JPH11504939A - Bismuth-containing composition for treatment and prevention of gastrointestinal disorders - Google Patents
Bismuth-containing composition for treatment and prevention of gastrointestinal disordersInfo
- Publication number
- JPH11504939A JPH11504939A JP8534217A JP53421796A JPH11504939A JP H11504939 A JPH11504939 A JP H11504939A JP 8534217 A JP8534217 A JP 8534217A JP 53421796 A JP53421796 A JP 53421796A JP H11504939 A JPH11504939 A JP H11504939A
- Authority
- JP
- Japan
- Prior art keywords
- bismuth
- per day
- days
- subject
- group
- 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
- 229910052797 bismuth Inorganic materials 0.000 title claims abstract description 50
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 208000018522 Gastrointestinal disease Diseases 0.000 title claims abstract description 22
- 239000000203 mixture Substances 0.000 title claims description 16
- 238000011282 treatment Methods 0.000 title claims description 7
- 230000002265 prevention Effects 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 29
- 244000000040 protozoan parasite Species 0.000 claims abstract description 14
- 230000001404 mediated effect Effects 0.000 claims abstract description 13
- 208000010643 digestive system disease Diseases 0.000 claims abstract description 9
- 208000018685 gastrointestinal system disease Diseases 0.000 claims abstract description 9
- 241001465754 Metazoa Species 0.000 claims abstract description 6
- ZQUAVILLCXTKTF-UHFFFAOYSA-H bismuth;tripotassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[K+].[K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZQUAVILLCXTKTF-UHFFFAOYSA-H 0.000 claims description 9
- 241000223935 Cryptosporidium Species 0.000 claims description 7
- KKMOSYLWYLMHAL-UHFFFAOYSA-N 2-bromo-6-nitroaniline Chemical compound NC1=C(Br)C=CC=C1[N+]([O-])=O KKMOSYLWYLMHAL-UHFFFAOYSA-N 0.000 claims description 6
- SULICOHAQXOMED-YDXPQRMKSA-H dibismuth;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Bi+3].[Bi+3].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O.[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O.[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O SULICOHAQXOMED-YDXPQRMKSA-H 0.000 claims description 6
- 244000045947 parasite Species 0.000 claims description 6
- 241000567229 Isospora Species 0.000 claims description 5
- 229940104825 bismuth aluminate Drugs 0.000 claims description 5
- PDSAKIXGSONUIX-UHFFFAOYSA-N hexaaluminum;dibismuth;oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Al+3].[Bi+3].[Bi+3] PDSAKIXGSONUIX-UHFFFAOYSA-N 0.000 claims description 5
- LNTHITQWFMADLM-UHFFFAOYSA-N gallic acid Chemical compound OC(=O)C1=CC(O)=C(O)C(O)=C1 LNTHITQWFMADLM-UHFFFAOYSA-N 0.000 claims 4
- 229910000014 Bismuth subcarbonate Inorganic materials 0.000 claims 3
- MGLUJXPJRXTKJM-UHFFFAOYSA-L bismuth subcarbonate Chemical compound O=[Bi]OC(=O)O[Bi]=O MGLUJXPJRXTKJM-UHFFFAOYSA-L 0.000 claims 3
- 229940036358 bismuth subcarbonate Drugs 0.000 claims 3
- 241000277331 Salmonidae Species 0.000 claims 2
- 229960004645 bismuth subcitrate Drugs 0.000 claims 2
- 229940074391 gallic acid Drugs 0.000 claims 2
