FR2852844A1 - Compositions for the prevention of cardiovascular disorders containing aspirin and a homeopathic amount of Arnica Montana and/or Secale Cornutum - Google Patents

Abstract

Compositions for the prevention of cardiovascular disorders containing: a) an anti-platelet aggregation agent selected from acetylsalicylic acid and its derivatives, and b) a vascular protecting agent selected from Arnica Montana and Secale Cornutum that is active at an infinitesimal dosage. ACTIVITY : Cardiant. MECHANISM OF ACTION : Thromboxane A2 synthesis inhibitor; anti-platelet aggregation agent; vascular protecting agent.

Description

i

  The present invention relates to a new pharmaceutical composition intended for the prevention of cardiovascular accidents.

  The prevention of cardiovascular accidents constitutes one of the major concerns of medicine in the third millennium, with two essential components: correction of risk factors (diabetes, lipid metabolism disorders, smoking, hypertension, sedentary lifestyle), preventive treatment of the thrombotic risk (anti-aggregation treatments platelets and preventive treatments for arteriolar spasm).

  Acetylsalicylic acid, better known under the name of aspirin, is the reference platelet aggregation inhibitor and is therefore widely prescribed. The 75 mg dosage is commonly used in the prevention of thrombotic accidents linked to atherosclerosis. It works by blocking the platelet cyclo15 oxygenase by acetylation. In addition, it inhibits the synthesis of thromboxane A2, a physiological activating substance released by platelets and which plays a role in the complications of atheromatous lesions. In addition, it reduces the synthesis of endothelial prostacyclin.

  In addition to this action on the circulating element, it also appears desirable, in the context of prevention of the atherothrombotic risk, to act also on the vascular element, to provide effective vascular protection.

  The vasculoprotectors are very numerous, of uneven effectiveness, even disappointing, and of high cost.

  The homeopathic pharmacopoeia has two drugs which are particularly advantageous by their vasculoprotective action.

  These are: - ARNICA MONTANA, whose mother tincture is prepared from the whole plant. It contains flavonoids with venous tropism but also with cardiotonic, coronary vasodilator and antihypertensive action. Furthermore, it contains carotenoid pigments and manganese which explain the well-known anti-ecchymotic and anti-neuralgic action of Arnica Montana. Besides its remarkable action in trauma, Arnica is widely used as a vasculoprotective, especially active on the capillaries. It is a very useful capillary protector in hypertensive patients for the prevention of strokes, in the coronary artery, in arteritis.

  - SECALE CORNUTUM, also called Claviceps Purpurea or ergot of rye whose mother tincture is prepared from sclerotia. It contains alkaloids including Ergotamine and Ergotoxin. The toxic effects of ergot are well known with a picture of arterial and arteriolar constriction leading to gangrene of the extremities. Experimentation with sub-toxic doses (pathogenesis) highlights cramps, paraesthesia, headache, dizziness, burning sensations of the extremities improved by the cold. From these toxicological and experimental tables come the broad indications in arterial pathology (arteritis and arteriopathies, arterial and arteriolar spasms, Raynaud's syndrome, arterial retinopathies, cerebral circulatory insufficiency with vertigo, headache, tinnitus, visual disturbances).

  Furthermore, at the present time, no drug is proposed which allows both an antiplatelet action and effective vascular protection.

  The inventor of the present invention has now discovered that it is possible to combine, in the same composition, a product whose anti-platelet aggregating effect is no longer to be demonstrated but whose mode of administration by sublingual route is innovative with at least one other active ingredient known, for its part, for its sublingual efficacy and for its vasculoprotective activity.

  The invention therefore proposes to combine these active principles with the aim of proposing a simple formulation capable of providing effective vascular protection.

  Such an association is innovative for several reasons: * the association of a well-known drug, acetylsalicylic acid, whose anti-aggregation action at low doses has been well demonstrated, with one or two homeopathic medicines chosen in function of their tissue polarity (capillary for Arnica Montana, arteriolar for Secale Cornutum) is interesting as well from a theoretical point of view by the illustration that it brings complementarity between two pharmacologies, one of which uses dilutions infinitesimal, only from a practical point of view, by the therapeutic simplification that it allows; * the simplification made possible by this association (one tablet per day) and its interest both in terms of compliance and in economic terms; * in addition, the combination of a hair protector, such as Arnica Montana, makes it possible to limit the spontaneous hematomas observed in prolonged treatments with aspirin, especially in the elderly.

