IT202000017242A1 - ORAL COMPOSITION FOR MAINTAINING NORMAL BLOOD SUGAR LEVELS - Google Patents

Description

Title:

ORAL COMPOSITION FOR MAINTAINING NORMAL BLOOD SUGAR LEVELS

DESCRIPTION

FIELD OF THE INVENTION

The present invention relates to a composition and a method of use, wherein the composition effectively helps maintain normal blood sugar levels.

BACKGROUND OF THE INVENTION

Blood sugar? the concentration of sugar (glucose) present in the blood and, in physiological conditions, ? strictly controlled within precise intervals. Normal reference values for blood glucose measured by fasting blood test are between 60 and 110 mg/dl. If a fasting blood glucose test shows levels above the normal range, but not indicative of diabetes (? 126 mg/dl), this is called impaired fasting glucose. Can you? speak, instead, of real diabetes when fasting blood sugar, controlled in pi? measurements, ? greater than 126 mg/dl.

In addition to diabetes, hyperglycemia can be traced to numerous endocrinopathies, including: Cushing's syndrome, hyperthyroidism and pheochromocytoma. Other pathological conditions involving altered blood glucose values include acute or chronic pancreatitis, cystic fibrosis and hemochromatosis, metabolic syndrome.

In cases of blood sugar levels just above normal? advisable a dietary approach, increasing the? activity? physical fitness and assuming proper nutrition.

In cases of very high blood sugar values, oral antidiabetic drugs are used. The classes of oral antidiabetic drugs currently available are the following: biguanides, sulfonylureas, glinides, glitazones (or thiazolidinediones), DPP-4 enzyme inhibitors, intestinal alpha-glucosidase inhibitors, inhibitors of the renal glucose transporter SGLT-2. However, these drugs have side effects such as risk of hypoglycemia, weight gain, intestinal disorders (bloating, diarrhoea, abdominal pain), among others. Even in cases of very high values, proper nutrition does s? that the dosages of the drugs taken can be reduced.

Different substances or nutraceutical products show properties useful for maintaining normal blood sugar levels. Furthermore, from commercially available products or from scientific and patent literature, numerous attempts are known to associate various substances to try to obtain effective compositions for maintaining normal blood sugar levels.

? It is known that a milk protein hydrolyzate contains arginine-proline dipeptides (AP dipeptides) which inhibit the alpha-glucosidase enzyme, an enzyme which hydrolyses polysaccharides into glucose, facilitating their absorption. The inhibition action of alpha-glucosidase therefore allows for regulation of blood sugar levels. However, efficacy is obtained at doses of 1.2 g per day, which precludes administration in capsules or tablets. Furthermore, the bitter and unpleasant taste makes compliance low in other forms of oral administration such as powders.

? known that extracts of pomegranate, cos? like acorn flour, they are high in polyphenols.

? Polyphenols are known to influence blood sugar through a number of mechanisms, including decreasing glucose absorption through the intestine. The mechanism more probable ? the inhibition of the alpha-glucosidase enzyme, an enzyme that hydrolyzes polysaccharides into glucose, facilitating their absorption. The inhibition action of alpha-glucosidase therefore allows for regulation of blood sugar levels.

Although numerous attempts to associate various substances to try to obtain effective compositions for maintaining normal blood sugar levels are known (from products on the market or from scientific and patent literature), ? still felt the need to be able to combine different substances with properties? different, in such proportions as to exhibit synergistic effects in terms of maintaining normal blood sugar levels and at the same time able to be well tolerated.

Indeed, there are various technical problems that an ideal composition should solve. In particular, such compositions should:

- be effective,

- have good bioavailability? of the active ingredients, - be well tolerated,

- show very low toxicity,

- also be suitable for prolonged and repeated use, - be easy to administer, for example in the form of water-dispersible powders or oral semi-solid formulations, - have a not unpleasant smell and taste,

- not show interactions with other drugs or concomitant treatments to which the patient? subjected.

Overall, therefore, they should have good compliance by the subjects who take them, for example by providing an effective dose of numerous active ingredients that act in synergy, without the form of oral administration having large dimensions, and without requiring numerous administrations daily, preferably what? can be administered one to three times a day.

SUMMARY OF THE INVENTION

The above purpose ? been achieved by a composition comprising a unique combination of ingredients, including:

hydrolyzate of milk proteins,

pomegranate extract,

acorn flour,

monoglycerides and

sucrestere.

The inventors of the present invention have surprisingly found that the above ingredients show activity synergistic with each other in terms of effectiveness in maintaining normal blood sugar levels. Furthermore, the presence of monoglycerides and sucresteres added to the formula increases the intestinal absorption of the active ingredients contained in the hydrolysed milk proteins, in the pomegranate extract and in the acorn flour.

An object of the present invention ? then a composition based on:

hydrolyzate of milk proteins,

pomegranate extract,

acorn flour,

monoglycerides and

sucrestere,

as outlined in the attached claims 1 to 9.

