WO2006137423A1 - 肺胞破壊によって生じる肺疾患の治療または予防のためのクラリスロマイシンまたはその塩 - Google Patents
肺胞破壊によって生じる肺疾患の治療または予防のためのクラリスロマイシンまたはその塩 Download PDFInfo
- Publication number
- WO2006137423A1 WO2006137423A1 PCT/JP2006/312385 JP2006312385W WO2006137423A1 WO 2006137423 A1 WO2006137423 A1 WO 2006137423A1 JP 2006312385 W JP2006312385 W JP 2006312385W WO 2006137423 A1 WO2006137423 A1 WO 2006137423A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- clarithromycin
- emphysema
- salt
- pulmonary
- destruction
- Prior art date
Links
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Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
Definitions
- Claris mouth mycin or its salt for the treatment or prevention of lung disease caused by alveolar destruction
- the present invention relates to the use of clarithromycin or a salt thereof for the treatment or prevention of lung diseases caused by alveolar destruction. More specifically, the present invention comprises clarithromycin or a salt thereof for such treatment or prevention as an active ingredient, a therapeutic or prophylactic agent, a pharmaceutical composition containing clarithromycin or a salt thereof, The present invention relates to a method of administering clarithromycin or a salt thereof to a mammal, and the use of clarithromycin or a salt thereof in pharmaceutical production.
- Background art
- the alveoli are composed of alveolar epithelial cells, vascular cells, and the like, and an extracellular matrix (eg, elastin or collagen) that constitutes the alveolar wall.
- the alveoli are important sites for gas exchange in the body.
- Emphysema is a condition in which the alveolar wall is destroyed and the fine structure of the alveoli is hollowed out. Emphysema reduces gas exchange efficiency and the elastic contraction of the entire lung, ultimately reducing lung function.
- Pulmonary emphysema is strongly associated with inflammatory cells activated by smoking, air pollution, harmful gases, etc., or newly infiltrated into the lung (eg, alveolar macrophages or neutrophils).
- inflammatory cells activated by smoking, air pollution, harmful gases, etc., or newly infiltrated into the lung (eg, alveolar macrophages or neutrophils).
- Macrophages and neutrophils are activated by cigarette smoke or harmful compounds in the air pollution, but the details are unknown but activated, releasing substances that promote inflammation, such as cytokines and proteases, and the alveolar wall. It has been reported to be involved in destruction (Barnes PJ. Et al. Pharmacol Rev. 2004 Dec; 56 (4): 515_48).
- airway dilators that improve airflow limitation, such as anticholinergic agents and ⁇ receptor stimulants, are widely used as treatments for emphysema, but they themselves reduce alveolar destruction and pulmonary emphysema.
- An object of the present invention is to provide a therapeutic or prophylactic agent for lung diseases caused by alveolar destruction.
- the present invention also provides a pharmaceutical composition for treating or preventing lung disease caused by alveolar destruction, comprising an effective amount of clarithromycin or a salt thereof and a pharmaceutically acceptable carrier. Is done.
- a therapeutic or prophylactic agent for lung diseases caused by alveolar destruction comprising clarithromycin or a salt thereof as an active ingredient.
- the present invention provides the use of clarithromycin or a salt thereof in the manufacture of a medicament for the treatment or prevention of lung diseases caused by alveolar destruction in mammals.
- the pulmonary disease is emphysema.
- clarithromycin or its salt has excellent efficacy.
- the efficacy of clarithromycin or a salt thereof is particularly excellent when the emphysema is chronic obstructive pulmonary disease.
- an in vivo method for reducing the number of macrophage and Z or neutrophil cells in a mammal wherein the amount of clarithromycin or a salt thereof is sufficient to reduce the number of cells.
- a method comprising administering to a mammal.
- clarithromycin or a salt thereof is useful as a therapeutic or prophylactic agent for lung diseases caused by alveolar destruction.