- 235000004515 gallic acid Nutrition 0.000 claims 2
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 claims 1
- 241000282412 Homo Species 0.000 claims 1
- -1 Sumus Chemical compound 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 206010012735 Diarrhoea Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 150000001621 bismuth Chemical class 0.000 description 4
- 241000223936 Cryptosporidium parvum Species 0.000 description 3
- 241000224431 Entamoeba Species 0.000 description 3
- 208000030852 Parasitic disease Diseases 0.000 description 3
- 206010037075 Protozoal infections Diseases 0.000 description 3
- ZREIPSZUJIFJNP-UHFFFAOYSA-K bismuth subsalicylate Chemical compound C1=CC=C2O[Bi](O)OC(=O)C2=C1 ZREIPSZUJIFJNP-UHFFFAOYSA-K 0.000 description 3
- 229960000782 bismuth subsalicylate Drugs 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 229940101070 pepto-bismol Drugs 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000036281 parasite infection Effects 0.000 description 2
- 230000003071 parasitic effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 241000224482 Apicomplexa Species 0.000 description 1
- 241001235574 Balantidium Species 0.000 description 1
- 241000726108 Blastocystis Species 0.000 description 1
- 241000223782 Ciliophora Species 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000005156 Dehydration Diseases 0.000 description 1
- 241000157305 Dientamoeba Species 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- 241001126836 Enterocytozoon Species 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 241000224466 Giardia Species 0.000 description 1
- 241000224467 Giardia intestinalis Species 0.000 description 1
- 241000243190 Microsporidia Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000019790 abdominal distention Diseases 0.000 description 1
- 201000009840 acute diarrhea Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JAONZGLTYYUPCT-UHFFFAOYSA-K bismuth subgallate Chemical compound OC(=O)C1=CC(O)=C2O[Bi](O)OC2=C1 JAONZGLTYYUPCT-UHFFFAOYSA-K 0.000 description 1
- 229960000199 bismuth subgallate Drugs 0.000 description 1
- 208000024330 bloating Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940085435 giardia lamblia Drugs 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 244000000053 intestinal parasite Species 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000003108 parasitologic effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 208000026775 severe diarrhea Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/245—Bismuth; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
- A61K31/29—Antimony or bismuth compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
(57)【要約】 本発明は、１以上の寄生原生動物に起因した又は仲介された胃腸障害を有するヒト又は下等動物の被験体の予防及び治療方法であって、ビスマスを前記被験体へ投与することを含む方法。 (57) [Summary] The present invention is a method of preventing and treating a human or lower animal subject having a gastrointestinal disorder caused or mediated by one or more protozoan parasites, the method comprising administering bismuth to said subject. .
Description
