FR2868317A1 - PREPARATION AND THERAPEUTIC USE OF PLANTS AND PLANT EXTRACTS OF THE GENUS HYLOCEREUS - Google Patents

Abstract

The present invention describes the use of a plant or an extract or molecules isolated from a plant of the genus Hylocereus as a medicament. It also describes their use in the preparation of compositions intended for the prevention or treatment of lithiasis. It also relates to methods for obtaining extracts or isolated molecules and compositions mentioned above.

Description

2868317 1

  PREPARATION AND THERAPEUTIC USE OF PLANTS AND

  EXTRACTS FROM PLANTS OF THE GENUS HYLOCEREUS

  The present invention describes the use of a plant or an extract of a plant of the genus Hylocereus as a medicament. It also describes their use in the preparation of compositions intended for the prevention or treatment of a lithiasis. It also relates to methods for obtaining such extracts and compositions, as well as therapeutic compositions and biological extracts derived from these plants, including the active molecules isolated from these extracts.

  BACKGROUND OF THE INVENTION The term "lithiasis" refers to the disease characterized by the formation of insoluble solid deposits (or stones) composed of chemical substances and located in an excretory apparatus. The local concentration of these substances may be due to their excessive absorption, defective elimination and / or anatomical defect. The lithiases are not a pathology as such but the consequence of pathologies that can be very diverse (nutritional, digestive, renal, bone, etc.). In the human body, the excretory devices where these calculi can be formed are mainly urinary tract: urinary lithiasis bile ducts: gallstone lithiasis (biliary, bile duct) 25 and more rarely: salivary ducts: salivary lithiasis lacrimal ducts pancreatic duct The two major stones are urolithiasis (stones localized in the urinary tract) and vesicular lithiasis (stones located in the gallbladder).

  The overall prevalence of urolithiasis is 10% in the adult population (% of people who have had a calculation in their life) and is equivalent in the industrialized countries (Europe, USA, Japan). The annual incidence is 2 per 1000 inhabitants in France; it is a little higher in the United States (3/1000). Known risk factors are male sex (sex ratio H / F: 2/1), age with a peak at 40-50 years, diet (rich in calcium and animal protein) and dehydration. The composition of the stones varies according to their major compound: calcium oxalate (75%), calcium phosphate (15%), uric acid (6%), struvite (3%) and cystine (1%). Thus, 90% of the analyzed calculations are of calcium type.

  The overall prevalence of vesicular lithiasis is 10-15% in France and 10% in the USA. The annual incidence is 2 per 1000 inhabitants in France and 3.5 / 1000 in the USA. The risk factors are female (sex ratio H / F: 1/2), age with a peak at 40-60 years, metabolic disorders (obesity, digestive and nutritional disorders) and hormonal changes (pregnancy, menopause). Cholesterol is the main component of vesicular stones.

  The results obtained in the treatment of lithiasis in general show that the few existing pharmaceutical specialties (citrate, for example for urinary lithiasis, and bile acids for vesicular lithiasis) are not sufficiently effective or are poorly tolerated. Finally, the use of surgery for vesicular lithiasis and lithotripsy or surgery for urolithiasis remains the common solution with high costs.

  The object of the present invention is to overcome this deficit by providing a drug and effective compositions (curative and preventive), non-toxic, without side effects and well tolerated.

  SUMMARY OF THE INVENTION The present invention relates to the use of a plant or an extract of a plant of the genus Hylocereus as a medicament.

  The invention also relates to the use of a plant or an extract of a plant of the genus Hylocereus for the preparation of a pharmaceutical composition for preventing or treating a lithiasis or similar or related conditions.

  The present invention furthermore relates to compositions or medicaments comprising a plant or a biologically active extract of a plant of the genus Hylocereus, as well as methods for preventing and treating lithiases or related diseases by administration to humans. or the animal of these drugs or compositions.

  The invention also provides methods for obtaining extracts of the plants of interest as well as methods for extracting and purifying active molecules from the plane. from said extracts or plants.

  The invention thus relates to a process for obtaining a therapeutically active product comprising the implementation of one or more steps of purification or treatment of a sample of a plant of the genus Hylocereus in order to obtain one or more therapeutically active fractions or molecules.