- pulmonary disease caused by alveolar destruction refers to pulmonary disease caused by smoking, air pollution, harmful gas, etc., or destruction of alveolar cells due to aging. Particularly prominent is “pulmonary emphysema (symptoms)”, which is caused by the destruction of the alveoli, causing the alveolar membrane to collapse and the adjacent alveoli to join together to form an air space.
- pulmonary emphysema symptoms
- the alveoli in the peripheral airways are destroyed, causing airflow obstructive disorders, which are classified as “chronic obstructive pulmonary disease”.
- Diseases that exhibit symptoms characteristic of alveolar destruction are collectively referred to as “pulmonary diseases caused by alveolar destruction”. This pulmonary disease may be accompanied by infection with bacteria.
- Clarithromycin used in the present invention is a known substance, and its detailed description (production method, antibacterial activity, etc.) is disclosed in, for example, Japanese Patent Publication No. 61-52839. Accordingly, all disclosures thereof are incorporated herein.
- salt of clarithromycin refers to a pharmaceutically acceptable salt of clarithromycin. Examples include salts with organic acids such as tartaric acid, citrate, stearic acid, and succinic acid; salts with methanesulfonic acid; salts with aminoethanesulfonic acid; salts with amino acids such as aspartic acid and glutamic acid.
- a pharmaceutically acceptable derivative of clarithromycin may be used instead of clarithromycin.
- This derivative is Claris It has a basic skeleton of romycin, is derivatized, and shows the same pharmacological action as clarithromycin.
- Particularly useful derivatives are esters of clarithromycin, which undergo hydrolysis in vivo to liberate clarithromycin.
- Such derivatives are also called prodrugs, and certain esters are well known to those skilled in the art.
- clarithromycin When clarithromycin is used in the present invention, it is prepared as a general pharmaceutical preparation.
- clarithromycin or a salt thereof is mixed with a pharmaceutically acceptable carrier (excipient, binder, disintegrant, corrigent, emulsifier, diluent, solubilizer, etc.) to obtain a pharmaceutical composition.
- a pharmaceutically acceptable carrier excipient, binder, disintegrant, corrigent, emulsifier, diluent, solubilizer, etc.
- This pharmaceutical composition is suitable for oral or parenteral preparations such as tablets, pills, powders, granules, capsules, solutions, emulsions, suspensions, injections, suppositories, inhalants, and transdermal absorption agents. Administered to a mammal in the form.
- solvents In order to produce these preparations, solvents, solubilizers, tonicity agents, preservatives, antioxidants, excipients, binders, lubricants, stabilizers and the like can be added.
- Examples of the solvent include water and physiological saline
- examples of the solubilizer include ethanol, polysorbates, and taremorpha.
- examples of the excipient include lactose, starch, crystalline cellulose, mannitol, and maltose. Calcium hydrogen phosphate, light anhydrous caustic acid, calcium carbonate, etc.
- binder examples include starch, polybutyropyrrolide, hydroxypropenoresenorelose, ethinoresenorelose, canoleboxymethinoresenorelose, arabian
- starch carboxymethylcellulose calcium, etc., as lubricants, eg, magnesium stearate, talc, hydrogenated oil, etc., as stabilizers, eg, lactose, mannitol, maltose, polysorbates, etc.
- Macrogol polyoxyethylene
- polyoxyethylene examples include ren hardened castor oil.
- glycerin, dimethylacetamide, 70% sodium lactate, surfactant, basic substance for example, sodium hydroxide, ethylenediamine, ethanolamine, sodium carbonate, arginine, megnolemin, Trisaminomethane
- basic substance for example, sodium hydroxide, ethylenediamine, ethanolamine, sodium carbonate, arginine, megnolemin, Trisaminomethane
- an "effective amount" refers to a desired pharmacological effect when clarithromycin or a salt thereof is administered to a mammal in need of treatment or prevention, preferably as a pharmaceutical composition. Sufficient amount or composition amount to provide For treatment, clarithromycin Alternatively, when the salt is used, the desired pharmacological effect means that it can be cured or alleviated in a mammal exhibiting past symptoms. When clarithromycin or a salt thereof is used for prevention, the desired pharmacological effect means that the onset is suppressed in a mammal. In this case, it is administered prophylactically before the onset to mammals suspected of having onset or at high risk of onset.
