JP4357624B2 - Composition containing a disinfectant and digestive enzyme - Google Patents
Composition containing a disinfectant and digestive enzyme Download PDFInfo
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- JP4357624B2 JP4357624B2 JP08519999A JP8519999A JP4357624B2 JP 4357624 B2 JP4357624 B2 JP 4357624B2 JP 08519999 A JP08519999 A JP 08519999A JP 8519999 A JP8519999 A JP 8519999A JP 4357624 B2 JP4357624 B2 JP 4357624B2
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- disinfectant
- digestive enzyme
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【０００１】
【発明の属する技術分野】
本発明は、殺菌剤、該殺菌剤と配合禁忌の消化酵素および水膨潤性物質からなる組成物に関する。さらに詳しくは、殺菌剤の作用によって失活し易い消化酵素の安定化技術に関する。
【０００２】
【従来の技術】
殺菌剤および消化酵素を配合した製剤は、細菌性の下痢の治療に効果があり、かつ整腸作用をも促すという点で極めて有用な止瀉薬である。
【０００３】
しかしながら、水難溶性の殺菌剤および該殺菌剤と配合禁忌の消化酵素を混合して造粒し製剤化すると、殺菌剤の作用によって消化酵素が経時的に失活してしまうという問題があった。
【０００４】
斯かる配合禁忌の関係にある水難溶性の殺菌剤と消化酵素を配合して安定な固形製剤を製造するには、両者を別顆粒とした後にそのうちの少なくとも一方を被覆した上で、多顆粒の散剤、顆粒剤若しくは錠剤とするか、または、殺菌剤および消化酵素を含有した顆粒を別々に製造し、殺菌剤と消化酵素が接触しないように多層錠とすることによって、消化酵素の失活を防止するという方法も考えられるが、こうした製造法では製造工程の数が増え、手間が掛かり、製造コスト面での不利益が著しく大きい。
【０００５】
【発明が解決しようとする課題】
本発明は、水難溶性の殺菌剤および該殺菌剤と配合禁忌の消化酵素を配合し、消化酵素の経時的な失活を防止した組成物を、簡易な製造法により、低コストで提供することを課題とする。
【０００６】
【課題を解決するための手段】
本発明者らは、かかる課題を解決すべく鋭意検討した結果、水難溶性の殺菌剤および該殺菌剤と配合禁忌の消化酵素を水膨潤性物質とともに混合して湿式造粒するという極めて簡易な製造法によって、消化酵素の経時的な失活を抑えた組成物を製造できることを見い出し、本発明を完成するに至った。
【０００７】
すなわち、本発明は、水難溶性の殺菌剤、該殺菌剤と配合禁忌の消化酵素および水膨潤性物質を混合して湿式造粒したことを特徴とする組成物である。
【０００８】
【発明の実施の形態】
本発明の水難溶性の殺菌剤とは、水に対する溶解度が１００ｍｇ／Ｌ以下である殺菌作用を有する薬剤である。このような殺菌剤としては、例えば、塩化ベルベリン、タンニン酸ベルベリン、クレオソートおよびサリチル酸フェニルのような殺菌剤を挙げることができる。これら殺菌剤は単独で配合してもよく、また、２種以上を組み合わせて配合してもよい。
【０００９】
本発明の消化酵素とは、水難溶性の殺菌剤と配合禁忌の関係にある消化作用を有する酵素であって、例えば、アミラーゼ、プロテアーゼ、リパーゼおよびこれらの複合酵素（例えば、アミラーゼとプロテアーゼの複合酵素）が挙げられる。これら消化酵素は単独で配合してもよく、また、２種以上を組み合わせて配合してもよい。
【００１０】
本発明の水膨潤性物質とは、水分を吸収して体積が膨張する性質を有する繊維系の高分子であって、固形製剤においては主に賦形剤として使用されているものである。例えば、低置換度ヒドロキシプロピルセルロース、クロスカルメロースナトリウムおよびカルメロースカルシウムが挙げられる。これら水膨潤性物質は単独で配合してもよく、また、２種以上を組み合わせて配合してもよい。
【００１１】
