JPH10295374A - Production of stable enzyme granules - Google Patents
Production of stable enzyme granulesInfo
- Publication number
- JPH10295374A JPH10295374A JP12804597A JP12804597A JPH10295374A JP H10295374 A JPH10295374 A JP H10295374A JP 12804597 A JP12804597 A JP 12804597A JP 12804597 A JP12804597 A JP 12804597A JP H10295374 A JPH10295374 A JP H10295374A
- Authority
- JP
- Japan
- Prior art keywords
- polyethylene glycol
- enzyme
- agent
- granules
- solid
- 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
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、安定な酵素顆粒の製造
法に関する。更に詳細には、球形の核剤に常温で液体の
ポリエチレングリコールを被覆し、酵素剤、常温で固体
のポリエチレングリコール及び造粒促進物質を含む三種
の混合物を添加した後、攪拌し、加熱して、造粒促進物
質存在下、常温で固体のポリエチレングリコールを溶融
することによって、該液体と固体のポリエチレングリコ
ール及び酵素剤を混和せしめた後、冷却して該混和物を
核剤に固着することを特徴とする安定な酵素顆粒の製造
法に関する。The present invention relates to a method for producing stable enzyme granules. More specifically, a spherical nucleating agent is coated with polyethylene glycol which is liquid at room temperature, and after adding an enzyme agent, three kinds of mixtures containing polyethylene glycol which is solid at room temperature and a granulation promoting substance, the mixture is stirred and heated. Melting the solid polyethylene glycol at room temperature in the presence of a granulation promoting substance to mix the liquid, the solid polyethylene glycol and the enzyme agent, and then cooling to fix the mixture to the nucleating agent. The present invention relates to a method for producing stable enzyme granules.
【０００２】本製造法によって、粒径のそろった球形で
且つ酵素の安定性良好なコーティング用酵素顆粒、カプ
セル充填用酵素顆粒が短時間、高収率且つ再現性良好で
得られる。According to the present production method, enzyme granules for coating and capsules for filling capsules having a uniform particle diameter and good enzyme stability can be obtained in a short time with high yield and good reproducibility.
【０００３】[0003]
【従来の技術】従来、酵素顆粒は湿式法による顆粒の製
造方法によって、造粒工程及び乾燥工程を経て製造され
てきた（特開昭58-214333号、特開昭60-37983号、特開
昭60-37984号）が、こうして製造された顆粒中に含まれ
ている酵素剤は不安定であり、保存中に失活が見られ
た。2. Description of the Related Art Conventionally, enzyme granules have been produced through a granulation step and a drying step by a method for producing granules by a wet method (JP-A-58-214333, JP-A-60-37983, JP-A-60-37983). (Showa 60-37984), however, the enzyme preparation contained in the granules thus produced was unstable and inactivated during storage.
【０００４】この酵素の失活は、製造工程の加圧、加熱
等による酵素の変性によるものと考えられるので、顆粒
の製造工程において、酵素変性の少ない方法が求められ
ていた。[0004] It is considered that the inactivation of the enzyme is caused by denaturation of the enzyme due to pressurization, heating or the like in the production process. Therefore, in the granule production process, a method with less enzyme denaturation has been required.
【０００５】最近、塩類及び／又は糖類を核剤として低
融点物質及び酵素剤を溶融して被覆した後に、より高い
融点物質を添加する方法（特公平3-64108号）が開発さ
れ、それにおいて、使用する低融点物質が、酵素顆粒の
結合剤としてのみならずコーティング剤、マスキング剤
として作用して造粒操作における乾燥工程を省略するこ
とが可能となり、酵素顆粒の製造工程の著しい短縮化が
なされ、酵素の失活が防止された。Recently, a method (Japanese Patent Publication No. 3-64108) has been developed in which a low-melting substance and an enzymatic agent are melted and coated using a salt and / or saccharide as a nucleating agent, and then a higher-melting substance is added. The low-melting substance used acts not only as a binder for the enzyme granules, but also as a coating agent and a masking agent, so that the drying step in the granulation operation can be omitted, and the production process of the enzyme granules can be significantly shortened. This prevented the inactivation of the enzyme.
