JP3083169B2 - Bifidobacterium preparation and its production method - Google Patents
Bifidobacterium preparation and its production methodInfo
- Publication number
- JP3083169B2 JP3083169B2 JP03053589A JP5358991A JP3083169B2 JP 3083169 B2 JP3083169 B2 JP 3083169B2 JP 03053589 A JP03053589 A JP 03053589A JP 5358991 A JP5358991 A JP 5358991A JP 3083169 B2 JP3083169 B2 JP 3083169B2
- Authority
- JP
- Japan
- Prior art keywords
- bifidobacterium
- enteric
- preparation
- solution
- powder
- 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.)
- Expired - Fee Related
Links
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、ビフィズス菌の菌体粉
末の表面を被覆してなるビフィズス菌製剤と、同製剤の
製造方法とに関するものである。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a bifidobacterium preparation obtained by coating the surface of a cell powder of bifidobacteria, and a method for producing the preparation.
【０００２】[0002]
【従来の技術】これまでにビフィズス菌のような腸内有
効細菌類を分散した油を直径３mm以下のカプセルに充填
し、さらに該被覆材の上に腸溶性コーティングを行い製
造する方法（特開昭６２−２０１８２３号）や、ビフィ
ズス菌を酸素等からの外的要因から保護するため体温で
溶融する油脂でコーティングする方法（特開昭５７−３
３５４３号）等が提案されている。2. Description of the Related Art A method in which an oil in which intestinal effective bacteria such as Bifidobacterium is dispersed is filled in a capsule having a diameter of 3 mm or less, and an enteric coating is further applied on the coating material to produce the same (Japanese Patent Application Laid-Open (JP-A) no. 62-201823) and a method of coating bifidobacteria with fats and oils that melt at body temperature to protect them from external factors such as oxygen (Japanese Patent Laid-Open No. 57-3).
No. 3543) has been proposed.
【０００３】しかし、上記特開昭６２−２０１８２３号
の方法によれば特殊な装置と多くの時間と工程がかかり
さらに、カプセル皮膜の水分により菌が死滅する可能性
があり、保存安定性に問題がある。However, according to the method disclosed in Japanese Patent Application Laid-Open No. 62-201823, a special device and a lot of time and steps are required, and furthermore, there is a possibility that the bacteria may be killed by the moisture of the capsule film, which causes a problem in storage stability. There is.
【０００４】さらに特開昭５７−３３５４３号の方法に
よれば、３５℃以上で流動性を示す油脂を用いるので油
脂でコーティングされたビフィズス菌は腸内に達する前
にコーティングの油脂が流動化する結果胃液でほとんど
死滅するという問題がある。Further, according to the method disclosed in Japanese Patent Application Laid-Open No. 57-33543, since a fat or oil having fluidity at 35 ° C. or more is used, the fat or oil of the bifidobacterium coated with the fat or oil is fluidized before reaching the intestine. As a result, there is a problem that gastric juice almost kills.
【０００５】[0005]
【発明が解決しようとする課題】ビフィズス菌の生理学
的意義については、多数の報告がなされており、腸内腐
敗の原因菌である大腸菌、ウェルシュ菌、バクテロイデ
ス菌等の増殖を抑制し、下痢、便秘を予防し、乳酸、酢
酸等の有機酸およびビタミン類等を産生する秀れた生理
効果を有することが既に知られている。There have been many reports on the physiological significance of Bifidobacteria, which suppresses the growth of Escherichia coli, Welsh bacteria, Bacteroides bacteria, etc., which are the causative bacteria of intestinal rot, and reduces diarrhea. It is already known that it has an excellent physiological effect of preventing constipation and producing organic acids such as lactic acid and acetic acid and vitamins.
【０００６】しかし、ビフィズス菌は一般に生存性が悪
く活性が低下しやすい。また、ビフィズス菌特有の臭
気、保護剤の澱粉臭などのために食感が悪かった。[0006] However, Bifidobacteria generally have poor viability and tend to have low activity. In addition, the texture was poor due to the odor peculiar to Bifidobacterium and the odor of starch as a protective agent.