【発明の詳細な説明】 胃腸障害の治療及び予防用のビスマス含有組成物 技術分野 細菌及びウイルスが世界中で下痢の誘発原因であると長いこと認識されている 一方で、寄生虫は、およそ２０年前になって初めて病因学において考慮された。 これが貧しい開発国の病気であると一般に信じられていたので、寄生原生動物に 関係する下痢の重大性は、合衆国において理解されていない。寄生虫、例えばク リプトスポリディウム(Cryptosporidium)、ガイアルディア(Giardia)及びエンタ モエーバ(Entamoeba)は中でも、合衆国以外では高い罹患率で、また合衆国内部 では増加する頻度で、下痢及び他の胃腸障害に関係している。例えば、合衆国の １４の州での飲料水供給の最近の調査では、研究者らは、１／４がクリプトスポ リディウム・パルヴァム(Cryptosporidium parvum)に汚染されていることを発見 した。Health,July/August 1993 p14。従って、寄生原生動物に関係した下痢及 び他の胃腸障害は、深刻な健康問題を指摘し、効果的な抗寄生虫治療療法に対す る必要性が大きくなり続けている。 本発明によって、ビスマス塩の投与が寄生原生動物に起因した又は仲介された 胃腸障害の予防及び／又は治療に効果的であるかもしれないことが発見された。 従って、本発明の目的は、寄生原生動物に起因した又は仲介された胃腸障害を予 防する及び／又は治療する安全で効果的な方法を提供することである。本発明の 更なる目的は、ビスマスの投与を含むこのような方法を提供することである。 本発明のこれらの及び他の目的は、下記の詳細な説明によりすぐに明らかとな るであろう。 発明の要約 本発明は、１以上の寄生原生動物に起因した又は仲介された胃腸障害を有する ヒト又は下等動物被験体の治療方法に関し、これは、１日当たり約５０ｍｇから 約５０００ｍｇのビスマスを約１から５６日間、該被験体に投与することを含む 。 本発明は、また、１以上の寄生原生動物に起因した又は仲介された胃腸障害の ヒト又は下等動物被験体の予防方法に関し、これは、１日当たり約５０ｍｇから 約５０００ｍｇのビスマスを約１から２８日間、被験体に投与することを含む。 発明の詳細な記載 本発明の方法は、１以上の寄生原生動物に起因した又は仲介された胃腸障害の 予防及び／又は治療を含む。このような胃腸障害は、ビスマスの投与によって予 防及び／又は治療される。本発明の成分は、後でより十分に定義される。胃腸障害 用語「胃腸障害」は、ここで用いられる場合、１以上の寄生原生動物に起因し た又は仲介された体の、通常は上部及び／又は下部の胃腸管の感染、疾患又は他 の障害のいずれをも包含する。このような障害には、１以上の下記の条件が含ま れる：下痢、腹痛及び／又は痙攣、鼓腸、悪心、腹部膨満、発熱、便秘、便中の 血液、粘膜及び／又は膿の存在、嘔吐、胃腸炎、体重減少、食欲不振、倦怠感並 びに、寄生原生動物による感染に一般に関連した他の如何なる状態。 免疫無防備体及び子供では、寄生原生動物に起因した又は仲介された胃腸障害 は、上掲した一般の障害よりも一層深刻であり生命脅威となり得る。従って、用 語「胃腸障害」は、また、免疫無防備体及び子供における原生動物感染に一般的 に関係した如何なる状態をも含み、これには、急性の下痢、脱水、電解質不均衡 、大腸炎及び腸の致命的な壊死が含まれるが、これらに限定されない。寄生原生動物 原生動物は、単数又は複数の核と細胞質とを含む単細胞の原核生物である。原 生動物門の４つの群が、本発明において意図される寄生虫を含む。これらの生物 は、Zinsser Microbiology,第20版、1163-1173(1992)及び T.L.Kuhls,M.D.,“Pr otozoal Infections of the Intestinal Tract in Children”，Advances In Pe diatric Infectious Diseases ,第8巻、177-202（1993）に十分に記述されており 、これらを援用して本文の一部とする。用語「寄生原生動物」とは、ここで用い られる場合、フリヤ サルコマスチゴフォーラ(phlya Sarcomastigophora)、例え ば エンタモエーバ、ガイアルディア、ジエンタモエーバ(Dientamoeba)及びブラス トシスチス(Blastocystis)；クリオフォーラ(Ciliophora)、例えばバランチディ ウム(Balantidium)；アピコムプレクサ(Apicomplexa)、例えばイソスポーラ(Iso spora)及びクリプトスポリディウム；並びにマイクロスポーラ(Microspora)、例 えばエンテロサイトゾーン(Enterocytozoon)の原生動物を指す。好ましい寄生原 生動物は、エンタモエーバ、クリプトスポリディウム、ガイアルディア、イソス ポーラ及びこれらの組み合わせである。最も好ましい寄生原生動物は、エンタモ エーバ、クリプトスポリディウム、ガイアルディア及びこれらの組み合わせであ る。 寄生原生動物に起因した又は仲介された胃腸障害の診断は、医療団体で一般に 用いられる如何なる方法によっても成し遂げられ得る。このような方法は、上記 で参照した Zinsser Microbiology 及び T.L.Kuhls,M.D.“Protozoal Infection s of the Intestinal Tract in Children”に十分に記述されている。ビスマス 本発明の治療方法及び／又は予防方法は、ビスマスの投与に関係している。こ こで用いられる場合、ビスマスの量は、ビスマスの元素の重量による。 ビスマス投与の好ましい期間は、治療すべき特定の胃腸障害及び治療される被 験体の身体の状態によって変更し得る。一般に、治療方法としては、ビスマスは 、１日当たり約５０ｍｇから約５０００ｍｇ、好ましくは約５０ｍｇから約２５ ００ｍｇの量で、約１から約５６日間、好ましくは約２から約２８日間、最も好 ましくは約７から約２１日間投与され得る。 一般に、予防方法としては、ビスマスは、１日当たり約５０ｍｇから約５００ ０ｍｇ、好ましくは約５０から約２５００ｍｇの量で、約１から約２１日間、好 ましくは約１から約１４日間投与され得る。予防方法では、ビスマスは、寄生原 生動物に対する潜在的な暴露の前に投与され得る。ビスマスのこのような投与は 、寄生原虫動物の暴露の見込み及び被験体の状態に依存して変更してもよく、医 療団体によって利益があると期待されるいずれかのときに開始され得、これには 、潜在的な暴露の約１から約７日、約２から約５日、及び約３から約４日前が含 まれる。 本発明の方法では、ビスマスは、医薬的に許容可能な塩の形態としてもよく、 又は活性配合物としてビスマスを含む有機複合体の形態としてもよい。このよう な有機複合体には、２，２’−スピロビ［１，３，２−ベンゾドクサビスモール ］(2,2'-spirobi[1,3,2-benzodoxabismole])が含まれる。好ましくは、ビスマス は、本発明において医薬的に許容可能な塩として投与される。このようなビスマ ス塩には、アルミン酸ビスマス、次炭酸ビスマス、次クエン酸ビスマス、クエン 酸ビスマス、トリカリウムジシトラトビスマセート、次没食子酸ビスマス、次シ ョウ酸ビスマス、酒石酸ビスマス、次サリチル酸ビスマス、及びこれらの混合物 が含まれる。