WO1985003638A1 - Compositions containing active lipids - Google Patents

Compositions containing active lipids Download PDF

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Publication number
WO1985003638A1
WO1985003638A1 PCT/FR1985/000032 FR8500032W WO8503638A1 WO 1985003638 A1 WO1985003638 A1 WO 1985003638A1 FR 8500032 W FR8500032 W FR 8500032W WO 8503638 A1 WO8503638 A1 WO 8503638A1
Authority
WO
WIPO (PCT)
Prior art keywords
treatment
active lipids
cystic fibrosis
lipids
aerosol
Prior art date
Application number
PCT/FR1985/000032
Other languages
French (fr)
Inventor
Claude Motta
Meir Shinitzky
Original Assignee
Yeda Research And Development Ltd.
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 Yeda Research And Development Ltd. filed Critical Yeda Research And Development Ltd.
Publication of WO1985003638A1 publication Critical patent/WO1985003638A1/en

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Classifications

    • 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
    • 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

Definitions

  • the invention relates to a preparation for the treatment and attenuation of the symptoms of cystic fibrosis.
  • This treatment consists in applying an aerosol of certain active lipids.
  • Cystic fibrosis (PK or cystic fibrosis) is a genetic disease of children and is characterized by the fact that the pulmonary passages are obstructed by a viscous mucus (RE ood, et al, Cystic Fibrosis, Am.Rev. Resp.Dis. L1J5 833-877 (1976)).
  • a pharmaceutical composition is provided in the form of an aerosol containing as active principle lipi ⁇ active agents, which are a mixture of phosphatidylcholine, phosphatidylethanolamine and glycerides of egg yolk, designed to fluidize cell membranes (D. Heron and al. Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids, Eur. J. Pharmacol, 83_ 253-261 (1982)).
  • active principle lipi ⁇ active agents which are a mixture of phosphatidylcholine, phosphatidylethanolamine and glycerides of egg yolk, designed to fluidize cell membranes (D. Heron and al. Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids, Eur. J. Pharmacol, 83_ 253-261 (1982)).
  • This product is marketed by Natural Pharmaceutical Corporation, Los Angeles, E.U.A.
  • FIRE2 L ⁇ OF REPLACEMENT The active principle, designated here by the initials LA, was dispersed in distilled water, by vortex. Other aerosol formulas can be used. In general, a concentration of 1 to 5 percent by weight is satisfactory. The treatments of which it is reported here have been carried out with 2% by weight of LA, by "aerosolization". The amount administered was 3 to 5 ml of this dispersion for 15 to 20 minutes, twice a day. The efficacy of the new compositions was evaluated by measuring the average time necessary to expectorate a certain volume of mucus, 10 ml for example, and from the total amount of expectorated mucus during a coughing fit. The patients were children 8 to 12 years old.
  • Duration of cough 30 minutes (two or three times a day) with expectoration of approximately 10 ml of mucus.
  • Example 1 age 11, male.
  • Aerosol production average volume of expectoration by pneumatic device: from 40 ml to 60 ml, duration of cough reduced to an average of 5 minutes, no antibiotic therapy during the duration of administration of LA , no change in tachypnea.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Otolaryngology (AREA)
  • Pulmonology (AREA)
  • Medicinal Preparation (AREA)

Abstract

Preparation for the treatment of the attenuation of cystic fibrosis symptoms. Said treatment comprises the application of a pharmaceutical composition in the form of a spray containing as active principle active lipids (L.A.), which are a mixture of phosphatidylcholine, phosphatidylethanolamine and ovi vitellus glycerides, intended to fluidize the cell membranes. The figure herewith appended shows the expectoration volume and the duration of cough before and after the administration of a composition of active lipids (L.A.) according to the invention.