本発明の殺菌剤、該殺菌剤と配合禁忌の消化酵素および水膨潤性物質の配合重量比は、０．５〜６：１：１〜１０であり、消化酵素の失活を防止して安定な消化酵素配合組成物とするためには１〜３：１：２〜５が好ましい。
【００１２】
ここで、配合禁忌とは、二種以上の薬物を混ぜ合わせて製剤化したときに、少なくともいずれか一方の薬物の含量値が、薬物を単独で配合した場合に比べて著しく低下したり、製剤が変色したりする薬物相互の関係をいうものである。本発明では、水難溶性の殺菌剤と消化酵素を混ぜ合わせた後に造粒して製剤化した場合に、該殺菌剤の作用によって製剤中の消化酵素の含量値が経時的に低下する相互の関係をいうものである。
【００１３】
失活とは、組成物中の消化酵素の含量値が経時的に低下することをいう。本発明で消化酵素の失活を防止するとは、消化酵素を含有した組成物を４０℃で６ヶ月間保存したときの消化酵素の活性残存率が８０％以上であることをいう。
【００１４】
本発明の混合とは、殺菌剤、消化酵素、水膨潤性物質を混ぜ合わせることをいい、この混合にはＶ型混合機やロッキングミキサー等の各種粉体混合機を用いることができる。
【００１５】
本発明の湿式造粒とは、水または水とアルコール等の混合液を造粒用溶剤として粉体を造粒し製剤化する方法であって、攪拌造粒、流動層造粒、練合造粒、押し出し造粒等各種造粒法が挙げられる。
【００１６】
本発明における組成物は、次のように製造することができる。
【００１７】
所要の水難溶性の殺菌剤、該殺菌剤と配合禁忌の消化酵素および水膨潤性物質を混合し、粉体をより均一にするために粉砕機で粉砕する。この際、メタケイ酸アルミン酸マグネシウムを粉砕前に混合しておくと、粉砕時の静電気の発生を防止して粉砕をスムーズに行うことができる。得られた混合粉末を水または水とアルコール等の混合液を造粒溶剤として湿式造粒することにより製造することができる。
【００１８】
本発明の水難溶性の殺菌剤、該殺菌剤と配合禁忌の消化酵素および水膨潤性物質からなる組成物は、主に内服固形製剤として供されるものであり、錠剤、散剤、顆粒剤、カプセル剤等の種々の固形製剤に製剤化することができる。
【００１９】
本発明よって、水難溶性の殺菌剤および該殺菌剤と配合禁忌の消化酵素を別個に造粒して別顆粒とした後にいずれか一方をコーティングしたり、多層錠とすることによって殺菌剤と消化酵素の接触を回避するような複雑な製造法によることなく、同一の顆粒として製造しても消化酵素の経時的な安定性を確保することができる。
【００２０】
また、本発明にかかる組成物には必要に応じて、ビタミン類、乳酸菌、ビフィズス菌等を適宜に配合することができ、本発明の効果を損なわない範囲で他の賦形剤、例えば、結晶セルロース、乳糖、澱粉等を配合することもできる。
【００２１】
【発明の効果】
本発明により、水難溶性の殺菌剤および該殺菌剤と配合禁忌の消化酵素を配合し、消化酵素の失活を防止した内服固形製剤を低コストで提供することが可能となった。
【００２２】
【実施例】
以下に実施例、比較例および試験例を挙げ、本発明をさらに詳しく説明する。
なお、ビオヂアスターゼ（天野製薬（株））はアミラーゼとプロテアーゼの複合酵素である。
【００２３】
実施例１
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
低置換度ヒドロキシプロピルセルロース ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、粉体を均一にするために粉砕機で粉砕した。得られた混合粉末をセイセイスイ１８０ｇを溶剤としてバーチカルグラニュレータ（パウレック（株）製）で造粒し、流動層乾燥機にて乾燥した。ステアリン酸マグネシウム５ｇを添加混合して打錠し、１錠重量１８０ｍｇの錠剤を得た。
【００２４】
実施例２
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
クロスカルメロースナトリウム ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、実施例１に準拠し１錠重量１８０ｍｇの錠剤を得た。
【００２５】
実施例３
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
カルメロースカルシウム ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、実施例１に準拠し１錠重量１８０ｍｇの錠剤を得た。
【００２６】
比較例１
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
