Pharmaceutical or dietary composition containing aqueous extract of lavender and usable as an antidiabetic

Abstract

A pharmaceutical or dietary composition based on aqueous extracts of lavender for use in treating metabolic syndrome and diabetes. According to the invention, this composition may further comprise an aqueous extract of at least one other plant from List 1.

Description

Title of the invention: Pharmaceutical or dietetic composition containing the aqueous extract of lavender and usable as an antidiabetic.

[0001] The present invention relates to a new therapeutic or dietary use of the aqueous extract of Lavender as a hypoglycemic agent. Some definitions.

[0002] To better understand this text it is desirable to define some of the words and terms used in it. The majority of all the terms and terms used are defined in the Illustrated Dictionary of Medical Terms by Garnier Delamare, 28th edition.

[0003] Biological barriers: Set of structures that separate one biological compartment from another. Among the biological barriers we can cite the intestinal barrier which separates the contents of the intestine (mucous compartment) and the blood (serous compartment). The most important biological barriers are: the intestine, the skin, the cornea, the blood-brain barrier and the alveolar-capillary barrier.

[0004] Excipient: It is a vehicle for a drug. It is a substance into which the active ingredients are incorporated to make them easily absorbable.

[0005] Nutrient: a food substance that can be directly and completely assimilated, without having to undergo the changes of digestion and that can be introduced by intravenous injection. Example: glucose, vitamins, mineral salts, etc.

[0006] Medicine: Substance or combination of substances presented as having curative or preventive properties with regard to human or animal diseases, as well as any product which can be administered to humans or animals with a view to establishing a medical diagnosis, restoring, correcting or modifying their organic functions.

[0007] Essential medicine: A medicine that meets the priority health care needs of the population. These medicines are generally used for priority conditions and are included on the national list of essential medicines.

[0008] Xenobiotics: Chemical products, household or industrial, foreign to biological chemistry and behaving like a toxin or an allergen towards the organism.

[0009] Metabolic syndrome: The syndrome is a collection of a group of signs (symptoms) that occur simultaneously in a number of diseases. In this context, we understand metabolic syndrome to be the combination of symptoms of insulin resistance, hypertension and dyslipidemia. These symptoms are often found in patients with type 2 diabetes, cardiovascular diseases such as hypertension, and overweight (obesity).

[0010] Aqueous extract: We mean by aqueous extract, the extract using as solvent only water in liquid or vapor form.

[0011] Alpha amylase and alpha glucosidase: These are intestinal enzymes that transform starch and sugar chains into glucose.

[0012] OGTT, stands for Oral Glucose Tolerance Test. This test involves giving glucose orally and measuring the amount of glucose in the blood to assess glucose tolerance.

[0013] The present invention relates to a new therapeutic or dietary use of the aqueous extract of the aerial part of Lavender as a hypoglycemic agent and as an inhibitor of intestinal glucose absorption. By lavender we mean the different types of lavender (non-exhaustive) preferably the following types of lavender:

[0014] Lavandula angustifolia Mill,

[0015] Lavandula x intermedia Emeric ex Loisel,

[0016] Lavandula stoechas L,

[0017] Lavandula dentata L,

[0018] Lavandula pedunculata (Mill) Cav,

[0019] Lavandula multifida L.

[0020] But the preferable species according to the invention is Lavandula pedunculata (Mill) Cav,

[0021] The applicant has found, surprisingly, that an aqueous extract of lavender is usable in a pharmaceutical or dietary composition to block or reduce the intestinal absorption of sugars. Consequently, the composition according to the invention can also be used as a medicine or food supplement to combat diabetes, metabolic syndrome or weight gain.

[0022] The aqueous extract, according to the invention, may also contain one or more other natural substances such as aqueous extracts (seed, grain, leaves, bark) of the following plants (list 1):

[0023] List 1

[0024] Nigella sativa (seed)

[0025] Hibiscus sabdariffa (calyx, leaves)

[0026] Catharanthus reeds (leaves);

[0027] Salvia officinalis (leaves);

[0028] Galega officinalis (leaves);

[0029] Jugions regia (leaves);

[0030] Eucalyptus globulus (leaves);

[0031] Trigonella foenum graecum (seed);

[0032] Phyllanthus amarus (leaves).