【０００７】そして、ビフィズス菌は、酸性溶液中で死
滅しやすく活性を維持したままｐＨ１.２〜５.０の胃中
を通過して腸まで到達させることは困難であった。[0007] Bifidobacteria are easily killed in an acidic solution, and it is difficult to reach the intestine through the stomach of pH 1.2 to 5.0 while maintaining the activity.
【０００８】従って、このヒトの健康に有用なビフィズ
ス菌を経口的に投与した場合に、ビフィズス菌を胃中で
死滅させることなく確実に腸まで到達せしめる手段の解
明が求められていた。[0008] Therefore, there has been a need for elucidation of means for ensuring that the bifidobacteria reach the intestine without being killed in the stomach when the bifidobacterium useful for human health is orally administered.
【０００９】更にビフィズス菌を製剤とする場合、長期
間にわたり生存させる必要があり、従って長期間の保存
にたえる製剤の開発が必要とされたのである。[0009] Further, when a bifidobacterium is used as a preparation, it is necessary to survive for a long period of time, and therefore, there is a need to develop a preparation that can be stored for a long period of time.
【００１０】[0010]
【課題を解決するための手段】本発明者らは上記した課
題を解決すべく鋭意研究した結果、腸溶性基材でビフィ
ズス菌の菌体粉末の表面を被覆してビフィズス菌製剤と
することによって、長期間の保存にもたえ、かつまた経
口的に投与した場合に胃中でビフィズス菌が死滅するこ
となく確実に生存状態で腸まで到達させうることを見出
して本発明を完成したのである。Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, by coating the surface of the cell powder of bifidobacteria with an enteric base material, to obtain a bifidobacterium preparation The present invention has been completed by finding that it can be stored for a long period of time, and that when administered orally, the bifidobacteria can reach the intestine in a living state without dying in the stomach. .
【００１１】すなわち、本発明は腸溶性基材で表面が被
覆されたビフィズス菌の菌体粉末からなるビフィズス菌
製剤を提供するものである。That is, the present invention provides a bifidobacterium preparation comprising a cell powder of bifidobacteria having a surface coated with an enteric substrate.
【００１２】本発明のビフィズス菌の菌体粉末の表面を
被覆するのに用いられる腸溶性基材は、製剤の技術分野
で用いられる造膜性を有し経口的に投与された場合に腸
管内に至ってはじめて被覆した内容物を放出する物質の
いずれのものであっても良くこれらの具体例としてカル
ボキシメチルセルロース、ヒドロキシメチルセルロース
フタレート、オイドラギットなどの合成または半合成高
分子物質、セラックなどの天然物を挙げることができ
る。The enteric substrate used for coating the surface of the Bifidobacterium cell powder of the present invention is a film-forming material used in the technical field of pharmaceutical preparations, and has an intestinal tract when administered orally. May be any of the substances that release the coated contents until they reach the above. Specific examples thereof include carboxymethylcellulose, hydroxymethylcellulose phthalate, synthetic or semi-synthetic polymer substances such as Eudragit, and natural substances such as shellac. be able to.
【００１３】ビフィズス菌の菌体粉末の表面のこれらの
腸溶性物質による被覆に当っては、腸溶性物質を溶媒中
に溶解または分散させ、得られた溶液また分散液中に菌
体粉末を加えて分散させ、この分散体を噴霧乾燥法によ
って噴霧するのと同時に乾燥させてビフィズス菌の菌体
粉末の表面に腸溶性物質を被覆させるか、または腸溶性
物質を溶媒中に溶解または分散させ、得られた溶液また
は分散液をノズルを介して高速気流中に供給し、別にノ
ズルを介して高速気流中に菌体粉末を供給し、高速気流
中で腸溶性物質の溶液または分散液と菌体粉末とを接触
させ菌体粉末の表面を腸溶性物質で被覆すると共に乾燥
させ、もって腸溶性物質の被膜で表面が被覆されたビフ
ィズス菌の菌体粉末を得る方法が用いられる。In coating the surface of the cell powder of Bifidobacterium with these enteric substances, the enteric substance is dissolved or dispersed in a solvent, and the cell powder is added to the resulting solution or dispersion. Spraying the dispersion by a spray-drying method and drying at the same time to coat the enteric substance on the surface of the Bifidobacterium cell powder, or dissolving or dispersing the enteric substance in a solvent, The obtained solution or dispersion is supplied into a high-speed air stream through a nozzle, and the bacterial cell powder is supplied into a high-speed air stream through a separate nozzle. A method is used in which the powder is brought into contact with a powder to coat the surface of the bacterial cell powder with an enteric substance and dried to obtain a bacterial cell powder of bifidobacterium whose surface is coated with a coating of the enteric substance.