【０００６】[0006]
【発明が解決しようとする課題】上記の特公平3-64108
号においては、顆粒の主成分である酵素剤は、結合剤の
低融点物質と共に添加され、加熱によって溶融した低融
点物質中に混和されるが、重層されるより高い融点物質
と低融点物質とは、混和しないので、より高い融点物質
にはほとんど含まれず、そして又、顆粒の団粒化防止の
ために結合剤の使用量が制限される結果、全顆粒中の酵
素剤量は、最大でも15〜16％量に抑えられていた。[Problems to be Solved by the Invention]
In No., the enzyme agent, which is the main component of the granules, is added together with the low-melting substance of the binder and is mixed with the low-melting substance melted by heating. Is immiscible, so it is hardly contained in the higher melting point material, and the amount of the enzyme agent in the whole granule is at most as a result of the restriction of the amount of the binder used to prevent the agglomeration of the granule. It was kept at 15-16%.
【０００７】一般に、酵素顆粒を医薬原料として種々の
用途に使用する場合、酵素顆粒中の主成分である酵素剤
含量が多ければ多いほど好ましく、上記の特公平3-6410
8号の方法では、顆粒中の酵素剤含有量が余りにも少な
すぎるという問題点があり、その為に改良すべき点があ
った。In general, when enzyme granules are used as a pharmaceutical raw material in various applications, it is preferable that the content of the enzyme agent, which is the main component in the enzyme granules, be as large as possible.
In the method of No. 8, there is a problem that the content of the enzyme agent in the granules is too small, and there is a point to be improved.
【０００８】[0008]
【課題を解決するための手段】そこで、本発明者は、上
記の特公平3-64108号の方法を改良し、製造工程の簡略
化を図りつつ酵素含量の高い安定な酵素顆粒の製造法を
求め鋭意検討を試みた。Accordingly, the present inventors have improved the above-mentioned method of Japanese Patent Publication No. 3-64108 and provided a method for producing a stable enzyme granule having a high enzyme content while simplifying the production process. We sought to make an eager study.
【０００９】そして、常温で液体のポリエチレングリコ
ールと常温で固体の低融点ポリエチレングリコールを混
和し、該混合物を加熱溶融し、冷却後固化したものが、
軟膏及び座剤等の製剤用基材として用いられることに着
目し、これを酵素顆粒の製造に応用することによって本
発明を完成した。Then, polyethylene glycol which is liquid at room temperature and low melting point polyethylene glycol which is solid at room temperature are mixed, and the mixture is heated and melted, and then solidified after cooling.
The present invention was completed by paying attention to use as a base material for preparations such as ointments and suppositories, and applying this to the production of enzyme granules.
【００１０】即ち、球形の核剤に常温で液体のポリエチ
レングリコールを被覆し、酵素剤、常温で固体のポリエ
チレングリコール及び造粒促進物質の三種を含む混合物
を添加した後、攪拌し、加熱して、造粒促進物質存在
下、常温で固体のポリエチレングリコールを溶融するこ
とによって、該液体と固体のポリエチレングリコール及
び酵素剤を混和せしめた後、冷却して該混和物を核剤に
固着することを特徴とする安定な酵素顆粒の製造法であ
る。That is, a spherical nucleating agent is coated with polyethylene glycol which is liquid at room temperature, and a mixture containing an enzyme agent, polyethylene glycol which is solid at room temperature and a granulation promoting substance is added, followed by stirring and heating. Melting the solid polyethylene glycol at room temperature in the presence of a granulation promoting substance to mix the liquid, the solid polyethylene glycol and the enzyme agent, and then cooling to fix the mixture to the nucleating agent. This is a method for producing stable enzyme granules characterized by the following.
