JP4998988B2 - 他の抗結核薬と組み合わせて使用する結核治療に有効な免疫療法治療剤 - Google Patents
他の抗結核薬と組み合わせて使用する結核治療に有効な免疫療法治療剤 Download PDFInfo
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- JP4998988B2 JP4998988B2 JP2006537326A JP2006537326A JP4998988B2 JP 4998988 B2 JP4998988 B2 JP 4998988B2 JP 2006537326 A JP2006537326 A JP 2006537326A JP 2006537326 A JP2006537326 A JP 2006537326A JP 4998988 B2 JP4998988 B2 JP 4998988B2
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- tuberculosis
- therapeutic agent
- isoniazid
- treatment
- immunotherapy
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/04—Mycobacterium, e.g. Mycobacterium tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
- A61K2039/541—Mucosal route
- A61K2039/543—Mucosal route intranasal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Description
ミドルブルック(Middlebrook)7H11型の寒天の80−100枚のプレートをNational Collection of Type Cultures (NCTC)に保管されているH37Rv培養体(保管番号NC007416)で培養した。各プレートで培養されたコロニーを形成するユニット(colony-forming units)の濃度は、105−106UFCである。これらのプレートを21日間(3週間)、34℃から38℃の間の温度で培養した。
実験例1で得られた740−770mgの生成物をビーカーで重りを量る。その後、エタノール中に薬剤品質(pharmacy-quality)の大豆レシチンの20mLが分散したもの(1リットルの純粋エタノール中に1kgのレシチンをいれたものに相当する)と、水中の薬剤品質のナトリウム・コール酸塩の7mL溶液(1リットルの2回蒸留水中に200gのナトリウム・コール酸塩をいれたものに相当する)を追加した。
感染モデルにおいて、生後6−8週間の特定の病原体に感染していない、雌のBALB/c、129/Sv、C57BL/6、DBA/2のマウスを用意した。
(Aグループ)− 1日あたり25mg/kgのイソニアジドのみの投与を1週間に5日間6週間にわたり行い治療したグループ(対照標準)。
(Bグループ)− 1日あたり25mg/kgのイソニアジドの投与を1週間に5日間6週間にわたり行い、リポソーム状の免疫療法治療剤180μgを鼻孔を介して投与したことにより治療したグループ(本発明)。
(Cグループ)− 1日あたり25mg/kgのイソニアジドの投与を1週間に5日間6週間にわたり行い、リポソーム状の免疫療法治療剤180μgを腹膜を介して投与したことにより治療したグループ(本発明)。
(表1)
マウスグループ 肺 脾臓
A 対照標準 7.5±2.89 0.75±0.33
B 鼻孔経由 2±0*以下 0.4 ±0.2
C 腹膜経由 2±0*以下 0.52±0.44
*=対照標準と比較して統計的に意味のある数字 p<0.05
(Aグループ)− 1日あたり25mg/kgのイソニアジドを1週間に5日間4週間にわたり投与し、1日あたり10mg/kgのリファンピンを1週間に5日間4週間にわたりで投与して治療したグループ(対照標準)。
(Bグループ)− リファンピンとイソニアジドの治療の後、180μgのリポソーム状の免疫療法治療剤を3回皮下経由で投与して治療したグループ(本発明)。
(表2)
マウスグループ 肺 脾臓
A 対照標準 2.67±0.83 2.35±1.18
B 皮下経由 1.61±0.58* 1.37±1.02
*=対照標準と比較して統計的に意味のある数字p<0.05
(Aグループ)− 1日あたり25mg/kgのイソニアジドのみを1週間に5日間8週間にわたり治療したグループ(対照標準)。
(Bグループ)− 上記の治療と共に、リポソーム状の免疫療法治療剤を180μgを鼻孔経由で3回投与して治療したグループ(本発明)。
(表3)
マウスグループ 第15週(1回投与) 第28週(3回投与)
A 対照標準 2.34±0.24 3.86±0.41
B 鼻孔経由 1.59±0.61* 3.48±0.18*
*=対照標準と比較して統計的に意味のある数字p<0.05
(表4)
マウスグループ 第15週 第28週
A 対照標準 1.47±0.44 3.84±0.48
B 鼻孔経由 1.41±0.58 3.43±0.29*
*=対照標準と比較して統計的に意味のある数字p<0.05
(表5)
実験 抗生イソニアジド リポソーム状免疫療法治療剤
1 No No
2 Yes No
3 No Yes
4 Yes Yes
(表6)
実験 抗生イアオニジド リポソーム状の免疫療法治療剤 log 10 UFC/mL
1 No No 5.37±0.27
2 Yes No 3.29±0.8*
3 No Yes 5.69±0.22
4 Yes Yes 0.69±0**
* 実験1、3、4に比較して、統計的に意味ある値 p<0.05
** 実験1、2、3に比較して、統計的に意味ある値 p<0.05
Claims (10)
- 複合結核菌(Mycobacterium tuberculisis-complex (MTB−C))の細胞壁小片を含む結核治療に用いられ免疫療法治療剤を生成する方法において、
(A)複合結核菌を3週間以上にわたって培養するステップと、
