JPH0475888B2 - - Google Patents
Info
- Publication number
- JPH0475888B2 JPH0475888B2 JP7367886A JP7367886A JPH0475888B2 JP H0475888 B2 JPH0475888 B2 JP H0475888B2 JP 7367886 A JP7367886 A JP 7367886A JP 7367886 A JP7367886 A JP 7367886A JP H0475888 B2 JPH0475888 B2 JP H0475888B2
- Authority
- JP
- Japan
- Prior art keywords
- enteric
- substance
- substances
- capsules
- intestinal
- 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
Links
- 239000000126 substance Substances 0.000 claims description 39
- 239000002775 capsule Substances 0.000 claims description 31
- 230000000968 intestinal effect Effects 0.000 claims description 17
- 210000000936 intestine Anatomy 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 15
- 241000186000 Bifidobacterium Species 0.000 claims description 12
- 230000036760 body temperature Effects 0.000 claims description 10
- 238000002844 melting Methods 0.000 claims description 10
- 230000008018 melting Effects 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 6
- 239000012907 medicinal substance Substances 0.000 claims 1
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- 210000004051 gastric juice Anatomy 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000011162 core material Substances 0.000 description 11
- 239000000463 material Substances 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000005538 encapsulation Methods 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 239000003925 fat Substances 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000001035 drying Methods 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 210000002784 stomach Anatomy 0.000 description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 240000004668 Valerianella locusta Species 0.000 description 2
- 235000003560 Valerianella locusta Nutrition 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 230000001112 coagulating effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000002609 medium Chemical group 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 102000057297 Pepsin A Human genes 0.000 description 1
- 108090000284 Pepsin A Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- 239000005062 Polybutadiene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920007962 Styrene Methyl Methacrylate Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- -1 atebrin Chemical compound 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 229960002001 ethionamide Drugs 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940040461 lipase Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000006402 liver broth Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- ADFPJHOAARPYLP-UHFFFAOYSA-N methyl 2-methylprop-2-enoate;styrene Chemical compound COC(=O)C(C)=C.C=CC1=CC=CC=C1 ADFPJHOAARPYLP-UHFFFAOYSA-N 0.000 description 1
- IQSHMXAZFHORGY-UHFFFAOYSA-N methyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound COC(=O)C=C.CC(=C)C(O)=O IQSHMXAZFHORGY-UHFFFAOYSA-N 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 229940116369 pancreatic lipase Drugs 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 229920002857 polybutadiene Polymers 0.000 description 1
- 239000005518 polymer electrolyte Substances 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Description
【発明の詳細な説明】
産業上の利用分野
本発明は、腸溶性カプセル、更に詳しくは、経
口摂取した際、腸内有効物から成る内臓物（芯
部）を保護被覆している、カプセルの壁膜が腸内
に達して始めて崩壊することにより、腸内有効物
が胃液や胃液中酵素等の作用を受けてその活性が
損なわれることなく、腸内で有効に利用され得る
ようにしたカプセルに関する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to enteric-coated capsules, and more particularly to capsules having a protective coating over the internal organs (core) consisting of substances effective in the intestine when ingested orally. Capsules whose wall membrane disintegrates only after reaching the intestines, allowing effective intestinal substances to be effectively utilized in the intestines without losing their activity due to the action of gastric juices or enzymes in gastric juices. Regarding.
従来の技術
従来、ビフイズス菌のような腸内有効物を体温
で溶融する油脂でコーテイングすることによりビ
フイズス菌を酸素等の外囲条件から保護すること
（特開昭57−33543号）、ビフイズス菌の生菌体と
その保護膜形成溶液の混合液を、凝固用塩類溶液
に注入して凝固させ、該凝固物を乾燥し、必要に
応じて体温以上の融点を有する油脂でコーテイン
グすることにより、長期保存に適した菌体顆粒を
得る方法（特開昭60−141281号）等が提案されて
いる。Conventional technology Conventionally, bifidobacteria have been protected from ambient conditions such as oxygen by coating intestinal active substances such as bifidobacteria with fats and oils that melt at body temperature (Japanese Unexamined Patent Publication No. 57-33543). By pouring a mixture of viable bacterial cells and their protective film-forming solution into a coagulating salt solution to coagulate, drying the coagulated product, and optionally coating it with an oil or fat having a melting point higher than body temperature, A method for obtaining bacterial granules suitable for long-term storage (Japanese Patent Application Laid-Open No. 141281/1981) has been proposed.
