JPH11139978A - Enteric live bacterium preparation - Google Patents
Enteric live bacterium preparationInfo
- Publication number
- JPH11139978A JPH11139978A JP9319134A JP31913497A JPH11139978A JP H11139978 A JPH11139978 A JP H11139978A JP 9319134 A JP9319134 A JP 9319134A JP 31913497 A JP31913497 A JP 31913497A JP H11139978 A JPH11139978 A JP H11139978A
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- JP
- Japan
- Prior art keywords
- enteric
- coating
- copolymer
- acid bacteria
- organic solvent
- 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.)
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- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、有機溶媒を使用せ
ずに水溶媒系で腸溶被膜を施した生菌製剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a viable bacterial preparation coated with an enteric coating in an aqueous solvent system without using an organic solvent.
【０００２】[0002]
【従来の技術】乳酸菌、ビフィズス菌、酪酸菌などは、
ヒトの健康と密接な関わりがあり、整腸作用、免疫賦活
作用、抗コレステロール作用など人体に有益な働きを持
つことが知られており、広く医薬品、医薬部外品、食品
などに利用されている。例えば、生菌製剤としては、錠
剤、カプセル、顆粒剤などが利用されている。しかしな
がら、乳酸菌、ビフィズス菌、酪酸菌などの多くは酸や
水分に弱く、服用後胃内の胃酸や水分により生菌数が減
少する。そこで、乳酸菌、ビフィズス菌、酪酸菌などを
生きたまま腸管内に届けるべく腸溶被膜を施した錠剤や
顆粒が今日までに開発されてきた。乳酸菌、ビフィズス
菌、酪酸菌などの生菌粉末を含有する固形物に施すべく
開発された腸溶被膜のコーティング液は、上記の細菌が
水分に弱いため腸溶被膜基剤を有機溶媒系に混合もしく
は分散したものである。このコーティング液を用いた腸
溶性生菌製剤としては、メタアクリル酸とアクリル酸エ
チルエステルの共重合体及びメタアクリル酸とメタアク
リル酸とメタアクリル酸メチルエステルの混合物を有機
溶媒（無水エタノール）に分散させたコーティング液を
塗布して腸溶性被膜を被覆したビフィスズ菌含有固形剤
（特開平３−７２３３）や、乳酸菌粉末を含有する錠剤
にヒドロキシメチルセルロースフタレート等の腸溶性物
質をメチレンクロリド、エタノールなどの有機溶媒に分
散させたコーティング液を塗布して腸溶性被膜を施した
乳酸菌錠剤（特開平４−４１４３４）が開示されてい
る。2. Description of the Related Art Lactic acid bacteria, bifidobacteria, butyric acid bacteria, etc.
It is closely related to human health and is known to have beneficial effects on the human body, such as intestinal action, immunostimulatory action, and anticholesterol action, and is widely used in medicines, quasi-drugs, and foods. I have. For example, tablets, capsules, granules and the like are used as live bacterial preparations. However, many of lactic acid bacteria, bifidobacteria, butyric acid bacteria and the like are vulnerable to acid and water, and the number of viable cells decreases due to gastric acid and water in the stomach after administration. Therefore, enteric coated tablets and granules have been developed so far to deliver lactic acid bacteria, bifidobacteria, butyric acid bacteria, and the like to the intestinal tract alive. The enteric coating coating solution developed to be applied to solids containing viable bacterial powders such as lactic acid bacteria, bifidobacteria, butyric acid bacteria, etc. Or they are dispersed. As the enteric coated bacterial preparation using this coating solution, a copolymer of methacrylic acid and ethyl acrylate and a mixture of methacrylic acid, methacrylic acid and methyl methacrylate in an organic solvent (anhydrous ethanol) are used. Entering an enteric substance such as hydroxymethylcellulose phthalate into methylene chloride, ethanol or the like on a bifidobacterium-containing solid preparation (JP-A-3-7233) coated with an enteric coating by applying a dispersed coating solution or a tablet containing lactic acid bacteria powder. A lactic acid bacterium tablet coated with an enteric coating by applying a coating liquid dispersed in an organic solvent (Japanese Patent Application Laid-Open No. 4-41434) is disclosed.