(B)前記複合結核菌の培養物を、非イオン性表面活性剤の存在下で、均質化するステップと
を有し、
前記非イオン性表面活性剤は、アルキルフェノール・エトキシレート基(alcyphenol ethoxylat )とエトキシ化ソリビタン・エステル(ethoxylated sorbitan esters)からなるグループから選択され、
前記ステップにより得られた免疫療法治療剤は、イソニアジド(isoniazid)又はリファムピシン(rifampicion)と併用される
ことを特徴とする結核治療に用いられる免疫療法治療剤を生成する方法。 - 前記培養期間は、3週間から4週間の間である
ことを特徴とする請求項1記載の方法。 - 前記非イオン性表面活性剤は、オクチルフェノール・エトキシレート化合物(octylphenol ethoxylat compounds)から選択される
ことを特徴とする請求項1記載の方法。 - 前記非イオン性表面活性剤は、エチレン酸化物(ethylene oxide)を7−8モル有するオクチルフェノール・エトキシレート(octylphenol ethoxylat)である
ことを特徴とする請求項3記載の方法。 - 前記ステップ(B)は、中性pHの干渉媒体中で実行される
ことを特徴とする請求項1−4のいずれかに記載の方法。 - (C) 小片化されていない細胞と可溶性化合物とを遠心分離するステップと、
(D) 前記細胞壁の小片を有する部分内の残留毒性細胞を非活性化するステップと、
(E) 前記ステップにより得られた免疫療法治療剤を凍結乾燥させるステップと
を更に有する
ことを特徴とする請求項1−5のいずれかに記載の方法。 - イソニアジド(isoniazid)又はリファムピシン(rifampicion)と併用される、請求項1−6のいずれかの方法により生成された結核治療に用いられる免疫療法治療剤。
- イソニアジド(isoniazid)又はリファムピシン(rifampicion)と併用される、請求項7記載の免疫療法治療剤を含む結核治療薬剤。
- 前記結核治療に用いられる免疫療法治療剤をリポソームの形態で含む
ことを特徴とする請求項8記載の結核治療薬剤。 - イソニアジド(isoniazid)又はリファムピシン(rifampicion)と併用される、請求項7記載の結核治療に用いられる免疫療法治療剤を含む結核治療薬剤。
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ES200302551A ES2231037B1 (es) | 2003-10-31 | 2003-10-31 | Agente inmunoterapico util para el tratamiento combinado de la tuberculosis en asociacion con otros farmacos. |
ESP200302551 | 2003-10-31 | ||
PCT/ES2004/000482 WO2005042013A1 (es) | 2003-10-31 | 2004-10-29 | Agente immunoterápico útil para el tratamento combinado de la tuberculosis en associación con otros fármacos |
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US (1) | US8246944B2 (ja) |
EP (1) | EP1690549B1 (ja) |
JP (1) | JP4998988B2 (ja) |
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ES2231037B1 (es) | 2003-10-31 | 2005-12-16 | Archivel Technologies, Sl | Agente inmunoterapico util para el tratamiento combinado de la tuberculosis en asociacion con otros farmacos. |
EP2027865A4 (en) * | 2006-05-12 | 2010-08-18 | Univ Hokkaido Nat Univ Corp | LIPOSOME HAVING A LIPIDIC MEMBRANE CONTAINING A BACTERIAL CELLULAR COMPONENT |
ES2307402B1 (es) | 2006-10-30 | 2009-09-30 | Archivel Farma, S.L. | Vacuna profilactica contra la tuberculosis. |
ES2335177B1 (es) * | 2008-09-19 | 2011-02-28 | Archivel Farma, S.L. | Agente inmunoterapeutico apropiado para la profilaxis primaria de la tuberculosis. |
EP2471511A1 (en) | 2011-01-04 | 2012-07-04 | Archivel Farma, SL | Liposome formulation suitable for treating or preventing tuberculosis |
WO2012093137A1 (en) * | 2011-01-04 | 2012-07-12 | Archivel Farma, Sl | Liposome formulation suitable for treating or preventing tuberculosis |
EP2802345B1 (en) | 2012-01-12 | 2018-03-07 | Archivel Farma, S.l. | Mtb-c vaccine against allergic responses |
ES2758400B2 (es) | 2018-11-02 | 2021-01-20 | Univ Granada | Nanoparticulas biomimeticas mediadas por mamc |
