JPH01503537A - Orally administrable therapeutic composition for reducing the effects of beta-lactamines - Google Patents
Orally administrable therapeutic composition for reducing the effects of beta-lactaminesInfo
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Abstract
(57)【要約】本公報は電子出願前の出願データであるため要約のデータは記録されません。 (57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】 β−ラクタミン類の効果を減少させる ための、経口投与可能な治療用組成物 不発明は腸内菌相（１ｎｔｅｓｔｉｎａｌ ｆｌｏｒａ ） に対するβ−ラク タミン類（β−１ａｃｔａｍｉｎｅｓ ） の好ましくない作用を減少させるだ めの、経口投与可能々治療用組成物に関する。特に本発明はヒトに対して非病原 性である、選択された細Ｍを含有する組成物に関する。[Detailed description of the invention] Reduces the effects of beta-lactamines Orally administrable therapeutic composition for Non-invention is β-lactam against intestinal flora. It reduces the undesirable effects of tamins (β-1actamines). The present invention relates to an orally administrable therapeutic composition. In particular, the present invention is non-pathogenic to humans. The present invention relates to a composition containing selected microorganisms which have a specific property.
担汁路（ｂｉｌｉａｒｙ ｒｏｕｔｅ ）によって冥質的に除去されるβ−ラク タミンが使用された場合、広範囲のβ−ラクタミンに：る処置を行う間に、正常 な微生物相（ｍ１ｃｒｏｂｉａｌ ｆｌｏｒａ ） 、％に、腸内薗相に重大な 異変（ｍｏｄｉｆｉｃａｔｉｏｎ ） が出現することは周知である。β-lacquer removed subtly by the biliary route When tamins are used, normal microbial flora (m1crobial flora), which is important for the intestinal flora. It is well known that modifications occur.
この異変は、特に、腸内菌相Ｏ主体をなす個体群（ｐｏｐｕｌａｔｉｏｎ ） であシかつその存在によシ、通常、腸内細菌（ｅｎｔｅｒｏｂａｃｔｅｒｉａ ）、 プソイドモナス（ｐｓｅｕｄｏｍｏｎａｓ ）、ブドウ球菌（５ｔａｐｈ ｙｌｏｃｏｃｃｕｓ ） ％酵母菌のごとき潜在的に病原体である微先物の侵入 （ｉｍｐｌａｎｔａｔｉｏｎ ） と増殖（ｄｅｖｅｌｏｐｒｎｅｎｔ ） が 阻止される偏性嫌気性ｌｆＢ菌（５ｔｒｉｃｔｌｙ ａｎａｅｒｏｂｉｃ ｂａ ｃｔｅｒｉａ ）に関係がある。従って、上記の主体となっている腸内菌相の少 なくとも一部が破壊されることによシ、感染性の微生物が増殖するという好まし くない結果を生ずるが、こＯことはある８ｉの患者には極めて危険である。This abnormality is particularly observed in the population consisting mainly of intestinal microbiota O. Due to its presence, enterobacteria ), pseudomonas, staphylococcus (5taph ylococcus)% Invasion of microorganisms that are potentially pathogenic, such as yeast (implantation) and proliferation (developrnent) 5 strictly anaerobic lfB bacteria cteria). Therefore, the intestinal flora, which is the main cause of the above, is If at least a portion of the virus is destroyed, infectious microorganisms will likely grow. However, this can be extremely dangerous for some 8i patients.
種々の細菌又は酵母菌を同時に経口投与することがすでに提案されている：しか しながら、この方法は腸内に通常存在する菌相（ｆｌｏｒａ ）であってかつ抗 生物質による処ｔＧｃよって破項された微生物群と置換するために行われてｂる に過ぎない。The simultaneous oral administration of various bacteria or yeasts has already been proposed: However, this method uses flora that normally exists in the intestines and Treatment with biological substances is carried out to replace the microbial population destroyed by Gc. It's nothing more than that.