しかし、特開昭57−33543号が開示のものでは、
35℃以上で流動性を示す油脂を用いるので、この
ような油脂でコーテイングされたビフイズス菌
は、経口摂取した際、口内や胃内で油脂の被膜が
崩壊し、そのためにビフイズス菌は腸内に達する
前に胃液でほとんど死滅するという問題があり、
加うるに、ビフイズス菌を溶融した油脂で直接コ
ーテイングするため熱による菌への悪影響もみら
れる。また、特開昭60−141281号が開示の方法
は、菌体液を凝固させ、更にそれを乾燥するとい
う煩雑な工程が必要であるうえ、凍結乾燥の際凍
結障害により菌が死滅することがあり、さらに、
菌体は保護膜の上に硬化油のような体温以上の融
点を有する油脂でコーテイングされるが、その
際、上記凝固、乾燥して得られる菌体顆粒の保護
膜が薄いため、菌体がコーテイングの際融解した
高温の硬化油に接触して死滅する可能性がある。 However, as disclosed in JP-A No. 57-33543,
Since oils and fats that are fluid at temperatures above 35°C are used, when bifidobacteria coated with such oils are ingested orally, the oil coating disintegrates in the mouth or stomach, and as a result, the bifidobacteria enter the intestines. The problem is that the gastric juices kill most of them before they reach the target.
In addition, since the Bifidobacterium is directly coated with molten oil and fat, heat can have an adverse effect on the bacteria. Furthermore, the method disclosed in JP-A-60-141281 requires a complicated process of coagulating the bacterial fluid and then drying it, and the bacteria may die due to freezing injury during freeze-drying. ,moreover,
The bacterial cells are coated on the protective film with an oil or fat such as hydrogenated oil that has a melting point above body temperature. There is a possibility that it will be killed by contact with the melted hot hydrogenated oil during coating.
また、上記方法で得られる菌体顆粒は、上述の
ように、保護膜の上に更に硬化油の被膜が施され
ているため、腸内では硬化油の被膜の崩壊後、更
に保護膜も崩壊しないと腸内で有効に利用されな
いという問題点もみられる。 In addition, as mentioned above, the bacterial granules obtained by the above method have a hydrogenated oil coating on top of the protective membrane, so in the intestines, after the hydrogenated oil coating collapses, the protective membrane also collapses. Otherwise, there is a problem that it will not be used effectively in the intestines.
一方、腸溶性マイクロカプセルとしては、エチ
ルセルロースから成る壁膜中に腸溶性物質を芯物
質として含有させたもの（特開昭58−67616号）、
さらには壁膜物質にポリスチレン、ポリブタジエ
ン、スチレン−メタクリル酸メチル共重合体のよ
うな高分子物質の膜とその上にゼラチンと腸溶性
高分子電解質（例えばアクリル酸メチル−メタク
リル酸共重合体）とよりなるコンプレツクスコア
セルベート膜との二重に構成されたものを用いた
もの（特開昭55−105615号）等が提案されてい
る。 On the other hand, enteric-coated microcapsules include those in which an enteric substance is contained as a core material in a wall made of ethyl cellulose (Japanese Patent Application Laid-Open No. 58-67616);
Furthermore, the wall material is a film of a polymer material such as polystyrene, polybutadiene, or styrene-methyl methacrylate copolymer, and gelatin and an enteric polymer electrolyte (e.g., methyl acrylate-methacrylic acid copolymer) are added thereon. A method using a double structure with a complex coacervate film (Japanese Patent Application Laid-open No. 105615/1983) has been proposed.
