９】表３から鶏用プレミックス中の硫酸コリス
チンの安定性は、本発明製剤のいずれにおいても差がな
く、また対照の鶏用プレミックス中の硫酸コリスチンの
安定性と比較しても同等以上の良好な結果が得られた。From Table 3, it can be seen that the stability of colistin sulfate in the chicken premix is not different in any of the preparations of the present invention, and is equivalent to the stability of colistin sulfate in the control chicken premix. The above good results were obtained.
【００２０】〔実施例１０及び１１〕豚用プレミックス
の調製 実施例３および５で得られた硫酸コリスチン製剤８０g
を豚用プレミックス（グルフィードミックス−S、科学
飼料研究所製）９２０ｇに混合し、硫酸コリスチン含有
豚用プレミックスを調製し、それぞれ実施例１０及び１
１とした。対照として明治製菓製、旭化成製製剤を用い
て同様に調製し、それぞれ比較例５、比較例６とした。Examples 10 and 11 Preparation of Premix for Pigs 80 g of colistin sulfate preparation obtained in Examples 3 and 5
Was mixed with 920 g of a premix for pigs (Guru Feed Mix-S, manufactured by Kagaku Kenkyu Kenkyusho) to prepare a colistin sulfate-containing premix for pigs.
It was set to 1. Controls were similarly prepared using formulations manufactured by Meiji Seika and Asahi Kasei, respectively, and Comparative Examples 5 and 6 were used.
【００２１】〔試験例５〕製剤の安定性試験 前記で得られた豚用プレミックスをそれぞれポリエチレ
ン袋に２００g入れヒートシーラーにて溶着する。更に
三層クラフト袋に入れテープにて封印する。封印された
試料を４０℃、湿度７５％の条件下で保管し、開始時、
１週間、２週間、３週間、４週間後の力価を生物検定法
により測定し、開始時の力価を１００％として、硫酸コ
リスチンの残存率を経時的に調べる。抽出法は公定法に
準拠して実施し、各検体の測定データ数値６個の平均を
もって判定データとした。得られた結果を表４に示す。Test Example 5 Stability Test of Formulation 200 g of each of the pig premixes obtained above was placed in a polyethylene bag and welded with a heat sealer. Furthermore, it puts it in a three-layer craft bag and seals it with tape. The sealed sample was stored under the conditions of 40 ° C. and 75% humidity.
The titer after one week, two weeks, three weeks, and four weeks is measured by a bioassay method, and the residual ratio of colistin sulfate is determined over time with the titer at the start as 100%. The extraction method was performed in accordance with the official method, and the average of six measured data values of each sample was used as judgment data. Table 4 shows the obtained results.
【００２２】[0022]
【表４】 [Table 4]
【００２３】表４から豚用プレミックス中の硫酸コリス
チンの安定性は、本発明製剤のいずれにおいても差がな
く、また、対照の豚用プレミックス中の硫酸コリスチン
の安定性と比較しても、同等以上の良好な結果が得られ
た。From Table 4, it can be seen that the stability of colistin sulphate in the swine premix is not different in any of the formulations of the present invention, and also compared with the stability of colistin sulphate in the control swine premix. And good results equivalent to or better than those obtained were obtained.