結晶セルロース ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、実施例１に準拠し１錠重量１８０ｍｇの錠剤を得た。
【００２７】
比較例２
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
コーンスターチ ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、実施例１に準拠し１錠重量１８０ｍｇの錠剤を得た。
【００２８】
比較例３
（処方）
塩化ベルベリン ２９４ ｇ
ビオヂアスターゼ １５８ ｇ
マンニトール ４３８ ｇ
メタケイ酸アルミン酸マグネシウム ３５ ｇ
ヒドロキシプロピルセルロース ３５ ｇ
前記の各成分および分量を秤量し均一に混合した後、実施例１に準拠し１錠重量１８０ｍｇの錠剤を得た。
比較例４
（処方）
上層および下層顆粒
結晶セルロース １５０ ｇ
水酸化アルミニウム・炭酸水素ナトリウム共沈物 ２８８０ ｇ
ヒドロキシプロピルセルロース ６００ ｇ
前記各成分および分量をそれぞれ秤量し均一に混合した後、得られた混合粉末に対して、エタノール３８５ｇを溶剤としてバーチカルグラニュレータ（パウレック（株）製）で造粒し、流動層乾燥機にて乾燥後、ビオジアスターゼ２２５０ｇ、低置換度ヒドロキシプロピルセルロース１３００ｇ、水酸化アルミニウム・炭酸水素ナトリウム共沈物３０００ｇおよびステアリン酸マグネシウム２５ｇを添加して均一に混合し、上層および下層顆粒を得た。
【００２９】
中層顆粒
結晶セルロース ３０ ｇ
水酸化アルミニウム・炭酸水素ナトリウム共沈物 １８００ ｇ
塩化ベルベリン ２２５０ ｇ
ヒドロキシプロピルセルロース ３００ ｇ
前記各成分および分量をそれぞれ秤量し均一に混合した後、得られた混合粉末に対して、エタノール１３７５ｇを溶剤としてバーチカルグラニュレータで造粒し、流動層乾燥機にて乾燥後、低置換度ヒドロキシプロピルセルロース２５０ｇおよびステアリン酸マグネシウム１２．５ｇを添加して均一に混合し、中層顆粒を得た。
【００３０】
上記したそれぞれの顆粒につき下層、中層および上層の順で打錠し、上層１１０ｍｇ、中層１８０ｍｇ、下層１１０ｍｇの１錠重量４００ｍｇの三層錠を得た。
【００３１】
（試験例１）
実施例１〜３および比較例１〜３で得た錠剤をそれぞれ５０℃の恒温室に保存し、８週間経過後の錠剤中のビオヂアスターゼの安定性を比較した。
ビオヂアスターゼの安定性は、日本薬局方収載の消化力試験法でんぷん糖化力試験法によりアミラーゼの活性残存率として表した。
試験結果を図１に示す。
【００３２】
（試験例２）
実施例１で得た錠剤と比較例４で得た三層錠を４０℃の恒温室に保存し、製造直後から６月経過後の錠剤中のビオヂアスターゼの安定性を試験例１と同様の方法により評価した。
試験結果を図２に示す。
【００３３】
図１より、ビオヂアスターゼを配合した錠剤において、低置換度ヒドロキシプロピルセルロース（水膨潤性物質）を配合して湿式造粒した場合（実施例１〜３）は、水膨潤性の小さい繊維系賦形剤（結晶セルロース）または水膨潤性物質でない賦形剤（コーンスターチ、マンニトール）を配合して湿式造粒した場合（比較例１〜３）に比べてビオヂアスターゼの失活が緩やかであった。
【００３４】
また、図２より、低置換度ヒドロキシプロピルセルロースと共に湿式造粒した場合（実施例１）は、三層錠とした場合（比較例４）とほぼ同様のビオヂアスターゼの安定性を確保することができた。
【図面の簡単な説明】
【図１】 実施例１〜３および比較例１〜３のビオヂアスターゼの経時的な安定性を表すグラフである。
【図２】 実施例１および比較例４のビオヂアスターゼの経時的な安定性を表すグラフである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a composition comprising a bactericide, a bactericide, a contraindicated digestive enzyme, and a water-swellable substance. More specifically, the present invention relates to a digestive enzyme stabilization technique that is easily deactivated by the action of a bactericide.
