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
  • A61K31/12—Ketones
  • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
  • A23L33/15—Vitamins
  • A23L33/155—Vitamins A or D
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
  • A23L5/00—Preparation or treatment of foods or foodstuffs, in general; Food or foodstuffs obtained thereby; Materials therefor
  • A23L5/40—Colouring or decolouring of foods
  • A23L5/42—Addition of dyes or pigments, e.g. in combination with optical brighteners
  • A23L5/43—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives
  • A23L5/44—Addition of dyes or pigments, e.g. in combination with optical brighteners using naturally occurring organic dyes or pigments, their artificial duplicates or their derivatives using carotenoids or xanthophylls
• • 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
  • A61K31/01—Hydrocarbons
• • 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
  • A61K31/01—Hydrocarbons
  • A61K31/015—Hydrocarbons carbocyclic
• • 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
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• • 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
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
  • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P39/00—General protective or antinoxious agents
  • A61P39/06—Free radical scavengers or antioxidants
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

• This invention relates to pharmaceutical and dietary compositions comprising a combination of compounds useful in preventing cancer and to the use of said compositions and said combination of compounds for said purpose.
• This invention more particularly relates to a pharmaceutical or dietary composition for lowering the plasma level of insulin-like growth factor I (IGF-I) levels in mammals.
• IGF-I insulin-like growth factor I
• the IGF-I level was found to be a major risk factor for prostate (Chan J.M., Stampfer M.J., Giovannucci E., Gann P.H., Winkinson P., Hannekens C.H., and Pollak M.
• Carotenoids are colored pigments with lipophilic properties, widely distributed in f uits and vegetables (e.g. ⁇ -carotene in carrots and lycopene in tomatoes) and active in interfering with IGF-I action (Unpublished results). Carotenoids are transported within circulating lipoproteins when ingested in the human body.
• Carotenoids consumption was shown in previous epidemiological studies to be associated with reduced cancer mortality, although recent data did not demonstrate similar beneficial effects (see e.g.: Hennekens C.h., Buring J.E., Manson J.E., Stampfer M., Rosier B., Cook N.R., Belanger C, LaMotte F., Gaziano J.M., Ridker P.M., Willet W. and Peto R, "Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease" (N. Engl. J. Med. 1996; 334: 1145-1149).
• Data on the ability of ⁇ -carotene supplementation in vitro or in vivo to protect from cancer are conflicting: Some studies found an inhibitory effect of ⁇ -carotene supplementation, whereas several others did not find such an effect.
• Lycopene the open chain analog of ⁇ -carotene, shares with it a similar structure comprising extended conjugated double bonds. In human plasma, lycopene and ⁇ -carotene are quantitatively the major carotenoids. Lycopene was shown to possess the greatest quenching ability of singlet oxygen among the various carotenoids (DiMascio P., Kaiser S. and Sies H., "Lycopene as the most efficient biological carotenoid singlet oxygen quencher," Arch. Biochem.
• Lycopene has been shown to significantly reduce IGF-induced tyrosine phosphorylation of insulin receptor substrate-I and up-regulation of binding capacity of the AP-I transcription complex (Karas et al. 2000. Nutr. Cancer 36(1): 101-111). However, until now lycopene has not been shown to cause a decrease in the plasma levels of IGF-I.
• the present invention is based on the discovery that there is an unexpected and surprising reduction in plasma levels of insulin like growth factor-I (IGF-I) after lycopene or other carotenoid supplementation in mammals.
• IGF-I insulin like growth factor-I
• the present invention provides a pharmaceutical or dietary composition which comprises a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin astaxantine and mixtures thereof, wherein said composition is effective in reducing IGF-I levels in plasma in a mammal.
• the present invention further provides a use of a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantine and mixtures thereof in the preparation of a pharmaceutical or dietar - composition which is effective in reducing IGF-I levels in plasma in a mammal.
• a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantine and mixtures thereof in the preparation of a pharmaceutical or dietar - composition which is effective in reducing IGF-I levels in plasma in a mammal.
• the present invention provides a method for reducing IGF-I levels in plasma in a mammal wherein said method comprises administering to a mammal in need thereof, an IGF-I reducing effective amount of a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantine and mixtures thereof.
• a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantine and mixtures thereof.
• the carotenoids referred to throughout the specification are from natural or synthetic sources or from genetically modified organisms.
• the invention comprises a method for reduction in plasma level of IGF-I which comprises administering to a patient lycopene or a carotenoid selected from, but not limited to, a group comprising of alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin astaxantine and mixtures thereof, in the amount of at least 3 mg per day.