  According to a first essential characteristic, the invention relates to a pharmaceutical composition comprising at least two active ingredients, namely acetylsalicylic acid or one of its derivatives acting as an anti-platelet aggregator and a second active ingredient, namely Arnica Montana and / or Secale Cornutum which act in infinitesimal doses as vascular protectors.

  Thus, the invention relates to a pharmaceutical composition intended for the prevention of cardiovascular accidents, characterized in that it contains: * a first active principle with anti-aggregating platelet activity chosen from the group consisting of acetylsalicylic acid and derivatives of the pharmacologically active salicylic acid as antiplatelet agents.

  * at least one second active principle acting in infinitesimal dose as active vascular protector chosen from the group consisting of Arnica Montana and Secale Cornutumn.

  Thus, the composition of the invention has the originality of combining an active ingredient well known in allopathic medicine and one or two active ingredients well known in homeopathic medicine.

  By infinitesimal dilutions, within the meaning of the invention, is meant successive dilutions according to the method hereinafter called "Hahnemannian" (from the name of S. Hahnemann who perfected this method), in accordance with the 1965 Codex (maceration during three weeks, expression of the mother tincture, filtration, 30 successive 1 / 100th dilutions for the centesimal dilutions in separate bottles, then impregnation of the support).

  The name Arnica Montana 5 CH thus designates the fifth centesimal dilution of an Arnica mother tincture. Similarly, the name Secale Cornutum 5 CH denotes a fifth centesimal dilution of Secale Cornutum.

  The composition of the invention is advantageously formulated in a form compatible with sublingual administration.

  It is advantageously offered in the form of tablets comprising a substrate compatible with sublingual administration. This substrate is advantageously based on a mixture of sucrose and lactose, preferably in respective proportions of 85% and 15%. The substrate will also advantageously comprise a binder, for example magnesium stearate or xylitol.

  The first active ingredient acetylsalicylic acid or its derivative, preferably D, L lysine acetylsalicylate, is distributed homogeneously in the substrate.

  As explained above, the composition of the invention may contain, as a second active ingredient, either Arnica Montana alone, or Secale 15 Cornutum alone, or a mixture, preferably in equal parts, of these two active ingredients.

  However, given the well-known properties of these two active ingredients, a composition where the two active ingredients are present is preferably chosen and which provides protection for both capillary and arteriolar properties.

  The impregnation of the tablet with the active ingredient will advantageously be carried out with an amount of this active ingredient corresponding to 1% of the weight of the support, by three successive impregnations with 0.333% of the amount of active ingredient on each impregnation. . The concentration of the first active ingredient in the tablet of the invention as well as the dilution height of the solution of the second active ingredient are not critical and depend on the pathology treated or on the simple prevention sought.

  Advantageously, however, the tablet will comprise 75 mg of acetylsalicylic acid or an equivalent amount of derivative (for example 135 mg of D, L lysine acetylsalicylate). Such a dosage proves to be particularly advantageous in the context of prevention of vascular risk.

  Larger dosages, for example from 75 mg to 160 mg of acetylsalicylic acid, may also be used in the context of secondary prevention, that is to say in the aftermath of a pathological episode or in a context of risk. plus.

  The dilutions of the solutions of the second active principle may also vary within wide proportions, in particular between 5 CH and 9 CH for Arnica Montana and between 5 CH and 15 CH for Secale Cornutum. However, we will preferably choose 5 CH dilutions for each of these two active ingredients.

  Thus, the preferred compositions of the invention will contain: 10 * Acetylsalicylic acid 75 mg * Arnica Montana 5 CH * Secale Cornutum 5 CH The invention also relates to the use of acetylsalicylic acid or one of its derivatives with anti-aggregating platelet activity and a solution in infinitesimal dilution of at least one active principle chosen from the group of Arnica Montana and Secale Cornutum for the manufacture of a pharmaceutical composition according to the invention intended for the prevention of cardiovascular disorders.

  These compositions will be particularly useful in primary prevention, the dose of acetylsalicylic acid can be increased in secondary prevention.

  The invention also relates to a therapeutic method intended for the prevention of cardiovascular disorders, comprising the sublingual administration of a pharmaceutical composition as defined above.

  The invention also relates, according to another characteristic, to a process for the manufacture of this composition.

  This process comprises two essential steps for preparing a compressed substrate homogeneously containing within it the first active principle, namely acetylsalicylic acid or its derivative and for impregnating this substrate with a solution of the second active principle, know one of the two solutions in infinitesimal dilutions or the mixture of the two.