【００１１】本発明の造粒方法において、顆粒の主成分
である酵素剤は、溶融した液体と固体のポリエチレング
リコール混和物中に含有されており、これらの混和物が
結合剤を形成しているので、顆粒中の酵素剤含量が約50
%を有する顆粒を得ることが可能となり、且つ、液体と
固体のポリエチレングリコール混和物は、結合剤として
の働きのみならずコーティング剤、マスキング剤として
の効果をも示すので、造粒操作の際に乾燥工程を省略で
き、従って、酵素顆粒の製造工程の著しい短縮化がなさ
れ、酵素の失活も防止できる。[0011] In the granulation method of the present invention, the enzyme agent, which is the main component of the granules, is contained in a mixture of a molten liquid and a solid polyethylene glycol, and the mixture forms a binder. Therefore, the content of enzyme agent in granules is about 50
%, And the mixture of liquid and solid polyethylene glycol exhibits not only the function as a binder but also the effect as a coating agent and a masking agent. The drying step can be omitted, so that the production process of the enzyme granules can be significantly shortened, and the inactivation of the enzyme can be prevented.
【００１２】本発明の造粒方法をより詳細に説明すると
以下のごとくであり、その原理は、図１の模式図に示さ
れる。The granulation method of the present invention will be described in more detail as follows, the principle of which is shown in the schematic diagram of FIG.
【００１３】まず球形の核剤表面に常温で液体のポリエ
チレングリコール（PEG 400）を分散させた後、予め混
合しておいた酵素剤粉末、常温で固体のポリエチレング
リコール（PEG 6000）粉末及び造粒促進物質の合成ケイ
酸アルミニウム（合成珪酸Ａｌ）の三種の混合物を投入
し付着させる。First, a polyethylene glycol (PEG 400) liquid at room temperature is dispersed on the surface of a spherical nucleating agent, and then an enzyme agent powder previously mixed, a polyethylene glycol (PEG 6000) powder solid at room temperature, and granulation A mixture of three types of synthetic aluminum silicate (synthetic Al silicate) as an accelerating substance is charged and adhered.
【００１４】尚、顆粒中の酵素含量を高めるためには、
これら三種の混合物を１度に投入するよりはむしろ複数
回に分けて投入するのが好ましい。In order to increase the enzyme content in the granules,
It is preferable to charge these three kinds of mixtures in a plurality of times, rather than once.
【００１５】次いで加熱によりポリエチレングリコール
6000が溶融し、ポリエチレングリコール 400と混和し
て、均一な混合物となると共に、余分なポリエチレング
リコール は合成ケイ酸アルミニウムに吸収され、出粒
後に冷却することによって、酵素剤が球形の核剤に固着
され、しかも、合成ケイ酸アルミニウムは、顆粒のの付
着防止能力をも有するので団粒のない顆粒が得られる。Then, the polyethylene glycol is heated by heating.
6000 melts and mixes with polyethylene glycol 400 to form a homogeneous mixture, and excess polyethylene glycol is absorbed by synthetic aluminum silicate and cooled after granulation, so that the enzyme agent adheres to the spherical nucleating agent. In addition, the synthetic aluminum silicate also has the ability to prevent the adhesion of granules, so that granules without aggregation can be obtained.
【００１６】次に本発明の安定な酵素顆粒の配合剤につ
いて述べる。Next, the compounding agent of the stable enzyme granules of the present invention will be described.
【００１７】本発明の球形核剤としては、セルロース
系、糖質系等の顆粒剤が使用され、具体的に例示すれ
ば、ノンパレル（フロイント産業社製品）、セルフィア
（旭化成工業社製品等が挙げられ、これらの使用量は、
顆粒全体の25〜30％である。As the spherical nucleating agent of the present invention, cellulosic or carbohydrate-based granules are used, and specific examples thereof include nonpareil (product of Freund Corporation) and selfia (product of Asahi Kasei Corporation). And their usage is
25-30% of the total granules.
