Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-08-17
2002-08-13
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
Reexamination Certificate
active
06432961
ABSTRACT:
The present invention relates to a method for preventing the onset of asthma with cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof.
The prevalence of asthma, atopic dermatitis and hay fever has increased over the last three decades in many countries (ISAAC, Lancet 1998: 351: 1225-32) and the health and economic burden of these diseases are considerable. So far, no intervention has been shown to alter the natural history of asthma and hay fever. It is known that exposure to high levels of allergen in early life is a major trigger for asthma (U. WAHN et al., Pediatr. Allergy Immunol. 1997:8 (10 suppl): 16-20). Attempts at prevention of allergen avoidance have produced conflicting results with no benefit at all (R. S. ZEIGER et al., Pediatr. Allergy Immunol. 1992: 3: 110-27), only transient effects or, in the case of one study, a long lasting effect (U. M. SAARINEN et al., Lancet 1995: 346: 1065-69; D. W. HIDE et al., Allergy: 51(2): 89-93). There is also a strong association between atopic dermatitis and the subsequent development of asthma. Around 40% of infants with atopic dermatitis in early infancy will develop asthma at the age of 3 to 4 years.
Clearly, the prevalence of asthma and its consequences call for effective methods of preventing asthma.
There are two studies reporting the prophylactic use of ketotifen for the prevention of asthma in preasthmatic children with non specific elevated IgE level (Y. likura et al., Ann. Allergy 1992: 68: 233-36; G. J. BUSTOS et al., Clin. Exp. Allergy 1995: 25(6): 568-73). However, the use of ketotifen in infants and very young children is often associated with side-effects such as drowsiness or nervous excitation.
Therefore, it remains desirable to find other therapeutic methods and pharmaceutical compositions for preventing the onset of asthma, in particular in infants or young children.
The first purpose of the invention concerns the primary prevention of asthma prevention of sensitisation of infants at risk of developing asthma diseases.
The second purpose of the invention is the prevention of allergic asthma in infants at high risk and evidence of aeroallergen (grass pollen or house dust mite) sensitization.
The present invention is based on the unexpected recognition that administration of pharmaceutical compositions comprising cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof to infants prevents the onset of asthma.
The present invention encompasses a method for preventing or retarding the onset of asthma which comprises administering to a patient a therapeutically effective amount of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof.
The present invention also encompasses the use of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof for the preparation of a medicament intended for the prevention of asthma.
The present invention also concerns the use of cetirizine intended for preventing the onset of asthma in a patient, the said medicament being administered to the patient to the patient prior the onset of asthma (e.g. before any biological or clinical symptoms of allergic disease occurs (primary prevention) or after biological signs of sensitization to allergens but before the onset of symptoms of asthma (secondary prevention)).
The present invention also concerns the use of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof for the preparation of a medicament intended for preventing the onset of asthma in a patient, the said medicament being administered to the patient prophylactically prior to the onset of asthma.
The present invention also concerns the use of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof for the preparation of a medicament intended for preventing the sensitisation of patient at risk of developing asthma diseases.
The term cetirizine as used herein refers to 2-[2-[4-(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid. Processes for preparing cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof have been described in European Patent 0 058 146, Great Britain Patent 2.225.320, Great Britain Patent 2.225.321, U.S. Pat. No. 5,478,941, European Patent application 0 601 028, European Patent Application 0 801 064 and International Patent Application WO 97/37.982.
The term “pharmaceutically acceptable salts” as used herein refers not only to addition salts with pharmaceutically acceptable non-toxic organic and inorganic acids, such as acetic, citric, maleic, succinic, ascorbic, hydrochloric, hydrobromic, sulfuric, and phosphoric acids and the like, but also its metal salts (for example sodium or potassium salts) or ammonium salts, the amine salts and the aminoacid salts. The best results have been obtained with cetirizine dihydrochloride.
The term “individual optical isomer” as used herein means the levorotatory and the dextrorotatary enantiomers of cetirizine. More precisely, it means that the active substance comprises at least 90% by weight, preferably at least 95% by weight, of one individual optical isomer of cetirizine and at most 10% by weight, preferably at most 5% by weight, of the other individual optical isomer of cetirizine. Each individual optical isomer may be obtained by conventional means, i.e., resolution from the corresponding racemic mixture or by asymmetric synthesis.
By patient, we understand infants and children, in particular young children. Generally, the patients are infants or children aged 3 months to 10 years, preferably aged 6 months to 5 years, and more preferably 10 months to 5 years. The best results have been obtained with patients aged 1 to 4 years.
According to the invention, the patient is not affected by asthma disease. Preferably, the patient has never been affected by asthma diseases.
Asthma is an inflammatory disease. Symptoms are presence of cough and/or wheezing, in particular recurrent cough and/or wheezing, and more specifically allergic wheezing or nocturnal cough with sleep disturbance lasting for at least 2 consecutive nights. Asthma can be defined as at least 2 separate episodes of nocturnal cough with sleep disturbances lasting for 2 consecutive nights or 2 separate episodes of wheezing. Asthma attack is defined as any episode of nocturnal cough with sleep disturbances lasting for 2 consecutive nights or any episode of wheezing requiring treatment; the second episode of wheezing or nocturnal cough is to be considered as the first asthma attack.
A therapeutically effective amount of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof is used to alleviate the effects of an asthma attack or to prevent or retard onset of an asthma attack. The dosage depends essentially on the specific method of administration and on the purpose of the prophylaxis. The size of the individual doses and the administration program can best be determined based on an individual assessment of the relevant case. The methods required to determine the relevant factors are familiar to the expert.
A preferred daily dosage provides from about 0.0005 mg to about 2 mg of cetirizine, an individual optical isomer thereof or a pharmaceutically acceptable salt thereof, per kg of body weight per patient. A particularly preferred daily dosage is from about 0.005 to about 2 mg per kg of body weight per patient. The best results have been obtained with a daily dosage from about 0.05 to 1 mg per kg of body weight per patient. The dosage may be administered once per day of treatment, or divided into smaller dosages, for examples 1 to 4 times a day, and preferably 1 to 3 times a day, and administrated over about a 24 hours time period to reach a total given dosage. Best results have been obtained with an administration twice a day; the pharmaceutical compositions of the invention are taken in two equal doses per day. The exact d
De Clercq Johan
De Longueville Marc
Uylenbroeck Luc
Wilmes Anne
Spivack Phyllis G.
UCB S.A.
Wenderoth , Lind & Ponack, L.L.P.
LandOfFree
Method for preventing the onset of asthma does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preventing the onset of asthma, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preventing the onset of asthma will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2933828