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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/19—Carboxylic acids, e.g. valproic acid
  • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
  • C07C59/235—Saturated compounds containing more than one carboxyl group
  • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups

Definitions

• the present invention is related to a pharmaceutical composition containing levorotatory hydroxycitrate; (-)HCA, prepared synthetically by a new synthesis method based on citric acid as a starting compound.
• the composition is to be used as an appetite reducer, a lipid-reducing agent and in other physiological processes wherein the substance has effect.
• inventive subject matter may also be used as a flavour additive and a preservative.
• (-)HCA is naturally found as fruit acid in a number of fruits.
• the fruit that normally is used for the preparation of (-)HCA is Garccinia Cambogia.
• this product contains a number of other substances, and the proportion of (-)HCA constitutes less than 50 % of the total content.
• a synthetic (-)HCA product is developed that is 100 % pure. The synthesis is based on citric acid as starting point.
• Citric acid is structurally close related to (-)HCA, and differs only by containing two hydrogen atoms (H) in the molecule instead of two hydroxyl groups. By such a substitution the HCA molecule obtains optical isomerism.
• the structure of the two molecules is shown in Figure 1. From animal studies it appears that the levorotatory isomer is slightly more effective than the dextrorotatory.
• an object of the present invention is to provide an effective, non-toxic substance having clearly documented appetite-reducing properties to be used in human nutrition.
• the toxicity of (-)HCA is at the same level as citric acid.
• (-)HCA should be administered in a dosis from 1-3 g per day. Whether it should be administered before or after a meal to obtain the best possible effect is still not elucidated. The possibility that the timed administration, as compared with the energy intake, does not have any decisive importance for the effect is also present. Only future clinical applications may provide an answer to this question.
• the present invention is directed to a synthetic ( - ) HCA to be used for medical/pharmaceutical/nutritional purposes .
• the synthesis of HCA has significant points of difference from the previously described Hoffman La Roche synthesis.
• the HCA of the present invention is physical-chemical characterised by the following parameters :
• Solubility in water about lOOg/100 ml at 25 °C
• the synthesis pathway is as follows:
• the daily dosis is 3-4 capsules per day.
• Example 1 Hydroxycitrate (HCA) in the treatment of overweight. Erling Thorn. Abstract presented on the 7 th European Overweight Congress in Barcelona, May 1996. Sixty patients, 44 women and 16 men with overweight were included in a randomised placebo controlled double-blind study to investigate the effect and tolerance of hydroxycitrate (-)- HCA by weight reduction. The double-blind study persisted for 8 weeks . HCA, or an identical placebo capsule, was ingested 3 times per day (e.i.d.) , 30 minutes before breakfast, lunch and dinner. In addition, all the patients were given a diet having a low fat content of 1 200 kcal/d. Also, the patients were encouraged to perform physical exercise 3 times/week. The daily dosis of HCA was 1 320 mg/d.
• the average weight reduction in the HCA group (30 patients) was 6,4 kg, whereas the patients in the placebo group showed an average weight reduction of 3,8 kg.
• the difference in weight reduction is highly statistical significant p ⁇ 0,001.
• the distribution of the weight loss determined by NIR (near infrared light) , shows that 87 % of the weight loss in the HCA group is due to the loss of fat, whereas corresponding figures in the placebo groups are 80 %.
• Blood pressure, total cholesterol and hip and waist measures were also significantly reduced in both groups.
• a statistical significant difference in favour of the HCA group was observed in all these parameters (p ⁇ 0,001).
• Appetite score by using visually analogous scales, showed a significant reduction in the HCA group, but not in the placebo group (p ⁇ 0,001) .
• the tolerability of the treatment was excellent. Two patients terminated the treatment due to abdominal pains, one in the HCA group and one in the placebo group.
• Example 2 The patients were subsequently observed for 12 months in an open follow-up study (Example 2) wherein all the patients were given HCA.
• HCA is an effective and tolerable short time treatment of overweight and obesity when it is combined with a sensible low fat diet and exercise. Long term data are necessary to judge effect and tolerability by continuous use over time .
• Example 2 Long term data regarding effect and tolerability of HCA in the treatment of overweight. 52 of the patients that participated in the above- mentioned short time study were further observed in 12 months where all the patients were given the same dosis of HCA as above (1 320 mg/d) . The previously placebo treated patients now experienced a considerable weight loss, and after 12 months the average weight loss for the whole group was 13,8 kg. This constitutes 15 % of the initial weight. This must be regarded as a very satisfactory weight reduction in 1 year. The tolerability was excellent.
• HCA has a documented long-term effect as a weight reduction agent, combined with a low fat diet and exercise. There are no signs of development of tolerance, even after long term use (14 months) .

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical 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)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

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• 1998
  • 1998-06-18 NO NO982818A patent/NO982818L/no not_active Application Discontinuation
  • 1998-12-14 CN CN 98808260 patent/CN1309559A/zh active Pending
  • 1998-12-14 AU AU55368/99A patent/AU5536899A/en not_active Abandoned
  • 1998-12-14 WO PCT/NO1998/000379 patent/WO2000000188A2/en not_active Application Discontinuation
  • 1998-12-14 EP EP98967120A patent/EP1007027A2/en not_active Withdrawn

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