- the dose of clarithromycin or a salt thereof is determined so that the total dose does not exceed a certain amount after single and repeated administration in consideration of the results of animal experiments and various situations.
- the specific dose depends on the method of administration, the condition of the patient or the treated animal, for example, within the range of 10 mg lOOOmg, age, weight, sex, sensitivity, diet (food), administration time, concomitant drugs, or symptoms thereof Needless to say, the appropriate dose and the number of doses under certain conditions must be determined by a specialist's appropriate dose determination test based on the above guidelines.
- Clarithromycin, lactose, corn starch, crystalline cellulose, and carmellose calcium are mixed uniformly, 10% hydroxypropylcellulose aqueous solution is added thereto, kneaded and dried, and the granules are sieved through a 30M sieve. As a uniform granule, magnesium stearate was added and compressed into tablets.
- clarithromycin improved of pulmonary emphysema symptoms
- Cigarette smoke-induced emphysema model mice that mimic human emphysema are Hauta thigh ki, RD et al., Science 1997, 277: 2002-2004, or Shapiro, SD et al., Am. J. Pathol (2003) 163: 2329 -2335 It was produced according to the method described in 1. That is, C57black / 6 female mice 12 weeks of age were exposed to two cigarette smokes every day for 6 days and 6 months.
- Clarithromycin was administered at a rate of 25, 50, lOOmg / kg body weight orally twice a day during the exposure period of cigarette smoke. Change in plasma concentration after a single dose of 50mg / kg to mice What is AUC? ⁇ Ah ⁇ Up ⁇ ! ⁇ Dari, when a single dose of clarithromycin 200mg is administered to a healthy person ⁇
- a hematoxin-eosin pathological specimen of a model mouse was prepared, and the average alveolar size of 10 fields randomly selected under a microscope was measured. An increase in the average alveolar size is an indicator of alveolar destruction or emphysema status.
- Table 1 shows the improvement of emphysema in cigarette smoke-induced emphysema model mice of clarithromycin.
- Six months of smoking increased the rate of emphysema by 20% compared to the non-smoking (control) group.
- the emphysema improved to 47% in the clarithromycin 25 mg / kg group and up to 85% in the 50 mg / kg group. This result indicates that clarithromycin is effective against emphysema (pulmonary emphysema symptoms).
- clarithromycin or a salt thereof is useful as a therapeutic or prophylactic agent for lung diseases caused by alveolar destruction.
- FIG. 1A and FIG. 1B show the number of inflammatory cells (macrophages, neutrophils) in lung lavage fluid after 6 months exposure in cigarette smoke-induced emphysema model mice.
- FIG. 1A represents the number of macrophage cells
- FIG. 1B represents the number of neutrophil cells.
- Fig. 2 shows the results of measuring lung compliance after 6 months of exposure in cigarette smoke-induced emphysema model mice.