【００１８】そして、本発明の造粒促進物質とは、上記
のように加熱溶融後に生じる余分なポリエチレングリコ
ールを吸収する能力及び顆粒の付着防止能力の２つの能
力を兼ね備えている物質であり、具体的に例示すれば、
合成ケイ酸アルミニウム、合成ヒドロタルサイト等が挙
げられる。これらの単独或いは両者の組み合わせたもの
の添加量は、顆粒全体の３〜15％である。The granulation accelerating substance of the present invention is a substance having both the ability to absorb excess polyethylene glycol generated after heating and melting and the ability to prevent adhesion of granules as described above. For example,
Examples include synthetic aluminum silicate and synthetic hydrotalcite. The added amount of these alone or in combination of both is 3 to 15% of the whole granule.
【００１９】更に、本発明の安定な酵素顆粒の製法に使
用される酵素剤としては、医薬用に用いられる、消化酵
素剤及び消炎酵素剤等が挙げられる。Furthermore, examples of the enzyme preparation used in the method for producing the stable enzyme granules of the present invention include digestive enzyme preparations and anti-inflammatory enzyme preparations used for pharmaceuticals.
【００２０】具体的に例示すれば、ビオヂアスターゼ、
リパーゼ、セルラーゼ、ニューラーゼ、プロザイム、膵
臓性消化酵素８ＡＰ（何れも天野製薬社製品）等が挙げ
られ、その添加量としては、顆粒全体の60％以下であ
り、好ましくは40〜60％である。Specifically, biodiastase,
Examples thereof include lipase, cellulase, neurolase, prozyme, and pancreatic digestive enzyme 8AP (all manufactured by Amano Pharmaceutical Co., Ltd.). .
【００２１】更に又、本発明の結合剤としては、常温で
液体のポリエチレングリコール及び常温で固体のポリエ
チレングリコールを組み合わせたものであり、通常顆粒
全体の10〜20％使用される。Further, the binder of the present invention is a combination of polyethylene glycol which is liquid at room temperature and polyethylene glycol which is solid at room temperature, and is usually used in an amount of 10 to 20% of the whole granule.
【００２２】結合剤を具体的に例示すれば、常温で液体
のポリエチレングリコールとして、ポリエチレングリコ
ール400（日本油脂社製品）等が挙げられ、常温で固体
のポリエチレングリコールとして、ポリエチレングリコ
ール4000又はポリエチレングリコール6000（何れも日本
油脂社製品）等が挙げられる。Specific examples of the binder include polyethylene glycol 400 (manufactured by NOF Corporation) and the like as polyethylene glycol which is liquid at ordinary temperature, and polyethylene glycol 4000 or 6000 as polyethylene glycol which is solid at ordinary temperature. (Both products of NOF Corporation) and the like.
【００２３】尚、本発明の安定な酵素顆粒の製法におい
ては、造粒性に影響を与えない範囲の量ならば、上記配
合剤に更に適当な賦形剤例えば、乳糖、コーンスターチ
等の配合も可能である。In the method for producing a stable enzyme granule of the present invention, a suitable excipient such as lactose, corn starch, etc. may be added to the above-mentioned excipients as long as the amount does not affect the granulation properties. It is possible.
【００２４】以下、実施例、比較例にて本発明をより具
体的に説明するが、本発明は、これらにより何等限定さ
れるものではない。Hereinafter, the present invention will be described more specifically with reference to Examples and Comparative Examples, but the present invention is not limited thereto.
