ITCL20080016A1 - PREPARATION FOR FLEBOTONIC ACTION, FLEBOTROPA, ANTIEDEMIGENA AND ANTIOXIDANT OF THE VASAL WALL BASED ON DIOSMINE, CENTELLA ASIATICA (E.S. TITLE 20% OF ASIATICOSIDE) VITIS VINIFERA (E.S. TIT. 95% OF PROANTOCIANIDINE), RUSCUS ACULEATUS (E.S. TITLE 5% - Google Patents

Description

DESCRIPTION

Of the industrial invention entitled: preparation based on Diosmin 300 mg, Centella asiatica (E.S. tit. 20% of asiaticoside) 50 mg, Vitis vinifera (E.S. tit. 95% of proanthocyanidins) 50 mg, Ruscus aculeatus (E.S. tit. 5) % ruscogenins) 50 mg.

FIELD OF TECHNIQUE TO WHICH THE INVENTION REFERS: food supplement with phlebotropic, phlebotonic, anti-edema and antioxidant action of the vessel wall.

BACKGROUND OF THE TECHNIQUE:

there are pre-existing drugs and / or food supplements in which the active ingredients we use are present either individually or in mixtures different from ours by type of active ingredients, dosage and titration.

OBJECTIVE THAT INNOVATION INTENDS TO ACHIEVE:

Improving the parameters of rapidity, duration and efficacy of treatment for the treatment and prevention of diseases affecting the vessels with single-dose administration.

BRIEF DESCRIPTION OF THE DRAWINGS:

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ANALYSIS OF THE ACHIEVED RESULT:

The preparation based on Diosmin 300 mg, Centella asiatica (E.S. tit. 20% of asiaticoside) 50 mg, Vitis vinifera (E.S. tit. 95% of proanthocyanidins) 50 mg, Ruscus aculeatus (E.S. tit. 5% of ruscogenine) 50 mg , has properties and active ingredients described below.

1. Gotu kola

HABITAT: it is native to the East, widespread in an area ranging from Madagascar to Indonesia.

FAMILY: Apiaceae

PART USED: the leaves.

RECOMMENDED PHARMACEUTICAL PREPARATIONS: nebulized and titrated dry extract

in total triterpene derivatives (Asiatic acid and madecassic acid 60% and Asiaticoside 40%) min.

5% (Italian Pharmacopoeia X).

CHEMICAL COMPOSITION: it is a plant rich in saponosides, which are Asian acid, madecassic acid and Asiaticoside.

THERAPEUTIC PROPERTIES: Protective action on venous vessels: it is particularly suitable for the treatment of chronic venous insufficiency and complications of varicose veins such as varicophlebitis, varicose ulcers and skin alterations.

Centella stimulates the production of collagen by human fibroblasts, and this improves and strengthens the wall of the venous vessels. In fact, the triterpene fraction of centella causes, in human fibroblast cultures grown in the laboratory, an increase in fibronectin, which is an important structural protein for the sealing of the venous vessel wall, and in collagen. Five clinical studies were carried out to evaluate the effect of centella in patients with venous insufficiency, for a total of 361 patients. Patients treated with centella had a significant increase in capillary cutaneous blood flow. They also showed a reduction in the subjective symptoms present before therapy, ankle swelling and venous distensibility. They also had a significant drop in the flow of fluids from blood vessels to surrounding tissues, which is primarily responsible for swelling in the ankles. No relevant side effects were observed in any of these studies.

Centella is therefore very useful in the treatment of venous insufficiency with a sense of weight in the lower limbs, swelling of the ankles, pain in the veins, night cramps, itching in the lower limbs and the presence of capillaries and venules in them.

Furthermore, this plant accelerates the healing of skin sores of any origin and first and second degree burns, and is indicated for the treatment of cellulite both topically and generally. The usefulness of centella in the treatment of cellulite is due to the fact that the extract of this plant improves the capillary venous circulation in the skin, whose insufficiency is one of the main causes of the onset of cellulite itself.

Main action: phleboprotective.

Other actions: anti-cellulite, healing.

Main indications: peripheral venous insufficiency, hemorrhoids, cellulite.

Centella shows a particular trophism for the connective tissue by mainly stimulating the synthesis of glycosaminoglycans, fundamental components of the amorphous matrix of the connective tissue, to a lesser extent the synthesis of the fibrillar components (collagen and elastin). Its activity is manifested by two main therapeutic actions: vasoprotective and trophycocicating.

The vasoprotective action improves venous function by toning the vessel walls and decreasing venous stasis, favoring the venous return from the periphery to the heart.

The trophic-cicatrizing action is expressed by producing a better vascularization, stimulating the reticulo-endothelial system favoring tissue repair both internally and externally.

This action is due to an anabolic-like effect, capable of stimulating the synthesis of structural connective proteins; in fact, centella acts only on amino acids such as proline, hydroxyproline and alanine which make up 40% of the total amino acids of the connective tissue itself.

Centella favoring the use of two amino acids (alanine and proline) in the formation of collagen determines an increase in production. A better supply of collagen favors an improvement of prevaricosis processes, a decrease in weight in the lower limbs, night cramps and orthostatic edema.

