IT201900010800A1 - COMPOSITION CONTAINING PRICKLY PEAR EXTRACT IN SERENOA OIL FOR THE MAINTENANCE OF PROSTATE FUNCTIONALITY - Google Patents

Description

Title: COMPOSITION CONTAINING PRICKLY PEAR EXTRACT IN OIL

DESCRIPTION

FIELD OF THE INVENTION

The present invention relates to a composition, a method for its production and a method of use, in which the composition effectively helps to maintain the functionality of the prostate. The composition includes a precise blend of highly active agents, including:

prickly pear flower extract in microencapsulated serenoa oil,

green coffee extract containing chlorogenic acids, chitosan.

BACKGROUND OF THE INVENTION

A product for the maintenance of prostate functions is a product that has the characteristic of avoiding the onset of prostate disorders such as hyperplasia, inflammation and prostatic infection.

Benign prostatic hyperplasia (BPH) is characterized by an increase in the volume of the prostate gland. The causes are not fully understood, but correlations have been observed between the onset of BPH and factors such as:

- elevated blood levels of estrogen;

- reduced blood levels of free testosterone;

- elevated blood levels of dihydrotestosterone;

- old age;

- inheritance;

- lifestyle, for example smoking and alcohol consumption habits, and a sedentary lifestyle.

Prostate inflammation is caused by:

- bacterial infections;

- lifestyles such as smoking, alcohol consumption and a sedentary lifestyle;

- excessive or too little muscle stress in the prostate area.

Prostate infection is caused by:

- colonization by pathogenic microorganisms that go up the urethra and are localized in the prostate;

- colonization by pathogenic microorganisms localized at the rectal level that spread through the prostate;

- sexual intercourse.

In order to obtain products for the maintenance of prostate functionality, various substances have been developed, with different effects and mechanisms of action, which can act on the numerous causes that give rise to hyperplasia, inflammation and prostatic infection. . In fact, these active ingredients can have different effects such as:

• anti-inflammatory effect;

• antimicrobial effect;

• prostatic antihyperplasia effect: this action is mediated by the inhibitory activity against the target enzyme 5-alpha reductase. 5-alpha-reductase (also known as 3-oxo-5-alpha-asteroid 4-dehydrogenase) converts testosterone into dihydrotestosterone. The latter is a hormone that stimulates and controls the development and maintenance of male characteristics;

• antiproliferative effect on prostate cancer cells;

• effect of improving erectile function.

Several substances or products show properties useful for maintaining the functionality of the prostate, exerting one or more of the aforementioned effects. Furthermore, numerous attempts to associate various substances in order to obtain effective compositions for maintaining the functionality of the prostate are known from products available on the market or from the scientific and patent literature. For example, it is known that:

Prickly pear flower extract contains, among the various phytocomponents, various polyphenols that are particularly abundant in flowers.

Serenoa oil (Serenoa repens) is an oil particularly rich in fatty acids and phytosterols. The active ingredients of Serenoa stimulate estrogen receptors in the prostate and inhibit progestogens and are also capable of producing anti-estrogenic and antiandrogenic effects which occur with blockage caused by the inhibition of type I and II 5-alpha-reductase of the binding by dihydrotestosterone. at the level of androgen receptors [Silverio et al. Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations andregional distribution of androgens andepidermal growthfactor in benign prostatic hyperplasia, in Prostate, vol. 37, 1998, pp.

77-83; Sultan et al. Inhibition of androgen metabolism and binding by a liposterolic extract of "Serenoa repens B" in human foreskin fibroblasts, in J Steroid Biochem, vol. 20, 1984, pp.

515-519].

The chlorogenic acids contained in green coffee are polyphenols and show anti-benign prostatic hyperplasia [Huang Y, Chen H, Zhou X, Wu X, Hu E, Jiang Z. Inhibition effects of chlorogenic acid on benign prostatic hyperplasia in mice. Eur. J. Pharmacol. 2017; 809: 191-195. doi: 10.1016 / j.ejphar.2017.04.017]. The dosages reported are from 1.6 mg / kg to 3.2 mg / kg in rats which correspond to 112-224 mg for a 70 kg man.