【０００３】[0003]
【発明が解決しようとする課題】しかし、有機溶媒系を
用いて腸溶被膜をコーティングすると、製剤中の残留有
機溶媒、作業時の安全性、公害などの問題が生じる。し
たがって、有機溶媒を使用しない水溶媒系で腸溶被膜を
施し、乳酸菌、ビフィズス菌、酪酸菌などを生きた状態
で腸内に届けることのできる腸溶性生菌製剤の開発が望
まれている。However, when the enteric film is coated with an organic solvent system, problems such as residual organic solvent in the preparation, safety at work, and pollution arise. Therefore, there is a demand for the development of a viable enteric bacterial preparation capable of providing an enteric coating with an aqueous solvent system that does not use an organic solvent to deliver lactic acid bacteria, bifidobacteria, butyric acid bacteria and the like to the intestine in a live state.
【０００４】水溶媒系コーティング法については既に多
くの医薬品などに利用されている。その例として、アク
リル酸エチルとメタアクリル酸の乳化重合で得た水分散
性の共重合体とショ糖脂肪酸エステル及び水を主成分と
することを特徴とする腸溶性皮膜組成物（特公平２−５
０８８５）や、薬理活性物質を含有する固形成型物の表
面に、水不溶性高分子の微粉を粉末状態で添加し皮膜形
成後、水系コーティング法によってコーティングするこ
とを特徴とする被コーティング製剤の製法（特開平９−
１４３０５６）が開示されているが、生菌粉末を含有す
る固形物をコーティングできるとの記載はない。[0004] The aqueous solvent-based coating method is already used for many pharmaceuticals and the like. As an example, an enteric coating composition comprising a water-dispersible copolymer obtained by emulsion polymerization of ethyl acrylate and methacrylic acid, a sucrose fatty acid ester and water as main components (Japanese Patent Publication No. -5
0885) or a method for producing a preparation to be coated, characterized in that a fine powder of a water-insoluble polymer is added in the form of a powder to the surface of a solid molded product containing a pharmacologically active substance, a film is formed, and the film is coated by an aqueous coating method ( JP-A-9-
No. 143056), but there is no description that solids containing viable bacterial powder can be coated.
【０００５】水系コーティング法では乳酸菌、ビフィズ
ス菌、酪酸菌などの生菌製剤への応用はいまだ実用化さ
れていない。何故なら、乳酸菌、ビフィズス菌、酪酸菌
などの多くが水分に弱く、水溶媒系にて腸溶被膜をコー
ティング中に生菌数が減少したり、コーティング後生菌
数が減少したりして、長期間にわたって安定な生菌数を
確保することが難しいからである。[0005] In the aqueous coating method, application to live bacterial preparations such as lactic acid bacteria, bifidobacteria and butyric acid bacteria has not been put to practical use yet. Because many lactic acid bacteria, bifidobacteria, butyric acid bacteria, etc. are vulnerable to moisture, the number of viable bacteria decreases during coating the enteric coating with an aqueous solvent system, and the number of viable bacteria decreases after coating, This is because it is difficult to secure a stable viable cell count over a period.
【０００６】したがって、本発明の目的は、有機溶媒を
使用しない水溶媒系で腸溶被膜を施し、乳酸菌、ビフィ
ズス菌、酪酸菌などを生きた状態で腸内に届く腸溶性生
菌製剤を提供することにある。Accordingly, an object of the present invention is to provide a live enteric bacterial preparation which is capable of providing lactic acid bacteria, bifidobacteria, butyric acid bacteria and the like in a living state by providing an enteric coating in an aqueous solvent system without using an organic solvent. Is to do.
【０００７】[0007]
【課題を解決するための手段】前記目的を達成するため
に、本発明者らが鋭意研究した結果、水溶媒系に腸溶被
膜物質を分散化しコーティングすることにより、有機溶
媒を使用せずに腸溶被膜を施し、かつ、配合した生菌数
の減少がほとんどなく、保存安定性の良好な腸溶性生菌
製剤が得られることを見出し、本発明を完成した。Means for Solving the Problems In order to achieve the above object, the present inventors have conducted intensive studies. As a result, it is possible to disperse and coat an enteric coating substance in an aqueous solvent system without using an organic solvent. The present inventors have found that an enteric coating is applied, and that the number of mixed viable bacteria hardly decreases and that a viable enteric bacterial preparation having good storage stability can be obtained, and the present invention has been completed.