本発明は腸内薗相と置換するためＯものではなく、自然に発生する腸内菌相Ｏ破 壊を防止するための細菌を含有する新規な組成物を提供することを目的とする。Since the present invention replaces the intestinal flora, it is not an O type, but a naturally occurring intestinal bacterial flora. The purpose of the present invention is to provide a novel composition containing bacteria for preventing bacterial damage.
従って不発明によれば、β−ラクタアーゼを産生すｂことができるかつヒト（２ ）ＦＪｋ内国相に対するβ−ラクタミン■好ましく力い作用を減少させることの できる、以下に示すごとき偏性嫌気性紅菌を含有する経口投与可能な治療用組成 物が提供される： バクテロイデス メチシリン （Ｂａｃｔｅｒｏｉｄｅｓ ｆｒａｇｉｌｉｓ）バクテロイデス メラニノグニ クス （Ｂａｃｔｅｒｏｉｄｅｓ ｍｅｌａｎｉｎｏｇｅｎｉｃｕｓ）バクテロイデス インテルメデイウス （Ｂａｃｔｅｒｏｉｄｅｓ ｉｎｔｅｒｍｅｄｉｕｓ）バクテロイデス ノン７ ラギリス （Ｂａｃｔｅｒｏｉｄｅｓ ｎｏｎｆｒａｇｉｌｉｓ）バクテロイデス アサツ カロリテイクス（Ｂａｃｔｅｒｏｉｄｅｓ ａｓａｃｃｈａｒｏｌｙｔｉｃｕｓ ）ハ／テロイデス ビビウス （Ｂａｃｔｅｒｏｉｄｅｓ ｂｉｖｉｕｓ）バクテロイデス ディ７ェンス （Ｂａｃｔｅｒｏｉｄｅｓ ｄｉｓｉｅｎｓ）バクテロイデス オラリス （Ｂａｃｔｅｒｏｉｄｅｓ ｏｒａｌｉｓ）バクテロイデス ルミニ；う （Ｂａｃｔｅｒｏｉｄｅｓ ｒｕｍｉｎｉｃｏｌａ）バクテロイデス カヒロス ス （Ｂａｃｔｅｒｏｉｄｅｓ ｃａｐｉｌｌｏｓｕｓ）バクテロイデス ユニフォ ルミス （Ｂａｃｔｅｒｏｉｄｅｓ ｕｎｉｆｏｒｍｉｓ）クロストリジウム プチリク ム （Ｃｌｏｓｔｒｉｄｉｕｍ ｂｕｔｙｒｉｃｕｍ）フンバクテリウム ヌクレア タム （Ｆｕｓｏｂａｃｔｅｒｉｕｍ ｎｕｃｌｅａｔｕｍ）（上記ＯｇＷ ｌ： Ｎ ｏｒｄ Ｃ，Ｅ、 １９Ｂ６ Ｒｅｖ、 Ｉｎｆｅｃｔ Ｄｉｓ、 ８−５ ５ ４３、５４８に記載されている）これらＯ細菌は健康なヒトの個体群の一部の腸 内菌相中に存在しかつこれらの細菌が失われた被検体（ヒト）の胎内に導入した 場合に何ら毒性を示すことがない。Therefore, according to the invention, it is possible to produce β-lactase and human (2 ) β-lactamine on FJk domestic phase An orally administrable therapeutic composition containing obligate anaerobic fungi as shown below. Items provided: Bacteroides methicillin (Bacteroides fragilis) Bacteroides melaninogni Kusu (Bacteroides melaninogenicus) Intermedius (Bacteroides intermedius) Bacteroides non 7 Lagiris (Bacteroides nonfragilis) Bacteroides asaccharolyticus )Ha/Theroides Bibius (Bacteroides bivius) (Bacteroides disiens) Bacteroides oralis (Bacteroides oralis) Bacteroides lumini; (Bacteroides ruminicola) Bacteroides kahilos vinegar (Bacteroides capillosus) Bacteroides Unifo Lumis (Bacteroides uniformis) Clostridium petilik Mu (Clostridium butyricum) Humbacterium nuclea Tam (Fusobacterium nucleatum) (OgW l:N ord C, E, 19B6 Rev, Infect Dis, 8-5 5 43, 548) These O bacteria are found in the intestines of some healthy human populations. introduced into the womb of a subject (human) that is present in the endophytic flora and these bacteria have been lost. It does not show any toxicity in some cases.