【００１４】これらの腸溶性物質を溶解または分散させ
る溶媒は、選択する腸溶性物質に応じて異なりうるが、
水、メタノール、エタノール、プロパノール、ブタノー
ルなどのアルコール、アセトン、メチルエチルケトンな
どのケトン、酢酸エチル、酢酸ブチルなどのエステル、
ジメチルエーテル、ジエチルエーテル、テトラヒドロフ
ランなどのエーテル、ヘキサン、ペンタンなどの炭化水
素などを１種または数種混合して用いることができる。The solvent for dissolving or dispersing these enteric substances can vary depending on the enteric substance selected,
Alcohols such as water, methanol, ethanol, propanol and butanol; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate and butyl acetate;
Ethers such as dimethyl ether, diethyl ether and tetrahydrofuran, and hydrocarbons such as hexane and pentane may be used alone or as a mixture of several kinds.
【００１５】上記の方法のいずれにおいても腸溶性物質
の溶液または分散液に適当な可塑化剤例えばグリセリン
モノ脂肪酸エステル、ヒマシ油などを添加することがで
き、そしてこの溶液または分散液の腸溶性物質濃度は５
〜５０（ｗ／ｗ）％、好ましくは１０〜３２（ｗ／ｗ）
％程度の濃度であるものとする。In any of the above methods, a suitable plasticizer such as glycerin monofatty acid ester, castor oil, or the like can be added to the solution or dispersion of the enteric substance, and the enteric substance of the solution or dispersion can be added. The concentration is 5
５０50 (w / w)%, preferably 10-32 (w / w)
%.
【００１６】上記した噴霧乾燥法による腸溶性基材で表
面が被覆された菌体粉末を製造するのに用いる装置は通
常のスプレイドライヤーであって良い。また高速気流中
での菌体と腸溶性基材溶液または分散液との接触と引き
続く乾燥による方法での目的物の製造に用いる装置には
例えば日清エンジニアリング（株）製のディスパコート
Ｒがある。The apparatus used for producing the bacterial cell powder coated on the surface with the enteric substrate by the above-mentioned spray drying method may be an ordinary spray dryer. Examples of an apparatus used for producing a target substance by a method of contacting a bacterial cell with an enteric substrate solution or dispersion in a high-speed air stream and subsequent drying include, for example, Dispacoat manufactured by Nisshin Engineering Co., Ltd.
There is R.
【００１７】上記のようにしてビフィズス菌の菌体粉末
の表面を被覆で保護するために、このようにして得られ
た腸溶性基材による被膜のために有効細菌を長期間にわ
たり保存することができかつ、経口摂取する場合には、
調製時の生菌数を減らすことなく、上記有効細菌を腸に
到達させることができる。さらに、腸溶性基剤を有効細
菌粉末に直接皮膜を施すため、酸化安定性、耐湿度安定
性の向上が可能となる。In order to protect the surface of the bacterial cell powder of Bifidobacterium with a coating as described above, it is necessary to preserve the effective bacteria for a long period of time for coating with the enteric substrate thus obtained. If possible and if taken orally,
The effective bacteria can reach the intestine without reducing the number of viable bacteria at the time of preparation. Furthermore, since the enteric base is directly coated on the effective bacterial powder, the oxidation stability and the humidity resistance stability can be improved.