【０００８】すなわち、本発明は、乳酸菌、ビフィズス
菌、酪酸菌などの生菌粉末を含有する固形物に有機溶媒
を使用せずに水溶媒を使用して腸溶被膜を施したことを
特徴とする腸溶性生菌製剤である。好ましくは、腸溶被
膜は、メタアクリル酸とアクリル酸エチルエステルの共
重合体、メタアクリル酸とアクリル酸メチルエステルの
共重合体、ヒドロキシプロピルメチルセルロースアセテ
ートサクシネートのうち、少なくとも１種を含有する。[0008] That is, the present invention is characterized in that an enteric coating is formed on a solid containing viable bacterial powders such as lactic acid bacteria, bifidobacteria, and butyric acid bacteria using an aqueous solvent without using an organic solvent. Enteric-coated viable bacterial preparation. Preferably, the enteric coating contains at least one of a copolymer of methacrylic acid and ethyl acrylate, a copolymer of methacrylic acid and methyl acrylate, and hydroxypropylmethylcellulose acetate succinate.
【０００９】本発明に使用する乳酸菌、ビフィズス菌、
酪酸菌などの生菌粉末は、常法により凍結乾燥して調製
した保存性のよいものが好ましい。使用できる乳酸菌は
ラクトバチルス・アシドフィルス、ストレプトコッカス
・フェカリス、ビフィズス菌はビフィドバクテリウム・
ロンガム、ビフィドバクテリウム・ビフィダス、酪酸菌
はクリストリジウム・ブチリカムなどがある。The lactic acid bacterium, the bifidobacterium used in the present invention,
The viable bacterial powder such as butyric acid bacterium is preferably one having good preservability prepared by freeze-drying according to a conventional method. The lactic acid bacteria that can be used are Lactobacillus acidophilus, Streptococcus faecalis, and Bifidobacterium are Bifidobacterium
Longum, Bifidobacterium bifidus, and butyric acid bacteria include C. butyricum.
【００１０】上記生菌粉末を含有する固形物を構成する
成分は一般に医薬品添加物として添加されるものであれ
ば何でもよく、賦形剤、結合剤、崩壊剤、コーティング
剤、滑沢剤、凝集防止剤、吸着剤、防腐剤、湿潤剤、帯
電防止剤、などが例示され、その固形物の形態も特に限
定されず、錠剤、細粒、顆粒剤、丸剤、カプセル剤など
の種々の形態のものを好適に使用することができる。こ
れらの固形物を製造する方法はそれ自体公知の方法が選
択される。たとえば、乳酸菌やビフィズス菌の生菌粉末
を含有する固形物の製造法としては特開平０３−７２２
３や特開平４−４１４３４に記載の方法があげられる。The components constituting the solid containing the viable microbial powder may be any components which are generally added as pharmaceutical additives, and include excipients, binders, disintegrants, coating agents, lubricants, and coagulants. Examples include an inhibitor, an adsorbent, a preservative, a wetting agent, an antistatic agent, and the like. The form of the solid is not particularly limited, and various forms such as tablets, fine granules, granules, pills, and capsules are available. Can be suitably used. As a method for producing these solids, a method known per se is selected. For example, a method for producing a solid containing live bacterium powder of lactic acid bacteria and bifidobacteria is described in JP-A-03-722.
3 and the method described in JP-A-4-41434.
【００１１】生菌粉末を含有する固形物に施した腸溶被
膜に含まれる腸溶性物質としては、メタアクリル酸とア
クリル酸エチルエステルの共重合体及びメタアクリル酸
とアクリル酸メチルエステルの共重合体、ヒドロキシプ
ロピルメチルセルロースアセテートサクシネート等の一
般的な胃酸耐性の物質を利用することができる。中でも
メタアクリル酸とアクリル酸エチルエステルの共重合体
であるEudragit (登録商標) L30D-55（ロームファーマ
社製、商品名）が好適である。これらの物質は水に分散
後、パンコーティング法、流動層コーティング法等の常
法により錠剤にコーティングすることができる。コーテ
ィングする量は、胃液の浸透を十分に防止でき、かつ長
期保存性を高める量を必要とし、錠剤の総重量あたり４
〜１２％、好ましくは６〜１０％の範囲で使用される。The enteric substance contained in the enteric coating applied to the solid containing the viable bacterial powder includes a copolymer of methacrylic acid and ethyl acrylate and a copolymer of methacrylic acid and methyl acrylate. Common gastric acid-resistant substances such as coalescing, hydroxypropylmethylcellulose acetate succinate can be used. Among them, Eudragit (registered trademark) L30D-55 (trade name, manufactured by Rohm Pharma Co., Ltd.), which is a copolymer of methacrylic acid and ethyl acrylate, is preferred. After these substances are dispersed in water, tablets can be coated by a conventional method such as a pan coating method or a fluidized bed coating method. The amount to be coated is sufficient to prevent gastric juice from penetrating and to increase the long-term preservability, and is required to be 4% per the total weight of the tablet.