【００２４】[0024]
【発明の効果】このように、本発明で得られた硫酸コリ
スチン製剤は安定であり、かつ鶏や豚用プレミックス中
においても安定であった。また、本発明の製造法は、従
来の製造法に比較して製造工程の簡略化とともにコリス
チンの十分な安定性が保証される硫酸コリスチン安定化
製剤の製造法として有用である。As described above, the colistin sulfate preparation obtained according to the present invention was stable, and was also stable in chicken and swine premixes. Further, the production method of the present invention is useful as a method for producing a stabilized colistin sulfate preparation that simplifies the production process and ensures sufficient stability of colistin as compared with the conventional production method.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 ＦＩ テーマコート゛(参考） Ａ６１Ｐ 31/04 １７１ Ａ６１Ｋ 37/02 (72)発明者 福与 義宣 静岡県藤枝市源助301番地 科研製薬株式 会社静岡工場内 (72)発明者 石川 隆康 静岡県藤枝市源助301番地 科研製薬株式 会社静岡工場内 Ｆターム(参考） 2B005 DA01 2B150 AA01 AA03 AA05 AB01 AB02 AB20 BA04 CE01 CE03 CE06 DG30 4C076 AA31 BB01 BB36 CC31 EE38Q FF63 4C084 AA01 BA01 BA09 BA17 BA28 MA01 MA05 NA03 ZA732 ZB352 ZC612 ──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme coat ゛ (Reference) A61P 31/04 171 A61K 37/02 (72) Inventor Yoshinobu Fukuyo 301 Gensuke, Fujieda-shi, Shizuoka Kaken Pharmaceutical Co., Ltd. (72) Inventor Takayasu Ishikawa 301 Gensuke, Fujieda-shi, Shizuoka Prefecture Kaken Pharmaceutical Co., Ltd.F-term in Shizuoka Plant (reference) FF63 4C084 AA01 BA01 BA09 BA17 BA28 MA01 MA05 NA03 ZA732 ZB352 ZC612
Claims (9)
合し、次いでその混合物に水を添加し、造粒することを
特徴とする硫酸コリスチン製剤の製造法。1. A method for producing a colistin sulfate preparation, comprising mixing colistin sulfate and starches, adding water to the mixture, and granulating the mixture.
１：１〜３０の重量比にて混合することを特徴とする請
求項１記載の硫酸コリスチン製剤の製造法。2. The process for producing a colistin sulfate preparation according to claim 1, wherein the colistin sulfate and the starch are mixed in a weight ratio of 1: 1 to 30.
デンプン類との混合物の１０〜４０V／Ｗ％であること
を特徴とする請求項１または２記載の硫酸コリスチン製
剤の製造法。3. The process for producing a colistin sulfate preparation according to claim 1, wherein the amount of water to be added is 10 to 40 V / W% of a mixture of colistin sulfate and starch.
徴とする請求項３記載の硫酸コリスチン製剤の製造法。4. The method for producing a colistin sulfate preparation according to claim 3, wherein the water is added by spraying.
求項１ないし４記載の硫酸コリスチン製剤の製造法。5. The method for producing a colistin sulfate preparation according to claim 1, wherein a mixed granulator is used.
ることを特徴とする請求項５記載の硫酸コリスチン製剤
の製造法。6. The method for producing a colistin sulfate preparation according to claim 5, wherein the mixing granulator is a high-speed stirring type mixing granulator.
を３０〜７０℃にて造粒することを特徴とする請求項６
記載の硫酸コリスチン製剤の製造法。7. The granulation at a jacket temperature of a high-speed stirring type mixing granulator at 30 to 70 ° C.
A method for producing the colistin sulfate preparation according to the above.
た硫酸コリスチン製剤。8. A colistin sulfate preparation produced by the production method according to claim 1.