クエン酸ビスマス、次クエン酸ビスマス、トリカリウムジシトラト ビスマセート、酒石酸ビスマス、次サリチル酸ビスマス及びこれらの混合物が、 本発明に使用される好ましいビスマス塩である。 ここで有用なビスマスは、単独で又はビスマス含有組成物中の他の医薬的に許 容可能な成分との組み合わせで投与され得る。ビスマス塩を含有する種々のこの ような組成物は、市販されている。 このような組成物には、トリカリウムジシトラトビスマセートを含有するDe N ol(Brocadesから)；アルミン酸ビスマスを含有する Bislumina（Mazuelosから） ；次ショウ酸ビスマスを含有する Roter(Roterpharmaから)；次没食子酸ビスマ スを含有する Devrom(商品名)(The Pharthenon Co.,Inc.から)；及び、次サリチ ル酸ビスマスを含有する Pepto-Bismol(商品名)(The Procter & Gamble Company から)が含まれる。 ここで用いられる場合、用語「投与」とは、安全な医学的方法において本発明 に用いられる成分又は組成物を、治療されるべき被験体へ、胃腸障害の治療に効 果的となるような方法で配送（デリバリー）する如何なる方法をも指す。好まし くは、ビスマスは経口投与される。 下記の非限定実施例は、本発明の方法及び使用を説明する。 実施例１ 深刻な下痢を患っているある被験者を、本発明の方法によって治療する。便試 料を被験者から採取して、生物体、卵、嚢、胞子小体などを含む腸内寄生虫の存 在について解析する。臨床寄生虫学の標本は、クリプトスポリディウム・パルヴ ァムの存在を示す。それから被験者を、“Pepto-Bismol(商品名)”の名称で The Proctor & Gamble Companyから販売されている次サリチル酸ビスマスを含む組 成物を投与することによって治療する。この組成物は液状であり、これを１日当 たり約２５００ｍｇのビスマスを配送するために、等量で１日に４回２１日間投 与する。その後、この被験者からの便試料を再度解析し、その結果、寄生虫感染 の痕跡は見つからない。被験者は、無症状を保持し、５カ月後に実施された他の 便解析は正常である。 上記実施例において、トリカリウムジシトラトビスマセート、酒石酸ビスマス 、クエン酸ビスマス及び次ショウ酸ビスマスは、それぞれ次サリチル酸ビスマス と置換され、実質的に同様の結果となる。 実施例II 糖尿病であり託児所にいる３歳の子供は、慢性下痢と腹部膨満を患っている。 便標本の解析は、ガイアルディア・ラムブリア(Giardia lamblia)の存在を示す 。感染が診断され、次ショウ酸ビスマスの形態のビスマス(Brocadesから販売さ れている“DeNol”)約４００ｍｇを、毎日等量で４回２８日間経口投与すること により治療を行う。その後、被験者からの便試料を再度解析し、その結果、寄生 虫感染の痕跡は見つからない。 実施例III 標準以下の衛生設備及び水浄化システムを備えた開発国へ旅行する準備をして いる平和部隊のボランティアに対し、ガイアルディア・ラムブリア、クリプトス ポリディウム・パルヴァム及びエンタモエーバ・ヒストリティカ(Entamoeba his tolytica)の存在について便試料の臨床的解析を行う。臨床結果は、寄生虫の証 拠を示さない。被験者は約１２００ｍｇのビスマス(The Proctor & Ganble Comp anyから販売されている組成物 Pepto-bismol（商品名）における次サリチル酸ビ スマスとして投与)を毎日等量で４回、約２１日間与える。最初の臨床解析から 約３０日後の合衆国に帰国する際、被験者は無症状を保持している。被験者から の便試料を解析し、その結果、寄生虫感染の証拠は見られない。DETAILED DESCRIPTION OF THE INVENTION While the bismuth-containing compositions for the treatment and prevention of gastrointestinal disorders art bacteria and viruses have been recognized that long and is induced causes of diarrhea worldwide, parasites, approximately 20 Only years ago was it considered in etiology. The significance of diarrhea associated with protozoan parasites is not understood in the United States, as it was generally believed that this was a disease in poor developing countries. Parasites, such as Cryptosporidium, Giardia, and Entamoeba, among others, are associated with diarrhea and other gastrointestinal disorders, with high prevalence outside the United States and with increasing frequency in the United States. doing. For example, in a recent survey of drinking water supplies in 14 states in the United States, researchers found that one quarter was contaminated with Cryptosporidium parvum. Health , July / August 1993 p14. Thus, diarrhea and other gastrointestinal disorders associated with protozoan parasites point to serious health problems and the need for effective antiparasitic treatments continues to grow. In accordance with the present invention, it has been discovered that the administration of bismuth salts may be effective in preventing and / or treating gastrointestinal disorders caused or mediated by protozoan parasites. Accordingly, it is an object of the present invention to provide a safe