-12%, preferably 6-10%.
【００１２】[0012]
【発明の効果】本発明によれば、乳酸菌、ビフィズス
菌、酪酸菌などを含む錠剤に有機溶媒を使用しない水溶
媒系で胃酸耐性腸溶被膜を施すことによって、含有生菌
を胃酸から守り、生菌の減少を防止することができる。
また、錠剤が胃を通過して腸に達した時には、腸液の作
用により速やかにコーティング剤が溶解し、生菌数の減
少なく、生菌を腸内に届けることができる。According to the present invention, tablets containing lactic acid bacteria, bifidobacteria, butyric acid bacteria, etc. are protected from gastric acid by providing a gastric acid-resistant enteric coating with an aqueous solvent system that does not use an organic solvent. Viable bacteria can be prevented from decreasing.
In addition, when the tablet passes through the stomach and reaches the intestine, the action of the intestinal juice rapidly dissolves the coating agent, and the live bacteria can be delivered to the intestine without a decrease in the number of live bacteria.
【００１３】更に、コーティング工程において有機溶媒
系を使用しないので、製剤中の残留有機溶媒、作業時の
安全性、環境面への悪影響などの問題を著しく改善でき
るという利点もある。以上のようなことから、本発明は
非常に有用な腸溶性生菌製剤であると判断される。Furthermore, since no organic solvent system is used in the coating step, there is the advantage that problems such as residual organic solvent in the preparation, safety during operation, and adverse effects on the environment can be remarkably improved. Based on the above, the present invention is considered to be a very useful enteric coated bacterial preparation.
【００１４】[0014]
【実施例】以下に実施例および試験例を示すが、本発明
はこれらに限定されるものではない。 （実施例１）乳糖、結晶セルロース、ヒドロキシプロピ
ルセルロース、軽質無水ケイ酸およびステアリン酸マグ
ネシウムをそれぞれ１２０２、３００、１００、９、お
よび９重量部の割合で含む混合粉末を添加剤として用意
した。EXAMPLES Examples and test examples are shown below, but the present invention is not limited to these. Example 1 A mixed powder containing lactose, crystalline cellulose, hydroxypropylcellulose, light anhydrous silicic acid and magnesium stearate in the proportions of 1202, 300, 100, 9, and 9 parts by weight, respectively, was prepared as an additive.
【００１５】この添加剤１６２０重量部に、ストレプト
コッカス・フェカリス（Streptococcus faecalis）、ラ
クトバチルス・アシドフィルス（Lactobacillus acidop
hilus）、およびビフィドバクテリウム・ロンガム（Bif
idobacterium longum）を含む原末を各６０重量部ずつ
加えた。これらを混合後、乾式直接打錠法により錠剤を
製造した。製造した錠剤に、メタアクリル酸とアクリル
酸エチルエステルの共重合体（以下、Eudragit（登録商
標）L30D-55 と記す。）３８．５重量部、タルク５．５
重量部、クエン酸トリエチル１重量部、精製水５５重量
部からなるコーティング液を調製し、パンコーティング
法により錠剤に対して約１０％（Ｗ／Ｗ）の被覆率にな
るようコーティングした。吸入温度は、５０〜６５℃、
排気温度３３〜３６℃、パン回転数は８〜１５ｒｐｍで
あった。To 1620 parts by weight of this additive, Streptococcus faecalis, Lactobacillus acidop
hilus), and Bifidobacterium longum (Bif)
The raw powder containing idobacterium longum) was added in an amount of 60 parts by weight. After mixing these, tablets were produced by a dry direct compression method. 38.5 parts by weight of a copolymer of methacrylic acid and ethyl acrylate (hereinafter referred to as Eudragit (registered trademark) L30D-55) was added to the produced tablets, and talc 5.5.