有する家禽及び家畜用プレミックス。9. A premix for poultry and livestock containing the colistin sulfate preparation according to claim 8.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000097420A JP2001278806A (en) | 2000-03-31 | 2000-03-31 | Colistin sulfate stabilized preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2000097420A JP2001278806A (en) | 2000-03-31 | 2000-03-31 | Colistin sulfate stabilized preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2001278806A true JP2001278806A (en) | 2001-10-10 |
Family
ID=18612043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000097420A Pending JP2001278806A (en) | 2000-03-31 | 2000-03-31 | Colistin sulfate stabilized preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2001278806A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004024151A1 (en) * | 2002-09-13 | 2004-03-25 | New Pharma Research Sweden Ab | Composition and potentiating method |
| WO2010086339A1 (en) * | 2009-01-30 | 2010-08-05 | Andersen, S. A. | Process for the preparation of colistin medicated feeds and feeds obtainable by said process |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH053759A (en) * | 1991-06-28 | 1993-01-14 | Asahi Chem Ind Co Ltd | Colistin preparation for feed additive |
| JPH05168421A (en) * | 1991-12-24 | 1993-07-02 | Kaken Pharmaceut Co Ltd | Stable preparation of colistin sulfate-containing feed |
| JPH06189691A (en) * | 1992-12-24 | 1994-07-12 | Meiji Seika Kaisha Ltd | Stabilized colistin preparation |
| JPH10501982A (en) * | 1994-06-29 | 1998-02-24 | 明治製菓株式会社 | Stabilized composition comprising colistin sulfate |
-
2000
- 2000-03-31 JP JP2000097420A patent/JP2001278806A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH053759A (en) * | 1991-06-28 | 1993-01-14 | Asahi Chem Ind Co Ltd | Colistin preparation for feed additive |
| JPH05168421A (en) * | 1991-12-24 | 1993-07-02 | Kaken Pharmaceut Co Ltd | Stable preparation of colistin sulfate-containing feed |
| JPH06189691A (en) * | 1992-12-24 | 1994-07-12 | Meiji Seika Kaisha Ltd | Stabilized colistin preparation |
| JPH10501982A (en) * | 1994-06-29 | 1998-02-24 | 明治製菓株式会社 | Stabilized composition comprising colistin sulfate |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004024151A1 (en) * | 2002-09-13 | 2004-03-25 | New Pharma Research Sweden Ab | Composition and potentiating method |
| WO2010086339A1 (en) * | 2009-01-30 | 2010-08-05 | Andersen, S. A. | Process for the preparation of colistin medicated feeds and feeds obtainable by said process |
| EP2218336A1 (en) * | 2009-01-30 | 2010-08-18 | Andersen S.A. | Process for the preparation of colistin medicated feeds and feeds obtainable by said process |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR930008951B1 (en) | Process for preparing vitamin containing granules | |
| US4486435A (en) | Spray-dried vitamin powders using hydrophobic silica | |
| GB2049388A (en) | Process for powering high fat foodstuffs | |
| JP3188657B2 (en) | Tablet or granular product | |
| KR930001831B1 (en) | Process for the preparation of thiamine salt | |
| IE61910B1 (en) | Stabilised feed additive and process for the preparation thereof | |
| BR102013016575A2 (en) | PARTICULAR ANIMAL FEED SUPPLEMENTS WITH MEDICINAL PRODUCT AND METHODS FOR PREPARATION | |
| JP2012205545A (en) | Bottled beverage comprising cap containing supplement and bottle filled with dispersion medium for supplement | |
| JPH037230A (en) | Composition of vitamin b group compound and production thereof | |
| KR20180131579A (en) | Granule formulation for oral administration | |
| CN110279667A (en) | A kind of tablets of vacyclovir hydrochloride and preparation method thereof | |
| CN103652366B (en) | A kind of stabilization micro-capsule coating Mercaptamine and preparation method thereof | |
| US6989464B2 (en) | Process for the preparation of granules of methionine | |
| US4665100A (en) | Process for formulating a synthetic drug for use in animal feed, and resulting formulation | |
| JP2001278806A (en) | Colistin sulfate stabilized preparation | |
| EP0091767A2 (en) | Stabilization of unstable drugs or food supplements | |
| EP0060680B1 (en) | Process for formulating a medicated animal feed premix | |
| CN1938014A (en) | Solid preparation containing dibenz[b,e]oxepine derivative | |
| FI109760B (en) | A process for the preparation of a semduramycin-containing animal feed premix | |
| EP3043872A1 (en) | Solid compositions based on minerals and orally disintegrating formulations containing the same. | |
| EP0804088B1 (en) | Stabilized composition comprising colistin sulfate | |
| JPH0977669A (en) | Vitamin b group granular product composition and its production | |
| AU692284B2 (en) | Novel encapsulated leavening acid composition | |
| JPH05168421A (en) | Stable preparation of colistin sulfate-containing feed | |
| JP3457012B2 (en) | Amorphous magnesium citrate granular material and method for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20061222 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100309 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101116 |