and effective method of preventing and / or treating gastrointestinal disorders caused or mediated by protozoan parasites. It is a further object of the present invention to provide such a method which involves the administration of bismuth. These and other objects of the present invention will become more readily apparent from the following detailed description. SUMMARY OF THE INVENTION The present invention relates to a method of treating a human or lower animal subject having a gastrointestinal disorder resulting from or mediated by one or more protozoan parasites, comprising administering about 50 mg to about 5000 mg of bismuth per day. Administering to said subject for 1 to 56 days. The present invention also relates to a method of preventing a human or lower animal subject of gastrointestinal disorders resulting from or mediated by one or more protozoan protozoa, comprising from about 50 mg to about 5000 mg of bismuth per day to about 1 to about 5000 mg of bismuth. For 28 days. DETAILED DESCRIPTION OF THE INVENTION The methods of the present invention include the prevention and / or treatment of gastrointestinal disorders caused or mediated by one or more protozoa. Such gastrointestinal disorders are prevented and / or treated by the administration of bismuth. The components of the present invention are more fully defined later. Gastrointestinal disorder The term "gastrointestinal disorder" as used herein refers to the infection, disease or other disorder of the body, usually in the upper and / or lower gastrointestinal tract, caused or mediated by one or more protozoa. Both are included. Such disorders include one or more of the following conditions: diarrhea, abdominal pain and / or cramps, flatulence, nausea, bloating, fever, constipation, presence of blood, mucous and / or pus in stool, vomiting , Gastroenteritis, weight loss, anorexia, malaise, and any other condition commonly associated with infection by protozoan parasites. In immunocompromised and children, gastrointestinal disorders resulting from or mediated by protozoan parasites can be more severe and life threatening than the general disorders listed above. Thus, the term "gastrointestinal disorder" also includes immunocompromised and any condition commonly associated with protozoal infections in children, including acute diarrhea, dehydration, electrolyte imbalance, colitis and intestinal disorders. But not limited to, catastrophic necrosis. Parasitoids Protozoa are unicellular prokaryotes that contain one or more nuclei and cytoplasm. Four groups of Protozoa include the parasites contemplated in the present invention. These organisms are described in Zinsser Microbiology , 20th edition, 1163-1173 (1992) and TLKuhls, MD, "Protozoal Infections of the Intestinal Tract in Children", Advances In Pediatric Infectious Diseases , Vol. 8, 177-202 ( 1993), which are incorporated herein by reference. The term `` parasitic protozoa '' as used herein refers to Phrya Sarcomastigophora, such as Entamoeba, Gaialdia, Dientamoeba and Blastocystis; Ciliophora, e.g. Balantidium; refers to the protozoa of