WO1992000085A1 - Freeze-dried hybrid mild pumpkin and drugs containing same - Google Patents

Abstract

The novel freeze-dried total extract of hybrid mild pumpkin has a homogeneous powdery appearance, a permanent yellow-organe colour, a pH between 6.44 and 6.47, a carbohydrate content of 63-67 %, a lipid content of 6 % 0.5 %, a protein content of 10 % 1 %, and a total carotenoid content of 25 mg 10 % per gramme of the freeze-dried extract. This substance has therapeutical applications, particularly as an orally or transcutaneously administered drug having an anti-inflammatory, antipyretic and pain-killing activity at least as great as that of betamethasone.

Description

 L yoph i l i sat de p iti ron d oux hybride et medicaments l e contain.

 Cucurbits are a family of annual broadleaf plants widespread in all countries of the world whose edible fruits such as squash, pumpkins, pumpkins (cucurbita), melons, cucumbers (cucumis), watermelons (citrullus), casays (Lagenaria) are widely consumed .

 Since ancient times, these plants have been known for their beneficial therapeutic properties and certain inedible varieties, Bryone (Bryonia), donkey cucumber (Echallium) for their toxicity.

 They have given rise to numerous botanical, pharmacochemical, pharmacodynamic research and various therapeutic applications as well as to numerous publications and patent applications.

 This research came up against the chemical complexity of these plants and consequently the instability of the results collected, due to the infinite variety of the different species studied, not only in relation to each other, but also in each species with the variation of the sources, the seasons, the years, the sown grounds, the cultural ways.

 The present invention relates to a new lyophilisate of total extract of hybrid sweet pumpkin.

 This lyophilisate is obtained from a variety selected for 12 years by successive hybridizations. The plant is raised under organic cultivation contract. The controls are carried out periodically at the level of the ground and the runoff during and at the end of production. This pumpkin picked at maturity, washed, crushed with bark, pulp and seeds is lyophilized according to a conventional process, then made bacteriologically stable by irradiation with gamma radiation.

The genetic stability obtained by a tightly controlled culture over a long period, facilitates the standardization of the physico-chemical constants of the lyophilisate thus obtained. It has the following characteristics:

Macroscopic and organoleptic characters

 Fine, homogeneous powder and indelible yellow-orange color.

 Herbal odor, floury taste.

 Macroscopic characters

 Examination under an optical microscope of a lyophilisate preparation in a drop of distilled water according to FIG. 1 detects the presence of fibers and the absence of elongated starch grains.

 Bacteriological characters

- quantity of aerobic mesophilic germs less than or equal to 5.0. 10 ² .

- quantity of yeast and mold less than or equal to 5.0. 10 ² .

 - absence of pathogenic germs, namely absence:

- from Escherichia Coli

 - Staphylococcus aureus

 - of Pseudomonas aeruginosa

 - of Salmonella typhimurium

 Physico-chemical characters

 - pH between 6.44 and 6.47

 - heavy metals <2ppm

 - carbohydrate content between 63 and 67% - lipid content of 6% ± 0.5

 - protein content of 10% ± 1%

 - total carotenoid content of 25mg ± 10% per gram of lyophilisate.

 The assay is carried out by ultraviolet spectrophotometry using a Perkin-Elmer device, by comparison with a control batch of β carotene, reference Merck 2236 according to FIGS. 2 and 3.

 The product is insoluble in water, sparingly soluble in ethanol and methanol, sparingly soluble in ether and oils, soluble in chloroform.

The conservation of these parameters is linked to the storage of the product away from photosynthesis or oxidation due to heat. The cocinetic pharma study of lyophilisate reveals that the richness in provitamins A (β carotene) and in lipids of this lyophilisate is three times greater than the corresponding contents of common pumpkin or carrot; by its high concentration of carotenoxdes, the compound induces the bio-synthesis of Retinol and promotes rapid cell regeneration accelerating the healing process by stimulation of cell mitosis.

The seed oil by incorporating more lipids and more unsaturated fatty acids, linoleic and linolenic, to it is itself an important factor of the penetrating power of topical preparations for dermatological and cosmetic use made with the compound. The half-life of the lyophilisate has been determined to the extent of four to five hours for a therapeutic dose of 100 mg / kg / day.

 The t.oxicol ngigiift study of this compound showed:

 - very low acute toxicity, the LD 50 determined per os in mice and rats being greater than 5 g per kilo;

 - perfect tolerance after six months of repeated administration in rats of both sexes, demonstrated by weight, hematological, biochemical and anatomo-pathological examinations

 The pharmaenlogical study: the anti-inflammatory activity was demonstrated both per os and topically according to the methods of:

 - carrageenan edema

 - edema with kaolin.

The examination of the results given in FIG. 4 shows that the pumpkin hypohilisate administered both in powder form by the oral route and in gel by the cutaneous route has a highly significant anti-inflammatory activity the first hour and significant the second and third hours after each taken. Under the same experimental conditions, the action of betamethasone was shown to be significant at the first hour, not significant at the second hour, zero at the third. The analgesic activity was sought and objectified in rats according to the La Belle technique and

Tislow. The results recorded in FIG. 5 show that the lyophilisate tested compared to betamethasone has an activity equal to, or even greater than, this.

 The examples of therapeutic applications indicated below illustrate the invention in more detail without limiting its scope, the product can be prescribed and used alone or in combination with other active ingredients.

 EXAMPLE 1

 Oral preparation in the form of a microencapsulated granule allowing, thanks to a support, the release in less than an hour of a half dose of 1.5 g of active principle and five hours after a second dose of 1.5 g . Administered in a dosage of two doses a day, one in the morning, the other in the evening, this pharmaceutical form absorbed for one to two weeks, completely reduces inflammatory and painful manifestations.

EXAMPLE 2

 Topical preparation (gel, cream or ointment) allowing, thanks to an excipient, oily or not, suitably chosen an application every 2 or 3 hours on the injured parts; an active ingredient dosage of between 2 and 10% provides rapid disappearance of the inflammation and / or pain. EXAMPLE 3

 Topical preparation of the active ingredient suspended in an amount of 50 to 60 mg of lyophilisate in 100 ml of liquid propelled by an authorized inert gas such as nitrogen, this type of pharmaceutical form being particularly indicated in the treatment of burns and bedsores.

Claims

1. Lyophilisate of total extract of hybrid sweet pumpkin obtained from a variety of cucurbits selected for twelve years by successive hybridizations. The genetic stability obtained by a tightly controlled culture over a long period makes it possible to obtain an active principle having the following physicochemical characteristics:  - pH between 6.44 and 6.47  - heavy metals <2ppm  - carbohydrate content between 63 and 67% - lipid content of 6% ± 0.5  - protein content of 10% ± 1%  - total carotenoid content of 25mg ± 10% per gram of lyophilisate. 2. Antalgic and anti-pyretic anti-inflammatory drug, characterized in that it consists of an active principle according to claim 1. 3. Pharmaceutical compositions characterized in that they contain, as active principle, a medicament according to claim 2, associated with one or more excipients and presented in granules, microencapsulated beads in granules or capsules, cream, gel, ointment, spray .