不発明によれば、こＯ治療用組成物はβ−２クタミンに二る通常の処ｔ′５ｒ行 う数時間前又はこの処ｔを行うのと同時に８口投与される。こ０投与はβ−ラク タミンに２る処置を行う間、反復して行い得る。According to the invention, this O therapeutic composition can be used in a conventional manner as compared to β-2-cutamine. Eight doses are administered several hours before or at the same time as this treatment. 0 administration is β-lac It may be repeated during the second treatment with Tamin.
こＯ治療用組成物は、特に、下記Ｏごときβ−ラクタミンに：る処置と同時に使 用すべきであるニーペニシリン類 すなわち、ペニシリンＧ及び７ニノキシメテルはニジリン、メチシリン及びイン キサゾリルベニシ’）７Ｃ例、ｔはオキサシリン及びクロキサシリン）、アミノ ズニシリン（例えばアンピシリン及びアモキシリン）、アミジノにニジリン（例 えばビプメシリナム）、カルボキシはニジリン（例えばカルベニシリン、テカル クリン）、メトキシカルボキシペニシリン（例えばテモシリン）、アシルウレイ ドにニジリン（例えばメズ；シリン、アモキシリン、ピ５ラシリン）、アシルに ニジリン（例えばアモキシリン）。This O treatment composition is particularly suitable for use concurrently with β-lactamine-based treatments such as O, as described below. Nipenicillins that should be used That is, penicillin G and 7-ninoxy methane are 7C examples, t is oxacillin and cloxacillin), amino Zunicillin (e.g. ampicillin and amoxicillin), amidino and nigiline (e.g. (e.g. bipmecillinum), carboxy is nigiline (e.g. carbenicillin, tecal). clin), methoxycarboxypenicillin (e.g. temocillin), acylurei Nigilin (e.g. mes; sirin, amoxicillin, pi5racillin), acyl Nigilin (e.g. amoxicillin).
一セファロスポリン類 例えばセファロテン、セファゾリン、セファマンドール、セフ０キシム、セフ０ キシム、セフ０キシム、セフタジジム、セ７トリアクノン。-Cephalosporins For example, cephalotene, cefazolin, cefamandole, cef0xime, cef0 Xime, cef0xime, ceftazidime, cef7triacnone.
−モノバクタム煩（アゼチジン環を有するもの）、例えばアズトセナム。- Monobactams (those with an azetidine ring), such as aztocenam.
本発明に従って使用される偏性嫌気性細菌菌株は例えばバクテロイド属に属する β−ラクタマーゼ産産性性菌株下記のごとき試験管内試験を使用し得る。この試 験においてはβ−ラクタマーゼ活性を有すると考えられる溶液と接触させつめで β−ラクタミンの残存量を測定する（ Ｒｏｌｆｅ ＲＤ及びＣｏ１１． Ｊ、 Ｉｎｆｅｃｔ Ｄｉｓ、 １４７．２２７． ｔ９ｓｓ参照）。The obligate anaerobic bacterial strains used according to the invention belong to the genus Bacteroides, for example. β-Lactamase-Producing Strains In vitro tests such as those described below may be used. this test In experiments, it is recommended that the product be brought into contact with a solution thought to have β-lactamase activity. Measuring the residual amount of β-lactamine (Rolfe RD and Co11. J, Infect Dis, 147.227. (See t9ss).
この試験の後、少なくとも０．０２μｍｏｌ のセファロリジン（ｃｅｐｈａＪ ｏｒｉｄｉｎ ）／分／蛋白質１．９Ｃ，酵素活性を示す菌株が選択される。After this test, at least 0.02 μmol of cephaloridine (cephaJ (oridin)/min/1.9 C of protein, a strain exhibiting enzyme activity is selected.