Another object of the invention are the compositions of the invention for use in maintaining normal blood sugar levels, as outlined in the appended claim 10.

The text of the annexed claims forms an integral part of the present description.

Further characteristics and advantages of the compositions and of the process according to the invention will result from the following description of embodiments, given by way of non-limiting example.

DETAILED DESCRIPTION OF THE INVENTION

According to a first embodiment, the present invention relates to a composition based on:

hydrolyzate of milk proteins,

pomegranate extract,

acorn flour,

monoglycerides and

sucrestere.

In certain embodiments, the composition of the invention comprises the following percentages by weight, calculated on the total weight of the mixture of said components:

hydrolyzate of milk proteins 45-90%,

pomegranate extract 5-30%,

acorn flour 1-25%,

monoglycerides 0.2-3%, e

sucrester 0.2-3%.

According to a preferred embodiment, the present invention relates to a dosage form of said composition comprising:

hydrolysed milk proteins from 1200 mg to 1600 mg, pomegranate extract from 200 mg to 400 mg,

acorn flour from 35 mg to 350 mg,

monoglycerides 10 mg to 30 mg, e

sucrestere from 10 mg to 30 mg.

According to a particularly preferred embodiment, the present invention relates to a dosage form of said composition comprising:

hydrolysed milk proteins from 1300 mg to 1500 mg, pomegranate extract from 250 mg to 350 mg,

acorn flour from 40 mg to 200 mg,

monoglycerides 15 mg to 25 mg e

sucrestere 15 mg to 25 mg.

According to an embodiment even more? preferred invention, the above composition comprises a quantity? of the aforementioned active ingredients such as to provide a content of:

- punicalagin punicaline from 50 to 500 mg,

- polyunsaturated fatty acids (PUFA) from 20 to 100 mg.

Furthermore, the inventors have surprisingly found that some flavors cover the bitter taste of milk protein hydrolyzate and pomegranate extract significantly effectively. According to a particularly preferred embodiment, the present invention thus relates to a composition further comprising a flavor selected from the group consisting of: cherry flavour, black cherry flavour, chocolate flavour, coffee flavour, caramel flavour, cola flavour.

As used herein, the term ?milk protein hydrolyzate? means a mixture of amino acids and peptides pi? or less complex obtained from the hydrolysis of milk. A non-limiting example of milk protein hydrolyzate? PEP2DIA product? (manufactured by Ingredia S.A., France).

As used herein, the term ?pomegranate extract? means a dry powdered extract obtained from the fruit of Punica granatum L. by extraction, for example, with ethanol/water mixtures. This extract? characterized by having a content of polyphenols, such as the hydrolysable tannins punicaline and punicalagine, overall greater than or equal to 30% w/w. A non-limiting example of pomegranate extract? the Pomanox product? (manufactured by Euromed S.A., Spain).

As used herein, the term ?acorn meal? means a flour obtained by grinding the fruit of the oak tree, after washing with water. Such flour? characterized by having a total polyphenol content greater than or equal to 2% w/w and a dietary fiber content greater than or equal to 20% w/w.

As used herein, the term ?edible oil? means a product of a lipid nature, in a liquid state at room temperature, used for food purposes. Non-limiting examples of edible oils are olive oil, sunflower seed oil, corn seed oil, grapeseed oil, sesame seed oil, pumpkin seed oil, soybean oil, flax seed oil, peanut, etc..

As used herein, the terms ?monoglyceride? or ?monoacylglycerol? mean a particular class of glycerides whose molecule ? made up of a fatty acid chain added by esterification to a glycerol molecule. Depending on the position of the ester linkage on the glycerol molecule, monoglycerides can be divided into two groups: 1-monoacylglycerols and 2-monoacylglycerols.

As used herein, the terms ?sucrestere? or ?sucrose ester? mean a sucrose ester of fatty acids. These are emulsifying compounds widely used in the food industry. From a chemical point of view, they consist of a molecule of sucrose to which they bind by esterification of the fatty acids at the level of the hydroxyl groups. Different sucresters can be obtained depending on the fatty acids used and how many bonds are formed with the sugar (sucrose has 8 hydroxyl groups).

As used herein, the term ?polyphenols? does it mean the quantity? total of compounds with a polyphenolic structure, expressed as caffeic acid equivalents and determined analytically by the Folin-Ciocalteu method [Ainsworth EA and Gillespie KM. Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent. Nature Protocols 2007;2:875-875]. Non-limiting examples of polyphenols are quercetin, apigenin, resveratrol, isoflavones, catechins. Non-limiting examples of sources of polyphenols are plant extracts such as tea extract green, acai fruit extract, red vine extract, pomegranate extract, olive leaf extract, etc..