Apicomplexa, such as Isospora and Cryptosporidium; and Microspora, such as the enterocyte zone (Enterocytozoon). Preferred parasitic protozoa are entamoeva, cryptosporidium, gaialdia, isospora, and combinations thereof. The most preferred parasite protozoa are entamoeva, cryptosporidium, gaialdia and combinations thereof. Diagnosis of gastrointestinal disorders caused or mediated by protozoan parasites can be accomplished by any of the methods commonly used by medical organizations. Such methods are fully described in Zinsser Microbiology , referenced above, and in TLKuhls, MD, "Protozoal Infections of the Intestinal Tract in Children." Bismuth The therapeutic and / or prophylactic methods of the invention involve the administration of bismuth. As used herein, the amount of bismuth is by weight of the element of bismuth. The preferred duration of bismuth administration may vary depending on the particular gastrointestinal disorder to be treated and the physical condition of the subject being treated. Generally, for treatment, bismuth will be present in an amount of about 50 mg to about 5000 mg, preferably about 50 mg to about 2500 mg per day, for about 1 to about 56 days, preferably for about 2 to about 28 days, most preferably for about 2 to about 28 days. It can be administered for 7 to about 21 days. Generally, as a prophylactic method, bismuth may be administered in an amount of about 50 mg to about 5000 mg, preferably about 50 to about 2500 mg per day, for about 1 to about 21 days, preferably about 1 to about 14 days. In a prophylactic method, bismuth may be administered prior to potential exposure to the protozoan parasite. Such administration of bismuth may vary depending on the likelihood of exposure of the protozoan and the condition of the subject, and may be initiated at any time expected to be beneficial by the medical community, Includes about 1 to about 7 days, about 2 to about 5 days, and about 3 to about 4 days before potential exposure. In the method of the present invention, the bismuth may be in the form of a pharmaceutically acceptable salt, or in the form of an organic complex containing bismuth as an active formulation. Such an organic complex includes 2,2′-spirobi [1,3,2-benzodoxabismole] (2,2′-spirobi [1,3,2-benzodoxabismole]). Preferably, bismuth is administered in the present invention as a pharmaceutically acceptable salt. Such bismuth salts include bismuth aluminate, bismuth hypocarbonate, bismuth hypocitrate, bismuth citrate, tripotassium dicitrate bismuthate, bismuth hypogallate, bismuth hypooxalate, bismuth tartrate, bismuth hyposalicylate, And mixtures thereof. Bismuth citrate, bismuth hypocitrate, tripotassium dicitrate bismuthate, bismuth tartrate, bismuth hyposalicylate and mixtures thereof are preferred bismuth salts for use in the present invention. The bismuths useful herein can be administered alone or in combination with other pharmaceutically acceptable ingredients in a bismuth-containing composition. Various such compositions containing bismuth salts are commercially available. Such compositions include De Nol containing