【００２５】[0025]
実施例１ ハイスピードミキサーLF-GS-1J型（深江工業社製品）に
球形核剤ノンパレル101 26-36メッシュ（フロイント産
業社製品）137.5g、ポリエチレングリコール400（日本
油脂社製品）25gを投入、攪拌した後、予め混合してお
いた酵素剤ビオヂアスターゼ350（天野製薬社製品）250
g、ポリエチレングリコール6000（日本油脂社製品）50g
及び造粒促進剤の合成ケイ酸アルミニウム（協和化学社
製品）37.5gの混合粉末を半量ずつ分割して投入、攪拌
して酵素顆粒を製造した。Example 1 A high-speed mixer LF-GS-1J type (product of Fukae Kogyo Co., Ltd.) was charged with 137.5 g of spherical nucleating agent nonpareil 101 26-36 mesh (Freund Sangyo Co., Ltd.) and 25 g of polyethylene glycol 400 (product of NOF Corporation). After stirring, premixed enzyme agent Biodiastase 350 (manufactured by Amano Pharmaceutical Co.) 250
g, polyethylene glycol 6000 (product of NOF Corporation) 50 g
A mixed powder of 37.5 g of synthetic aluminum silicate (manufactured by Kyowa Chemical Industry Co., Ltd.), which is a granulation accelerator, was divided and charged in half and stirred to produce enzyme granules.
【００２６】造粒条件は、ジャケット水温60℃、ミキサ
ー回転数600〜1000min-1、造粒時間12分で、16〜42メッ
シュの重量収率は、95.1％であり、顆粒中に占める酵素
含量は50％であり、酵素活性収率は、アミラーセ゛活性で88.9
％、フ゜ロテアーセ゛活性で86.6％であった。尚、アミラーセ゛活性
は、可溶性澱粉を基質とし、pH4.5で酵素を作用させ、
生成するグルコースをフェ−リング・レーマン・シュー
ル（Fehling Lehman Schoorl）法により測定し、フ゜ロテアー
セ゛活性は、ミルクカゼインを基質としてpH8.0で酵素を
作用させ、生成するアミノ酸をフォーリン（Ｆｏｌｉ
ｎ）法で比色定量した。The granulation conditions are as follows: jacket water temperature 60 ° C., mixer rotation speed 600-1000 min −1 , granulation time 12 minutes, weight yield of 16-42 mesh is 95.1%, enzyme content in granules Is 50%, and the enzymatic activity yield is 88.9% in terms of amylase activity.
%, And the activity of the fluorescein was 86.6%. The amylase activity was determined by using an enzyme at pH 4.5 with soluble starch as a substrate.
The produced glucose was measured by the Fehling Lehman Schoorl method, and the activity of the protease was determined by reacting the enzyme with milk casein as a substrate at pH 8.0 and converting the produced amino acid to Folin.
Colorimetric determination was performed by the method n).
【００２７】実施例２ ハイスピードミキサーLF-GS-1J型（深江工業社製品）に
球形核剤ノンパレル101 26-36メッシュ（フロイント産
業社製品）140.0g、ポリエチレングリコール400（日本
油脂社製品）30gを投入、攪拌した後、予め混合してお
いた膵臓性消化酵素8AP（天野製薬社製品）250g、ポリ
エチレングリコール6000（日本油脂社製品）60g及び造
粒促進剤の合成ケイ酸アルミニウム（協和化学社製品）
20gの混合粉末を半量ずつ分割して投入、攪拌して酵素
顆粒を製造した。Example 2 A high-speed mixer LF-GS-1J (Fukae Kogyo Co., Ltd.) with spherical nucleating agent nonpareil 101 26-36 mesh (Freund Sangyo Co., Ltd.) 140.0 g, polyethylene glycol 400 (Nippon Yushi Co., Ltd.) 30 g After mixing and stirring, 250 g of pancreatic digestive enzyme 8AP (manufactured by Amano Pharmaceutical Co., Ltd.), 60 g of polyethylene glycol 6000 (manufactured by NOF CORPORATION) and synthetic aluminum silicate granulating accelerator (Kyowa Chemical Co., Ltd.) Product)
Twenty grams of the mixed powder was divided and charged in half, and stirred to produce enzyme granules.