β−−ラクタマーゼ生性菌株はヒトの便から単離し得る。β-lactamase producing strains can be isolated from human stool.
β−−ラクタマーゼ産生する偏性嫌気性でかつ非病原性の菌株は投与前に、経口 的に吸収され得る担体にその場で添力するために凍結乾燥した形で提供し得る。An obligately anaerobic and non-pathogenic strain that produces β-lactamase should be administered orally before administration. It may be provided in lyophilized form for in situ loading onto a carrier that can be absorbed.
この菌株は、また、必要ならば逼に）な担体と混合されたゼラチンカプセル、錠 剤等の形でらシ得る。胃中でのバクテリアの破壊を防止するためには、上記製剤 は耐酸性担体及び／又は腸溶皮を含有し得る。This strain can also be used in gelatin capsules, tablets mixed with a tough carrier (if necessary). Recipes are available in the form of medicines, etc. To prevent the destruction of bacteria in the stomach, the above preparations may contain an acid-resistant carrier and/or an enteric coating.
ヒトの場合、通常の経口にニジ投与する投与薬剤は約１０８〜１ｏ” 個の生存 バクテリア細胞を含有し得る。In humans, drugs administered orally usually have a survival rate of approximately 108 to 10". May contain bacterial cells.
本発明によれば、治療用組成物の活性はセフ） ＩＪアクンンで処理された多宿 主性（ｈｅｔｅｒｏｘｅｎｉｃ ）マウスについて示される。β−ラクタマーゼ 産生性嫌気性細Ｍを予めヒトの便試料から採取し、このａ菌から生じた培養株（ ｃｕｅｔｕｒｅ ）を投与に使用する。この実験を以下で詳述する： １、 β−２クタマ−ゼ産生性偏性嫌気性細菌株の採取健康な被検者の便を厳密 に嫌気性の条件下で単離した。According to the present invention, the activity of the therapeutic composition is determined by Shown for heteroxenic mice. β-lactamase Productive anaerobic bacteria M were collected in advance from human stool samples, and the cultured strain ( cueture) is used for administration. This experiment is detailed below: 1. Collection of β-2 catamase-producing obligate anaerobic bacterial strains. Strictly collect stool from healthy subjects. isolated under anaerobic conditions.
各々の被検者にお込て主要なりローン（（ｌｏｎｅ ）を同定しかつ単離された 菌株のβ−ラクタマーゼ活性を試験管内で測定した。The primary loan in each subject was identified and isolated. The β-lactamase activity of the strain was measured in vitro.
β−ラクタマーゼｕ Ｒｏｌｆｅ ＲＤ 等によシ報告されている早足量的微生 物学的方法（Ｊ、 Ｉｎｆｅｃｔ Ｄｉｓ、 １４７．２２７゜１９８３ ） にニジ検呂した。活性番−〇＋〜４＋の任意的な尺度で評価する。最大β−ラク タマーゼ活性は４＋で示される。３＋、２＋、１＋で示される中間の活性は抗生 物質の部分的加水分解か生じたことに対応する。０＋の場合はβ−ラクタマーゼ 活性がないものと考えられる。β-Lactamase u Fast mass microorganisms reported by Rolfe RD et al. Physical methods (J, Infect Dis, 147.227゜1983) I checked it out. Evaluation is made using an arbitrary scale of activity number -〇+ to 4+. Maximum β-Easy Tamase activity is indicated by 4+. Intermediate activity indicated by 3+, 2+, and 1+ is antibiotic. Corresponds to partial hydrolysis of the substance. If 0+, β-lactamase It is considered inactive.
この試旅ではグロース メジウム（Ｇｅ１ｏｓｅ Ｍｅｄｉｕｍ ） ５（Ｄｉ ｆｃｏ ）及びＢ、スプテリス（Ｂ、 ５ｕｂｔｉｌｉｓ ） ＡＴＣＣ６６３ ３対照菌株を使用した。On this test trip, we used Growth Medium (Ge1ose Medium) 5 (Di fco) and B, spteris (B, 5ubtilis) ATCC663 Three control strains were used.