  Another object of the invention is a method of extracting at least one therapeutically active product from a sample of a plant of the genus Hylocereus comprising the following steps: a) preparation of an extract from a sample of Hylocereus, b) fractionation of said extract obtained at the end of step a) using separation methods, and optionally c) isolation of the active product (s).

  Another particular and preferred object of the invention relates to a process for preparing an active extract comprising the following steps: (a) preparation of an extract of the plant by drying and crushing whole plant or roots of a plant of the genus Hylocereus, (a ') maceration or infusion of the extract obtained at the end of step (a) in osmosis water at a temperature of between approximately 20 and 150 ° C. for a sufficient duration, and (a ") one or more successive filtration (s) of all or part of the product of step (a ') to obtain an active extract.

  According to preferred embodiments, additional steps of.

  treatment can be performed, including concentration, sterilization, lyophilization and / or packaging, etc., to improve the properties or qualities of the active agent.

  The invention also relates to all products that can be obtained at the end of one of the steps of a process as defined above, characterized in that they are endowed with antilithiasis activity in humans or the animal.

  The invention also relates to the use of a product that can be obtained at the end of one of the steps of a process as defined above, for the preparation of a medicinal product intended for prevention or treatment. of a lithiasis or related pathology.

  Detailed description of the invention

  The present invention describes for the first time the use of a plant or an extract of a plant of the genus Hylocereus as a medicament.

  The inventors have for the first time demonstrated the powerful anti-lithiasic properties of products obtained from a plant of the genus Hylocereus. These products are particularly active when used in humans or animals suffering from renal, vesicular or parotid lithiasis.

  The present invention describes various examples of methods for obtaining a therapeutically active drug and product from a plant of the genus Hylocereus. It is understood that the invention encompasses any process likely to be implemented by those skilled in the art to obtain a product having antilithiasic properties in humans or animals, from such a plant.

  Plants of the genus Hylocereus are probably native to the Caribbean, widespread in Central America and Mexico and widely introduced as a garden plant in tropical countries. This genus that includes about 24 species is currently considered invasive in many ecosystems.

  The present invention can be carried out from plants or plant extracts belonging to the genera Hylocereus (cactaceae), including those belonging to the related genera of Hylocereus, including: Phyllocereus Miq., Cephalocereus Pfeiff., Cephalophorus Lem., Cleistocactus Lem ., Echinocereus Engelm., Echinonictanthus Lem., Echinopsis Zuc. and Pilocereus Lem.

  All species and varieties of plants belonging to the genera Hylocereus can be used. Thus, extracts of different Hylocereus have been active in the context of the invention, the species Hylocereus trigonus (Haw.) Safford providing the best activity in humans. The identified synonyms of Hylocereus trigonus which can also be used in the context of the present invention are the following: Hylocereus trigonus (Haw) Safford, Hylocereus antiguensis, Hylocereus napoleonis, Hylocereus plumieri, Cereus triangonus, Cereus napoleonis and Cereus plumieri.

  A process for obtaining a therapeutically active product according to the invention comprises carrying out one or more purification steps from a sample of a plant of the genus Hylocereus in order to obtain a or more therapeutically active moieties or molecules.

  The term "active" or "active" refers more particularly to the meaning of the invention a product, an extract, a fraction or a molecule having antilithiasic activity.

  The term "active product" refers to any fraction or molecule isolated from a Hylocereus plant, exhibiting anti-lithiasis activity.

  An "extract" refers, in a broad sense, to any complex, more or less purified and / or enriched preparation or mixture derived from a plant of the genus Hylocereus. It may be for example a crude extract, for example an aqueous fraction or a water-soluble dry extract.

  By "active molecule" is meant any active molecule isolated or initially identified from the plant, and optionally produced synthetically.

  By purification stage, it is meant any processing step for preparing, extracting, fractionating, separating or isolating an active product, ie, a product having anti-lithiasic properties, in humans or humans. 'animal.

  The plant sample used can be chosen from the whole plant, the roots, the stem, the flowers, the seeds, the fruits or a mixture of these.

  A particular method of extracting at least one therapeutically active product from a sample of a plant of the genus Hylocereus comprises the following steps: a) preparation of an extract from a sample of Hylocereus, b) fractionation of said extract obtained at the end of step a) by means of separation methods, and possibly c) isolation of the active product (s).