しかし、体温以上の融点を有する硬化油を壁膜
として用いた腸溶性カプセルについては未だ報告
はみられない。 However, there have been no reports yet on enteric-coated capsules using a hydrogenated oil having a melting point above body temperature as a wall membrane.
発明が解決しようとする課題
本発明は、腸内有用微生物（例えばビフイズス
菌）や腸内で吸収される医薬物質、及び腸内で吸
収されずに活性を示す医薬物質のような腸内有効
物をカプセル化して経口摂取する際、口内や胃内
でカプセルの壁膜が崩壊せずに、腸内に達して始
めて容易に崩壊し、かつ従来公知の方法で簡易に
カプセル化し得る腸溶性カプセルを提供すること
を課題とする。Problems to be Solved by the Invention The present invention relates to beneficial intestinal microorganisms (e.g. Bifidobacteria), pharmaceutical substances that are absorbed in the intestine, and intestinal effective substances such as pharmaceutical substances that are active without being absorbed in the intestine. Enteric-coated capsules that are easily disintegrated once they reach the intestines without the capsule wall disintegrating in the mouth or stomach when encapsulated and ingested orally, and that can be easily encapsulated by conventionally known methods. The challenge is to provide.
本発明者は、腸内有効物を液状物質に溶解もし
くは分散させたものを芯部形成物質とし、体温以
上の融点を有する硬化油を壁膜形成物質として用
いてカプセル化する場合、上述した課題を達成し
得る腸溶性カプセルを提供できることの知見を得
て本発明を成すに至つた。 The present inventor has solved the above-mentioned problem when encapsulating an intestinal effective substance dissolved or dispersed in a liquid substance as a core-forming substance and a hardened oil having a melting point higher than body temperature as a wall-forming substance. The present invention was achieved based on the knowledge that it is possible to provide an enteric-coated capsule that can achieve the following.
以下本発明を詳しく説明する。 The present invention will be explained in detail below.
発明の構成
本発明に係る腸溶性カプセルの特徴は、腸内有
効物を液状物質に溶解もしくは分散して成る芯部
と、体温以上の融点を有する硬化油から成る壁膜
から構成されていることにある。Structure of the Invention The enteric-coated capsule according to the present invention is characterized in that it is composed of a core made of an enteric substance dissolved or dispersed in a liquid substance, and a wall made of a hydrogenated oil having a melting point higher than body temperature. It is in.
ここでいう“腸内有効物”とは、腸壁から吸収
されて活性を示す各種の医薬物質及び腸壁から吸
収されずに活性を示す各種医薬物質並びにビフイ
ズス菌のような腸内での活性を示す腸内有効微生
物などを意味する。 The term "intestinal effective substances" as used herein refers to various pharmaceutical substances that are active after being absorbed through the intestinal wall, various pharmaceutical substances that are active without being absorbed through the intestinal wall, and active substances in the intestine such as Bifidobacteria. Intestinal effective microorganisms that show
課題を解決するための手段
本発明は、腸内有効物質を液状物質に溶解もし
くは分散させたものを芯部とするものであつて、
ここで用いる液状物質は常温で液状を呈する物質
であれば何ら制限がなく、例えば水、液状油脂
類、アルコール及びそれらのエマルジヨン等であ
つて、実際にはこれらに溶解または分散させる腸
内有効物の種類に応じて選択するとよい。例え
ば、ビフイズス菌の場合にはグリセリン、中鎖ト
リグリセライド（MCT）並びにコーン油等の該
菌に対して不活性な物質を選択して使用する。Means for Solving the Problems The present invention has a core made of an intestinal effective substance dissolved or dispersed in a liquid substance,
The liquid substance used here is not limited in any way as long as it is liquid at room temperature, such as water, liquid fats and oils, alcohol, and emulsions thereof, and in reality, the intestinal active substance to be dissolved or dispersed in these substances. It is best to choose according to the type. For example, in the case of Bifidobacterium, substances inactive against the Bifidobacterium such as glycerin, medium chain triglyceride (MCT), and corn oil are selected and used.