便試料を濃度既知の抗生物質：アモキシシリン、アモキシシリン＋クラグラン酸 （Ｃ１ａｖｕｌａｎｉｃ ａｃｉｄ ）、チカルシリン、セ７オタキシム、セフ トリアクノン又はセ７オベラゾンと共に３７°Ｃで３０分間、保温しついで残留 抗生物質活性を測定した。Antibiotics with known concentrations: amoxicillin, amoxicillin + claglanic acid (C1avulanic acid), ticarcillin, se7otaxime, cef Incubate at 37°C for 30 minutes with triacone or se7oberazone and remain Antibiotic activity was measured.
選択された菌株の活性を第１表に示す。表中の数字は種々のβ−ラクタミン抗生 物質の仄水分解兆（支）を表わす。The activities of selected strains are shown in Table 1. The numbers in the table are for various β-lactamine antibiotics. Represents the sign of water decomposition of a substance.
第 ■ 表 第１表 β−ラクタマーゼ活性を更に分光測光法（Ｏ″Ｃａｌ ｌａｇｈａｎ等、Ａｎｔ ｉｍｉｃｒｏ ｂｉａｌ ＡＨｅｎｔｓ Ｃｈｅｒｎｏｔｈｅｒａｐｙ １．２ ８３．１９７２参照）に＝９測定した。得られた結果を第■表に示す。■Table Table 1 β-lactamase activity was further determined spectrophotometrically (O″Cal laghan et al., Ant imicro vial AHents Chernotherapy 1.2 83.1972) = 9 measurements were taken. The results obtained are shown in Table ①.
無ＳマウスＣ３Ｈ（Ｃｅｎｔｒｅ ｄｅ ５ｅｌｅｃｔｉｏｎ ｄｅｓバクテリ ア抽出物のβ−ラクタマーゼ活性（セファロリジンＯμｍｏ Ｉ ｅ／分／蛋臼 質ＩＦ）Ａｎｉｍａｕｘ ｄｅ Ｌａｂｏｒａｔｏｉｒｅｓ、フランス オルレ アン所在ニジ入手）を軟質ヲラステツクアイソレーター千に収容した。飲料とし てマウスに熱殺菌したｐ８３０水だけを与倍に稀釈しついで得らり、た調製液を 無菌マウスを収容したアイソレーター中に放置した。この細菌溶液が酸素と接触 することを防止するために、上記溶液を嫌気室同に装入するのに密閉チューブを 使用した。前記の場合と同様に、予め水だけを与えたマウスに胃及び直腸経由で 投餌した。投餌は２４時間後に繰返した。ヒト（便提供者）におけると同様Ｏ腸 内のバランスとバリヤー効果（ｂａｒｒｉｅｒ ｅｆｆｅｃｔ ） を得るのに １０〜１５１３を要した。No S mouse C3H (Centre de 5 selection des bacterium β-lactamase activity of A. extract (cephaloridine Quality IF) Animaux de Laboratoires, Olle, France (Obtained at the current location) was housed in a soft-walled isolator. As a drink Heat-sterilized p830 water was diluted to a volume of 100% to mice, and the prepared solution was given to mice. The mice were placed in an isolator containing sterile mice. This bacterial solution comes into contact with oxygen To prevent this, a sealed tube is used to introduce the above solution into the anaerobic chamber. used. As in the previous case, the mice were given water only beforehand and then administered via the stomach and rectum. I threw bait. Baiting was repeated 24 hours later. O intestine as in humans (fecal donor) To achieve inner balance and barrier effect It took 10-1513.