The generally recommended dose is 30 mg, of the total fraction of Centella asiatica, twice a day. There have been no reported cases of interactions with other drugs, it is recommended not to use the extract during pregnancy and breastfeeding.

Centella possesses well-known sedative properties. There is therefore the possibility that, when co-administered with anticonvulsants (carbamazepine), antidepressants (sertraline), anticholinergics (atropine), or first generation antihistamines (cetirizine), it may, due to the additive effect on the central nervous system, facilitate the onset of sedation.

2. Ruscus aculeatus (Butcher's Broom, Ruscus aculeatus, Butcher's Broom)

HABITAT: Evergreen woody plant up to 80 cm high widespread in Europe and the Middle East, the term "ruscus aculeatus" derives from the Latin, the Romans indicated a shrub with thorns. FAMILY: Liliaceae,

PART USED: rhizomes and roots, the fruits (red and spherical berries),

CHEMICAL COMPOSITION: sterolic saponins (ruscogenin, neoruscogenin) with anti-inflammatory and vasoconstrictive activity, trace essential oil, mineral salts, resin, potassium and calcium salts, flavonoids (rutoside, rhamnoglucoside, quercetol), rutoside has a diuretic and antirheumatic activity

THERAPEUTIC PROPERTIES: anti-inflammatory, astringent, diuretic, vasopro tetri ce and venotonic action useful in venous and hemorrhoidal insufficiency. Its activity is anti-inflammatory and anti-edema.

Ruscus is useful in all pathologies affecting the venous system, feeling of heaviness in the legs, cramps in the calves, varicose veins, venous stasis, hemorrhoids, chilblains, gout, kidney stones, adjuvant for heavy legs and for venous-lymphatic stenosis to be associated with other plants. Also useful in disorders of the retinal circulation.

ACTIONS FOR EXTERNAL USE: to treat hemorrhoids, vascular inflammation in sunburn, in the fragility of capillaries. For cosmetic use for its soothing, protective, refreshing action, useful for delicate skin and easy to redness, it protects the skin from the action of the wind.

The properties of Ruscus are contained in the rhizome which is protein and diuretic. Ruscus is probably the most powerful vegetable venous tonic and that is why it is often added to the composition of many antihemorrhoidal and antivaricosis drugs.

3. Vitis vinifera

HABITAT: It is a plant native to southern Europe and western Asia, deciduous climber with erect climbing branches, tendrils, palmate leaves, clusters of small pale green flowers and clusters of fruit (grapes) whose color varies from green to black . The young branches, often hairy, have a cirrus on the opposite side of the leaf that allows the plant to attach itself to the supports. The vine is grown in the warm temperate regions of the world for the fruit and for the production of wine. The leaves are harvested in the summer.

FAMILY: Vitaceae

PART USED: leaves, seeds, peel, juice.

CHEMICAL COMPOSITION:

Flavonoids: quercetin (leaves);

Flavanols: OPC (seeds var. Rubra);

Anthocyanins;

Resveratrol (peel, berries);

Tannins, trace elements, mineral salts;

Organic acids: malic, oxalic, succinic;

Tartrates (2%): potassium and calcium bitartrate;

Vit. C

THERAPEUTIC PROPERTIES: The oligomeric proanthocyanidins (OPCs) present in grape berries belong to a class of polyphenolic compounds very common in nature.

Their concentration in grapes is extraordinary: dry extracts obtained from the seeds of Vitis vinifera can in fact reach titrations in OPCs of 85-95%. From the molecular point of view, they are complex polyphenolic molecules composed of several monomer units (catechins and epicatechins). whose counteracting activity against degenerations connected to radical reactions (oxidative damage to all tissues and organs of our body) is extremely high, in some cases even fifty times that of vitamin C and E. It also seems that grape extract contains gallic acid and related esters, other compounds known for their antioxidant properties. Similarly to what happens for the anthocyanosides present in blueberry, OPCs are able to stabilize the walls of blood vessels by strengthening collagen and proteins present in the skin, tendon, cartilage and muscle. For these reasons, grape extract is recommended in cases of capillary fragility (which manifests itself as visible redness even in the skin) and difficulties in microcirculation.

Numerous experimental researches support the application of grape extract in subjects suffering from venous insufficiency. A recent study conducted on rats has highlighted the protective properties of the OPCs contained in the grape extract against erythrocytes, especially as regards the peroxidation of membrane phospholipids and hemolysis resulting from exposure to UVB radiation. In particular, this action was effective in the sub-epidermal capillaries. All this seems to encourage the application of grape berry extract in preparations aimed at counteracting the onset and exacerbation of skin photo-damage caused by exposure to UVB rays.

Precisely because of their strong antioxidant and circulation adjuvant properties, the OPCs contained in the grape berry extract are able to represent a valid aid for the prevention of diseases affecting the cardiovascular system, first of all the arteriosclerosis and heart attack.