【００１８】本発明において、使用するビフィズス菌
は、通常のビフィズス菌であって、ビフィドバクテリウ
ムロンガム（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ｌｏｎ
ｇｕｍ）、ビフィドバクテリウムインファンテス（Ｂｉ
ｆｉｄｏｂａｃｔｅｒｉｕｍｉｎｆａｎｔｉｓ）、ビフ
ィドバクテリウムアドレッセンテス（Ｂｉｆｉｄｏｂａ
ｃｔｅｒｉｕｍ ａｄｏ１ｅｓｃｅｎｔｉｓ）、ビフィ
ドバクテリウムブレーベ （Ｂｉｆｉｄｏｂａｃｔｅｒ
ｉｕｍ ｂｒｅｖｅ）等である。In the present invention, the bifidobacterium used is a common bifidobacterium, and is used as a bifidobacterium longum (Bifidobacterium longum).
gu), Bifidobacterium infantes (Bi)
fidobacterium minfantis, Bifidobacterium adressentes (Bifidoba)
cterium ado1escentis), Bifidobacterium breve (Bifidobacter)
ium is a br eve) and the like.
【００１９】つぎに本発明を実施例によって説明する。Next, the present invention will be described with reference to examples.
【００２０】実施例１ ビフィドバクテリウム・ロンガム（Bifidobacterium lo
ngum）澱粉粉末（生菌数８.５×１０9／ｇ）１００ｇを
セラック溶液（３０％エタノール溶液）に分散せしめ
た。この分散液を噴霧乾燥装置（大川原化工機（株）
製）Ｌ−８型を用い噴霧乾燥し、ビフィズス菌含有物を
得た。Example 1 Bifidobacterium longum
ngum) starch powder (live bacteria count 8.5 × 10 9 / g) (100 g) was dispersed in a shellac solution (30% ethanol solution). This dispersion is spray-dried (Okawara Kakoki Co., Ltd.)
Spray-dried using L-8 type to obtain a bifidobacterium-containing substance.
【００２１】実施例２ ビフィドバクテリウム・ロンガム（Bifidobacterium lo
ngum）澱粉粉末（生菌数８.５×１０9／ｇ）１００ｇを
セラック溶液（２５％エタノール溶液）に分散せしめ
た。この分散液を実施例１と同様に操作を用いビフィズ
ス菌含有物を得た。Example 2 Bifidobacterium longum
ngum) starch powder (live bacteria count 8.5 × 10 9 / g) (100 g) was dispersed in a shellac solution (25% ethanol solution). This dispersion was used in the same manner as in Example 1 to obtain a bifidobacterium-containing substance.
【００２２】実施例３ ビフィドバクテリウム・ロンガム（Bifidobacterium lo
ngum）澱粉粉末（生菌数９.１×１０9／ｇ）１００ｇを
セラック溶液（２５％エタノール溶液）に分散せしめ
た。この分散液を粉体表面改質装置（日清エンジニアリ
ング（株）製）ＤＣ−０８型を用い表面改質を行いビフ
ィズス菌含有物を得た。Example 3 Bifidobacterium longum
ngum) 100 g of starch powder (live cell count 9.1 × 10 9 / g) was dispersed in a shellac solution (25% ethanol solution). This dispersion was subjected to surface modification using a powder surface modification apparatus (Model DC-08, manufactured by Nisshin Engineering Co., Ltd.) to obtain a bifidobacterium-containing substance.
【００２３】保存試験 耐湿度試験 本実施例で得たビフィズス菌含有物を開放の状態で３０
°、７５％ＲＨに１週間保存し生菌数を測定した。（表
１）Storage test Humidity test The bifidobacterium-containing material obtained in this example was left open for 30 minutes.
°, and stored at 75% RH for 1 week, and the number of viable bacteria was measured. (Table 1)
【００２４】[0024]
【表１】 [Table 1]
【００２５】 耐酸性試験 本実施例で得たビフィズス菌含有物を日本薬局方第一液
（pH１.２）を用い、第一液中で１時間及び２時間の耐
酸性試験を実施した。（表２）Acid Resistance Test The bifidobacterium-containing substance obtained in this example was subjected to an acid resistance test for 1 hour and 2 hours in the first solution using Japanese Pharmacopoeia First Solution (pH 1.2). (Table 2)
【００２６】[0026]
【表２】 [Table 2]
【００２７】 生存試験 本実施例１で得たビフィズス菌含有物をグリセリン脂肪
酸エステルに分散し、ソフトカプセルを製造し菌の生存
実験を行った。（表３）ソフトカプセル皮膜は、ゼラチ
ン１００部、グリセリン３５部、精製水適量の割合で調
製したものを用いた。Survival Test The bifidobacterium-containing substance obtained in Example 1 was dispersed in glycerin fatty acid ester to prepare soft capsules, and a survival test of the bacteria was performed. (Table 3) As the soft capsule film, one prepared with a ratio of 100 parts of gelatin, 35 parts of glycerin and an appropriate amount of purified water was used.