[0033] Scots pine or Pinus sylvestris L. buds or branch

[0034] Boscia senegalensis (bare seed)

[0035] Strawberry tree (Arbutus unedo) root bark or leaves

[0036] Pomegranate (fruit) or Punica granatum

[0037] African Pyrethrum or Anacyclus pyrethrum.

[0038] Preferably, the aqueous extract according to the invention contains between 1% and 80% by weight of the dry aqueous extract of lavender relative to the total weight of the composition or medicament. This composition or medicament may also contain one or more aqueous extracts of plants from list 1 between 0.1% and 50% by weight relative to the total weight of the composition or medicament. Dosage forms

[0039] According to the invention, the composition can be presented in the form of tablets, capsules, granules, syrup, oral solution or any other forms known to those skilled in the art comprising lavender extract.

[0040] Those skilled in the art know and use various excipients as binders or lubricants for manufacturing powders, granules or other preparations. Examples of excipients which can thus be used according to the invention are: lactose, starch, dextrin, calcium phosphate, calcium carbonate, natural or synthetic aluminum silicate, magnesium oxide, hydrated aluminum hydroxide, magnesium stearate, sodium bicarbonate, rice starch. Other excipients not mentioned above but which are also suitable are described in "Remington's Pharmaceutical Sciences" by EW Martin, and can be used according to the invention.

[0041] In these different formulations, and for example those mentioned above, the composition can also be presented in powder for dilution or syrup. This powder may contain only the active ingredients. This is obtained for example by atomization, drying, or lyophilization from aqueous extract, hydroalcoholic or the extract by CO2.

[0042] The aim of the invention is therefore to propose a new pharmaceutical and / or dietary composition for blocking or reducing the intestinal absorption of sugar and total blood sugar and which can be used to combat type 2 diabetes, metabolic syndrome and overweight and as a hypoglycemic agent.

[0043] The applicant achieves that the oral administration (per os) of an effective quantity of the mixture of an aqueous extract of lavender causes a reduction in the passage of sugars into the blood and hypoglycemia. Implementation of the invention

[0044] The implementation of the invention can be done on the action of the composition according to the invention on the reduction or inhibition of the passage of sugars into the blood when these sugars are administered orally at the same time as the pharmaceutical or dietary composition according to the invention. The implementation of the invention can be done by measuring the total blood sugar in humans or laboratory animals such as rats and mice after oral absorption of a sufficient quantity of the preparation according to the invention.

[0045] An example of simplified preparation of the invention is made by a mixture of the powder of the aqueous dry extract of lavender with or without association with a second plant among the plants cited in list 1 and obtained by oven drying or by atomization or freeze-drying. Materials and methods used Chemicals

[0046] Phloridzin and glucose were purchased from Sigma (St Quentin-Fallavier, France). The pharmaceutical composition according to the invention of dry extracts was prepared by TBC laboratories, Faculty of Pharmacy of Lille (France). Tissue preparation

[0047] Seven-week-old mice (C57BL / 6JRJ strain) were obtained from Janviers SA (France) and were fed standard laboratory chow (UAR, Vil-lemoisson s / Orge, France) until these studies were performed. Food was withdrawn 18 h before the experiments, but the animals had free access to drinking water. For electrophysiology studies, animals were killed by cervical dislocation after anesthesia and intestinal segments from fasted animals were removed and rinsed of intestinal contents with fresh Ringer's solution. The stomachs of all animals were found empty. Tissue pieces were then opened along the mesenteric border and were mounted well flattened between two acrylic Ussing half-chambers (Biomécatronics SAS, ZI de Ruitz, France).

[0048] Studies of short-circuit current in Ussing chambers

[0049] The isotonic Ringer's solution used in the experiments is composed of (in mM) 115 Na Cl, 25 NaHCO3, 1.2 MgCl2, 1.2 CaCl2, 2.4 K2HPO4 and 0.4 KH2PO4. The pH was 7.40 at 37°C.

[0050] An intestinal preparation is mounted between two plexiglass half-chambers determining a mucous compartment and a serous compartment.

[0051] These half-chambers, the opening of which is applied against the exposed surface of the intestinal tissue, are perforated into compartments containing Ringer's liquid, which is a buffered solution at pH = 7.6, tempered at 37°C. The pH of the Ringer's liquid and its oxygen saturation are constantly maintained by permanent bubbling of carbogen, a gaseous mixture composed of oxygen and carbon dioxide in the pro 95% O2 and 5% CO2 portions. Bubbling also ensures continuous mixing of the incubation medium in both compartments.