tripotassium dicitrate bismuthate (from Brocades); Bislumina containing bismuth aluminate (from Mazuelos); Roter containing bismuth suboxalate (from Roterpharma) Devrom (trade name) containing bismuth subgallate (from The Pharthenon Co., Inc.); and Pepto-Bismol (trade name) containing bismuth subsalicylate (from The Procter & Gamble Company) . As used herein, the term "administering" refers to a method of administering a component or composition used in the present invention in a safe medical manner to a subject to be treated in a manner that is effective in treating gastrointestinal disorders. Means any delivery method. Preferably, bismuth is administered orally. The following non-limiting examples illustrate the methods and uses of the present invention. Example 1 A subject suffering from severe diarrhea is treated by the method of the present invention. A stool sample is collected from the subject and analyzed for the presence of intestinal parasites including organisms, eggs, sac, spore bodies, and the like. Clinical parasitological specimens indicate the presence of Cryptosporidium parvum. The subject is then treated by administering a composition comprising bismuth subsalicylate sold by The Proctor & Gamble Company under the name “Pepto-Bismol®”. The composition is liquid and is administered in equal amounts four times a day for 21 days to deliver about 2500 mg of bismuth per day. The stool sample from this subject was then re-analyzed and no evidence of parasite infection was found. Subjects remained asymptomatic and other stool analyzes performed after 5 months are normal. In the above example, tripotassium dicitrate bismuthate, bismuth tartrate, bismuth citrate and bismuth hypooxalate are each replaced by bismuth hyposalicylate with substantially similar results. Example II A 3-year-old child who is diabetic and in a nursery suffers from chronic diarrhea and abdominal distention. Analysis of stool specimens indicates the presence of Giardia lamblia. The infection is diagnosed and the treatment is performed by oral administration of approximately 400 mg of bismuth in the form of bismuth hypooxalate ("DeNol", sold by Brocades) in equal doses four times daily for 28 days. Thereafter, the stool sample from the subject was analyzed again, and as a result, no evidence of parasite infection was found. EXAMPLE III Peace Corps volunteers preparing to travel to a developing country with substandard sanitation and water purification systems were given to Gaialdia Lambria, Cryptosporidium parvum and Entamoeba historica. Clinical analysis of stool samples for the presence of his tolytica) is performed. Clinical results show no evidence of parasites. Subjects receive approximately 1200 mg of bismuth (administered as bismuth subsalicylate in the composition Pepto-bismol (trade name) sold by The Proctor & Ganble Company) in four equal doses daily for about 21 days. Upon returning to the United States approximately 30 days after the initial clinical analysis, the subject remains asymptomatic. Analysis of stool samples from subjects showed no evidence of parasitic infection.