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US11/917,845 US8017588B2 (en) | 2005-06-24 | 2006-06-21 | Clarithromycin or salt thereof for use in the treatment or prevention of pulmonary disease induced by destruction of pulmonary alveoli |
ES06767044T ES2397232T3 (es) | 2005-06-24 | 2006-06-21 | Claritromicina o una sal derivada para su uso en un procedimiento para tratar el enfisema pulmonar |
EP06767044A EP1908473B1 (en) | 2005-06-24 | 2006-06-21 | Clarithromycin or salt thereof for use in the treatment pulmonary emphysema |
CA2610773A CA2610773C (en) | 2005-06-24 | 2006-06-21 | Clarithromycin or a salt thereof for use in the treatment or prevention of pulmonary disease induced by destruction of pulmonary alveoli |
JP2006540062A JP4045301B2 (ja) | 2005-06-24 | 2006-06-21 | 肺胞破壊によって生じる肺疾患の治療または予防のためのクラリスロマイシンまたはその塩 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US11/165,201 US20060293261A1 (en) | 2005-06-24 | 2005-06-24 | Clarithromycin or a salt thereof for the treatment or prevention of pulmonary disorders caused by the destruction of pulmonary alveoli |
US11/165,201 | 2005-06-24 |
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WO2006137423A1 true WO2006137423A1 (ja) | 2006-12-28 |
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PCT/JP2006/312385 WO2006137423A1 (ja) | 2005-06-24 | 2006-06-21 | 肺胞破壊によって生じる肺疾患の治療または予防のためのクラリスロマイシンまたはその塩 |
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US (2) | US20060293261A1 (ja) |
EP (1) | EP1908473B1 (ja) |
JP (1) | JP4045301B2 (ja) |
CN (1) | CN101203229A (ja) |
CA (1) | CA2610773C (ja) |
ES (1) | ES2397232T3 (ja) |
WO (1) | WO2006137423A1 (ja) |
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WO2023048125A1 (ja) * | 2021-09-27 | 2023-03-30 | 国立大学法人新潟大学 | 骨組織及び肺組織の再生剤、並びに、骨組織及び肺組織の再生用医薬組成物 |
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US20060293261A1 (en) | 2005-06-24 | 2006-12-28 | Taisho Pharmaceutical Co., Ltd. | Clarithromycin or a salt thereof for the treatment or prevention of pulmonary disorders caused by the destruction of pulmonary alveoli |
US8415390B2 (en) | 2008-05-30 | 2013-04-09 | Microdose Therapeutx, Inc. | Methods and compositions for administration of oxybutynin |
US9119777B2 (en) | 2008-05-30 | 2015-09-01 | Microdose Therapeutx, Inc. | Methods and compositions for administration of oxybutynin |
WO2012047674A2 (en) * | 2010-09-27 | 2012-04-12 | Microdose Therapeutx, Inc. | Methods and compositions for disease treatment using inhalation |
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JP2004531539A (ja) * | 2001-04-27 | 2004-10-14 | プリバ ディー.ディー. | 非感染性炎症性疾患を治療するためのアジスロマイシンの新規治療適応 |
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JPS6152839A (ja) | 1984-08-21 | 1986-03-15 | 松下電器産業株式会社 | 電気掃除機 |
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KR890005273A (ko) * | 1987-09-09 | 1989-05-13 | 이정오 | 2중 실관 반응기에 의한 구연산의 연속 생산방법 |
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- 2006-06-21 US US11/917,845 patent/US8017588B2/en not_active Expired - Fee Related
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- 2006-06-21 WO PCT/JP2006/312385 patent/WO2006137423A1/ja active Application Filing
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- 2006-06-21 CN CNA2006800225969A patent/CN101203229A/zh active Pending
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WO2023048125A1 (ja) * | 2021-09-27 | 2023-03-30 | 国立大学法人新潟大学 | 骨組織及び肺組織の再生剤、並びに、骨組織及び肺組織の再生用医薬組成物 |
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CA2610773C (en) | 2014-02-11 |
JP4045301B2 (ja) | 2008-02-13 |
EP1908473A1 (en) | 2008-04-09 |
EP1908473B1 (en) | 2012-10-17 |
CN101203229A (zh) | 2008-06-18 |
US20090088395A1 (en) | 2009-04-02 |
ES2397232T3 (es) | 2013-03-05 |
EP1908473A4 (en) | 2009-11-11 |
CA2610773A1 (en) | 2006-12-28 |
US20060293261A1 (en) | 2006-12-28 |
US8017588B2 (en) | 2011-09-13 |
JPWO2006137423A1 (ja) | 2009-01-22 |
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