[0052] The transepithelial electrical potential reflecting the asymmetry of electrical charges between the mucosal and serous side of the membrane, was measured by calomel electrodes connected (Biomécatronics SAS, France) by agarose bridges immersed in a 3 molar KC1 solution in 4% (w / v). These bridges were placed on both sides of the tissue and are adapted to each half-chamber. The whole is connected to a high impedance voltmeter (Biomécatronics SAS, France).

[0053] The potential difference was short-circuited by a short-circuit current (Icc or Isc) via 3M KC1 agarose bridges placed in each reservoir, adapted to Ag-AgCl electrodes, the whole being connected to a voltage-clamp system (Biomécatronics SAS, France). Isc delivered and corrected for the physiological liquid resistance, was recorded continuously on a computer using BioDaqsoft software (Biomécatronics SAS, France). Isc represents the sum of the net ion fluxes transported across the epithelium in the absence of an electrochemical gradient (mainly Na+, Cl2 and HCO3). Oral glucose tolerance test (OGTT)

[0054] The OGTT is carried out on Wistar rats. This test consists of measuring blood sugar levels as a function of time on a living rat after having previously made it absorb glucose, and after oral administration or not of the preparation according to the invention. Then the results obtained are compared.

[0055] The principle consists of putting the rat on an empty stomach the day before for 17 hours (individual wire cages, bottle of fresh water). On the day of the tests, the very clean 20% D-glucose solution is prepared (20g / 100 ml or 200 mg / ml, prepare 2 g in 10 ml). The preparation according to the invention is administered to the rat orally at a rate of 1 g of preparation per kg of body weight, then wait 30 minutes before administering 2 g / kg of D-glucose orally. Blood glucose is measured on the tail vein using Accu Check Active strips (Roche diagnostic).

[0056] Implementation and testing of the pharmaceutical composition

[0057] The invention is currently implemented under the name Lavandula pedunculata (Mill) Cav (LP)

[0058] Within the scope of the invention, it is possible to make a combination of the lavender extract, in whole or in part, with other plants providing such common or similar compounds. As shown below, this combination of LP and Nigella sativa, Boscia senegalensis, Trigonella foenum graecum, Punica granatum, Galega officinalis presents a synergy producing better results than the addition of the results obtained individually by each of these plants. This synergy is probably due to the presence of common or similar compounds, between the aqueous extracts of these two plants.

[0059] The invention thus provides a composition comprising, in addition to the aqueous extract of Lavender, an aqueous extract of at least one second plant from Table 1. Example of preparation of the total aqueous extract

[0060] The aerial part of dried lavender is preferably ground cold. The powder is mixed with water and left to macerate. The maceration is then filtered and atomized to obtain a fine powder or first dried in the oven and then ground to obtain a fine powder.

[0061] The same process is used to obtain the powder of the aqueous extracts of the second plant. The two powders are mixed to obtain the active ingredient. As non-limiting examples but relating to a model for producing the formulation, the active ingredient of the LP can be produced with a concentration of the dry aqueous extract of lavender which varies between 0.1 to 80% and a concentration of the aqueous extract of another plant in list 1 above of 0.1 to 50%.

[0062] Effect of (combined) lavender active ingredients on the inhibition of intestinal glucose transport

[0063] After stabilization of the electrical parameters of the tissues, the pharmaceutical preparation according to the invention as well as D-glucose were introduced into the mucous compartment of the preparation (LP at different concentrations while glucose at 10 rnM). To avoid the osmotic pressure generated by the introduction of D-Glucose into the mucous compartment, the same concentrations of mannitol (10 mM) were added to the serous side of the preparation. The variations of the electrical parameters are then noted and recorded on the computer. Statistics

[0064] The results, shown in the attached figures, are reported as mean (M) of measurements plus standard deviation (M ± SD). All determinations were made with an average of at least 7 pieces of tissue (n). One-way analysis of variance was performed followed by Dunnett's test using GraphPad Prism 5 software (GraphPad Software, Inc. CA 92037 USA). Comparisons of the action of Lavender on alpha amylase and alpha glucosidase activity were performed by the students' t-test. Presentation of the invention

[0065] Effect of Lavender extract combined with another plant extract from list 1 for its hypoglycemic and inhibitory activity on intestinal absorption of glucose.