Description

COMPOSITIONS CONTENANT DES LIPIDES ACTIFS Domaine de 1'invention COMPOSITIONS CONTAINING ACTIVE LIPIDS Field of the Invention
L'invention concerne une préparation pour le trai¬ tement et l'atténuation des symptômes de la fibrose kystique. Ce traitement consiste à appliquer un aérosol de certains lipides actifs.The invention relates to a preparation for the treatment and attenuation of the symptoms of cystic fibrosis. This treatment consists in applying an aerosol of certain active lipids.
Arrière-plan de l'inventionInvention background
La fibrose kystique (PK ou mucoviscidose) est une maladie génétique des enfants et se caractérise par le fait que les voies pulmonaires sont obstruées par un mu¬ cus visqueux (R.E. ood, et al, Cystic Fibrosis, Am.Rev. Resp.Dis .L1J5 833-877 (1976)) .Cystic fibrosis (PK or cystic fibrosis) is a genetic disease of children and is characterized by the fact that the pulmonary passages are obstructed by a viscous mucus (RE ood, et al, Cystic Fibrosis, Am.Rev. Resp.Dis. L1J5 833-877 (1976)).
L'étiologie de la maladie n'est pas connue et il n'existe aucune thérapie efficace ; l'issue est gênéra- lement fatale. La thérapie actuelle est basée sur le soulagement des difficultés respiratoires par kinésithé¬ rapie (R.B. Mellins, Pulmonary physiotherapy in the pé¬ diatrie âge group, Am.Rev.Resp.Dis 110 Supp.pl37 (1974)) . Certains types de thérapie par aérosol sont utilisés (P.O. Alderson et al, Pulmonary déposition of aérosols in children with cystic fibrosis, J.Pediatr. 8_ 479 (1974)).The etiology of the disease is unknown and there is no effective therapy; the outcome is usually fatal. Current therapy is based on the relief of breathing difficulties by physiotherapy (R.B. Mellins, Pulmonary physiotherapy in the pediatrics age group, Am.Rev.Resp.Dis 110 Supp.pl37 (1974)). Certain types of aerosol therapy are used (P.O. Alderson et al, Pulmonary deposition of aerosols in children with cystic fibrosis, J. Pediatr. 8_ 479 (1974)).
Résumé de l'inventionSummary of the invention
Il est fourni une composition pharmaceutique sous forme d'aérosol contenant comme principe actif des lipi¬ des actifs, qui sont un mélange de phosphatidylcholine, de phosphatidylethanolamine et de glycerides du jaune d'oeuf, conçu pour fluidiser les membranes cellulaires (D. Héron et al. Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids, Eur. J. Pharmacol, 83_ 253-261 (1982)) . Ce produit est mis dans le commerce par Natural Pharmaceutical Corporation, Los Angeles, E.U.A.A pharmaceutical composition is provided in the form of an aerosol containing as active principle lipi¬ active agents, which are a mixture of phosphatidylcholine, phosphatidylethanolamine and glycerides of egg yolk, designed to fluidize cell membranes (D. Heron and al. Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids, Eur. J. Pharmacol, 83_ 253-261 (1982)). This product is marketed by Natural Pharmaceutical Corporation, Los Angeles, E.U.A.
FEU2 LΞ DE REM ACEMENT Le principe actif, désigné ici par les initiales LA, était dispersé dans de l'eau distillée, par tourbillone- ent. D'autres formules d'aérosol peuvent être utilisées. En général, une concentration de 1 à 5 pour cent en poids est satisfaisante. Les traitements dont il est rendu comp¬ te ici ont été effectués avec 2 % en poids de L.A., par "aérosolisation" . La quantité administrée était de 3 à 5 ml de cette dispersion pendant 15 à 20 minutes, deux fois par jour. On a évalué l'efficacité des nouvelles compositions en mesurant le temps moyen nécessaire pour expectorer un certain volume de mucus, 10 ml par exemple, et à partir de la quantité totale de mucus expectoré au cours d'une quinte de toux. Les patients étaient des enfants de 8 à 12 ans. Certains de ces patients souffraient d'une infec¬ tion pulmonaire chronique par Pseudo onas aeruginosa. Chez tous les enfants soumis au traitement, on a observé une réduction progressive de la durée de la toux. Au bout de 7 jours de traitement, la durée de la toux était réduite d'un facteur de 6 à 10, et la quantité de mucus expectoré était augmentée d'un facteur de 4 à 6. L'état physique et clinique était nettement amélioré. On n'a observé d'effet néfaste chez aucun des patients. Un résumé est donné di-dessous.FIRE2 LΞ OF REPLACEMENT The active principle, designated here by the initials LA, was dispersed in distilled water, by vortex. Other aerosol formulas can be used. In general, a concentration of 1 to 5 percent by weight is satisfactory. The treatments of which it is reported here have been carried out with 2% by weight of LA, by "aerosolization". The amount administered was 3 to 5 ml of this dispersion for 15 to 20 minutes, twice a day. The efficacy of the new compositions was evaluated by measuring the average time necessary to expectorate a certain volume of mucus, 10 ml for example, and from the total amount of expectorated mucus during a coughing fit. The patients were children 8 to 12 years old. Some of these patients suffered from chronic lung infection with Pseudo onas aeruginosa. In all children treated, there was a gradual reduction in the duration of cough. After 7 days of treatment, the duration of the cough was reduced by a factor of 6 to 10, and the quantity of expectorated mucus was increased by a factor of 4 to 6. The physical and clinical condition was markedly improved. . No adverse effects were observed in any of the patients. A summary is given below.
Avant traitement par L.A.Before treatment with L.A.
Durée de la toux : 30 minutes (deux ou trois fois par jour) avec expectoration d'environ 10 ml de mucus.Duration of cough: 30 minutes (two or three times a day) with expectoration of approximately 10 ml of mucus.
Aspect de 1'expectoration : Couleur verte, contenant des agrégats de mucus, gran¬ de viscosité (appréciation visuelle) , forte adhérence aux tubes de verre ou de matière plastique, difficulté d'obte¬ nir un surnageant clair par centrifugation. Après traitement par L.A.Aspect of the sputum: Green color, containing aggregates of mucus, large viscosity (visual appreciation), strong adhesion to glass or plastic tubes, difficulty in obtaining a clear supernatant by centrifugation. After treatment with LA
Durée de la toux remarquablement réduite à une moyenne de 5 minutes, avec production de 30 à 60 ml de mucus. Aspect de 1'expectoration :Duration of cough remarkably reduced to an average of 5 minutes, with production of 30 to 60 ml of mucus. Aspect of sputum:
Couleur verte à blanche, pas d'agrégats de mucus (vérifié sur tous les échantillons) , très fluide, pas d'adhérence au verre ni à la matière plastique, surna¬ geant clair très facile à séparer des particules solidesGreen to white color, no mucus aggregates (checked on all samples), very fluid, no adhesion to glass or plastic, clear surface very easy to separate from solid particles
Exemple typeTypical example
Exemple 1 : âge 11 ans, sexe masculin.Example 1: age 11, male.
Diagnostic de mucoviscidose dans le premier mois de la vie. Hypotrophie notable. Infection chronique par Pseudomonas (pas de forme aiguë ni de surinfection) .Diagnosis of cystic fibrosis in the first month of life. Noticeable hypotrophy. Chronic Pseudomonas infection (no acute form or secondary infection).
Radiologie : dilatation des bronches des deux lobes supérieurs des poumons avec opacité nodulaire. Pas d'évo¬ lution au cours des 18 derniers mois. Volume d'expectoration : 8-10 mlRadiology: dilation of the bronchi of the two upper lobes of the lungs with nodular opacity. No change in the past 18 months. Sputum volume: 8-10 ml
Durée de la toux : 20 à 30 minutesDuration of cough: 20 to 30 minutes
Traitement par 3 ml de lipides actifs à 200 g/ml du 24 mai au 7 juillet 1983,Treatment with 3 ml of active lipids at 200 g / ml from May 24 to July 7, 1983,
Production d'aérosol : volume moyen d'expectoration à l'appareil pneumatique : de 40 ml à 60 ml, durée de la toux réduite à une moyenne de 5 minutes, pas d'antibiothé- rapie pendant la durée de l'administration des L.A. , pas de modification de la tachypnée. Aerosol production: average volume of expectoration by pneumatic device: from 40 ml to 60 ml, duration of cough reduced to an average of 5 minutes, no antibiotic therapy during the duration of administration of LA , no change in tachypnea.

