IT202000005818A1 - COMPOSITIONS CONTAINING VEGETABLE-DERIVED INGREDIENTS USEFUL TO IMPROVE THE LIPID STRUCTURE OF PATIENTS IN PRIMARY PREVENTION - Google Patents

Description

Description of the patent for industrial invention entitled:

COMPOSITIONS CONTAINING VEGETABLE-DERIVED INGREDIENTS USEFUL TO IMPROVE THE LIPID STRUCTURE OF PATIENTS IN PRIMARY PREVENTION?

The present invention relates to food or nutraceutical compositions containing ingredients of vegetable origin capable of improving the lipid structure of patients in primary prevention in the cardio-vascular field.

State of the art

Despite the improvement in available therapies, cardiovascular disease is the leading cause of death in the Western world (Lloyd-Jones D. et al. Circulation. 2009; 119 (3): e21-181). The risk stratification models pi? used, which integrate non-modifiable parameters such as age, sex and familiarity? with modifiable parameters such as dyslipidemia, hypertension, diabetes, obesity, smoking and sedentariness, are the FRS (Framingham Heart Study Risk Score) (D'Agostino RB et al. Circulation.

2008; 117 (6): 743-53), the SCORE (Systematic Coronary Risk Evaluation), Conroy RM Eur Heart J. 2003; 24 (11): 987-1003) and, in Italy, the "Project CUORE Risk Score? (Donfrancesco C et al. Eur J Cardiovasc Prev Rehabil.

2010; 17 (4): 403-9). Through these models? in theory it is possible to stratify the subjects in low, intermediate and high risk. Unfortunately the intermediate risk is not? sufficiently placeable and often fades into low or high risk.

Patients who most? are commonly considered, in a more? or less correct, low-risk, perceive conventional pharmacological therapies proposed by the doctor or cardiologist, including statins and ezetimibe, as excessive (Teressa N Harrison et al. Primary Nonadherence to Statin Therapy: Patients' Perceptions. Am J Manag Care, 19 (4), and133-9 2013).

In particular, statins are even perceived as harmful to the subject and this is not in relation to probable aspects of diabetogenicity? (Steven G Chrysant. New Onset Diabetes Mellitus Induced by Statins: Current Evidence Postgrad Med, 129 (4), 430-435 May 2017), but as promoting symptoms of myalgia and myopathy (Albert Selva-O'Callaghan et al. Statin -induced Myalgia and Myositis: An Update on Pathogenesis and Clinical Recommendations. Expert Rev Clin Immunol, 14 (3), 215-224; 2018). Recently, international guidelines have recognized a potentially effective role in the management of the lipid structure of patients in primary prevention, linked to the use of supplements formulated with active ingredients such as berberine, derivatives of fermented red rice containing monacolins, mixtures of phytosterols and phytostanols and mucilaginous fibers (Arrigo F et al., Combinations of Phytomedicines With Different Lipid Lowering Activity for Dyslipidemia Management: The Available Clinical Data, Phytomedicine, 23 (11), 1113-8; 2016). To obviate the possible side effects due to the use of high single-ingredient dosages (constipation for berberine; myalgia for monacolins, meteorism and flatulence for mucilaginous fibers), and to remedy the reduced effectiveness (phytosterols hardly lower total cholesterolemia by values greater than 10%), formulators normally resort to multi-ingredient formulations in the form of tablets or capsules. These for? are perceived by the user again as standard pharmacological therapies and often the adherence to the treatment over time tends to decrease, compromising the same purpose. pursued by the prescriber, and what? primary prevention continued over time. The nutritional approach to the patient, not perceived by the latter as pharmacological, would instead want to be able to control the lipid structure by resorting to a real diet therapy that uses ingredients such as fruit and vegetables. It should also be considered that other plant derivatives, currently not recognized by international guidelines for the management of primary cardio-vascular risk, are actually food ingredients. Pi? specifically, fruit or vegetable derivatives with an anti-dyslipidemic effect are bergamot, annurca apple, raspberry, grape, currant, kiwi, peach, mango, spinach, fennel. The preparation of a supplement in tablets or capsules (but also sachets) that contains these ingredients is complex due to a matter of dosages, volumes and compatibility? among the ingredients. It would therefore be desirable to include these ingredients in a real food that can even be perceived by the patient as a meal but which enhances the properties in a synergistic way? hypocholesterolemic and reducing the plasma concentration of triglycerides of the single active ingredients.

Description of the invention

Yup ? now found that the association of natural compounds to activity? hypocholesterolemic with selected fruit and vegetable derivatives determines a significant and statistically significant reduction in the plasma concentration of all the substances involved in the alteration of the lipid picture. The natural compounds with activity? lipid-lowering agents used according to the invention include phytosterols and / or phytostanols, fermented red rice, berberine or extracts of Berberis spp. containing berberine. By fruit or vegetable derivatives we mean both whole fruits and extracts, centrifuged, smoothies, juices, freeze-dried products, pulp, jellies or smoothies of bergamot, annurca apple, raspberry, grapes, currant, kiwi, peach, mango, spinach, fennel . The extracts can be aqueous, ethanolic or hydro-ethanolic.