また、液状物質に溶解もしくは分散させてカプ
セルの芯物質として用いる腸内有効物としては、
胃液や胃液中の酵素によりその生理活性機能が
低下するおそれのある医薬物質、例えばパンクレ
アチン等の酵素、エリスロマイシン等の抗生物
質、ホルモン剤、胃に対して刺激作用を与えた
り、その消化機能を阻害する作用をする物質、例
えばエチオナミド、アテブリン、サリチル酸、タ
ンニン酸、腸内において濃厚に作用させるため
の医薬物質、例えば駆虫剤、腸内防腐剤等、及び
胃酸等により死滅し易い腸内有効微生物、例え
ば、ビフイズス菌等を挙げられる。 In addition, effective intestinal substances that are dissolved or dispersed in liquid substances and used as capsule core materials include:
Pharmaceutical substances that may reduce the physiologically active functions of gastric juices or enzymes in the gastric juices, such as enzymes such as pancreatin, antibiotics such as erythromycin, hormonal drugs, and drugs that irritate the stomach or impair its digestive function. Substances that act to inhibit, such as ethionamide, atebrin, salicylic acid, tannic acid, medicinal substances that act intensively in the intestines, such as anthelmintics, intestinal preservatives, etc., and effective intestinal microorganisms that are easily killed by gastric acid, etc. , for example, Bifidobacterium and the like.
これらの腸内有効物を上記液状物質に溶解もし
くは分散させる割合（濃度）は特に制限的でな
く、液状形態を保持できればよい。 The proportion (concentration) at which these enteric substances are dissolved or dispersed in the liquid substance is not particularly limited, as long as the liquid form can be maintained.
本発明は、腸内有効物を液状形態に保持したも
のを芯部物質とし、一方体温以上の融点を有する
硬化油を壁膜物質として用いてカプセル化を行う
ことにより、目的とする腸溶性カプセルを得る。 The present invention is capable of producing enteric-coated capsules by encapsulating a substance that is effective in the intestines in a liquid form as a core material and using a hardened oil having a melting point higher than body temperature as a wall material. get.
ここで壁膜物質としての硬化油は、体温以上の
融点を有するものであれば何ら制限がなく用いる
ことができ、また必要に応じて乳化剤を加えるこ
とによりカプセルの表面に親水性を付与すること
もできる。 Here, the hardened oil as the wall material can be used without any restrictions as long as it has a melting point above body temperature, and if necessary, an emulsifier can be added to impart hydrophilicity to the surface of the capsule. You can also do it.
次に、本発明に係る腸溶性カプセルの調製法と
しては、液中乾燥法、噴霧乾燥法、噴霧冷却法等
によるカプセル化を例示し得るが、三流体ノズル
方式を用いた噴霧冷却法によるカプセル化によつ
て調製するのが好ましい。この三流体ノズル方式
を用いたカプセル化法は新しく開発された方法
（特開昭62−201635号）であつて、その概要は、
３重同心円筒部を有するノズルの内円筒管から芯
部物質としての液状物質を、中内円筒管から壁膜
物質としての硬化油の溶融物質を及び外円筒管か
ら加圧空気を、それぞれジエスト流として、冷却
気体中に噴霧してカプセル化を行うことから成る
方法であつて、カプセルの粒径を容易にコントロ
ールし得ること及びカプセルの乾燥工程を必要と
しない等の利点を有する。 Next, as a method for preparing enteric-coated capsules according to the present invention, encapsulation by a submerged drying method, a spray drying method, a spray cooling method, etc. can be exemplified. Preferably, it is prepared by chemical reaction. This encapsulation method using a three-fluid nozzle method is a newly developed method (Japanese Patent Application Laid-open No. 62-201635), and its outline is as follows.
A nozzle having three concentric cylindrical parts receives a liquid substance as a core material from the inner cylindrical tube, a molten substance of hardened oil as a wall material from the middle inner cylindrical tube, and pressurized air from the outer cylindrical tube. This method consists of encapsulation by spraying into a cooled gas as a liquid, and has advantages such as being able to easily control the particle size of the capsules and not requiring a step of drying the capsules.