Chitosan has the following structure:

It is a linear polysaccharide composed of D-glucosamine and N-acetyl-D-glucosamine, linked via β (1-4) bonds. Chitosan and its derivatives increase intestinal absorption, and therefore bioavailability, especially of hydrophilic macromolecules [Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives as intestinal absorption enhancers. Adv. Drug. Deliv. Rev. 2001; 50 Suppl. 1: S91-101] including catechins / polyphenols [Dube A, Nicolazzo JA, Larson I. Chitosan nanoparticles enhance the intestinal absorption of the green tea catechins (+) - catechin and (-) - epigallocatechingallate. Eur. J. Pharm. Sci. 2010; 41 (2): 219-225]. Generally its dosages are equal to 1/4 of the dosage of the total polyphenols associated with it.

Although, as mentioned above, there are known (from products on the market or from scientific and patent literature) numerous attempts to combine various substances to try to obtain effective compositions for the maintenance of prostate functionality, the need is still felt to be able to combine different substances with different properties, in such proportions as to exhibit synergistic effects in terms of efficacy for maintaining the functionality of the prostate and at the same time able to be well tolerated.

In fact, 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, - be suitable also for prolonged and repeated use, - be easy to administer, for example in capsule or tablet form, - have a non-unpleasant smell and taste, - be preferably made with natural ingredients - overall therefore they should have good compliance on the part of 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 (for example tablet or capsule) having large dimensions (for example should have a weight of less than 1.5 g), and without requiring numerous daily administrations, that is, preferably they can be administered only once a day.

It is a characteristic of the present compositions to contain only a relatively small amount of additives and / or excipients, given the high content of active ingredients. This allows for the production of physically small unit dosage forms. The total amount of additives and / or excipients in a given unit dosage may be about 70% by weight or less based on the total weight of the composition, more particularly about 60% or less. Preferably, the additive contained is in the range from about 20% to 60% by weight, more particularly the additive contained varies from about 30% to about 55% by weight.

SUMMARY OF THE INVENTION The above purpose was achieved by means of a composition comprising a unique combination of ingredients including:

prickly pear flower extract in microencapsulated Serenoa oil, green coffee extract containing chlorogenic acids, chitosan.

The inventors of the present invention have surprisingly found that the following ingredients:

prickly pear flower extract (OPUNTIA FICUS-INDICA) in microencapsulated Serenoa oil (SERENOA REPENS), green coffee extract (COFFEA ARABICA) containing chlorogenic acids,

chitosan,

they show synergistic activity with each other in terms of efficacy for maintaining the functionality of the prostate with antimicrobial, anti-inflammatory and antihyperlasia prostatic activity.

An object of the present invention is therefore a composition based on:

prickly pear flower extract in microencapsulated Serenoa repens oil,

green coffee extract containing chlorogenic acids, chitosan,

as outlined in the attached claims 1 to 8.

Another object of the invention is a composition production process, as outlined in the attached claim 9.

A further object of the invention are the compositions of the invention for use in maintaining the functionality of the prostate, as outlined in the attached claim 10.

The text of the attached 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 examples of embodiments, given for information only and not limitative.

DETAILED DESCRIPTION OF THE INVENTION

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

prickly pear flower extract in microencapsulated Serenoa repens oil,

green coffee extract containing chlorogenic acids, chitosan,

in which:

- The extract of prickly pear flowers in microencapsulated Serenoa repens oil is a fat-soluble extract of prickly pear flowers in Serenoa repens oil. This extract is then microencapsulated to give it a solid form and can also be used in pharmaceutical forms such as capsules, tablets and granules. This extract can be obtained by macerating prickly pear flowers in Serenoa repens oil, or by assembling a fat-soluble extract of prickly pear flowers obtained, for example, in supercritical fluids such as supercritical CO2 with Serenoa repens oil. , and subsequently microencapsulating the mixture. The extract of prickly pear flowers in microencapsulated Serenoa repens oil is characterized by a total fatty acid content equal to or greater than 60% w / w and a total polyphenol content equal to or greater than 10 ppm.

- Green coffee extract containing chlorogenic acids is a green coffee extract characterized by a content of total polyphenols expressed as chlorogenic acids equal to or greater than 50% w / w.

- Chitosan (CAS number 9012-76-4) is a polymer of D-glucosamine, which can be obtained by alkaline deacetylation of chitin. The industrial process currently used is that of starting from purified chitin obtained from crustaceans. Chitosan solubilizes easily and quickly in an acid solution due to the salification of the amino functional groups.