WO2023062066A1 (en) | 2021-10-14 | 2023-04-20 | Archivel Farma, S.L. | Liposome formulations for treatment of active tuberculosis |
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DE3125598A1 (de) * | 1981-06-30 | 1983-01-13 | Mahle Gmbh, 7000 Stuttgart | Einrichtung zur druckbeaufschlagung des presszylinders einer druckgiessmaschine |
JPS59161320A (ja) * | 1983-03-04 | 1984-09-12 | Maruyama Chisato | リポ多糖体およびその製造法 |
GB8404280D0 (en) | 1984-02-17 | 1984-03-21 | Stanford J L | Biological preparations |
JPS624701A (ja) * | 1985-06-29 | 1987-01-10 | Maruyama Chisato | リポ多糖体及びその製造法 |
US4744984A (en) * | 1985-10-08 | 1988-05-17 | Vetrepharm Research, Inc. | Antiviral immunotherapeutic agent and preparation thereof |
US5542935A (en) * | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US6641814B1 (en) * | 1997-04-02 | 2003-11-04 | Statens Serum Institut | Nucleic acids fragments and polypeptide fragments derived from M. tuberculosis |
US5785975A (en) * | 1995-06-26 | 1998-07-28 | Research Triangle Pharmaceuticals | Adjuvant compositions and vaccine formulations comprising same |
US6284255B1 (en) | 1996-08-29 | 2001-09-04 | Genesis Research & Development Corporation Limited | Compounds and methods for treatment and diagnosis of mycobacterial infections |
US6982085B2 (en) * | 1997-04-02 | 2006-01-03 | Statens Serum Institut | TB diagnostic based on antigens from M. tuberculosis |
CA2346218A1 (en) * | 1998-10-08 | 2000-04-20 | Statens Serum Institut | Tuberculosis vaccine and diagnostic reagents based on antigens from the mycobacterium tuberculosis cell |
RU2153354C1 (ru) * | 1999-03-31 | 2000-07-27 | Московский городской научно-практический центр борьбы с туберкулезом | Вакцина против туберкулеза |
AU2002239485A1 (en) * | 2000-12-08 | 2002-06-18 | The Johns Hopkins University | Methods for improved diagnosis and treatment of mycobacterial infections |
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EP1379529A2 (en) * | 2001-03-16 | 2004-01-14 | Sarawak Medichem Pharmaceuticals, Inc. | Pyranocoumarin compounds as a novel pharmacophore with anti-tb activity |
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WO2003018053A1 (en) | 2001-08-22 | 2003-03-06 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Vaccine against mycobacterial-induced diseases |
CA2474794A1 (en) | 2002-01-29 | 2003-08-07 | Modi, Rajiv Indravadan | Method of providing prophylaxis for tuberculosis in hiv positive individuals |
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DE102004053141A1 (de) * | 2004-11-03 | 2006-05-04 | Schülke & Mayr GmbH | Desinfektionsmittel mit verbesserter Wirksamkeit gegen Mykobakterien |
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