本発明に係るカプセルは、粒径が10〜2000μ
ｍ、好ましくは100〜1000μｍの範囲であり、ま
た、壁膜の厚さは、経口摂取した場合胃の伸縮に
よるカプセルの破壊を防止する目的から粒径に対
して合計で20〜80％、好ましくは50〜70％の範囲
である。 The capsule according to the present invention has a particle size of 10 to 2000μ.
m, preferably in the range of 100 to 1000 μm, and the wall thickness is preferably 20 to 80% in total of the particle size, in order to prevent capsule destruction due to expansion and contraction of the stomach when ingested orally. ranges from 50 to 70%.
以上述べたとおり、本発明に係る腸溶性カプセ
ルは、液状物質中に溶解もしくは分散した腸内有
効物を芯部物質として、体温以上の融点を有する
硬化油を壁膜物質として用いてカプセル化して得
られるものであるから、それを経口摂取した場
合、カプセルの芯部を形成している有効物質は、
固化した状態の硬化油からなる壁膜によつて保護
されていて胃液や胃液中の酵素の作用を受けるこ
となく、腸内に達して始めて腸液中の主として膵
リパーゼの作用による上記壁膜の崩壊により露出
して腸内で有効に利用されるようになる。 As described above, the enteric-coated capsule according to the present invention is encapsulated using an enteric active substance dissolved or dispersed in a liquid substance as a core material and a hardened oil having a melting point higher than body temperature as a wall material. Therefore, when taken orally, the active substance forming the core of the capsule is
It is protected by a wall membrane made of solidified hydrogenated oil and is not affected by the action of gastric juice or enzymes in the gastric juice, and it is not until it reaches the intestine that the wall membrane collapses mainly due to the action of pancreatic lipase in the intestinal fluid. It becomes exposed and effectively utilized in the intestines.
また、本発明の腸溶性カプセルは、その調製に
際して芯部物質としての腸内有効物は液状物質中
に溶解もしくは分散させるだけであつて、その間
に加熱や酵素あるいは水分等の影響をほとんど受
けることがないので、上記硬化油を壁膜物質とし
て用いてのカプセル化を例えば上述したような三
流体ノズル方式を用いた噴霧冷却法で行うと、芯
部物質である腸内有効物に悪影響を与えることな
くカプセル化することが可能となる。 In addition, the enteric-coated capsule of the present invention is prepared by simply dissolving or dispersing the enteric substance as a core substance in a liquid substance, and is hardly affected by heat, enzymes, moisture, etc. during its preparation. Therefore, if encapsulation using the above-mentioned hydrogenated oil as a wall material is carried out by the spray cooling method using the three-fluid nozzle system as described above, it will have an adverse effect on the intestinal effective substances, which are the core substances. It becomes possible to encapsulate without
以下に実施例を示して本発明及びその効果を具
体的に説明する。 EXAMPLES The present invention and its effects will be specifically explained below with reference to Examples.
実施例及び効果
実施例 １
ビフイドバクテリウム・ロンガム
（Bifidbacterium longum）ATCC−15707の生菌
体をコーンサラダ油にその１当り約100ｇの割
合で分散した上記菌の10％コーンサラダ油分散液
を芯部物質として用い、一方融点58℃を有する硬
化パーム油を壁膜物質として用い、前述した三流
体ノズルによる噴霧冷却法に従つて、カプセルを
行つた。得られたカプセルの粒径は平均で150μ
ｍであり、膜厚は40μｍであつた。Examples and Effects Example 1 A 10% dispersion of the above bacteria in corn salad oil was prepared by dispersing live bacteria of Bifidbacterium longum ATCC-15707 in corn salad oil at a rate of about 100 g per portion. Encapsulation was carried out according to the spray cooling method with the three-fluid nozzle described above, using hydrogenated palm oil as the wall material and having a melting point of 58° C. as the wall material. The average particle size of the resulting capsules is 150μ
m, and the film thickness was 40 μm.