  Step a) of preparation of the extract may comprise a step during which the Hylocereus sample chosen is dried, optionally milled. The use of a mass of between approximately 100 and 300 g of whole plant of the Hylocereus genus or of a mass of between approximately 50 and 150 g of roots of such a plant makes it possible, for example, to obtain between approximately 10 and 30 g of dried and optionally ground extract of said plant or said roots at the end of step a). Prior to step b), the crude extract thus obtained can be subjected to different treatments. Thus, it may be optionally mixed with a solvent, the resulting mixture being advantageously heated at a later stage to allow maceration or infusion. The solvent may be, for example, water, osmosis water, distilled water, bidistilled water, alcohol (eg ethanol or butanol), etc. The mixture is advantageously brought to a temperature of between 20 and 150 ° C., preferably between 80 and 100 ° C., depending on the solvent. It is advantageously brought to the boiling point of the solvent used. A zone of temperature favorable to the maceration is between 25 and 40 C approximately. A temperature zone favorable to infusion is between 80 and 100 C depending on the solvents.

  The extract may also (or alternatively) be processed for delipidation, for example by a lipophilic solvent such as petroleum ether, methylene chloride or chloroform. This delipidation step may also be carried out subsequently, and it is then preferably carried out by liquid-liquid extraction with one of the solvents mentioned above. The delipidation may also be carried out using a dry extract according to the invention, using such a solvent.

  The invention thus also relates to a method for extracting at least one therapeutically active product from a plant of the genus Hylocereus comprising at least one step of treating all or part of the plant with heat and / or or by a solvent.

  The extract may also be subjected to one or more successive filtration stages. The filtration can be carried out using sieves, cellulose filters and / or nitrocellulose.

  Thus, a particular preferred process for the preparation of a plant extract according to the invention comprises the following steps: (a) preparation of an extract by desiccation and crushed whole plant or roots of a plant of the genus Hylocereus, ( a ') maceration or infusion of the extract obtained at the end of step (a) in osmosis water at a temperature of between 20 and 150 C approximately, for a sufficient duration, and (a ") a or several successive filtration steps of all or part of the product of step (a ') to obtain an active extract.

  In a particular variant, the method further comprises the following steps: (a ') sterilization of the filtrate (soluble part) obtained at the end of step (a "), and (a" ") concentration or lyophilization of the sterilized preparation.

  The sterilization step (a "') can be carried out by a membrane passage of approximately 0.22p.

  The concentration step (a ") can be carried out by evaporation of the aqueous phase and drying of the powder obtained under vacuum and at a temperature preferably between 20 and 50 ° C., or can be carried out by freeze-drying.

  Lyophilization allows the preservation of fragile substances in an aqueous medium, obtaining a chemical stability of certain products and removal of the solvent. It also facilitates subsequent solubilization.

  A preferred process for the preparation of an active product according to the invention thus comprises the following steps: (a) preparation of an extract by drying and whole plant or root material of a plant of the genus Hylocereus, (a ') maceration or infusion of the extract obtained at the end of step (a) in osmosis water at a temperature of between 20 and 150 ° C., preferably between 25 and 100 ° C., for a sufficient duration, (a ") one or more successive filtrations of all or part of the product of step (a ') to obtain an active extract, (am) optionally, sterilization of the filtrate (soluble part) obtained at the end of step (a "), (a") optionally, concentration or lyophilization of the sterilized preparation, (b) fractionation of a portion of the mixture obtained at the end of step (a "), (am) or (a) ") and (c) recovering at least one active product.

  The fractionation step makes it possible in particular to remove residual contaminants and impurities, for example nucleic acids, toxins, etc., or to eliminate any cytotoxic compounds.

  The fractionation step b) may comprise one or more steps and may be carried out using different separation techniques known to those skilled in the art. Typical examples of separation methods include precipitation / centrifugation, filtrations, ultrafiltrations and / or clarifications of plant extracts of the genus Hylocereus. The separation methods are preferably chosen from hydrophobic interaction liquid chromatography, hydrophilic interaction chromatography (HILIC), ion exchange chromatography and gel filtration chromatography, applied alone or in combination. Chromatography can be carried out on various supports (in particular column such as Duolite S861, Sephadex LH2O, Aspartamide and Aspartamide SCX). Fractionation is preferably followed by analytical column HPLC. The fractionation step b) is preferably carried out by column chromatography or CPC (Centrifugal partition chromatography), said step b) being repeatable several times.