Claims

REVENDICATIONS
1. Suspension pour aérosolisation comprenant des lipides actifs, tels qu'ils sont définis ici, dans un véhicule convenable. 1. Suspension for aerosolization comprising active lipids, as defined herein, in a suitable vehicle.
2. Suspension selon la revendication 1, contenant de 1 à 5 pour cent en poids de lipides actifs dans un milieu aqueux.2. Suspension according to claim 1, containing from 1 to 5 percent by weight of active lipids in an aqueous medium.
3. Suspension selon la revendication 1 ou 2, dans laquelle le véhicule est de l'eau distillée.3. Suspension according to claim 1 or 2, wherein the vehicle is distilled water.
4. Composition selon l'une quelconque des revendications 1 à 3, pour le traitement de la fibrose kystique par traitement par aérosol.4. Composition according to any one of claims 1 to 3, for the treatment of cystic fibrosis by aerosol treatment.
5. Procédé d'atténuation des symptômes de la fibrose kystique, qui consiste à administrer au patient une quantité efficace de lipides actifs, tels qu'ils sont définis ici, dans un véhicule convenable, sous forme d'aérosol.5. A method of alleviating the symptoms of cystic fibrosis, which consists in administering to the patient an effective amount of active lipids, as defined herein, in a suitable vehicle, in the form of an aerosol.
6. Formules d'aérosol pour le traitement des symptômes de la fibrose kystique, en substance telles qu'elles sont décri¬ tes ci-avant et avec référence à l'exemple. 6. Aerosol formulas for the treatment of symptoms of cystic fibrosis, in substance as described above and with reference to the example.
PCT/FR1985/000032 1984-02-23 1985-02-25 Compositions containing active lipids WO1985003638A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL71051A IL71051A (en) 1984-02-23 1984-02-23 Compositions containing active lipids for the treatment of cystic fibrosis
IL71051 1984-02-23