[0066] [fig. 1]. Effect of aqueous extract of lavender (LP) on inhibition of glucose absorption is dose-dependent. LP does not cause total inhibition of intestinal absorption of glucose. This inhibition is partial

[0067] [fig.2]. Result of the oral glucose tolerance test (OGTT) on rats (A) and the area under the curve (B) obtained from A. This figure shows that the different plant extracts can each decrease blood glucose in fasting rats. CT = control, FGK = Trigonella foenum graecum, PG = Punica granatum, GO = Galega of-ficinalis, LP = Lavandula pedunculata (Mill) Cav, MET = Metformin.

[0068] [fig.3]. Result of the oral glucose tolerance test (OGTT) on rats when combines two plants (A) and the area under the curve (B) obtained from Figure A. This figure shows that different combinations of plant extracts can produce greater biological effects than individual extracts. For example, the combination of LP+PG gives an effect similar to the reference drug Metformin (MET), while the effect of the LP+FGK combination is greater than the individual effect of each of the plants used alone. CT = control, FGK= Trigonella foenum graecum, PG = Punica granatum, LP = Lavandula pedunculata (Mill) Cav, MET= Metformin.

[0069] According to the invention, the composition can be used: 1) as a medicament. 2) as a medicament against diabetes (antidiabetic). 3) as a medicament against metabolic syndrome. 4) as a medicament against obesity. 5) As a non-therapeutic product as a dietary product to combat weight gain. 6) as a composition containing between 1% and 80% by weight of dry lavender extract relative to the total weight of said composition. 7) as a composition presented in the form of a tablet or capsule and comprises between 30% and 80% by weight of dry lavender extract relative to the total weight of said composition.8) as a composition containing 0.1% to 50% by weight of the extract of at least one of the plants in list 1, of the following plants: Nigella sativa (seed), Hibiscus sabdariffa (calyx, leaves), Catharanthus reeds (leaves); Salvia officinalis (leaves); Galega officinalis (leaves); Juglans regia (leaves); Eucalyptus globulus (leaves); Trigonella foenum graecum (seed); Phyllanthus amarus (leaves); Scots pine or Pinus sylvestris L. buds or twig; Boscia senegalensis (barred seed); Strawberry tree (Arbutus unedo) root bark or leaves; Pomegranate (fruit) or Punica granatum; African Pyrethrum or Anacyclus pyrethrum relative to the total weight of said composition. 9) as a composition presented in the form of a tablet or capsule and comprises between 1% and 80% by weight of one of the plants of list 1 relative to the weight of Arbutus in said composition.10) as a composition presented in the form of powder for dilution or syrup, obtained by atomization or drying or lyophilization from the aqueous extract.

Claims

Claims

1. A composition, comprising an aqueous extract of Lavender pedunculata for its application in inhibiting intestinal sugar absorption as a medicament for treating diseases related to intestinal sugar absorption.

2. Composition as a medicament for inhibiting intestinal absorption of sugar, comprising an aqueous extract of Lavender pedunculata and an aqueous extract of at least one second plant from the following group: Trigonella foenum graecum, Arbutus unedo, Punica granatum.

3. Composition according to any one of claims 1 or 2, characterized in that it comprises between 1% and 80% by weight of dry extract of Lavandepedunculata relative to the total weight of said composition.

4. Composition according to any one of claims 1 to 3, characterized in that it is presented in the form of a tablet or capsule and comprises between 30% and 80% by weight of Lavandepedunculata relative to the total weight of said composition.

5. Composition according to any one of claims 1 to 4, characterized in that it comprises from 0.1% to 50% by weight of the extract of at least one of the plants of list 1 relative to the total weight of said composition.

6. Composition according to any one of claims 1 to 3 or 5, characterized in that it is presented in the form of powder for dilution or syrup, obtained by atomization or drying or lyophilization from the aqueous extract of Lavandepedunculata.

7. Composition according to claims 1 and 2 for its use as a medicament against diabetes.

8. Composition according to claims 1 and 2, for its use as a medicament against obesity.

9. Composition according to claims 1 and 2, for its use as a medicament against metabolic syndrome.

10. Composition according to any one of claims 1-2 and 3 to 6, for its non-therapeutic use as a dietary product to combat weight gain.

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