  Step c) of isolation of the active product (s) is preferably carried out by HPLC and is preferably obtained by recovering HPLC eluates in the form of fractions.

  These methods allow efficient and reproducible production of active products according to the invention. Each of the steps of the method described above can be controlled by analytical methods including HPLC or thin layer chromatography (TLC). Preferably, the obtaining methods according to the invention comprise one or more intermediate stages of characterization and measurement or quantification of the active molecules contained in the products obtained at the end of the different steps.

  The processes described above are preferably carried out using a plant of the species Hylocereus trigonus (Haw.) Safford.

  Another subject of the invention concerns the product (s) likely to be obtained at the end of one of the steps of a process according to the invention as described above. preferably at the end of one of the steps a ', a "," a ", a", b or c, characterized in that it is (are) gifted anti-lithiasis activity in humans or animals.

  The physical characteristics of the active product (s) can be obtained by mass spectrometry (MALDI-TOF), infrared spectroscopy or nuclear magnetic resonance (NMR). The antilithiasis activity can be evaluated for example by an in vitro test on isolated patient calculations.

  Preferred products according to the invention obtained at the end of one of the steps of a process according to the invention can be used as the active principle (s) of a drug intended for the prevention and / or treatment of lithiasis or related pathologies.

  The invention may in particular be used to treat or prevent renal and urinary lithiasis, vesicular lithiasis and bile ducts, lithiasis of the main salivary glands (in particular parotid, submaxillary and sublingual) and lithiasis of the salivary glands. accessories.

  Within the meaning of the invention, the term pathology related to lithiasis refers in particular to the conditions leading to excessive mineralization, pathological calcification processes leading to the formation of calculi or calcified nodules in an organ, crystal deposits (gout or tophi). ), inflammatory rheumatic diseases, atheromatosis, chondrocalcinosis and sequential calcifications.

  The invention also relates to a medicament and a pharmaceutical composition comprising one or more products according to the invention as described above.

  The amounts of active extract used in the preparation of the pharmaceutical composition depend on the desired effect, the duration of the treatment and the route of administration used. They are generally between 100 and 1500 mg, preferably between 500 mg and 1200 mg of active extract per day.

  In general, the doctor will determine the appropriate dosage depending on age, weight and all other factors specific to the subject to be treated.

  In the compositions and uses of the invention, the extract or the active product may be in the form of an aqueous solution (containing unit doses in an amount adapted to the treatment of the lithiasis in question) in any suitable vehicle or excipient. of aqueous or hydroalcoholic type or in an isotonic or sterile vehicle which optionally contains dispersing agents and / or warrants compatible pharmacologically. It is also conceivable to combine the administration of the extract with other compounds capable of potentiating its action, such as another plant extract or another active molecule used in the treatment of lithiasis.

  The compositions or products according to the invention are packaged in an appropriate manner (tablet, pill, powder, capsule, cachet, granules, solution for injection, solution, suspension, emulsion, syrup, elixir, suppository, rectal capsule, etc.) to allow oral, enteral or parenteral administration, eg intravenous, intramuscular or subcutaneous administration, intravenous infusion or dialysis membrane surface introduction, or system administration implant for subcutaneous infusion. The preferred route of administration is the oral or enteral route.

  In the compositions according to the invention intended to be administered orally and in a solid form, the active extract according to the invention is mixed with one or more inert diluents, such as starch, cellulose or sucrose. , lactose or silica. These compositions may also comprise substances other than diluents, for example one or more lubricants such as magnesium stearate or talc, a dye, a coating (dragees) or a varnish. Tablets, pills, powders, capsules, cachets and granules are preferred for oral administration.

  In the compositions according to the invention intended to be administered orally and in liquid form, pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs may contain inert diluents such as water, ethanol, glycerol, vegetable oils or paraffin oil. These compositions may furthermore comprise substances other than diluents, such as, for example, wetting agents, sweetening agents, thickeners, flavoring agents or stabilizers.

  It is also possible to administer the products or compositions according to the invention rectally. In this case, the unit dosage forms are prepared conventionally according to conventional techniques known to those skilled in the art, with the excipients commonly used in this field. The compositions for rectal administration are preferably packaged in the form of suppositories or rectal capsules which contain, in addition to the active extract, excipients such as cocoa butter and / or semi-synthetic glycerides.

  Whichever route of administration is chosen, plant-based compositions or extracts of plants of the genus Hylocereus preferred according to the invention are in a form favorable to the protection and optimal assimilation of the principle or principles assets.