ヒトの面相を保有するマウスに５．１０８ｃｆｕ ／ｒＪ０４ＳＯβ−ラクｐ ？ −セｇ生性菌株（Ｃ１，Ｃ６，Ｅ９． Ｖ４Ｅ３）を含有する、１−のＴＧ Ｙグロス（トリプチケース３０１／ｌ 、酵母抽出物２０ ｉ／ｌ 、グルコー ス５ Ｊ７ ／ ｔ 。5.108 cfu/rJ04SOβ-lacp in mice with human features ? -TG of 1- containing Segogenic bacterial strain (C1, C6, E9. V4E3) Y gloss (Tripticase 301/l, Yeast extract 20 i/l, Glucose S5 J7/t.
チオグリコール酸ナトリウム１ ｇ／ Ｌ 、 ｐＨ＝ ７．４ ）を胃内に接 種し、そ（ＤＨ後にセフトリアクンン（飲料水中、２１１Ｐ／ゴ）を経口投与し た。得られた結果を第ｍ表に示す。Inject sodium thioglycolate (1 g/L, pH = 7.4) into the stomach. Orally administered ceftriacunun (211P/go in drinking water) after DH. Ta. The results obtained are shown in Table m.
処理中、抗生物質ａ糞中に認められなかった。セフトリアクノンに対するβ−ラ クタツーゼ活性は処世の１４日後に認められた（１千〜４＋の間）。During treatment, no antibiotics were found in the feces. β-ra for ceftriacone Cutatuse activity was observed 14 days after death (between 1000 and 4+).
セフトリアクノン耐性腸内紀菌は排除された。二ンテ′：ｌ′ツシ数（Ｅｎｉｅ ｒｏｃｏｃｃｉ ｃｏｕｎｔ ）は非処理対象と同一であった。セントリアクン ンに耐性の外来性微生物（Ｅｎｔ、ｃｏｌｏａｃａｅ、 ＩＧＲ６７、Ｃ，ａｌ ｂｉｃａｒｓ ＩＧＲ６６）による転移増殖（ｃｏｌｏｎｉｚａｔｉｏｎ ） は活性バクテロイド菌株を予め接種したマウスにおいて保持された。Ceftriacone-resistant Enterobacteriaceae were eliminated. 2': l' Tsusi number (Enie rococci count) was the same as in the untreated subjects. Centria Kun Invasive microorganisms (Ent, coloacae, IGR67, C, al metastatic proliferation (colonization) due to bicars IGR66) was maintained in mice previously inoculated with active bacteroid strains.
バクテロイドを接種した群で＃′ｉ嫌気性細菌が依然として存在し、そして嫌気 性震内で得られた全菌株数は、対照と比較して、これらのバクテロイドの存在に よシ著しく変化しなかった。これらの細菌０ＭＩＣ５０及び９０は、それぞれ、 １−当り、セ７トリアクノン５１２及び１０２４μ２以上であった。グラム陰性 バチルヌがこの菌相の８４％を形成しそして１６％の胞子形成ダラム陽性／ぐテ ルスと己チＯコツシが存在した。In the group inoculated with bacteroids #'i anaerobic bacteria were still present and anaerobic The total number of bacterial strains obtained within the sexes was determined by the presence of these bacteroids compared to the control. There was no significant change. These bacteria 0MIC50 and 90 are, respectively. It was more than 512 and 1024 μ2 of ce7triacone per 1. gram negative Bacillus formed 84% of this flora and 16% spore-forming Durum positive/gute. Rusu and Chio Kotushi existed.
Ａｐｉ ２０Ａ系を使用する同定法によシ、セ７トリアクンンに２る処理の開始 直前トて投与されたものと同一〇性質を有するＣ、クロストリシフ万ルミスとム ユニホルミスの菌株の間で検出を行うことができる。Using the identification method using the Api 20A system, start the process in step 2. C, clostricifum lumis and mucilage having the same properties as those administered immediately before. Detection can be performed among strains of S. uniformis.
