Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-11-30
1997-02-25
Goldberg, Jerome D
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3135
Patent
active
056059280
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP93/01335, filed May 27, 1993.
The present invention relates to antiemetic pharmaceutical compositions for use in human medicine, and more particularly in pediatric oncologic medicine. The drugs are of special value as antiemetic in pediatric oncology.
Cannabis has been used for millenia as antiemetic. After the identification of delta-9-tetrahydro-cannabinol (delta-9-THC), as the psychoactive constituent of cannabis, it was evaluated as anti-vomiting agent. It was found useful as antiemetic in the chemotherapy of cancer, and is marketed today commercially under the name of Dronabinol. It has a limited effectivity, and prevents vomiting and nausea in about 20 to 30 per cent of treated patients, and reduces such symptoms in another 40 to 50 per cent, having little or no effect in the rest. Pronounced side effects are drowsiness, dizziness and in some cases--anxiety. Such symptoms are pronounced with elderly patients, while younger ones undergo mainly mood changes.
J. Pharm. Sci., 1972, vol. 61, pages 1106 to 1112, describes the oral and parenteral use of marijuana constituents.
Int. J. Pharmaceutics, 1988, vol. 43, pages 9 to 15, describes the skin permeation behaviour of tetrahydrocannabinol through rat and human skin in vitro.
J. Natl. Cancer Inst., 1975, vol. 55, p. 597 to 602, is a general article dealing with anti-cancer therapy based on cannabinoids.
The invention relates to pharmaceutical antiemetic compositions for use as a highly effective antiemetic agent in children undergoing cancer therapy.
The compositions of the invention comprise as active ingredient an effective quantity of delta-8-THC, of the formula(I) ##STR1##
This compound is an isomer of delta-9-THC, and has been found to be at least as effective for the intended use as delta-9-THC, but has considerably reduced side-effects, especially in pediatric medicine. The compound delta-8-THC is considerably more stable towards various chemicals than the delta-9 isomer, and is less prone to oxidation. Furthermore, it can be produced easily and is less expensive than the delta-9-THC isomer.
There administration is per os, and various dosage forms were prepared.
The compositions of the invention were tried on patients, mainly children, before the administration of a variety of anti-cancer drugs. In all of these causes of nausea and vomiting, the compositions proved highly effective, and had negligible undesired side-effects. The experiments were carried out in the framework of an open label evaluation and results indicate that this composition is by far superior to existing ones.
The dosage administered is in the range of from about 5 mg to 20 mg, and preferably in the range of from 6 mg to about 15 mg. In oncology (pediatrics) the dosage is about 4 mg/m.sup.2 to about 30 mg/m.sup.2, and preferably about 10-18 mg/m.sup.2 (surface area of the skin).
It was found that there can be administered to children doses which are larger than those which causes pronounced side-effects in adults. In pediatric use, essentially no side effects of significance were encountered. Doses of the order of 18 mg/m.sup.2 did not cause undesired side-effects.
The effective component is generally administered in a vehicle such as an edible oil. Preferably the active compound is at least 80 per cent pure.
In a trial, with 8 children of 3 to 13 years age, with various blood cancers, treated with a variety of antineoplastic drugs, 18 mg/m.sup.2, in edible oil, p.o. of delta-8-THC was given two hours before the antineoplastic drug, and repeated every 6 hours of 24 hours. Vomiting was completely prevented, with negligible side effects. So far these children have received .DELTA..sup.8 -THC nearly 500 times (see Table).
PATIENTS AND METHODS
Eight children with various blood cancers were administered delta-8-THC at a dose of 18 mg/m.sup.2 p.o. two hours before the start of the anticancer treatment. The drug was dissolved in corn or olive oil (6 mg/ml). The same dose was repeated every 6 hrs for 24 hrs. The treatment for each child is presented
Abrahamov Abraham
Mechoulam Raphael
Goldberg Jerome D
Yissum Research Development Company of The Hebrew University in
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