  In a particular variant embodiment, the pharmaceutical composition according to the invention comprises, in addition to the extract or the active product, pharmaceutically acceptable molecules chosen from among other active substances such as anti-lithiasis, other vegetable extracts and / or adjuvants for use in combination, separate or sequential manner.

  The adjuvant may be chosen from any substance, mixture, solution, buffer or composition known to those skilled in the art, in particular any substance, mixture, solution, buffer or composition that may be used in the treatment of gallstone. The adjuvant is preferably selected from diluent, lubricant, dye, coating, varnish, wetting agent, flavoring agent, sweetener, thickener, stabilizer and excipient. It is advantageously chosen from magnesium stearate, talc, starch, cellulose, sucrose, lactose, silica, water, ethanol, glycerol, vegetable oils, paraffin oil, cocoa butter, semi-synthetic glycerides. A composition that can be used in the treatment of lithiasis that can be used as an adjuvant is, for example, a composition comprising citrate. It can also be another plant extract. The adjuvant is moreover preferably packaged and administered separately from the composition comprising the plant extract or the active product according to the invention and / or at a distinct injection site.

  The invention also relates to a method of preventive or curative treatment of a lithiasis or related pathology, by administering to an affected subject, an effective amount of a product, extract or composition according to the invention.

  The drugs and compositions described above can indeed be used to prevent relapses of lithiasis disorders or be prescribed as a preventive measure in subjects at risk.

  The invention also relates to tools and kits for the implementation of one or the other of the methods as described above.

  Other aspects and advantageous properties of the invention are illustrated in the following examples, which should be considered as illustrative and not restrictive.

EXAMPLES

  EXAMPLE 1 Preparation and use of a plant extract according to the invention in the context of a clinical trial.

  The aqueous extract prepared (as indicated below) from the roots or from the whole plant Hylocereus trigonus (Haw.) Safford showed very marked renal and vesicular antilithiasis activity in the clinical study, described below. , performed in humans.

  Clinical trial made from antilithiasis product according to the invention Preparation method of the extract: Roots or the whole plant Hylocereus trigonus (Haw.) Safford are dried in the open air, protected from light , or in a vacuum oven at 30 C, then finely ground. The powder thus obtained is sieved using a 0.5 μm sieve.

  grams of sieved powder are macerated with mechanical stirring for 24 hours at 30 ° C. or infused in 1.5 liters of distilled water at 100 ° C. for 15 minutes. After filtration under vacuum or centrifugation, the insoluble material is removed, the aqueous solution is passed through the membrane at 0. 22 pm for sterilization and then lyophilized.

  Between 1.2 and 1.4 grams of cream solids are obtained. This extract is the drug used in the clinical trial in humans. The form used in humans is either an aqueous solution dosed at 1 gram per liter, or capsules at 250 milligrams of active extract or tablets dosed at 250 milligrams of active extract.

  The clinical trial involved 30 patients Renal lithiasis: 22 cases Vesicular esithiasis: 8 cases É 6 other patients (3 renal lithiases and 3 vesicular calculi) constituting the controls, received for treatment only the absorption of 30 patients. 1.5 liters of water daily. The protocol of the clinical trial, common to both forms of lithiasis has

  was the following: Day OJ: - complete observation of the patient - blood and urine tests by monitoring the following parameters: blood test uricemia creatinine calcium urea protein phosphorus ALAT ASAT gamma GT blood count hematocrit urine balance glucosuria proteinuria density and pH nitrites ketone red blood cells , urinary leukocyte bilirubinuria urinary crystals urate and calcium oxalate search for different types of cells (epithelial, granular, red blood cells and leukocytes) search for bacteria These biochemical parameters have been chosen to detect possible liver and / or liver toxicity. or renal, as well as an impact on the figured elements of the blood.

  Demonstration of the lithiasis The lithiasis was demonstrated and its evolution was followed by a series of ultrasounds carried out at 20 or 30 days apart during the duration of the treatment.

  Day D1: Following the results of the medical assessment, in particular the detection and measurement of lithiasis, their localization and the evaluation of renal and vesicular wall thickness (evaluation of an inflammatory state), the following treatment is proposed 1.2 liters of aqueous preparation containing 1.2 grams of the active extract defined according to the invention and corresponding to 30 grams of roots or whole plant.