A coating liquid consisting of 1 part by weight of triethyl citrate and 55 parts by weight of purified water was prepared, and coated by a pan coating method so as to have a tablet coverage of about 10% (W / W). Inhalation temperature is 50-65 ° C,
The exhaust temperature was 33 to 36 ° C, and the pan rotation speed was 8 to 15 rpm.
【００１６】得られた各コーティング錠に対して、第１
３改正日本薬局方：崩壊試験法第１液を用いて崩壊試験
を行ったところ、錠剤に変化は認められなかった。引き
続き第２液を用いて試験を行ったところ、８〜１３分の
間に崩壊し、良好な崩壊性が認められた。[0016] For each of the obtained coated tablets,
3 Revised Japanese Pharmacopoeia: Disintegration test was carried out using Disintegration Test Method No. 1, and no change was observed in the tablets. Subsequently, when a test was performed using the second liquid, it disintegrated in 8 to 13 minutes, and good disintegration was observed.
【００１７】（試験例）製造した錠剤のコーティング前
後の生菌数の変化、第１液（人工胃液）に対する耐性、
および錠剤保存中における生菌数の変化を試験した。 （１）コーティング前後の生菌数の変化 コーティング前後の生菌数の変化を表１に示した。表１
から明らかなようにコーティングによる生菌数の低下は
認められなかった。(Test Example) Changes in the number of viable bacteria before and after coating of the manufactured tablets, resistance to the first liquid (artificial gastric juice),
And the change in viable cell count during tablet storage was tested. (1) Change in viable cell count before and after coating Change in viable cell count before and after coating is shown in Table 1. Table 1
As is clear from the figure, no decrease in the viable cell count due to the coating was observed.
【００１８】[0018]
【表１】 （２）第１液（人工胃液）に対する耐性 第１液に１２０分浸した後の生菌数を表２に示した。表
２から明らかなように本錠剤中の生菌数が第一液によっ
て影響を受けないことが示された。[Table 1] (2) Resistance to first liquid (artificial gastric juice) Table 2 shows the viable cell count after immersion in the first liquid for 120 minutes. As is clear from Table 2, the number of viable bacteria in the tablet was not affected by the first liquid.
【００１９】[0019]
【表２】 （３）錠剤の保存中の生菌数変化 ３５℃、湿度７５％の状態における錠剤の保存中の生菌
数の変化を保存日数３０日および６０日で試験した。サ
ンプルとしては、実施例で製造した腸溶性コーティング
生菌含有錠剤を用いた。錠剤はガラス製サンプル瓶に入
れキャップをして保存した。[Table 2] (3) Change in viable cell count during storage of tablets Changes in the viable cell count during storage of tablets at 35 ° C. and 75% humidity were tested for 30 and 60 days of storage. As the sample, the enteric-coated live bacteria-containing tablet manufactured in the example was used. The tablets were placed in a glass sample bottle, capped and stored.
【００２０】３５℃、湿度７５％における保存結果を、
錠剤１錠当たりの生菌数の変化により表３に示した。表
３から明らかなように６０日後においても配合した菌の
生菌数の低下は認められなかった。The results of storage at 35 ° C. and 75% humidity were as follows:
Table 3 shows the change in the number of viable bacteria per tablet. As is clear from Table 3, no decrease in the viable cell count of the mixed bacteria was observed even after 60 days.
【００２１】[0021]
【表３】 [Table 3]
───────────────────────────────────────────────────── フロントページの続き (72)発明者 上野 雅男 東京都港区高輪３−24−18 株式会社樋口 商会内 ──────────────────────────────────────────────────の Continued on the front page (72) Inventor Masao Ueno 3-24-18 Takanawa, Minato-ku, Tokyo Higuchi Shokai Co., Ltd.
Claims (2)
菌粉末を含有する固形物に、有機溶媒を使用せずに水溶
媒を使用して、腸溶被膜を施した腸溶性生菌製剤。1. An enteric coated bacterial preparation obtained by applying an enteric coating to a solid containing live bacterial powder such as lactic acid bacteria, bifidobacteria, and butyric acid bacteria using an aqueous solvent without using an organic solvent.
