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WO2000037090A1 - Medicaments destines au traitement d'infections pulmonaires - Google Patents

Medicaments destines au traitement d'infections pulmonaires Download PDF

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Publication number
WO2000037090A1
WO2000037090A1 PCT/GB1999/004230 GB9904230W WO0037090A1 WO 2000037090 A1 WO2000037090 A1 WO 2000037090A1 GB 9904230 W GB9904230 W GB 9904230W WO 0037090 A1 WO0037090 A1 WO 0037090A1
Authority
WO
WIPO (PCT)
Prior art keywords
treatment
disinfectant
inhalation device
broad
lung infections
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.)
Ceased
Application number
PCT/GB1999/004230
Other languages
English (en)
Inventor
Fiona Woodcock
Ingrid Carlen-Brutsche
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to AU16732/00A priority Critical patent/AU1673200A/en
Publication of WO2000037090A1 publication Critical patent/WO2000037090A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • 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
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions

Definitions

  • the present invention concerns new uses for existing disinfectants in the manufacture of preparations for the treatment of lung infections, together with devices containing same for the treatment of lung infections, and methods of treatment of lung infections.
  • Antibiotics are nowadays widely used in the treatment of bacterial infections and include compounds such as penicillin, rifamycin, actinomycin, streptomycin, tetracyline, chloramphenicol, cycloheximide, erythromycin, puromycin, gramicidin A and valinomycin. They typically work by inhibiting biological processes - for example, penicillin acts by mimicking the translation state substrate of a transpeptidase enzyme involved in bacterial cell wall formation, forming a stable complex with the transpeptidase, preventing cell wall formation and causing cell lysis. Rifampicin and actinomycin specifically inhibit the initiation of RNA synthesis in bacteria, resulting in cell death.
  • antibiotics have specific molecular targets they are only effective against specific organisms, and antibiotic resistance genes, for example encoding an allelic form of the antibiotic's target but which is not affected by the antibiotics, rapidly evolve and sweep through populations. This has resulted in the modern-day phenomenon of multiple drug resistance (MDR) in bacteria, reducing the number of possible therapies available to treat infections. This is typically a problem in hospitals which may harbour e.g. multiply-resistant Staphylo coccus aureus (MRSA) which can only be the treated using highly toxic agents, a problem exacerbated by the fact that it is usually severely ill patients who become infected and who may not be able to tolerate the side effects of the drugs. Antibiotics are typically administered orally or intra venously to effect a systemic treatment of a patient.
  • MDR multiply-resistant Staphylo coccus aureus
  • the present inventors have overcome the prior art disadvantages and provide new uses for agents in treating lung infections, methods and devices for same.
  • a broad- spectrum disinfectant as a medicament for the treatment of lung infections.
  • a broad- spectrum disinfectant in the manufacture of a medicament for the treatment of lung infections.
  • the broad-spectrum disinfectant may be administered via an inhalation device.
  • a broad-spectrum disinfectant in the manufacture of an inhalation device for the treatment of lung infections.
  • a method of manufacture of an inhalation device for the treatment of lung infectious characterised in the use of a broad-spectrum disinfectant. Reference herein to the treatment of lung infections is also to the prophylaxis of infections.
  • Inhalation devices include any device which provides a medicament in the form of dispersed particles, for example spray devices, nebuliser devices and powder inhalers.
  • the present inventors have found that, surprisingly, general disinfectant compounds may be used to achieve a safe and effective treatment of lung infections. This is particularly advantageous since it means that a patient may be treated immediately with a disinfectant which can be expected to have a therapeutic effect, thereby limiting the need to perform tests and identify the infecting pathogen before treatment is begun.
  • Prior art teachings have been that the toxic nature of disinfectants against human cells and tissues means that they should not be used in the treatment of internal tissues, hence the warnings on disinfectant bottles not to consume the disinfectant.
  • Disinfectants are, of course, used during surgical procedures performed upon internal tissues, but there is no suggestion that disinfectants may be respired in order to effect treatment of lung infections.
  • the disinfectant may comprise a biguanide.
  • the biguanides include polyhexanidum (full name poly(l -hexamethylenbiguanidhydrochlorid, also known as polyhexanid) and chlorhexidin. They have excellent antimicrobial activity, destroying cell membranes and precipitating out cell contents. Activity is good against Staphylococcus aureus which is particularly useful when treating MRSA patients. Activity is also observed against fungi, Pneumocystis and Pseudomonas. Polyhexanid has been found to be particularly useful and effective at treating lung infections.