  Treatment applied daily for the duration of the test.

  The control ultrasounds are preferably performed every 20 or 30 days according to the evolution of the calculations and the availability of the patient.

  For each patient, the treatment is stopped when the total disappearance of the lithiasis or the inefficiency of the treatment after a maximum of 150 days can be observed.

RESULTS

  ] LITHIASE RENALE (22 cases plus 3 controls), see table 1 16 cases of disappearance cases of decrease 1 case of failure 3 control cases: (no significant change in lithiasis) Renal lithiasis (25 cases) Table 1 RG = kidney left RD = right kidney

Table 1

  Case Calculations / size Duration of treatment Observations in days 1 RG / 15 mm 20 Disappearance 2 RG / 4.2 mm 20 Disappearance 3 RD / 10 mm 30 Disappearance 4 RG / 6 mm 80 Disappearance bilateral RD / 9 mm RG / 5 mm 20 Disappearance 6 RG / 5 mm 115 Failure, unchanged 7 RG / 3 mm 20 Disappearance 8 RD / 3.3 mm 50 Disappearance 9 RG / 4 mm 40 Disappearance RD / 3 mm 50 Disappearance 11 RD / 3.7 and 2.1mm 40 Bilateral disappearance RG / 2.1 mm of the 3 stones 12 RD / 9 mm 50 Decrease to 3 mm 13 RD / 4 and 6 mm 50 Bilateral disappearance RG / 3 and 4 mm of the 4 stones 14 RD / 5 mm 40 RG disappearance / 3.1 mm 20 Disappearance 16 RG / 3 calculations of 4 mm 50 Disappearance of 3 calculations 17 RG / 3 calculations 60 Bilateral disappearance RD / 2 total calculations 18 RG / 3.5 mm 20 Disappear 19 RG / 3 and 5 mm 60 RG : disappearance RD / 8 calculations from 6 to 12mm RD: remainder 4 calculations on 8 RD / 5.5 mm 120 Decrease to 2.1 mm 21 RG / 2 mm 120 Decrease RG / 1 mm RD / 3 mm RD / 1.5 mm 22 RD / 15 mm 120 Decrease RD / 11.5 mm GR / small calcifications Disappearance of multiple calcifications Contr 23 RD / 5 mm 120 RD / 4.2mm Not significant 24 RG / 2.7 mm 120 RG / 2.4 mm RD / multiple calcifications RD / calcifications unchanged RD / 9 mm 120 RD / 9 mm 2] VESICULAR LITHIASIS (8 cases plus 3 controls), see table 2 5 cases of disappearance 3 cases of net decrease 3 control cases: (no significant change in lithiasis).

Table 2

  Case Calculations / size Duration of treatment Observations in days 1 15 mm 150 Fractionation in two stones of 5 and 2 mm 2 25 mm 90 Total disappearance thickened wall 6.6 mm Wall 1.5 mm 3 8.2 mm 80 Total disappearance 4 3 4 mm calculations 115 Decrease Rest 2 2 mm calculations 9 mm 30 Total disappearance 6 2 Calculations of 3.1 and 2.1 mm 60 Total disappearance 7 2 Calculations of 7 and 3 mm 90 Total disappearance Thickened wall 7 mm 8 2 Calculations 14 and 8 mm 80 Decrease 14 mm * 9 mm 8mm- * 4mm Checks 9 8 mm 120 8,5 mm 10 mm 120 13 mm 11 11 mm 120 10 mm 3] LITHIASE PAROTIDIAN (2 cases) see table 3

Table 3

  Duration of treatment in days Observations Case Calculations / size 1 7 mm 20 disappearance 2 15mmx6mm 60 disappearance REMARKS: 1) Prior to clinical trial, animal toxicity was determined in mice and rats. Acute toxicity results did not show lethality to the maximum oral absorption capacity of the animals. Moreover, no sign of chronic toxicity has appeared.

  2) The whole of the blood and urine tests did not show any incidence, either on the hepatic and renal functions, or on the figured elements of the blood and the hematocrit.

  The general tolerance of the product has been excellent even over a long period. In particular, no side effect has been observed.

  EXAMPLE 2: Particular Process for the Preparation of a Plant Extract According to the Invention This example describes a particular method for preparing an extract according to the invention from roots of Hylocereus trigonus (Haw.) Safford.