Publications (1)

Publication Number Publication Date
WO1985003638A1 true WO1985003638A1 (en) 1985-08-29

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EP (1) EP0172862A1 (en)
AU (1) AU3994085A (en)
IL (1) IL71051A (en)
WO (1) WO1985003638A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0450991A2 (en) * 1990-02-20 1991-10-09 Synthelabo Use of phosphatidylglycerol(diC 18:10)in the treatment of obstructive airway diseases
WO2000051578A2 (en) * 1999-03-03 2000-09-08 Florian Lang Use of ceramides for the treatment of cystic fibrosis
WO2002094283A2 (en) * 2001-05-21 2002-11-28 Britannia Pharmaceuticals Limited Use of phospholipids in the treatment of degenerative lung disease such as copd or cystic fibrosis and to enhance delivery of drugs

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR7107M (en) * 1967-12-27 1969-07-15
US3594476A (en) * 1969-05-12 1971-07-20 Massachusetts Inst Technology Submicron aqueous aerosols containing lecithin
GB2050832A (en) * 1979-06-02 1981-01-14 Tokyo Tanabe Co Surface active material containing phospholipid lipid carbohydrate and protein
EP0074251A1 (en) * 1981-09-04 1983-03-16 Yeda Research And Development Company, Ltd. Novel lipid fraction, its preparation and pharmaceutical compositions containing same

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR7107M (en) * 1967-12-27 1969-07-15
US3594476A (en) * 1969-05-12 1971-07-20 Massachusetts Inst Technology Submicron aqueous aerosols containing lecithin
GB2050832A (en) * 1979-06-02 1981-01-14 Tokyo Tanabe Co Surface active material containing phospholipid lipid carbohydrate and protein
EP0074251A1 (en) * 1981-09-04 1983-03-16 Yeda Research And Development Company, Ltd. Novel lipid fraction, its preparation and pharmaceutical compositions containing same

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 96, No. 5, 01 February 1982, Columbus, Ohio (US) A. SLOMIANY et al.: "Lipid Composition of Tracheobronchial Secretions from Normal Individuals and Patients with Cystic Fibrosis", see page 462, column 2, Abstract 32897w & Biochim. Biophys. Acta 1982, 710 (1), 106-11 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0450991A2 (en) * 1990-02-20 1991-10-09 Synthelabo Use of phosphatidylglycerol(diC 18:10)in the treatment of obstructive airway diseases
EP0450991A3 (en) * 1990-02-20 1992-12-16 Synthelabo Use of phospholipids in the treatment of obstructive airway diseases
WO2000051578A2 (en) * 1999-03-03 2000-09-08 Florian Lang Use of ceramides for the treatment of cystic fibrosis
WO2000051578A3 (en) * 1999-03-03 2001-01-04 Florian Lang Use of ceramides for the treatment of cystic fibrosis
WO2002094283A2 (en) * 2001-05-21 2002-11-28 Britannia Pharmaceuticals Limited Use of phospholipids in the treatment of degenerative lung disease such as copd or cystic fibrosis and to enhance delivery of drugs
WO2002094283A3 (en) * 2001-05-21 2003-11-27 Britannia Pharmaceuticals Ltd Use of phospholipids in the treatment of degenerative lung disease such as copd or cystic fibrosis and to enhance delivery of drugs

Also Published As

Publication number Publication date
IL71051A0 (en) 1984-05-31
AU3994085A (en) 1985-09-10
IL71051A (en) 1988-02-29
EP0172862A1 (en) 1986-03-05

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