[0002]
[Prior art]
A preparation containing a bactericidal agent and a digestive enzyme is an extremely useful antidiarrheal agent in that it is effective in treating bacterial diarrhea and also promotes intestinal regulation.
[0003]
However, when a poorly water-soluble disinfectant and the disinfectant and a contraindicated digestive enzyme are mixed and granulated into a preparation, the digestive enzyme is deactivated over time due to the action of the disinfectant.
[0004]
In order to produce a stable solid preparation by blending such a water-insoluble disinfectant and digestive enzyme, which are incompatible with such a combination, after forming both of them into separate granules, Inactivation of digestive enzymes can be achieved by preparing powders, granules or tablets, or preparing granules containing fungicides and digestive enzymes separately and making multilayer tablets so that the disinfectant and digestive enzymes do not come into contact with each other. Although a method of preventing it is conceivable, such a manufacturing method increases the number of manufacturing steps, takes time, and has a significant disadvantage in terms of manufacturing cost.
[0005]
[Problems to be solved by the invention]
The present invention provides a composition in which a sparingly water-soluble bactericidal agent and a bactericidal agent and a contraindicated digestive enzyme are blended to prevent inactivation of the digestive enzyme over time by a simple production method at a low cost. Is an issue.
[0006]
[Means for Solving the Problems]
As a result of diligent investigations to solve such problems, the present inventors have conducted extremely simple production in which a poorly water-soluble disinfectant and the disinfectant and a contraindicated digestive enzyme are mixed with a water-swellable substance and wet granulated. The present inventors have found that a composition that suppresses the inactivation of digestive enzymes over time can be produced by the method, and the present invention has been completed.
[0007]
That is, the present invention is a composition characterized by mixing a poorly water-soluble disinfectant, the disinfectant with a contraindicated digestive enzyme, and a water-swellable substance and performing wet granulation.
[0008]
DETAILED DESCRIPTION OF THE INVENTION
The poorly water-soluble fungicide of the present invention is a drug having a bactericidal action with a solubility in water of 100 mg / L or less. Examples of such bactericides include bactericides such as berberine chloride, berberine tannate, creosote and phenyl salicylate. These fungicides may be blended alone or in combination of two or more.
[0009]
The digestive enzyme of the present invention is an enzyme having a digestive action having a contraindicated relationship with a poorly water-soluble fungicide, such as amylase, protease, lipase, and a complex enzyme thereof (for example, a complex enzyme of amylase and protease). ). These digestive enzymes may be blended singly or in combination of two or more.
[0010]
The water-swellable substance of the present invention is a fiber-based polymer having the property of absorbing water and expanding its volume, and is mainly used as an excipient in solid preparations. Examples include low-substituted hydroxypropylcellulose, croscarmellose sodium and carmellose calcium. These water-swellable substances may be blended singly or in combination of two or more.
[0011]
The blending weight ratio of the disinfectant of the present invention, the disinfectant and the incompatible digestive enzyme and the water-swellable substance is 0.5 to 6: 1: 1 to 10 and is stable by preventing inactivation of the digestive enzyme. 1 to 3: 1: 2 to 5 is preferable to obtain a digestive enzyme composition.
[0012]
Here, the contraindication is that when two or more drugs are mixed to form a preparation, the content value of at least one of the drugs is significantly reduced compared to the case where the drug is added alone, Refers to the relationship between drugs that change color. In the present invention, when a poorly water-soluble disinfectant and a digestive enzyme are mixed and then granulated into a preparation, the relationship between the content of the digestive enzyme in the preparation decreases with time due to the action of the disinfectant. It means something.
[0013]
Inactivation means that the content value of the digestive enzyme in the composition decreases with time. In the present invention, preventing digestive enzyme deactivation means that the residual activity rate of digestive enzyme is 80% or more when a composition containing the digestive enzyme is stored at 40 ° C. for 6 months.