Claims (1)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US43785595A | 1995-05-09 | 1995-05-09 | |
| US08/437,855 | 1995-05-09 | ||
| PCT/US1996/006488 WO1996035435A1 (en) | 1995-05-09 | 1996-05-08 | Compositions containing bismuth, for the treatment and prevention of gastrointestinal disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH11504939A true JPH11504939A (en) | 1999-05-11 |
Family
ID=23738205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8534217A Pending JPH11504939A (en) | 1995-05-09 | 1996-05-08 | Bismuth-containing composition for treatment and prevention of gastrointestinal disorders |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0830134A1 (en) |
| JP (1) | JPH11504939A (en) |
| AU (1) | AU5733596A (en) |
| CA (1) | CA2219771A1 (en) |
| WO (1) | WO1996035435A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU775500B2 (en) | 1999-05-27 | 2004-08-05 | Euro-Celtique S.A. | Preparations for the application of anti-infective and/or anti-inflammatory agents |
| US7300667B1 (en) | 1999-05-27 | 2007-11-27 | Euro-Celtique, S.A. | Preparations for the application of anti-inflammatory, especially antiseptic agents and/or agents promoting the healing of wounds, to the lower respiratory tract |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR119F (en) * | 1963-10-26 | |||
| US4514421A (en) * | 1979-08-30 | 1985-04-30 | Herschler R J | Dietary and pharmaceutical uses of methylsulfonylmethane and compositions comprising it |
| US4940695A (en) * | 1987-12-10 | 1990-07-10 | The Procter & Gamble Company | Bismuth-containing pharmaceutical compositions |
-
1996
- 1996-05-08 EP EP96915593A patent/EP0830134A1/en not_active Withdrawn
- 1996-05-08 AU AU57335/96A patent/AU5733596A/en not_active Abandoned
- 1996-05-08 JP JP8534217A patent/JPH11504939A/en active Pending
- 1996-05-08 WO PCT/US1996/006488 patent/WO1996035435A1/en not_active Application Discontinuation
- 1996-05-08 CA CA002219771A patent/CA2219771A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO1996035435A1 (en) | 1996-11-14 |
| AU5733596A (en) | 1996-11-29 |
| CA2219771A1 (en) | 1996-11-14 |
| EP0830134A1 (en) | 1998-03-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Loeb et al. | Activity of a new antimalarial agent, chloroquine (SN 7618): Statement approved by the Board for coordination of malarial studies | |
| Burke | The clinical and laboratory diagnosis of giardiasis | |
| US5601848A (en) | Methods for the treatment of gastrointestinal disorders | |
| JPH01500356A (en) | drug therapy | |
| JPH0794390B2 (en) | Pharmaceutical composition for the treatment of gastrointestinal disorders | |
| US5559152A (en) | Pharmaceutical composition having antiacoholic activity | |
| Thomson | LECTURES ON MEDICAL JURISPRUDENCE, NOW IN COURSE OF DELIVERY, AT THE UNIVERSITY OF LONDON. | |
| Young et al. | The comparative efficacy of bephenium hydroxynaphthoate and tetrachloroethylene against hookworm and other parasites of man | |
| JPH11504939A (en) | Bismuth-containing composition for treatment and prevention of gastrointestinal disorders | |
| Markham et al. | Peritoneal dialysis in quinine sulfate intoxication | |
| US4608258A (en) | Medicament for treatment of diarrhea | |
| Taylor et al. | Targeted chemotherapy for parasite infestations in rural black preschool children | |
| Shinkawa et al. | Depressive state and common cold | |
| JPH11504940A (en) | Bismuth and one or more antimicrobial-containing compositions for the treatment and prevention of gastrointestinal disorders | |
| Khayyal et al. | The use of penicillamine as an adjuvant to tartar emetic in the treatment of experimental schistosomiasis | |
| WOODS et al. | Cutaneous porphyria with porphobilinogenuria: A review and report of a case treated by chelation | |
| Botero et al. | Clinical evaluation of a new drug for the treatment of ancylostomiasis | |
| TW421595B (en) | A pharmaceutical composition for use in prevention and treatment of a gastrointestinal disorder | |
| Muhleisen et al. | Therapy of strongyloidiasis with dithiazanine. | |
| CA1214993A (en) | Means for medicinal treatment and metaphylaxis of urate and mixed urate lithiase | |
| Ekabote | Pharmaceutico-Analytical and Antimicrobial Study of Bhagottar Gutika | |
| RU2009664C1 (en) | Method of bacterial infections treatment | |
| Rice | Mass treatment for hookworm infection on tea estates in Assam | |
| McFarland et al. | Tropical malaria in Hungary | |
| Young | Fever and Chills |