  The roots are dried in the open air and protected from light, crushed finely, sieved using a 0.5-μm sieve and the powder thus obtained undergoes the following treatment: a) maceration with stirring in water; water osmosis at a temperature between 25 and 30 C for a time between 18 and 30 hours, b) vacuum filtration and recovery of the solution, c) sterilization of the solution by passage on 0.22 micron membrane, d) evaporation of the aqueous phase under vacuum at a temperature of between 30 and 40 ° C. using a Buchi evaporator, and e) drying of the powder obtained under vacuum at a temperature of between 25 and 40 ° C. .

  Steps d) and e) of the process can be replaced by lyophilization.

  EXAMPLE 3: Particular Process for the Preparation of a Plant Extract According to the Invention This Example Describes Another Particular Process for the Preparation of an Extract According to the Invention from the Roots of Hylocereus Trigonus (Haw.) Safford. Hylocereus trigonus (Haw.) Safford are dried in the open air and protected from light, crushed finely, sieved with a 0.5 μm sieve and the powder thus obtained undergoes the following treatment: stirring with stirring in osmosis water for a period of between 10 and 15 minutes with a final temperature of between 70 and 90 ° C. (initial temperature 100 ° C.), b) vacuum filtration and recovery of the solution, c) sterilization 0.22 micron solution of the solution, d) evaporation of the aqueous phase under vacuum at a temperature of between 30 and 40 ° C. using a Buchi evaporator, and e) drying of the powder. obtained under vacuum at a temperature included between 25 and 40 C.

  Steps d) and e) of the process can be replaced by lyophilization.

  EXAMPLE 4: Particular Process for the Preparation of a Plant Extract According to the Invention This example describes another particular process for preparing an extract according to the invention from the whole plant of Hylocereus trigonus (Haw.) Safford.

  The whole plant of Hylocereus trigonus (Haw.) Safford is dried in the open air and protected from light, finely ground, screened with a 0.5 μm sieve and the powder thus obtained undergoes the treatment. following: a) maceration with stirring in osmosis water at a temperature between 25 and 30 C for a time between 18 and 30 hours, b) vacuum filtration and recovery of the solution, c) sterilization of the solution by 0.22 micron membrane passage, d) evaporation of the aqueous phase under vacuum at a temperature between 30 and 40 C using a Buchi brand evaporator, and e) drying of the powder obtained under vacuum at a temperature between 25 and 40 C.

  Steps d) and e) of the process can be replaced by lyophilization.

  EXAMPLE 5: Particular Process for the Preparation of a Plant Extract According to the Invention This example describes another particular process for preparing an extract according to the invention from the whole plant of Hylocereus trigonus (Haw.) Safford.

  The whole plant of Hylocereus trigonus (Haw.) Safford is dried in the open air and protected from light, finely ground, screened with a 0.5 μm sieve and the powder thus obtained undergoes the treatment. following: a) stirring infusion in osmosis water for a time between 10 and 15 minutes with a final temperature of between 70 and 90 C (initial temperature of 100 C), b) vacuum filtration and recovery of the solution c) sterilization of the solution by 0.22 micron membrane passage; d) evaporation of the aqueous phase under vacuum at a temperature between 30 and 40 ° C. using a Buchi evaporator; and ) drying of the powder obtained under vacuum at a temperature of between 25 and 40 C.

  Steps d) and e) of the process can be replaced by lyophilization.

  EXAMPLE 6: Particular Process for the Preparation of a Plant Extract According to the Invention Capsules are prepared according to the usual technique known to those skilled in the art. They comprise 250 mg of active extract and have the following composition: Active Extract 250 mg Cellulose 18 mg Lactose 55 mg Colloidal Silica 1 mg Sodium Carboxymethyl Starch 10 mg Talc 10 mg Magnesium Stearate 1 mg EXAMPLE 7 Process The capsules are prepared according to the usual technique known to those skilled in the art. They comprise 250 mg of active extract and have the following composition: Active extract 250 mg - Lactose 104 mg - Cellulose 40 mg - Polyvidone 10 mg - Sodium carboxymethyl starch 22 mg - Talc 10 mg - Magnesium stearate 2 mg - Colloidal silica 2 mg - Mixture of hydroxymethylcellulose, glycerin, titanium oxide (72 - 3.5 5 - 24, 5) qs 1 film-coated tablet terminated at 445 mg.