【００２８】造粒条件は、ジャケット水温60℃、ミキサ
ー回転数600〜1000min-1、造粒時間12分で、16〜42メッ
シュの重量収率は、95.3％であり、顆粒中に占める酵素
含量は50％であり、酵素活性収率は、リハ゜ーセ゛活性で87.4
％、フ゜ロテアーセ゛活性で94.3％であった。尚、リハ゜ーセ゛活性
は、オリーブ油乳化液を基質とし、pH7.0で酵素を作用
させ、遊離する脂肪酸量を測定し、フ゜ロテアーセ゛活性は、ミ
ルクカゼインを基質としてpH8.0で酵素を作用させ、生
成するアミノ酸をフォーリン（Ｆｏｌｉｎ）法で比色定
量した。Granulation conditions are as follows: jacket water temperature 60 ° C., mixer rotation speed 600-1000 min −1 , granulation time 12 minutes, weight yield of 16-42 mesh is 95.3%, and enzyme content in granules Is 50%, and the enzyme activity yield is 87.4% in terms of the recycle activity.
%, And 94.3% in terms of fluorescein activity. In addition, rehabilitation activity is performed by using an olive oil emulsion as a substrate, allowing the enzyme to act at pH 7.0, and measuring the amount of released fatty acids. Amino acids were colorimetrically determined by the Folin method.
【００２９】比較例１ ポリエチレングリコール4000とポリオキシエチレンフェ
ニールエーテルとの当量混合物にエタノールを加えて結
合剤とし、これを消化酵素剤ビオヂアスターゼ350（天
野製薬製薬社製品）と１：３の比率で練合して径１mmの
スクリーンより押し出して棒状顆粒とし、乾燥し、造粒
顆粒を得た。Comparative Example 1 Ethanol was added to an equivalent mixture of polyethylene glycol 4000 and polyoxyethylene phenyl ether to form a binder, which was kneaded at a ratio of 1: 3 with digestive enzyme agent Biodiastase 350 (manufactured by Amano Pharmaceutical Co., Ltd.). The mixture was extruded from a screen having a diameter of 1 mm to obtain rod-shaped granules, and dried to obtain granules.
【００３０】実施例３ 本発明の方法で得られた酵素顆粒と比較例１で得られた
従来の製造方法による酵素顆粒のそれぞれについて、40
℃，50日間後の酵素活性の残存率を測定した結果を表１
に示す。Example 3 Each of the enzyme granules obtained by the method of the present invention and the enzyme granules obtained by the conventional production method obtained in Comparative Example 1 was subjected to 40
Table 1 shows the results of measuring the residual ratio of enzyme activity after 50 days at 50 ° C.
Shown in
【００３１】[0031]
【表１】 [Table 1]
【００３２】表１の結果から明らかなように、本発明の
製造法によって得られた酵素顆粒は、従来の製法でつく
られたものより、何れの酵素活性の残存率も高く、従っ
て酵素の保存安定性に優れていることが明らかである。As is evident from the results in Table 1, the enzyme granules obtained by the production method of the present invention have a higher residual ratio of any enzyme activity than those produced by the conventional production method, and therefore, the preservation of the enzyme. It is clear that the stability is excellent.
【００３３】比較例２ ハイスピードミキサーLF-GS-1J型（深江工業社製品）に
核となる塩化ナトリウムの結晶３kg、溶融したポリオキ
シエチレンラウリルエーテル0.2kgを加え、900rpmで20
秒間回転し、ビオヂアスターゼ（天野製薬社製品）0.4k
gを加えた後、ポリエチレングリコール 6000（日本油脂
社製品）の粉末0.2kgを加え600rpmで１分回転した後、
出粒する方法（特公平3-64108号の方法）によって酵素
顆粒を製造した。Comparative Example 2 To a high-speed mixer LF-GS-1J (product of Fukae Kogyo Co., Ltd.), 3 kg of sodium chloride crystals serving as nuclei and 0.2 kg of molten polyoxyethylene lauryl ether were added, and the mixture was added at 900 rpm.
Spin for 2 seconds, Bio-D Astase (Amano Pharmaceutical) 0.4k
g, then add 0.2 kg of polyethylene glycol 6000 (product of NOF Corporation) and rotate at 600 rpm for 1 minute.