【００２８】[0028]
【表３】 [Table 3]
───────────────────────────────────────────────────── フロントページの続き (72)発明者 村田 博 埼玉県川越市岸町１丁目25番地49 増田 第一ハイツ306号 (56)参考文献 特開 昭64−66124（ＪＰ，Ａ) 特開 昭60−221078（ＪＰ，Ａ) 特開 昭62−212324（ＪＰ，Ａ) 特開 昭53−104787（ＪＰ，Ａ) 特公 昭43−3889（ＪＰ，Ｂ１) 特公 昭43−5014（ＪＰ，Ｂ１) (58)調査した分野(Int.Cl.7，ＤＢ名) A61K 35/74 ＣＡ（ＳＴＮ)──────────────────────────────────────────────────続 き Continuation of front page (72) Inventor Hiroshi Murata 1-25-25 Kishicho, Kawagoe-shi, Saitama 49 Masuda Daiichi Heights 306 (56) References JP-A-64-66124 (JP, A) JP-A Sho JP-A-62-212324 (JP, A) JP-A-53-104787 (JP, A) JP-B-43-3889 (JP, B1) JP-B-43-5014 (JP, A) B1) (58) Field surveyed (Int. Cl. 7 , DB name) A61K 35/74 CA (STN)
Claims (2)
せ、この溶液または分散液を高速気流中に供給し、別に
この高速気流中に供給したビフィズス菌の菌体粉末と高
速気流中で接触させ、ビフィズス菌の菌体粉末の表面を
腸溶性基材で被覆すると共に乾燥させることからなるビ
フィズス菌製剤の製法。1. An enteric substrate is dissolved or dispersed in a solvent, and this solution or dispersion is supplied into a high-speed air stream, and separately mixed with the bifidobacterium cell powder supplied into the high-speed air stream. A method for producing a bifidobacterium preparation, which comprises contacting, coating the surface of a bifidobacterium cell powder with an enteric substrate and drying.
ビフィズス菌製剤。2. A bifidobacterium preparation produced by the method according to claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03053589A JP3083169B2 (en) | 1991-02-27 | 1991-02-27 | Bifidobacterium preparation and its production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03053589A JP3083169B2 (en) | 1991-02-27 | 1991-02-27 | Bifidobacterium preparation and its production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH04273823A JPH04273823A (en) | 1992-09-30 |
| JP3083169B2 true JP3083169B2 (en) | 2000-09-04 |
Family
ID=12947054
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP03053589A Expired - Fee Related JP3083169B2 (en) | 1991-02-27 | 1991-02-27 | Bifidobacterium preparation and its production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3083169B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002005829A3 (en) * | 2000-07-17 | 2002-05-02 | Hansens Lab | Methods and formultations with probiotic microorganisms and medicaments |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19937361A1 (en) * | 1999-08-12 | 2001-02-22 | Merck Patent Gmbh | Oral dosage form |
| JP2006280263A (en) * | 2005-03-31 | 2006-10-19 | Snow Brand Milk Prod Co Ltd | Bacillus bifidus cell powder |
| CN105341940A (en) * | 2015-12-03 | 2016-02-24 | 贵州华南理工生物工程有限公司 | Preparation method of black garlic and bifidobacteria viable bacterium powder |
-
1991
- 1991-02-27 JP JP03053589A patent/JP3083169B2/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002005829A3 (en) * | 2000-07-17 | 2002-05-02 | Hansens Lab | Methods and formultations with probiotic microorganisms and medicaments |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH04273823A (en) | 1992-09-30 |
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