[0014]
The mixing of the present invention refers to mixing a bactericide, a digestive enzyme, and a water-swellable substance, and various powder mixers such as a V-type mixer and a rocking mixer can be used for this mixing.
[0015]
The wet granulation of the present invention is a method of granulating a powder by using water or a mixed liquid of water and alcohol as a granulating solvent, and stirring granulation, fluidized bed granulation, kneading Various granulation methods such as granulation and extrusion granulation can be mentioned.
[0016]
The composition in the present invention can be produced as follows.
[0017]
A required poorly water-soluble disinfectant, the disinfectant, a contraindicated digestive enzyme, and a water-swellable substance are mixed and pulverized with a pulverizer to make the powder more uniform. At this time, if the magnesium aluminate metasilicate is mixed before pulverization, generation of static electricity during pulverization can be prevented and pulverization can be performed smoothly. The obtained mixed powder can be produced by wet granulation using water or a mixture of water and alcohol as a granulating solvent.
[0018]
The composition comprising the poorly water-soluble disinfectant of the present invention, the disinfectant and a contraindicated digestive enzyme and a water-swellable substance is mainly provided as a solid preparation for internal use, and is a tablet, powder, granule, capsule It can be formulated into various solid preparations such as an agent.
[0019]
According to the present invention, a hardly water-soluble disinfectant and the disinfectant and a contraindicated digestive enzyme are separately granulated to form another granule, and then either one is coated or a multilayer tablet is used to disinfect the disinfectant and digestive enzyme. Even if it manufactures as the same granule without using the complicated manufacturing method which avoids contact of this, the stability with time of a digestive enzyme is securable.
[0020]
In addition, vitamins, lactic acid bacteria, bifidobacteria, and the like can be appropriately blended in the composition according to the present invention as necessary, and other excipients, for example, crystals, as long as the effects of the present invention are not impaired. Cellulose, lactose, starch and the like can also be blended.
[0021]
【The invention's effect】
According to the present invention, it has become possible to provide a low-cost oral solid preparation containing a sparingly water-soluble disinfectant and a disinfectant and a contraindicated digestive enzyme to prevent inactivation of the digestive enzyme.
[0022]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
Biodiastase (Amano Pharmaceutical Co., Ltd.) is a complex enzyme of amylase and protease.
[0023]
Example 1
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Low substituted hydroxypropylcellulose 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
Each of the above components and amounts were weighed and mixed uniformly, and then pulverized with a pulverizer to make the powder uniform. The obtained mixed powder was granulated with a vertical granulator (manufactured by POWREC Co., Ltd.) using 180 g of seiseisui as a solvent, and dried with a fluidized bed dryer. 5 g of magnesium stearate was added, mixed and tableted to obtain a tablet having a tablet weight of 180 mg.
[0024]
Example 2
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Croscarmellose sodium 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
After weighing and mixing the above components and amounts uniformly, a tablet having a tablet weight of 180 mg was obtained according to Example 1.
[0025]
Example 3
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Carmellose calcium 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
After weighing and mixing the above components and amounts uniformly, a tablet having a tablet weight of 180 mg was obtained according to Example 1.
[0026]
Comparative Example 1
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Crystalline cellulose 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
After weighing and mixing the above components and amounts uniformly, a tablet having a tablet weight of 180 mg was obtained according to Example 1.
[0027]
Comparative Example 2
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Corn starch 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
After weighing and mixing the above components and amounts uniformly, a tablet having a tablet weight of 180 mg was obtained according to Example 1.
[0028]
Comparative Example 3
(Prescription)
Berberine chloride 294 g
Biodiastase 158 g
Mannitol 438 g
Magnesium aluminate metasilicate 35 g
Hydroxypropylcellulose 35 g
After weighing and mixing the above components and amounts uniformly, a tablet having a tablet weight of 180 mg was obtained according to Example 1.
Comparative Example 4
(Prescription)
Upper and lower granular crystalline cellulose 150 g
Aluminum hydroxide / sodium bicarbonate coprecipitate 2880 g
Hydroxypropylcellulose 600 g
After weighing and mixing each of the above components and amounts uniformly, the obtained mixed powder was granulated with a vertical granulator (manufactured by POWREC Co., Ltd.) using 385 g of ethanol as a solvent, and fluidized bed dryer. After drying, 2250 g of biodiastase, 1300 g of low-substituted hydroxypropylcellulose, 3000 g of aluminum hydroxide / sodium bicarbonate coprecipitate and 25 g of magnesium stearate were added and mixed uniformly to obtain upper and lower granules.