Enzyme granules were produced by a granulation method (the method of Japanese Patent Publication No. 3-64108).
【００３４】実施例４ 本発明の方法で得られた酵素顆粒と比較例２で得られた
特公平3-64108号の製造方法によって得られた酵素顆粒
のそれぞれについて、顆粒中の複合酵素剤のビオヂアス
ターゼの含有量（顆粒中の酵素含量）及びビオヂスター
ゼ中に含まれるアミラーゼ及びプロテアーゼの40℃、50
日間後の酵素活性の残存率を測定した結果を表２に示
す。Example 4 For each of the enzyme granules obtained by the method of the present invention and the enzyme granules obtained by the production method of Japanese Patent Publication No. 3-64108 obtained in Comparative Example 2, the complex enzyme preparation in the granules was Biodustase content (enzyme content in granules) and amylase and protease contained in biodustase at 40 ° C and 50 ° C
Table 2 shows the results obtained by measuring the residual ratio of the enzyme activity after days.
【００３５】[0035]
【表２】 [Table 2]
【００３６】表２の結果から明らかなように、本発明の
製造法によって得られた酵素顆粒は、特公平3-64108号
の製法でつくられたものと比較した場合、酵素活性の残
存率は同程度であり、且つ顆粒中の酵素含量が著しく増
大していることがわかる。As is evident from the results in Table 2, the enzyme granules obtained by the production method of the present invention have a residual enzyme activity of less than that produced by the production method of Japanese Patent Publication No. 3-64108. It can be seen that they are almost the same and that the enzyme content in the granules is significantly increased.
【００３７】[0037]
【発明の効果】本発明の安定な酵素顆粒の製造法によっ
て、酵素の工程中での活性低下が、非常に僅かとなり、
又工程の簡略化に伴って造粒時間は、１バッチ１２分と
高速化され、しかも製造された顆粒は粒度が均一で、且
つ被覆された酵素は外部環境に対して長時間安定であ
る。According to the method for producing stable enzyme granules of the present invention, the activity decrease during the enzyme process is very small,
The granulation time is increased to 12 minutes per batch with the simplification of the process, and the produced granules have a uniform particle size, and the coated enzyme is stable for a long time against the external environment.
【図１】は、本発明の安定な酵素顆粒の製造原理を示す
模式図である。FIG. 1 is a schematic diagram showing the principle of producing stable enzyme granules of the present invention.
Claims (4)
リコールを被覆し、酵素剤、常温で固体のポリエチレン
グリコール及び造粒促進物質の三種を含む混合物を添加
した後、攪拌し、加熱して、造粒促進物質存在下、常温
で固体のポリエチレングリコールを溶融することによっ
て、該液体と固体のポリエチレングリコール及び酵素剤
を混和せしめた後、冷却して該混和物を核剤に固着する
ことを特徴とする安定な酵素顆粒の製造法。1. A spherical nucleating agent is coated with polyethylene glycol which is liquid at room temperature, and a mixture containing an enzyme agent, polyethylene glycol which is solid at room temperature and a granulation promoting substance is added, followed by stirring and heating. Melting the solid polyethylene glycol at room temperature in the presence of a granulation promoting substance to mix the liquid, the solid polyethylene glycol and the enzyme agent, and then cooling to fix the mixture to the nucleating agent. A unique method for producing stable enzyme granules.
点15℃以下のポリエチレングリコールである請求項１記
載の安定な酵素顆粒の製造法。2. The method for producing stable enzyme granules according to claim 1, wherein the polyethylene glycol liquid at room temperature is polyethylene glycol having a melting point of 15 ° C. or lower.
点20〜80℃のポリエチレングリコールである請求項１記
載の安定な酵素顆粒の製造法。3. The method for producing stable enzyme granules according to claim 1, wherein the polyethylene glycol which is solid at ordinary temperature is polyethylene glycol having a melting point of 20 to 80 ° C.