  • the disinfectant or medicament comprising the disinfectant may additionally be incorporated into a composition comprising a pharmaceutically acceptable carrier, diluent or excipient (Remington's Pharmaceutical Sciences and US Pharmacopeia, 1984, Mack Publishing Company, Easton, PA, USA).
  • disinfectants may be used in the present invention and these include alcohols such as isopropyl alcohol and ethyl alcohol.
  • Quarternary ammonium compounds may also be used, and these include cetrimide, benzalkonium chloride, benzethonium and toloconium.
  • the disinfectant In order to achieve a therapeutic effect the disinfectant must be correctly administered and that means providing the disinfectant at a particle size which is respirable, i.e. will enter into the lungs and reach the trachea, alveoli and bronchi rather than just be deposited on the mucosal tissues of the throat or bronchi.
  • inhalation devices In order to achieve this, inhalation devices must be used. Such devices include simple manually operated spray nozzles attached to a supply of disinfectant, as well as nebuliser and powder devices and suchlike. Such inhalation devices may for example produce a spray having an average particle size of less than 10 ⁇ m, preferably less than 5 ⁇ m. The smaller particle size in particular helps effect delivery of the disinfectant to the alveoli.
  • an inhalation device arrangement for treating lung infections comprising an inhalation device containing a broad-spectrum disinfectant and which produces a spray having a respirable particle size.
  • the disinfectants used in the present invention are all well known compounds.
  • polyhexanid (Fresenius, Germany) has been used for many years as a swimming pool disinfectant, to treat acanthamoeba keratitis, to disinfect dental instruments, in the poultry industry and to help preserve fruit by inhibiting microorganism activity.
  • the use to treat lung infections has never previously been suggested, and in particular there has been no suggestion of the inhalation devices of the present invention containing the disinfectants and producing a respirable spray, particularly a spray having an average particle size of less than 10 ⁇ m, for example less than 5 ⁇ m.
  • Also provided according to the present invention is a method of treatment of lung infections, comprising the step of administering to a patient a broad-spectrum disinfectant in a respirable form from an inhalation device, e.g. as a respirable spray.
  • the disinfectant In use, the disinfectant must be provided in a pharmaceutically acceptable dose, and in the case of polyhexanidum this may for example be a concentration of 0.2- 0.4 mg/ml. Suitable dosages may be readily determined using simple dose-response assays.
  • a study is conducted to determine the pharmacokinetics of polyhexanid in plasma and urine, its general toxicity and clinical tolerability after the administration of single-dose inhaled polyhexanid in a dose-escalating fashion.
  • the study is a single-centre, randomised, placebo-controlled, double blind study. 30 subjects (15 male, 15 female) aged 20-60 are used, half being healthy and half having chronic lung infections. They are tested before treatment is initiated, their medical history is examined, and a physical examination, 12-lead ECG and routine laboratory screening (haematology, clinical chemistry and urine analysis) is performed.
  • Medication is provided in the form of a single dose (2 ml) nebulised polyhexanid solution at an escalating concentration of 0.0025% up to 0.8%.
  • Polyhexanid is provided as the Lavasept (RTM) product (Fresenius, Germany).
  • Nebulisation is achieved using an ultrasonic nebuliser and dosage administered over a period of approximately 10 minutes with the patient in a sitting position, having fasted for 12 hours.
  • the patient should also not smoke for at least 12 hours before dosing until 12 hours after dosing, should not consume alcohol for at least 12 hours, should perform no strenuous exercise for 24 hours until 12 hours after dosing, should have recumbent rest until 1 hour after dosing, and remains under continuous medical supervision from 1 hour before dosing until at least 8 hours after dosing.
  • Patient analysis is achieved by assessing vital functions (pulse rate, respiratory rate, oscillometric blood pressure) before dosing and then at 15, 30 and 45 minutes after dosing and then at 1 hour intervals.
  • Chest X-rays are performed before and at 6 hours after dosing.
  • DL C0 , G AW , transcutaneous S a02 at baseline and at 1 hour after inhalation are analysed.
  • Spirometry at baseline, 15 minutes, 2 hours and 6 hours after dosing are analysed.
  • Pharmacokinetic sampling of plasma samples before dosing and at 30 minutes, 1, 3, 5 and 7 hours after dosing are performed, and urine collected for 24 hours starting from the time of inhalation. Clinical tolerability and any adverse events are monitored throughout.
  • a 12-lead ECG is performed before and after dosing.
  • Clinical chemistry, haematology and urine analysis is performed at recruitment and at 7 days after inhalation.