• a carotenoid selected from, but not limited to, a group comprising of alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin astaxantine and mixtures thereof, in the amount of at least 3 mg per day.
• Lycopene is a natural product and is present in tomatoes in various concentrations, but it can also be produced synthetically, and synthetic lycopene, compositions comprising it and their use are comprised in the present invention.
• the composition may contain other dietary components, additives, excipients, binding agents, coatings, etc., or other compounds that have no significant effect in reducing IGF-I.
• the compositions according to the invention in view of their purpose, are pharmaceutical composition. However, since their components are individually acceptable ingredients of the human diet, and, in fact, are individually present in foodstuffs, they may be considered and used as dietary or health compositions.
• Tomato oleoresin comprises a combination of lycopene with vitamin E, ⁇ -carotene, phytoene and phytofluene, and therefore the use of tomato oleoresin for the reduction of plasma levels of insulin like growth factor I is a specific aspect of the present invention. Both tomato oleoresin and pure lycopene reduce plasma levels of IGF-I by at least 10% in responding individuals.
• lycopene was obtained from tomato oleoresin.
• the oleoresin was supplied by LycoRed Natural Products Industries, Ltd., Beer Sheva, Israel. It contained crystalline lycopene (5%) suspended in the lipid phase of the tomato. Fatty acids as triglycerides constituted the major part (72%) of the oleoresin, whereas 19% were non-saponified materials including inter alia 5% lycopene, 0.1% ⁇ -carotene, 1% vitamin E, as well as phytoene and phytofluene.
• the lycopene used was extracted and purified mainly in the all-trans configuration. Lycopene can be extracted from tomato oleoresin, known in the art by crystallization followed by filtration.
• carotenoids selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantin and mixtures thereof are used in the preparation of pharmaceutical or dietary compositions effective in reducing IGF-I levels in mammalian plasma.
• the compositions are prepared according to common practices wherein a carotenoid in the amount of at least 3 mg is added to the composition.
• a pharmaceutical or dietary composition for lowering IGF-I levels in mammalian blood wherein said composition is characterized in that it comprises a carotenoid selected from, but not limited to, a group comprising of lycopene, alpha-, beta-, zeta-carotene, phytoene, phytofluene, lutein, zeaxanthin, cryptoxanthin and astaxantin and mixtures thereof.
• Said composition may be prepared according to common practices well known in the art wherein a carotenoid or a mixture thereof are added to the composition.
• Example 1 Effect of tomato oleoresin supplementation on plasma levels of IGF-1
• lycopene supplementation was studied. Lycopene (5% in tomato oleoresin, two 15 mg capsules per day) or a placebo were administered for three to four weeks prior to surgery. Lycopene concentration and isomer distribution in blood and in the excised tissues were measured by HPLC. Lycopene blood levels increased in most of the subjects who received lycopene supplementation . In the placebo group, the lycopene plasma level before supplementation was similar to that of the lycopene treated group and did not change significantly after supplementation. IGF-I level was measured using the IRMA kit (DSL-5600 Active. Diagnostic System Laboratories, Webster, TX).
• IGF-II Basal IGF-I plasma levels varied considerably between subjects. In 15 out of 28 patients in the lycopene-treated group (53%), IGF-I blood level decreased by more than 10%. In 7 patients (25%) there was no change. In contrast, only 4 out of 28 placebo-treated patients (14%) exhibited a decrease in IGF-I plasma level and in 20 (71%), no change was occurred. These data clearly indicate lycopene supplementation is effective in significantly reducing IGF-1 levels in a certain proportion of subjects who are "responders". In contrast, when the effects of lycopene supplementation on blood levels of IGF-II and IGF-BP-3 were examined, no differences were found between the lycopene treated group and the placebo group. IGF-II was measured by ELIZA (DSL- 10-91000) and IGF-BP-3 by IRMA (DSL-6600), using kits from Diagnostic System Laboratories, Webster, TX.

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• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)
• Coloring Foods And Improving Nutritive Qualities (AREA)
• Medicines Containing Plant Substances (AREA)

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• 1999
  • 1999-04-14 IL IL12944299A patent/IL129442A0/xx unknown
• 2000
  • 2000-03-29 WO PCT/IL2000/000195 patent/WO2000061130A1/en not_active Application Discontinuation
  • 2000-03-29 CN CN00808819A patent/CN1355695A/zh active Pending
  • 2000-03-29 CA CA002369084A patent/CA2369084A1/en not_active Abandoned
  • 2000-03-29 AU AU34526/00A patent/AU762968B2/en not_active Ceased
  • 2000-03-29 JP JP2000610463A patent/JP2002541193A/ja active Pending
  • 2000-03-29 BR BR0011171-6A patent/BR0011171A/pt not_active Application Discontinuation
  • 2000-03-29 RU RU2001127436/15A patent/RU2242220C2/ru not_active IP Right Cessation
  • 2000-03-29 EP EP00912886A patent/EP1173158A1/de not_active Withdrawn

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