[0029]
Medium-granular granular cellulose 30 g
Aluminum hydroxide / bicarbonate coprecipitate 1800 g
Berberine chloride 2250 g
Hydroxypropylcellulose 300 g
After weighing and mixing each of the above components and amounts uniformly, the obtained mixed powder was granulated with a vertical granulator using 1375 g of ethanol as a solvent, dried in a fluidized bed dryer, and then low-substituted hydroxy 250 g of propylcellulose and 12.5 g of magnesium stearate were added and mixed uniformly to obtain intermediate layer granules.
[0030]
Each of the granules described above was tableted in the order of the lower layer, the middle layer, and the upper layer to obtain a three-layer tablet having an upper layer of 110 mg, a middle layer of 180 mg, and a lower layer of 110 mg, each weighing 400 mg.
[0031]
(Test Example 1)
The tablets obtained in Examples 1 to 3 and Comparative Examples 1 to 3 were each stored in a thermostatic chamber at 50 ° C., and the stability of biodiastase in the tablets after 8 weeks was compared.
The stability of biodiastase was expressed as the residual rate of amylase activity by the digestion test method and the saccharification test method described in the Japanese Pharmacopoeia.
The test results are shown in FIG.
[0032]
(Test Example 2)
The tablet obtained in Example 1 and the three-layer tablet obtained in Comparative Example 4 were stored in a thermostatic chamber at 40 ° C., and the stability of biodiastase in the
The test results are shown in FIG.
[0033]
From FIG. 1, in the case of tablets containing biodiastase, when low-substituted hydroxypropylcellulose (water swellable substance) is blended and wet granulated (Examples 1 to 3), fiber-based shaping with low water swellability Inactivation of biodiastase was milder than when wet granulation was carried out by blending an agent (crystalline cellulose) or an excipient (corn starch, mannitol) that was not a water-swellable substance (Comparative Examples 1 to 3).
[0034]
Moreover, from FIG. 2, when wet granulation is performed with low-substituted hydroxypropylcellulose (Example 1), the stability of biodiastase which is almost the same as that of a triple-layer tablet (Comparative Example 4) can be secured. It was.
[Brief description of the drawings]
FIG. 1 is a graph showing the stability over time of biodiastases of Examples 1 to 3 and Comparative Examples 1 to 3.
FIG. 2 is a graph showing the stability over time of the biodiastase of Example 1 and Comparative Example 4.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP08519999A JP4357624B2 (en) | 1998-04-01 | 1999-03-29 | Composition containing a disinfectant and digestive enzyme |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10-88962 | 1998-04-01 | ||
| JP8896298 | 1998-04-01 | ||
| JP08519999A JP4357624B2 (en) | 1998-04-01 | 1999-03-29 | Composition containing a disinfectant and digestive enzyme |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000026310A JP2000026310A (en) | 2000-01-25 |
| JP4357624B2 true JP4357624B2 (en) | 2009-11-04 |
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| JP08519999A Expired - Fee Related JP4357624B2 (en) | 1998-04-01 | 1999-03-29 | Composition containing a disinfectant and digestive enzyme |
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| US8734867B2 (en) | 2007-12-28 | 2014-05-27 | Liveleaf, Inc. | Antibacterial having an extract of pomegranate combined with hydrogen peroxide |
| HUE049150T2 (en) * | 2009-03-04 | 2021-12-28 | Liveleaf Inc | Method and material for site activated complexing of biologic molecules |
| US9192635B2 (en) | 2011-06-24 | 2015-11-24 | Liveleaf, Inc. | Method of treating damaged mucosal or gastrointestinal tissue by administering a composition comprising a mixture of pomegranate and green tea extracts and releasably bound hydrogen peroxide |
| US8716351B1 (en) | 2012-12-23 | 2014-05-06 | Liveleaf, Inc. | Methods of treating gastrointestinal spasms |
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