Bergamot extracts and juices and annurca apple extracts, pulp or juice are preferred. The compositions of the invention therefore comprise:

a) at least one of the following components:

- phytosterols and / or phytostanols;

- fermented red rice;

- berberine or extracts of Berberis spp. containing berberine and b) one or more? fruit or vegetable derivatives chosen from bergamot, annurca apple, raspberry, grape, currant, kiwi, peach, mango, spinach, fennel. Preferred compositions include phytosterols and / or phytostanols, fermented red rice, berberine or extracts of Berberis spp. containing berberine, bergamot extract or juice and annurca apple extract, pulp or juice and possibly one or more? derivatives, preferably juices, of raspberry, grape, currant, kiwi, peach, mango, spinach, fennel.

The compositions of the invention can also contain antioxidants such as vitamins (C and E), extractive polyphenols (concentrated procyanidolic oligomers from Vitis vinifera, anthocyanosides and proanthocyanidins from Vaccinium myrtillus), glutathione, lipoic acid, ubidecarenone.

The compositions of the invention will be formulated in a manner suitable for oral administration and will be prepared according to well known conventional methods, such as those described in Remington's Pharmaceutical Handbook, Mack Publishing Co., N.Y., USA, using acceptable excipients. Suitable forms of administration include capsules, tablets, sachets, hydro-dispersible powders, jellies, solutions, suspensions, drinks, bars, functional foods.

According to one form of the invention, the compositions can be in the form of bi-layer tablets, with an immediate release layer comprising phytosterols and / or phytostanols, fermented red rice, berberine or extracts of Berberis spp. containing berberine and a controlled or delayed release layer comprising fruit and / or vegetable derivatives.

According to a preferred aspect of this invention, the blend of ingredients? formulated inside a functional food that also in the external form and in the packaging is presented to the consumer as a food or meal. A particularly favorite shape? the juice of the aforementioned plant species with added phytosterols and / or phytostanols, fermented red rice, berberine or extracts of Berberis spp. containing berberine.

Are phytosterols and phytostanols present in quantity? 300 to 3000 mg per unit dose.

Monascus purpureus fermented red rice? present in quantity? such as to provide from 1 to 10 mg of monacolin K (or monacolins in mixture including K) per unit dose, typically from 50 to 500 mg of fermented red rice.

Berberine? present in quantity? 100 to 500 mg per unit dose. Alternatively, it can? be used an extract of Berberis aristata in quantity? such as to provide the berberine dosage indicated above.

The dosage of fruit and vegetable derivatives can? vary within wide limits, depending on the derivative (whole fruit, dehydrated juice or pulp, extract) and the type of formulation. In principle, however, unitary doses ranging from pi? or less 50% of the quantities? shown in the examples below.

Both the fruit derivatives and the other components of the compositions are commercially available or can be prepared with known methods.

Phytosterols, phytostanols, berberine and fermented red rice, known hypocholesterolemic agents, alone or in combination with each other, are not able to determine the anti-dyslipidemic effect clinically shown by associating these components with fruit and vegetable derivatives according to the ? invention described with consequent favorable effects on the reduction of cardiovascular risk and, more? in general, of health. Part of this effect? due to the strong therapeutic adherence that the formula in the form of food determines. The compositions of the invention, in addition to the effects on the general lipid picture, also have positive effects on other cardiovascular risk factors such as homocysteine and trimethylamine-N-oxide.

The following examples illustrate the invention in greater detail.

Example 1 film-coated tablets:

Berberis aristata extract (97%) 515 mg Red rice fermented by Monascus purpureus (3%) 200 mg Dehydrated juice of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 100 mg Microcel 200 mg Dicafos 200 mg Vegetable magnesium stearate 0 mg PVP CL 40 mg Silicon dioxide 20 mg Schellac 50 mg Example 2 capsules size? 0 ?:

Berberis aristata extract (97%) 100 mg Phytosterols 250 mg Dehydrated pulp of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 500 mg Talc 10 mg Microcel 101 50 mg.

Example 3 sachets:

Bergamot extract 500 mg Dehydrated juice of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 1000 mg Methocel E5 20 mg Aerosol 50 mg Acesulfame K 10 mg E110 2 mg Citrus flavor 150 mg.

Example 4 sachets:

Berberis aristata extract (97%) 120 mg Fermented red rice (5%) 210 mg Phytosterols 1500 mg Dehydrated juice of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 1500 mg Aspartame 15 mg Citric acid 50 mg Silicon dioxide 20 mg Aroma 150 mg Acesulfame K 15 mg.