上記カプセルを、人工的に調製した胃液（ペプ
シン0.32％を含むBriggs Liver Brothを塩酸で
PH3.0にしたもの）に加え、37℃の恒温槽中で３
時間撹拌しながら、上記胃液と反応させた。反応
後、濾別したカプセルを水で充分に洗浄し、常法
によりビフイズス生菌数を測定した。 The above capsules were mixed with artificially prepared gastric juice (Briggs Liver Broth containing 0.32% pepsin) with hydrochloric acid.
In addition to the PH3.0), in a constant temperature bath at 37℃
The mixture was allowed to react with the gastric juice while stirring for a period of time. After the reaction, the filtered capsules were thoroughly washed with water, and the number of viable Bifidus bacteria was measured by a conventional method.
その結果、上記反応開始時にカプセル１ｇ中の
生菌数が４×108であつたものが反応後生菌数は
３×108となり、胃液による影響が実質上みられ
なかつた。これに対して、対照として上記ビフイ
ズス菌粉末をペプトン水に分散したものを同じく
上記胃液に加えて同様に反応を行つたものでは反
応開始時に菌体粉末１ｇ中の生菌数１×1011であ
つたものが反応後には10以下になりほとんど死滅
に至つた。 As a result, the number of viable bacteria in 1 g of capsules at the start of the reaction was 4 x 10 8 , but after the reaction the number of viable bacteria decreased to 3 x 10 8 , and there was virtually no influence from gastric juice. On the other hand, as a control, the above-mentioned Bifidobacterium powder dispersed in peptone water was added to the above-mentioned gastric juice and the reaction was carried out in the same manner . After the reaction, the temperature dropped to below 10 and almost died.
実施例 ２
アスピリン15ｇを中鎖トリグリセライド
（MCT）100ｇに分散したものを、実施例１と同
様にしてカプセル化を行つた。得られたカプセル
の粒径は平均500μｍであり、膜厚は150μｍであ
つた。Example 2 15 g of aspirin dispersed in 100 g of medium chain triglyceride (MCT) was encapsulated in the same manner as in Example 1. The average particle size of the obtained capsules was 500 μm, and the film thickness was 150 μm.
上記カプセルを、実施例１で用いたと同様の人
工胃液に加え、37℃で３時間反応させた後カプセ
ルを濾別した。得られた濾液中のアスピリン量を
測定したが検出されなかつた。 The above capsules were added to the same artificial gastric juice as used in Example 1, reacted at 37°C for 3 hours, and then the capsules were separated by filtration. The amount of aspirin in the obtained filtrate was measured, but it was not detected.
次に、濾別したカプセルにリパーゼを作用させ
たところ、15分以内に全てのカプセルが崩壊し、
アスピリンもほぼ100％回収された。 Next, when lipase was applied to the filtered capsules, all capsules collapsed within 15 minutes.
Aspirin was also recovered at almost 100%.