酸エチルエステルの共重合体、メタアクリル酸とアクリ
ル酸メチルエステルの共重合体、ヒドロキシプロピルメ
チルセルロースアセテートサクシネートのうち、少なく
とも１種を含有することを特徴とする請求項１記載の腸
溶性生菌製剤。2. The enteric coating contains at least one of a copolymer of methacrylic acid and ethyl acrylate, a copolymer of methacrylic acid and methyl acrylate, and hydroxypropylmethylcellulose acetate succinate. The enteric-coated viable bacterial preparation according to claim 1, wherein:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9319134A JPH11139978A (en) | 1997-11-06 | 1997-11-06 | Enteric live bacterium preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP9319134A JPH11139978A (en) | 1997-11-06 | 1997-11-06 | Enteric live bacterium preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11139978A true JPH11139978A (en) | 1999-05-25 |
Family
ID=18106841
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9319134A Pending JPH11139978A (en) | 1997-11-06 | 1997-11-06 | Enteric live bacterium preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH11139978A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19937361A1 (en) * | 1999-08-12 | 2001-02-22 | Merck Patent Gmbh | Oral dosage form |
| JP2006257049A (en) * | 2005-03-18 | 2006-09-28 | Kimura Sangyo Kk | Lactobacillus preparation and digestive enzyme and method for producing tablet containing both of them and tablet produced thereby |
| WO2008081539A1 (en) * | 2006-12-28 | 2008-07-10 | National University Corporation Akita University | Supplement containing useful bacterium such as lactic acid bacterium with the use of porous silica |
| JP2009102323A (en) * | 2008-11-27 | 2009-05-14 | Morishita Jintan Kk | Lactobacillus-containing agent for reducing homocysteine in blood |
| JP2009102324A (en) * | 2008-11-27 | 2009-05-14 | Morishita Jintan Kk | Lactobacillus-containing agent for reducing ammonia in blood |
| WO2011108826A3 (en) * | 2010-03-04 | 2012-03-01 | Hanmi Holdings Co., Ltd. | Complex formulation for oral administration comprising probiotic formulation and 5-ht4 receptor agonist and method for the preparation thereof |
| JP2012167131A (en) * | 2012-06-13 | 2012-09-06 | Kimura Sangyo Kk | Tablet containing probiotic agent, digestive enzyme agent, or both of them |
| JP2013226095A (en) * | 2012-04-26 | 2013-11-07 | Nisshin Pharma Inc | Food for improving intestinal environment |
-
1997
- 1997-11-06 JP JP9319134A patent/JPH11139978A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19937361A1 (en) * | 1999-08-12 | 2001-02-22 | Merck Patent Gmbh | Oral dosage form |
| JP2006257049A (en) * | 2005-03-18 | 2006-09-28 | Kimura Sangyo Kk | Lactobacillus preparation and digestive enzyme and method for producing tablet containing both of them and tablet produced thereby |
| WO2008081539A1 (en) * | 2006-12-28 | 2008-07-10 | National University Corporation Akita University | Supplement containing useful bacterium such as lactic acid bacterium with the use of porous silica |
| JPWO2008081539A1 (en) * | 2006-12-28 | 2010-04-30 | 国立大学法人秋田大学 | Supplements containing useful bacteria such as lactic acid bacteria using porous silica |
| JP2009102323A (en) * | 2008-11-27 | 2009-05-14 | Morishita Jintan Kk | Lactobacillus-containing agent for reducing homocysteine in blood |
| JP2009102324A (en) * | 2008-11-27 | 2009-05-14 | Morishita Jintan Kk | Lactobacillus-containing agent for reducing ammonia in blood |
| WO2011108826A3 (en) * | 2010-03-04 | 2012-03-01 | Hanmi Holdings Co., Ltd. | Complex formulation for oral administration comprising probiotic formulation and 5-ht4 receptor agonist and method for the preparation thereof |
| CN102753156A (en) * | 2010-03-04 | 2012-10-24 | 韩美科学株式会社 | Complex formulation for oral administration comprising probiotic formulation and 5-ht4 receptor agonist and method for the preparation thereof |
| JP2013521276A (en) * | 2010-03-04 | 2013-06-10 | ハンミ・サイエンス・カンパニー・リミテッド | Probiotic preparation, oral preparation containing 5-HT4 receptor agonist, and method for producing the same |
| JP2013226095A (en) * | 2012-04-26 | 2013-11-07 | Nisshin Pharma Inc | Food for improving intestinal environment |
| JP2012167131A (en) * | 2012-06-13 | 2012-09-06 | Kimura Sangyo Kk | Tablet containing probiotic agent, digestive enzyme agent, or both of them |
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