As used herein, the term ?polyunsaturated fatty acids? means fatty acids that are characterized by two or more? C=C double bonds within the molecule. They are also known as polyenoic fatty acids or PUFA (Poly Unsaturated Fatty Acids) and include omega-3, omega-6 and omega-9. Non-limiting examples of PUFA sources are sunflower oil, hemp seed oil, black currant seed oil, various fish oils, flaxseed oil, soybean oil, chia seeds, walnuts, etc.. Non-limiting examples of PUFAs are linoleic acid, ?linolenic acid, stearidonic acid, arachidonic acid, timnodonic acid, clupanodonic acid, cervonic acid, hexadecatrienoic acid, eicosatrienoic acid, juniperonic acid, eicosapentaenoic acid, docosapentaenoic acid, tetracosapentaenoic acid, trocosapentaenoic acid, ?linolenic acid, eicosadienoic acid, dihomo-gamma-linolenic acid, adrenic acid, calendic acid, oleic acid, eicosenoic acid, eicosatrienoic acid, erucic acid, nervonic acid, etc..

The components of the present formulation are all known and available individually on the market.

The term ?single dose administration? or ?dosage form?, as used herein, means the dose of composition in the form of a capsule, tablet, granule, powder, oral semi-solid formulation, solid dispersion in liquid taken in a single oral administration.

The composition of the invention can also include additional ingredients and excipients such as, but not limited to, vitamins, minerals, edible oils, other plant extracts, gelling agents, thickeners, pH adjusters, preservatives, fibers, flavors, water, and the like. For example, the composition of the invention can include pharmaceutically acceptable excipients and carriers such as xanthan gum, anhydrous or monohydrate citric acid, potassium sorbate, gum arabic, and the like.

Non-limiting examples of PUFA-rich edible oils are olive oil, sunflower oil, hemp seed oil, blackcurrant seed oil, various fish oils, linseed oil , soybean oil, chia seeds, walnuts, etc.

Non-limiting examples of flavors are natural flavors, synthetic flavors, pure volatile substances or essential oils of black cherry, cherry, chocolate, coffee, caramel, cola, etc..

A non-limiting example of another plant extract? an olive fruit extract, for example Mediteanox? (manufactured by Euromed S.A., Spain), etc.

The composition can furthermore contain further excipients or other active ingredients depending on the type of formulation to be prepared.

In certain embodiments, the dosage form of the composition is a sachet.

In certain embodiments, the dosage form of the composition is an oral gel.

The compositions and/or dosage forms of the invention can be prepared according to conventional methods, such as those described in Remington, The Science and Practice of Pharmacy, edited by Allen, Loyd V., Jr, 22nd<ma>edition, 2012 .

EXAMPLES

Example 1 - composition in sachets

A composition? was prepared using the following ingredients (Table 1):

Table 1.

The aforementioned ingredients were mixed and placed in sachets. A suitable dosage of the aforementioned sachets ? of 1 administration per day.

Example 2 - oral gel composition

A composition? was prepared using the following ingredients (Table 2):

Table 2.

Weigh A and heat to 70-75°C. Weigh B and heat to 70°C. Pour A on B and make the emulsion. Add C below 40?C. Add D. Density? of the sample: 1 g/ml. A suitable dosage of the aforementioned sachets ? of 1 administration per day.

? It is evident that only some particular embodiments of the present invention have been described, to which the expert in the art will be capable of making all those modifications necessary for its adaptation to particular applications, without however departing from the scope of protection of the present invention.

Claims (11)

1. A composition comprising: hydrolyzate of milk proteins, pomegranate extract, acorn flour, monoglycerides and sucrestere. 2. Composition according to claim 1, comprising the following percentages by weight, calculated on the total weight of the mixture of said components: hydrolyzate of milk proteins 45-90%, pomegranate extract 5-30%, acorn flour 1-25%, monoglycerides 0.2-3%, e sucrester 0.2-3%. The composition according to claim 1 or 2, in a dosage form comprising: hydrolysed milk proteins from 1200 mg to 1600 mg, pomegranate extract from 200 mg to 400 mg, acorn flour from 35 mg to 350 mg, monoglycerides 10 mg to 30 mg, e sucrestere from 10 mg to 30 mg. 4. Composition according to any one of claims 1 to 3, in a dosage form comprising: hydrolysed milk proteins from 1300 mg to 1500 mg, pomegranate extract from 250 mg to 350 mg, acorn flour from 40 mg to 200 mg, monoglycerides 15 mg to 25 mg e sucrestere 15 mg to 25 mg. The composition according to any one of claims 1 to 4 further containing an edible oil with 70% PUFA. 6. Composition according to any one of claims 1 to 5 wherein the edible oil with 70% PUFA is olive oil. 7. Composition according to any one of claims 1 to 6 further containing a flavor selected from the group consisting of: cherry flavor, black cherry flavor, chocolate flavor, coffee flavor, caramel flavor and cola flavor. 8. Composition according to any one of claims 1 to 7 such as to provide for each single administration dose a content of: - punicalagin punicaline from 50 to 500 mg, - PUFA from 20 to 100 mg. 9. Composition according to any one of claims 1 to 8, in sachet dosage form. The composition according to any one of claims 1 to 8, in oral gel dosage form. The composition according to any one of claims 1 to 10, for use in maintaining normal blood sugar levels.