Claims (1)
て成る芯部と、体温以上の融点を有する硬化油か
ら成る壁膜から構成されていることを特徴とする
腸溶性カプセル。 ２ 腸内有効物がビフイズス菌である特許請求の
範囲第１項記載の腸溶性カプセル。 ３ 腸内有効物が腸壁より吸収される医薬物質で
ある特許請求の範囲第１項記載の腸溶性カプセ
ル。[Scope of Claims] 1. An enteric-coated capsule characterized by comprising a core made of a substance effective in the intestines dissolved or dispersed in a liquid substance, and a wall made of a hydrogenated oil having a melting point higher than body temperature. . 2. The enteric-coated capsule according to claim 1, wherein the enteric active substance is Bifidobacterium. 3. The enteric-coated capsule according to claim 1, wherein the enteric substance is a medicinal substance that is absorbed through the intestinal wall.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61073678A JPS62230714A (en) | 1986-03-31 | 1986-03-31 | Enteric capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61073678A JPS62230714A (en) | 1986-03-31 | 1986-03-31 | Enteric capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS62230714A JPS62230714A (en) | 1987-10-09 |
| JPH0475888B2 true JPH0475888B2 (en) | 1992-12-02 |
Family
ID=13525123
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61073678A Granted JPS62230714A (en) | 1986-03-31 | 1986-03-31 | Enteric capsule |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS62230714A (en) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6632429B1 (en) | 1999-12-17 | 2003-10-14 | Joan M. Fallon | Methods for treating pervasive development disorders |
| US20070053895A1 (en) | 2000-08-14 | 2007-03-08 | Fallon Joan M | Method of treating and diagnosing parkinsons disease and related dysautonomic disorders |
| US8030002B2 (en) | 2000-11-16 | 2011-10-04 | Curemark Llc | Methods for diagnosing pervasive development disorders, dysautonomia and other neurological conditions |
| FR2863828B1 (en) * | 2003-12-23 | 2007-02-02 | Gervais Danone Sa | LIQUID FOOD PRODUCT COMPRISING PELLETS OF LACTIC ACID BACTERIA |
| US20080058282A1 (en) | 2005-08-30 | 2008-03-06 | Fallon Joan M | Use of lactulose in the treatment of autism |
| US8658163B2 (en) | 2008-03-13 | 2014-02-25 | Curemark Llc | Compositions and use thereof for treating symptoms of preeclampsia |
| US8084025B2 (en) | 2008-04-18 | 2011-12-27 | Curemark Llc | Method for the treatment of the symptoms of drug and alcohol addiction |
| US9320780B2 (en) | 2008-06-26 | 2016-04-26 | Curemark Llc | Methods and compositions for the treatment of symptoms of Williams Syndrome |
| PL2318035T3 (en) | 2008-07-01 | 2019-10-31 | Curemark Llc | Methods and compositions for treating the symptoms of neurological disorders and mental health disorders |
| US10776453B2 (en) | 2008-08-04 | 2020-09-15 | Galenagen, Llc | Systems and methods employing remote data gathering and monitoring for diagnosing, staging, and treatment of Parkinsons disease, movement and neurological disorders, and chronic pain |
| US20100092447A1 (en) | 2008-10-03 | 2010-04-15 | Fallon Joan M | Methods and compositions for the treatment of symptoms of prion diseases |
| JP5684725B2 (en) | 2009-01-06 | 2015-03-18 | キュレロン リミテッド ライアビリティ カンパニー | Compositions and methods for the treatment or prevention of S. aureus infections and compositions and methods for the eradication or reduction of S. aureus on the surface |
| CA2747703C (en) | 2009-01-06 | 2021-06-15 | Curemark Llc | Compositions and methods for the treatment or the prevention of infections by e. coli |
| US9056050B2 (en) | 2009-04-13 | 2015-06-16 | Curemark Llc | Enzyme delivery systems and methods of preparation and use |
| US9511125B2 (en) | 2009-10-21 | 2016-12-06 | Curemark Llc | Methods and compositions for the treatment of influenza |
| DK2701733T3 (en) | 2011-04-21 | 2019-05-27 | Curemark Llc | CONNECTIONS FOR TREATMENT OF NEUROPSYCIATRIC DISORDERS |
| US10350278B2 (en) | 2012-05-30 | 2019-07-16 | Curemark, Llc | Methods of treating Celiac disease |
| WO2018191233A1 (en) | 2017-04-10 | 2018-10-18 | Curemark, Llc | Compositions for treating addiction |
| JP2021114952A (en) * | 2020-01-28 | 2021-08-10 | ナットリオミックス, インコーポレイテッドNutriomix, Inc. | Enteric composition, food/beverage containing enteric composition, method for controlling disintegration time for enteric composition, and method for manufacturing enteric composition |
| US11541009B2 (en) | 2020-09-10 | 2023-01-03 | Curemark, Llc | Methods of prophylaxis of coronavirus infection and treatment of coronaviruses |
-
1986
- 1986-03-31 JP JP61073678A patent/JPS62230714A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS62230714A (en) | 1987-10-09 |
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