Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1999-02-24
2000-04-18
Cook, Rebecca
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514810, 514811, 514812, A61K 3166
Patent
active
060515643
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention concerns lipid-based compositions and use of such compositions in the treatment of withdrawal syndromes or cancer.
BACKGROUND OF THE INVENTION AND PRIOR ART
Withdrawal syndromes can occur during rehabilitation from addiction to drugs, alcohol, cigarettes and from an abrupt decline in the level of various hormones such as that occurring in menopause women. It is expressed in symptoms of seizures, sweat, tremor, nausea, depression, increase in rate of heart beat and in blood pressure, and others. Typically such addiction is treated by a "wash out" period in which the dependency is gradually removed with or without drug intervention. This process is painful and tedious and candidates are thus very often discouraged from entering it. There is thus a strong need for a solution that can ease the difficult period of withdrawal and that would allow people to return to normal life without much complications.
A basic biochemical phenomenon shared by most of the withdrawal syndromes is a change in the composition and in the structure of neuronal cell membranes which is expressed in membrane "fluidity" (Hannan, Am. Rev. Respir. Dis., 140 (1989), 1668-73; Crews, Psycho-pharmacology, 81 (1983), 208-13; Harris, Life Sci., 35 (1984), 2601-8; Heron et al., Eur. J. Pharmacol., 83 (1982), 253-261). These changes can at times be counteracted by administration of special natural preparations, resulting in the reduction of the symptoms related to the withdrawal processes (Heron et al., Eur. J. Pharmacol, 83 (1982) 253-261; Shinitzky, Physiology of membrane fluidity, (1984), Vol I, Chapt. 1).
Multi-drug resistance (MDR) is also related to change in the fluidity of the cell membrane (Seydel et al. Arch. Pharm., 327. 601-610, 1994). MDR is a major cause of failure of cancer therapy involving use of cytotoxic drugs, particularly in recurring cancer.
Phosphatidic acid (PA) is a natural phospholipid found in plants and animal tissues. Its content usually does not exceed 5% of the total phospholipids in any of these sources. Therefore, lipid extracts available for human consumption (e.g., soybean phospholipids) are low in PA. Other sources of processed lipid mixtures for per os consumption or intravenous injection are devoid of PA. These include AL 721 (Antonian et al., Neurosci. Biobehav. Rev. 11 (1987), 399-413); Bros.TM. (Fidia Sp. A. Abano-Terme, Italy) or Intralipid.TM. (Vitrum Inc., Stockholm, Sweden).
Enzymatic procedures utilizing the enzyme phospholipase D for the hydrolysis of phospholipids to PA are known (Waite, M. Ed. The phospholipases, Plenum Press, New York, 1987). However, hitherto no use of such procedures to enrich natural lipase preparations with PA has been made. PA incorporated in a liposome containing phosphatidyl choline preparation was shown to reduce toxicity and enhance anti-fungal activity of the anti-fungal drug Hamycin. It was shown that PA had a strong protective effect and increased the survival of mice by 90% after seven days of therapy, as compared to mice treated with Hamycin alone (Moonis M. et al., J. Anti. Microb. Chemother., 31:569-579, 1993). Furthermore, a liposome preparation comprising PA was shown to counter symptoms of kidney toxicity caused by amino glucoside antibiotics as demonstrated by a recuperation in the kidneys' phosphatase activity (Mingert-Leclercq, M. P., et al., Biochem. Pharmacol., 40:489-497, 1990).
GLOSSARY
The following is the meaning of some terms of which use will be made in the text below: body of a substance to which the body was exposed continuously over a period of time. Such a substance may be an exogenous substance, taken by the individual, or may be an endogenous one. Exogenous substances may include, for example, drugs of abuse, e.g. heroin, cocaine, morphine, and others, a variety of therapeutic drugs, e.g. sedatives; tobacco, alcohol, and others. Endogenous substances may include a variety of hormones, particularly such hormones the level of which changes at a certain age. Typical examples of withdrawal syndrom
REFERENCES:
patent: 4263286 (1981-04-01), Nakajima et al.
Moonis M, et al., "Liposomal hamycin in the control of experimental aspergillosis in mice: effect of phosphatidic acid with and without cholesterol." J Antimicrob Chemother, vol. 31, issue 4, Apr. 1993, pp. 569-579, abstract.
Seydel JK, et al., "Drug membrane interaction and the importance for drug transport, distribution, accumulation, efficacy and resistance." Arch Pharm (Weinhein) vol. 327, issue 10, Oct. 1994 , pp. 601-610, abstract.
Hannan SE, et al., "Cigarette smoke alters plasma membrane fluidity of rat alveolar macrophages." vol. 140, issue 6, Dec. 1989, pp. 1668-1673, abstract.
Shinitzky, M., "Physiology of Membrane Fluidity, vol. 1" CRC Press, Inc., pp. 1-51, 1984.
Heron, D.S., et al., "Alleviation of Drug Withdrawal Symptoms By Treatment With a Potent Mixture of Natural Lipds" European Journal of Pharmacology, vol. 83, 1982, pp. 253-261.
Crews, F.T., et al., "Changes in Cortical Synaptosomal Plasma Membrane Fluidity and Composition in Ethanol-Dependent Rats", Psychopharmacology, vol. 81, 1983, pp. 208-213.
Antonian, L., et al., "AL721, A Novel Membrane Fluidizer", Neuroscience & Biobehavioral Reviews, vol. 11, Aug. 24, 1987, pp. 399-413.
Mingeot-Leclerco et al., "Effect of Acidic Phospholipids on the Acitvity of Lysosomal Phospholipases and on Their Inhibition by Aminoglycoside Antibiotics-I", Biochemical Pharmacology, vol. 40, No. 3, 1990, pp. 489-497.
Harris, R.A., et al., "Relationship of Membrane Physical Properties to Alcohol Dependence in Mice Selected for Genetic Differences in Alcohol Withdrawal", Life Sciences, vol. 35, No. 26, 1984, pp. 2601-2608.
Patent Abstracts of Japan, JP 04267882, "Production of Phosphatidic Acid", Sep. 24, 1992, abstract.
Chemical Abstracts, vol. 95, No. 23, Dec. 7, 1981, abstract No. 95:202254h, Yoriko Nakayama et al.: "Decomposition of soybean spherosomes by soybean phospholipase D", p. 535.
Database WPI, Derwent Publications Ltd., AN 94-173655[21], JP 06116149, Apr. 26, 1994.
Shenfeld Avner
Shinitzky Meir
Cook Rebecca
Modus Biological Membranes Ltd.
Nath Gary M.
Yarnell Scott F.
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