  The first step is carried out by any technique which can be used for the preparation of tablets intended for the sublingual route for disintegration and according to porosity characteristics, in accordance with the pharmacopoeia.

  The second step includes the preparation, according to the Hahnemannian technique and in accordance with the 1965 Codex of a solution of the second active ingredient (or two solutions in the case where two active ingredients are used) and the use of this solution (or of these solutions) to impregnate the compressed substrate prepared during the first step.

  This impregnation is advantageously carried out in two or three successive steps with an amount of solution corresponding to approximately 1% of the weight of the compressed substrate prepared during the first step.

  Example 1 Tablets containing 75 mg of acetylsalicylic acid a / preparation of the substrate 300 mg tablets containing 75 mg of acetylsalicylic acid and an excipient based on a sucrose / lactose mixture (85% / 15%) with a binder, magnesium stearate.

  b / preparation of solutions in infinitesimal dilutions Solutions of 5 CH of Arnica Montana and Secale Cornutum are prepared from mother tinctures of these plants obtained by maceration, expression and filtration in accordance with the 1965 Codex. These mother tinctures are then diluted, according to the Hahnemannian technique, in 5CH in enclosures with a controlled and purified atmosphere.

  c / the substrate prepared in step ai is then subjected to 2 or 3 successive impregnations with each of the solutions prepared in step b / with an amount of each active ingredient solution representing 1% of the weight of the substrate.

  This sublingual tablet, 1 tablet per day, is particularly effective in primary prevention of cardiovascular risk.

  Example 2: Tablets containing a higher amount of acetylsalicylic acid.

  The same method of preparation is used as in Example 1 to make tablets containing different doses of acetylsalicylic acid of between 75 and 160 mg.

  These tablets taken at the rate of one tablet per day are useful in secondary prevention.

Claims (9)

  1 Pharmaceutical composition intended for the prevention of cardiovascular accidents, characterized in that it contains: * a first active principle with antiplatelet activity chosen from the group consisting of acetylsalicylic acid and pharmacologically active salicylic acid derivatives as than platelet aggregation inhibitors.   * at least one second active principle acting in infinitesimal dose as a vascular protector chosen from the group consisting of Arnica Montana and Secale Comutum.   2 Pharmaceutical composition according to claim 1 characterized in that said composition is formulated for sublingual administration.   3 Pharmaceutical composition according to claim 1 or 2, characterized in that said first active ingredient is acetylsalicylic acid.   4 Pharmaceutical composition according to claim 1 or 2, characterized in that said first active ingredient is a derivative of acetylsalicylic acid, acetylsalicylate of D, L lysine.   Pharmaceutical composition according to one of claims 1 to 4, 20 characterized in that said second active principle is Arnica Montana.   6 Pharmaceutical composition according to one of claims 1 to 4, characterized in that said second active ingredient is Secale Cornutum.   7 Pharmaceutical composition according to one of claims 1 to 6, characterized in that it contains, as second active principle, Arnica 25 Montana and Secale Comutum.   8 Pharmaceutical composition according to one of claims 1 to 7, characterized in that it is in the form of tablets consisting of a substrate compatible with sublingual administration incorporating within it acetylsalicylic acid or its derivative and impregnated with a solution, in infinitesimal dilution, of Arnica Montana and / or Secale Cornutum.   9 Pharmaceutical composition according to claim 8, characterized in that said substrate contains from 75 to 160 mg of acetylsalicylic acid or an equivalent amount of a derivative of acetylsalicylic acid.   Pharmaceutical composition according to one of claims 8 or 9, 5 characterized in that said substrate is impregnated with a solution in infinitesimal dilution of Arnica Montana at a dilution level of 5CH to 9CH, preferably in 5CH 11 Pharmaceutical composition according to one of claims 8 to 10, characterized in that said substrate is impregnated with an infinitesimal dilution solution 10 of Secale Cornutum at a dilution level of 5CH to 15CH, preferably in 5CH.   12 process for manufacturing a composition according to one of claims 1 to 11, characterized in that it comprises the steps of: * preparation of a substrate containing the first active principle * impregnation of said substrate with at least one solution infinitesimal dilution of the second active ingredient 13 Use of acetylsalicylic acid or one of its derivatives with antiplatelet activity and a solution in infinitesimal dilution of at least one active ingredient chosen from the group consisting of Arnica Montana and Secale 20 Cornutum, for the manufacture of a pharmaceutical composition according to one of claims 1 to 11, intended for the prevention of cardiovascular disorders.