Example 5 two-layer tablets with programmed release STRATO NORMAL-RELEASE

Berberis aristata extract (97%) 50 mg Fermented red rice (1.5% 100 mg Bergamot extract 150 mg Dicaphos 304 mg Aerosil 3 mg Vegetable magnesium stearate 6 mg Dye 1 mg SLOW-RELEASE STRATO

Dehydrated pulp of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 250 mg Metholose 80 mg Aerosil 2 mg Vegetable magnesium stearate 3 mg Microcel 80 mg Dicaphos 164 mg.

Example 6 gold-dispersible formulation

Phytosterols 500 mg Bergamot extract 250 mg Dehydrated juice of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 2500 mg Sorbitol 160 mg Orange flavor 20 mg Tangerine flavor 5 mg Acesulfame k 2 mg Aerosil 5 mg Fructose 1566 mg.

Example 7 rubbery discoid

Fermented red rice (1.5%) 200 mg Dehydrated juice of:

raspberry, apple, bergamot, grape,

currant, kiwi, spinach, mango, peach 200 mg Base gum 600 mg Aspartame 2 mg Menthol 2 mg Acesulfame 1 mg Levilite 20 mg Talc F.U. 20 mg Vegetable magnesium stearate 18 mg Shellac 12 mg Xylitol 250 mg Gum arabic 6 mg Titanium dioxide 6 mg Carnauba wax 0.2 mg.

Example 8 snack in jelly

Phytosterols 1000 mg Fermented red rice (2.5%) 200 mg Berberis aristata extract (90%) 55 mg Raspberry juice 250 mg Annurca apple juice 250 mg Bergamot extract 250 mg Dehydrated grape juice 250 mg Currant pulp 500 mg.

Example 9 snack in jelly

Phytosterols 2000 mg Fermented red rice (2.5%) 300 mg Berberis aristata extract (90%) 110 mg Kiwi pulp 250 mg Annurca apple pulp 250 mg Bergamot extract 500 mg Grape pulp 125 mg Spinach juice 125 mg.

Example 10 snack in jelly

Phytosterols 3000 mg Fermented red rice (2.5%) 400 mg Berberis aristata extract (90%) 550 mg Mango pulp 250 mg Annurca apple extract 250 mg Bergamot extract 250 mg Grape juice 50 mg Yellow peach pulp 250 mg Example 11 Juice

Phytosterols 1 g in 100 ml

Red rice 200 mg equivalent to 5 mg of monacolin K in 100 ml Berberine 50 mg in 100 ml (after pre-treatment with cyclodextrins)

Soy lecithin 5% of the total weight of the formulation Juices in equal parts of:

Raspberry

Annurca apple

Bergamot

Grape

and possibly Ribes

Example 12 Juice

Phytosterols 2 g in 100 ml

Red rice 300 mg equivalent to 7.5 mg of monacolin K in 100 ml Berberine 100 mg in 100 ml (after pre-treatment with cyclodextrins) Soy lecithin 5% of the total weight of the formulation Juices in equal parts of:

Kiwi

Annurca apple

Bergamot

Grape

and possibly Spinach

Example 13 Juice

Phytosterols 3 g in 100 ml

Red rice 400 mg equivalent to 10 mg of monacolin K in 100 ml Berberine 500 mg in 100 cc (after pre-treatment with cyclodextrins) Soy lecithin 5% of the total weight of the formulation Juices in equal parts of:

Mango

Annurca apple

Bergamot

Grape

and possibly Yellow Peach.

Claims (10)

CLAIMS 1. Compositions comprising a) at least one of the following components: - phytosterols and / or phytostanols; - fermented red rice; - berberine or extracts of Berberis spp. containing berberine and b) one or more? fruit or vegetable derivatives chosen from bergamot, annurca apple, raspberry, grape, currant, kiwi, peach, hand, spinach, fennel. 2. Compositions according to claim 1 comprising phytosterols and / or phytostanols, fermented red rice, berberine or extracts of Berberis spp. containing berberine and one or more? fruit or vegetable derivatives chosen from bergamot, annurca apple, raspberry, grape, currant, kiwi, peach, mango, spinach, fennel. 3. Compositions according to claim 1 or 2 wherein the fruit or vegetable derivative? an extract, centrifuged, smoothie, juice, lyophilisate, pulp, jelly. 4. Compositions according to claim 1, 2 or 3 wherein the fruit derivative? bergamot extract. 5. Compositions according to claim 1, 2 or 3 wherein the fruit derivative? extract, pulp or juice of annurca apple. 6. Compositions according to one or more? of the preceding claims comprising bergamot extract or juice and annurca apple extract, juice or pulp. 7. Compositions according to one or more? of the preceding claims comprising annurca apple, bergamot, raspberry, grape and currant juices. 8. Compositions according to one or more? of the preceding claims comprising juices of annurca apple, bergamot, kiwi, grape and spinach or juices of annurca apple, bergamot, mango, grape and yellow peach. 9. Compositions according to one or more? of the preceding claims in the form of capsules, tablets, sachets, hydro-dispersible powders, jellies, drinks, bars, functional foods. 10. Compositions of claims 1-9 for use in primary cardiovascular prevention.