第 ｍ 派 ヒト菌相を保有するマウスにおけるセ７トリアクノン（飲料水２岬／ｍ） の生 態学的性質に対する、β−ラクタマーゼ産生性嫌気性障の効果６個の採取物につ いて０便（’ｔｏｙ）ｏ平均−！＝ＳＥＭｕｆｃ／に’アンダーラインを引いｆ ｃ結来：顕著な差ｐ ＞ ｏ、、ｓ＊極端な値 Ｓ＝供試マウス０数 ｎ＝試験した便試料 ヒトの治療においては投与′ｊｋけ、腸溶皮を有する耐胃酸性（ｇａｓｔｒｏ− ｓｅｓｉｓｔａｎｔ ） ゼラチン カプセル（各ゼラチンカプセルは５ ｘ １０ ＠（Ｄ−＜クチリアを含有する）の場合、抗生物質処理１日当９、・ぐク チリア約１０〜約１０１１個でちる。Mth faction Growth of ce7triacnone (drinking water 2 capes/m) in mice harboring human microbiota Effect of β-lactamase-producing anaerobic disorder on morphological properties of six samples. 0 flights ('toy) o average -! =SEMufc/ underline f c result: significant difference p> o,,s*extreme value S = 0 number of test mice n = stool sample tested In the treatment of humans, gastro-acid resistant (gastro- gelatin capsules (each gelatin capsule is 5 x 10＠(D-<Contains Cutilia), antibiotic treatment daily allowance 9,・Guku Makes about 10 to 1011 chillies.
ｍｌ ｍ ｍ、 ＰＣ？／Ｔ−ＲεＢ１００１７２ml m m, PC? /T-RεB100172
Claims (7)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8705110A FR2613624B1 (en) | 1987-04-10 | 1987-04-10 | ORAL ADMINISTRATIVE PHARMACEUTICAL COMPOSITION FOR REDUCING THE EFFECTS OF B-LACTAMINES |
| FR87/05110 | 1987-04-10 |
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| Publication Number | Publication Date |
|---|---|
| JPH01503537A true JPH01503537A (en) | 1989-11-30 |
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|---|---|---|---|
| JP63503346A Pending JPH01503537A (en) | 1987-04-10 | 1988-04-08 | Orally administrable therapeutic composition for reducing the effects of beta-lactamines |
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| Country | Link |
|---|---|
| EP (1) | EP0309532A1 (en) |
| JP (1) | JPH01503537A (en) |
| AU (1) | AU604117B2 (en) |
| FR (1) | FR2613624B1 (en) |
| OA (1) | OA09023A (en) |
| PT (1) | PT87190B (en) |
| WO (1) | WO1988007865A1 (en) |
| ZA (1) | ZA882426B (en) |
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| FI920206A0 (en) * | 1992-01-17 | 1992-01-17 | Pekka Untamo Heino | MEDICINSK ANVAENDNING, MEDICINSKT FOERFARANDE OCH PREPARAT. |
| FR2843302B1 (en) | 2002-08-09 | 2004-10-22 | Centre Nat Rech Scient | GALENIC FORM FOR COLLECTIVE DELIVERY OF ACTIVE PRINCIPLES |
| US8273376B2 (en) | 2006-11-17 | 2012-09-25 | Da Volterra | Colonic delivery of metallo-dependent enzymes |
| FI20105572A0 (en) | 2010-05-24 | 2010-05-24 | Prevab R Lcc | Modified beta-lactamase and methods and uses related thereto |
| GB201117313D0 (en) | 2011-10-07 | 2011-11-16 | Gt Biolog Ltd | Bacterium for use in medicine |
| GB201306536D0 (en) | 2013-04-10 | 2013-05-22 | Gt Biolog Ltd | Polypeptide and immune modulation |
| WO2015161243A2 (en) | 2014-04-17 | 2015-10-22 | Synthetic Biologics, Inc. | Beta-lactamases with improved properties for therapy |
| CN106574273B (en) | 2014-08-28 | 2021-07-02 | 合成生物制品有限公司 | Coli-based production of beta-lactamases |
| CN107148473B (en) | 2014-10-08 | 2021-08-06 | 合成生物制品有限公司 | Beta-lactamase formulations and uses thereof |
| JP6427278B2 (en) | 2014-12-23 | 2018-11-21 | フォーディー ファーマ リサーチ リミテッド４Ｄ Ｐｈａｒｍａ Ｒｅｓｅａｒｃｈ Ｌｉｍｉｔｅｄ | pirin polypeptide and immune modulation |