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)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne de nouvelles utilisations de désinfectants existants dans la fabrication de préparations destinées au traitement d'infections pulmonaires, des appareils contenant ces désinfectants et destinés au traitement d'infections pulmonaires, ainsi que des méthodes de traitement d'infections pulmonaires. La présente invention concerne notamment l'utilisation de désinfectants à large spectre dans la fabrication d'un dispositif d'inhalation destiné au traitement d'infections pulmonaires, et une méthode de fabrication d'un dispositif d'inhalation destiné au traitement d'infections pulmonaires, se caractérisant par l'utilisation d'un désinfectant à large spectre. Le désinfectant utilisé peut contenir des membres de la famille des biguanides (par exemple le polyhexanidum), des alcools ou des composés à base d'ammonium quaternaire.
PCT/GB1999/004230 1998-12-18 1999-12-14 Medicaments destines au traitement d'infections pulmonaires Ceased WO2000037090A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU16732/00A AU1673200A (en) 1998-12-18 1999-12-14 Medicaments for the treatment of lung infections

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9827865.8 1998-12-18
GBGB9827865.8A GB9827865D0 (en) 1998-12-18 1998-12-18 Medicament

Publications (1)

Publication Number Publication Date
WO2000037090A1 true WO2000037090A1 (fr) 2000-06-29

Family

ID=10844455

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/004230 Ceased WO2000037090A1 (fr) 1998-12-18 1999-12-14 Medicaments destines au traitement d'infections pulmonaires

Country Status (3)

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AU (1) AU1673200A (fr)
GB (1) GB9827865D0 (fr)
WO (1) WO2000037090A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003061668A1 (fr) * 2002-01-17 2003-07-31 Britannia Pharmaceuticals Limited Utilisation de surfactant pulmonaire dans la prevention de maladies infectieuses
FR2856302A1 (fr) * 2003-06-20 2004-12-24 Anben Pharma Composition pharmaceutique utilisee en tant qu'agent anti-infectueux des voies respiratoires superieures
WO2007068007A1 (fr) * 2005-12-07 2007-06-14 Harm Benjamin Steyn Utilisation d'un desinfectant pour le traitement d'infections des voies respiratoires

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1202495A (en) * 1968-05-10 1970-08-19 Ici Ltd Bactericidal and detergent compositions
EP0109284A1 (fr) * 1982-11-12 1984-05-23 Riker Laboratories, Inc. L'acide 6,7-dihydro-5,8-diméthyl-9-fluoro-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxylique et ses dérivés
JPH08151323A (ja) * 1994-11-25 1996-06-11 Nippon Zenyaku Kogyo Kk 豚の呼吸器病の治療・予防方法及び治療剤
EP0788797A1 (fr) * 1996-02-08 1997-08-13 Fresenius AG L'usage de PHMB pour le traitement des infections causées par germes qui se propagent intracellulairement
WO1999026632A1 (fr) * 1997-11-20 1999-06-03 Statens Serum Institut Phospholipides presentant une activite antimicrobienne avec ou sans presence d'agents antimicrobiens

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1202495A (en) * 1968-05-10 1970-08-19 Ici Ltd Bactericidal and detergent compositions
EP0109284A1 (fr) * 1982-11-12 1984-05-23 Riker Laboratories, Inc. L'acide 6,7-dihydro-5,8-diméthyl-9-fluoro-1-oxo-1H,5H-benzo(ij)quinolizine-2-carboxylique et ses dérivés
JPH08151323A (ja) * 1994-11-25 1996-06-11 Nippon Zenyaku Kogyo Kk 豚の呼吸器病の治療・予防方法及び治療剤
EP0788797A1 (fr) * 1996-02-08 1997-08-13 Fresenius AG L'usage de PHMB pour le traitement des infections causées par germes qui se propagent intracellulairement
WO1999026632A1 (fr) * 1997-11-20 1999-06-03 Statens Serum Institut Phospholipides presentant une activite antimicrobienne avec ou sans presence d'agents antimicrobiens

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 33, 1996 Derwent World Patents Index; AN 329422, XP002130459 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003061668A1 (fr) * 2002-01-17 2003-07-31 Britannia Pharmaceuticals Limited Utilisation de surfactant pulmonaire dans la prevention de maladies infectieuses
FR2856302A1 (fr) * 2003-06-20 2004-12-24 Anben Pharma Composition pharmaceutique utilisee en tant qu'agent anti-infectueux des voies respiratoires superieures
EP1493444A1 (fr) * 2003-06-20 2005-01-05 Anben Pharma SARL Composition pharmaceutique utilisée en tant qu'agent anti-infectieux des voies respiratoires supérieures
WO2007068007A1 (fr) * 2005-12-07 2007-06-14 Harm Benjamin Steyn Utilisation d'un desinfectant pour le traitement d'infections des voies respiratoires

Also Published As

Publication number Publication date
GB9827865D0 (en) 1999-02-10
AU1673200A (en) 2000-07-12

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