合成ヒドロタルサイトもしくはこれらの混合物である請
求項１記載の安定な酵素顆粒の製造法。4. The method for producing stable enzyme granules according to claim 1, wherein the granulation promoting substance is synthetic aluminum silicate, synthetic hydrotalcite or a mixture thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12804597A JPH10295374A (en) | 1997-04-30 | 1997-04-30 | Production of stable enzyme granules |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP12804597A JPH10295374A (en) | 1997-04-30 | 1997-04-30 | Production of stable enzyme granules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH10295374A true JPH10295374A (en) | 1998-11-10 |
Family
ID=14975154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP12804597A Pending JPH10295374A (en) | 1997-04-30 | 1997-04-30 | Production of stable enzyme granules |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH10295374A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010014730A1 (en) * | 2008-07-30 | 2010-02-04 | Temptime Corporation | Freeze indicators, components therefor and preparative processes |
| US9259393B2 (en) | 2000-11-15 | 2016-02-16 | Aptalis Pharma S.R.L. | Microspheres of pancreatic enzymes with high stability and production method thereof |
| US9976171B2 (en) | 2011-08-08 | 2018-05-22 | Allergan Pharmaceuticals International Limited | Method for dissolution testing of solid compositions containing digestive enzymes |
| US10087493B2 (en) | 2008-03-07 | 2018-10-02 | Aptalis Pharma Canada Ulc | Method for detecting infectious parvovirus in pharmaceutical preparations |
| US10184121B2 (en) | 2013-06-28 | 2019-01-22 | Allergan Pharmaceuticals International Limited | Methods for removing viral contaminants from pancreatic extracts |
| US10206882B2 (en) | 2007-02-20 | 2019-02-19 | Allergan Pharmaceuticals International Limited | Stable digestive enzyme compositions |
| US10993996B2 (en) | 2013-08-09 | 2021-05-04 | Allergan Pharmaceuticals International Limited | Digestive enzyme composition suitable for enteral administration |
| US11364205B2 (en) | 2010-10-01 | 2022-06-21 | Societe Des Produits Nestle S.A. | Stable low digestive enzyme content formulation |
-
1997
- 1997-04-30 JP JP12804597A patent/JPH10295374A/en active Pending
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9259393B2 (en) | 2000-11-15 | 2016-02-16 | Aptalis Pharma S.R.L. | Microspheres of pancreatic enzymes with high stability and production method thereof |
| US9884025B2 (en) | 2000-11-15 | 2018-02-06 | Aptalis Pharma S.R.L. | Microspheres of pancreatic enzymes with high stability and production method thereof |
| US10206882B2 (en) | 2007-02-20 | 2019-02-19 | Allergan Pharmaceuticals International Limited | Stable digestive enzyme compositions |
| US10087493B2 (en) | 2008-03-07 | 2018-10-02 | Aptalis Pharma Canada Ulc | Method for detecting infectious parvovirus in pharmaceutical preparations |
| WO2010014730A1 (en) * | 2008-07-30 | 2010-02-04 | Temptime Corporation | Freeze indicators, components therefor and preparative processes |
| US8128872B2 (en) | 2008-07-30 | 2012-03-06 | Temptime Corporation | Freeze indicators, components therefor and preparative processes |
| US11364205B2 (en) | 2010-10-01 | 2022-06-21 | Societe Des Produits Nestle S.A. | Stable low digestive enzyme content formulation |
| US9976171B2 (en) | 2011-08-08 | 2018-05-22 | Allergan Pharmaceuticals International Limited | Method for dissolution testing of solid compositions containing digestive enzymes |
| US10184121B2 (en) | 2013-06-28 | 2019-01-22 | Allergan Pharmaceuticals International Limited | Methods for removing viral contaminants from pancreatic extracts |
| US10993996B2 (en) | 2013-08-09 | 2021-05-04 | Allergan Pharmaceuticals International Limited | Digestive enzyme composition suitable for enteral administration |
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