Claims (23)

  1. Use of a plant or an extract of a plant of the genus Hylocereus as a medicine.   2. Use of a plant or an extract of a plant of the genus Hylocereus for the preparation of a pharmaceutical composition for preventing or treating lithiasis or a related pathology, chosen among the conditions causing excessive mineralization, a pathological calcification process leading to calcification or calcified nodules in an organ, crystal deposition, rheumatic inflammatory disease, atheromatosis, chondrocalcinosis and sequential calcification.   3. Use according to claim 2, characterized in that the lithiasis is renal lithiasis and urinary tract, vesicular lithiasis and bile ducts, the lithiasis of the main salivary glands, lithiasis accessory salivary glands, parotid lithiasis, under -maxillary or sublingual.   4. Use according to claim 2, characterized in that the crystal deposit is the drop (tophus).   5. Use according to one of the preceding claims, characterized in that the extract is from a sample of the plant selected from the whole plant, roots, stem, flowers, seeds and fruits.   6. Use according to claim 5, characterized in that the extract is an aqueous fraction or a dry extract soluble in water.   7. Use according to any one of claims 2 to 6, characterized in that the pharmaceutical composition further comprises pharmaceutically acceptable molecules selected from other active substances and adjuvants.   8. Use according to claim 7, characterized in that the adjuvant is chosen from a diluent, a lubricant, a colorant, a coating, a varnish, a wetting agent, a flavoring agent, a sweetener, a thickener, a stabilizer and a stabilizer. excipient.   9. Use according to claim 8, characterized in that the adjuvant is selected from magnesium stearate, talc, starch, cellulose, sucrose, lactose, silica, water, ethanol, glycerol, vegetable oils, paraffin oil, cocoa butter, semi-synthetic glycerides.   10. Use according to any one of the preceding claims, characterized in that the plant or plant extract used belongs to the species Hylocereus trigonus (Haw.) Safford.   11. A method for obtaining a therapeutically active product comprising the implementation of one or more purification steps from a sample of a plant of the genus Hylocereus in order to obtain one or more fractions. or therapeutically active molecules.   A method of extracting at least one therapeutically active product from a sample of a plant of the genus Hylocereus comprising the steps of: a) preparing an extract from a sample of Hylocereus, b) fractionation of said extract obtained at the end of step a) using separation methods, and optionally c) isolation of the active product (s).   13. The method of claim 11 or 12, characterized in that the sample of the plant is selected from the whole plant, stem, roots, flowers, seeds and fruits.   14. The method of claim 12 or 13, characterized in that the step a) of preparation of the extract comprises a step during which the sample of the plant is desiccated, optionally milled and then mixed with a solvent, the The resulting mixture is heated in a subsequent step, preferably heated to the boiling point of the solvent.   15. Process for obtaining an active preparation from the plant or roots of a plant of the genus Hylocereus, characterized in that it comprises the following steps: (a) preparation of an extract by drying and crushing whole plant or roots of a plant of the genus Hylocereus, (a ') maceration or infusion of the extract obtained at the end of step (a) in osmosis water at a temperature of between 20 and 150 C for a sufficient time, and (a ") one or more successive filtration (s) of all or from the product of step (a '), to obtain an active preparation.   The process according to claim 15, further comprising the following steps: (am) sterilization of the filtrate (soluble portion) obtained at the end of step (a "), and (a") concentration of the preparation as well as sterilized.   17. The method of claim 15 or 16, characterized in that it further comprises the following steps: (b) fractionation of at least a portion of the preparation, and (c) recovery of at least one active fraction.   18. The method of claim 16, characterized in that the concentration step (a ") is carried out by evaporation of the aqueous phase and drying of the powder obtained under vacuum.   19. The method of claim 18, characterized in that step (a ") is carried out at a temperature between 20 and 50 C.   20. The method of claim 16, characterized in that the concentration step (a ") is carried out by lyophilization.   21. Process according to claim 17, characterized in that the fractionation is carried out by liquid chromatography or by CPC.   22. Product obtained at the end of one of the steps of a process according to one of claims 11 to 21, characterized in that it is endowed with antilithiasis activity in humans or animals.   23. Use of a product obtained at the end of one of the steps of a process according to one of claims 11 to 21, for the preparation of a medicament for the prevention or treatment of a pathology selected from lithiasis and related pathology.