| EP3236993B1 (en) | 2014-12-23 | 2023-09-13 | Theriva Biologics, Inc. | Methods and compositions for inhibiting or preventing adverse effects of oral antibiotics |
| SI3065748T1 (en) | 2014-12-23 | 2018-05-31 | 4D Pharma Research Limited | A bacteroides thetaiotaomicron strain and its use in reducing inflammation |
| JP6810697B2 (en) | 2015-02-23 | 2021-01-13 | シンセティック・バイオロジクス・インコーポレイテッド | Carbapenemase used with antibiotics to protect the intestinal microbiome |
| AU2016229976B2 (en) | 2015-03-06 | 2021-11-11 | Theriva Biologics, Inc. | Safe and effective beta-lactamase dosing for microbiome protection |
| CN114984057A (en) | 2015-06-15 | 2022-09-02 | 4D制药研究有限公司 | Compositions comprising bacterial strains |
| MA41060B1 (en) | 2015-06-15 | 2019-11-29 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
| RS59446B1 (en) | 2015-06-15 | 2019-11-29 | 4D Pharma Res Ltd | Blautia stercosis and wexlerae for use in treating inflammatory and autoimmune diseases |
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| SI3360559T1 (en) | 2015-06-15 | 2020-02-28 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| EP3209310B1 (en) | 2015-11-20 | 2018-01-31 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| GB201520497D0 (en) | 2015-11-20 | 2016-01-06 | 4D Pharma Res Ltd | Compositions comprising bacterial strains |
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| NZ745678A (en) | 2016-03-04 | 2019-03-29 | 4D Pharma Plc | Compositions comprising bacterial blautia strains for treating visceral hypersensitivity |
| TW201821093A (en) | 2016-07-13 | 2018-06-16 | 英商４Ｄ製藥有限公司 | Compositions comprising bacterial strains |
| GB201621123D0 (en) | 2016-12-12 | 2017-01-25 | 4D Pharma Plc | Compositions comprising bacterial strains |
| AU2018272291A1 (en) | 2017-05-22 | 2020-01-16 | 4D Pharma Research Limited | Compositions comprising bacterial strains |
| TW201907931A (en) | 2017-05-24 | 2019-03-01 | 英商4D製藥研究有限公司 | Composition comprising a bacterial strain |
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-
1987
- 1987-04-10 FR FR8705110A patent/FR2613624B1/en not_active Expired - Fee Related
-
1988
- 1988-04-07 ZA ZA882426A patent/ZA882426B/en unknown
- 1988-04-08 PT PT87190A patent/PT87190B/en not_active IP Right Cessation
- 1988-04-08 WO PCT/FR1988/000172 patent/WO1988007865A1/en not_active Application Discontinuation
- 1988-04-08 AU AU15786/88A patent/AU604117B2/en not_active Ceased
- 1988-04-08 EP EP88903277A patent/EP0309532A1/en not_active Withdrawn
- 1988-04-08 JP JP63503346A patent/JPH01503537A/en active Pending
- 1988-12-09 OA OA59487A patent/OA09023A/en unknown
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| Publication number | Publication date |
|---|---|
| AU1578688A (en) | 1988-11-04 |
| PT87190A (en) | 1988-05-01 |
| PT87190B (en) | 1992-08-31 |
| ZA882426B (en) | 1988-09-28 |
| AU604117B2 (en) | 1990-12-06 |
| FR2613624A1 (en) | 1988-10-14 |
| WO1988007865A1 (en) | 1988-10-20 |
| EP0309532A1 (en) | 1989-04-05 |
| OA09023A (en) | 1991-03-31 |
| FR2613624B1 (en) | 1990-11-23 |
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