The deflated virtues of the OPCs contained in the grape extract against post-operative edema are now known. Edema present in patients undergoing facelift and those resulting from hematomas or sports injuries also responded positively to treatment with OPCs.

OTHER POTENTIAL APPLICATIONS:

Although further research is needed in this regard, it seems that the OPCs contained in the grape berry extract can exert a beneficial and preventive effect also against: macular degeneration (i.e. one of the main causes of senile blindness), inflammation , allergies (especially hay fever), diabetic retinopathy and cancer. In fact, some recent studies seem to attribute definite anticancer properties to grape extract, which would be expressed above all against some cell lines involved in prostate cancer and that of the oral cavity.

4. Diosmin

Diosmin is a molecule of semi-synthetic origin, obtained from hesperidin, a flavonoid extracted from the pericarp of many citrus fruits, with an oxidation process, at the end of which there is a mixture of 90% diosmin and 10% hesperidin.

Diosmin is mainly indicated as a venotonic.

PHARMACODYNAMIC PROPERTIES:

Pharmacotherapeutic group: Diosmin is classified as a vasoprotective drug (capillary-protective substances / bioflavonoids - ATC Class C05CA03).

Mechanism of action / pharmacodynamic effects:

Diosmin carries out its activity through a mechanism consisting of several phases:

- constricting action on capillaries:

- enhancement of the action of adrenaline and ascorbic acid;

interference with histamine;

- inhibition of hyaluronidase. of catecholoxymethyl transferase (COMT) and dopadecarboxylase.

From all this derives an increase in the tone of the venous wall, due not only to a strengthening action of the orthosympathetic mediators but also to a direct, specific action on the venous wall.

In fact, the increase in tone is only partially inhibited in the presence of substances blocking the alpha and beta adrenergic receptors.

On the microcirculation, at the level of capillaries, Diosmin acts by increasing resistance and decreasing the permeability of the vessels (vitamin P action).

PHARMACOKINETIC PROPERTIES:

In humans, after oral administration of carbon 14-labeled diosmin it is observed that:

- the excretion is essentially fecal while the urinary excretion represents, on average, 14% of the administered quantity;

- the elimination half-life is 11 hours.

PRECLINICAL SAFETY DATA:

The active principle, from the toxicological tests, is practically devoid of toxicity for single administration (rat DL504000 mg / kg per os); (rat LD502000 mg / kg for i.p.); (mouse LD502000 mg / kg per os); (mouse LD502000 mg / kg for i.p.).

Chronic toxicity controls for doses up to 250 mg / kg / day in rats did not produce toxic phenomena.

Administration during the organogenetic period of pregnancy in rats and rabbits, at doses up to 100 mg / kg / day, did not show any teratogenic activity or fetal toxicity.

The aforementioned objectives are achieved thanks to the characteristics of the selected and standardized active principles with adequate titrations that make our product unique n preventive-curative treatment of diseases affecting the vessels, such as, telangiectasis venous insufficiency (varicose states, edema from blood stasis), states of capillary fragility, in the haemorrhoidal crisis and in all those cases in which it is necessary to use a preparation with phlebotropic, phlebotonic, anti-edema and antioxidant action of the vessel wall.

Claims (1)

CLAIMS Of the industrial invention entitled: Preparation based on Diosmin 300 mg, Centella asiatica (E.S. tit. 20% of asiaticoside) 50 mg, Vitis vinifera (E.S. tit. 95% of proanthocyanidins) 50 mg, Ruscus aculeatus (E.S. tit. 5) % ruscogenins) 50 mg. I claim: 1) synergistic formulation of active ingredients with phlebotropic, phlebotonic, anti-edema and antioxidant activity of the vessel wall (arteries, capillaries, veins) useful in the prevention and treatment of diseases affecting the circulatory system; the above formulation contains pharmaceutically acceptable dosages of extracts from Centella asiatica plants (E.S. tit. 20% of asiaticoside) 50 mg, Vitis vinifera (E.S. tit. 95% of proanthocyanidins) 50 mg and Ruscus aculeatus (E.S. tit. 5% d 'i ruscogenine) 50 mg in addition to Diosmin 300 mg. 2) synergistic formulation between active principles with phlebotropic, phlebotonic and antioxidant activity as per claim 1, where Centella asiatica is titrated in the range between 3% and 20% of asiaticoside, Vitis vinifera is titrated in the range between 50% and 95% proanthocyanidins, Ruscus aculeatus is titrated in the range between 5% and 10% of ruscogenine and Diosmin present in the range between 100 mg and 300 mg. 3) synergistic formulation between active principles with phlebotropic, phlebotonic, anti-edema and antioxidant activity as per claim 1, indicated in the symptoms attributable to telangiectasias, venous insufficiency (varicose states, edema from blood stasis), states of capillary fragility, in the haemorrhoidal crisis and in all those cases in which it is necessary to use a preparation with phlebotropic, phlebotonic, anti-edema and antioxidant action of the vessel wall. 4) synergistic formulation between active principles with phlebotropic, phlebotonic, anti-edema and antioxidant activity as per claim 1, present in capsules, tablets, tablets, syrup, suspension, suppositories, gels.