According to a preferred embodiment of the invention, the aforesaid composition comprises a quantity of extract of prickly pear flowers in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids and chitosan such as to provide for a single dose of administration a content of:

- total polyphenols equal to or greater than 50 mg, - total fatty acids equal to or greater than 150 mg,

- total polysaccharides equal to or greater than 20 mg.

According to a preferred embodiment of the invention, the aforesaid composition comprises a quantity of extract of prickly pear flowers in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids, pomegranate extract containing punicalagin and punicalin and chitosan such as to be made for a single dose of administration a content of:

- total polyphenols equal to or greater than 50 mg, - total fatty acids equal to or greater than 150 mg, - total polysaccharides equal to or greater than 20 mg, - total punicalins and punicalagins equal to or greater than 30 mg.

According to a preferred embodiment of the invention, the aforesaid composition comprises a quantity of extract of prickly pear flowers in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids, Capsicum powder and chitosan such as to provide for each individual administration dose a content of:

- total polyphenols equal to or greater than 50 mg, - total fatty acids equal to or greater than 150 mg, - total polysaccharides equal to or greater than 20 mg,

- capsaicin equal to or greater than 1 ppm.

According to a preferred embodiment of the invention, the aforesaid composition comprises an amount of prickly pear flower extract in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids, green tea extract containing epigallocatechin gallate and chitosan such to be made for a single dose of administration a content of:

- total polyphenols equal to or greater than 100 mg, - total fatty acids equal to or greater than 150 mg, - total polysaccharides equal to or greater than 20 mg.

According to a preferred embodiment of the invention, the aforesaid composition comprises a quantity of extract of prickly pear flowers in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids, Capsicum powder and chitosan such as to provide for each individual administration dose a content of:

- total polyphenols equal to or greater than 120 mg, - total fatty acids equal to or greater than 150 mg, - total polysaccharides equal to or greater than 20 mg, - capsaicin equal to or greater than 1 ppm.

The term "total polyphenols", as used herein, indicates the total amount 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].

The term "total fatty acids", as used here, indicates the total quantity of free fatty acids coming from the hydrolysis of their esters such as triglycerides, diglycerides, etc. They have a structure of aliphatic monocarboxylic acid, mainly, but not exclusively, long chain, with an even number of carbon atoms, without branching and acyclic; they can be saturated or unsaturated. They are determined analytically by gas-liquid chromatography [Horning EC, Arrens EH, Lipsky SR, Mattson FH, Mead JF, Turner DA, Goldwater WH. Quantitative Analysis of Fatty Acids by Gas-Liquid Chromatography. J. LipidRes., 1964; 5: 20-27]. Examples of fatty acids are myristic, palmitic, palmitoleic, stearic, oleic, linoleic, alpha-linolenic, arachidonic, eicosenoic, behenic, erucic acids and the like.

The term "total polysaccharides", as used herein, means the total amount of various polysaccharides. Polysaccharides are organic chemical compounds that belong to the class of carbohydrates (carbohydrates). They are characterized by a large number (greater than 20) of repeating units (monosaccharides), bound together to form large and complex molecules. Polysaccharides can be linear or branched. They are determined analytically by spectrophotometric methods or HPLC [Food Analysis, edited by S. Nielsen, 2010; Pomeranz Y, Meloan CE. Food Analysis - Theory and Practice, 2000]. In nature, polysaccharides are commonly found in plants, where they make up 50% to 90% of their dry weight.

The terms "punicalagine" and "punicalin" indicate substances with antioxidant activity present in the fruit of the pomegranate (Punica granatum) and are analytically determined by chromatographic analysis (HPLC).

The term "microencapsulation", as used herein, refers to a process which consists of coating minute droplets of liquid with a thin film, usually made of natural or synthetic polymers, to form microcapsules. This technique allows to improve or modify various characteristics and properties of the microencapsulated material, as well as providing protection, stabilization and optimizing its release and bioavailability. The term "microencapsulated", as used herein, refers to a plant extract or essential oil that has undergone the microencapsulation process.

The term "single dose administration", as used herein, means the dose of composition in capsule, tablet, granulate form taken with a single oral administration.

The composition of the invention may also comprise further ingredients and excipients such as, but not limited to, vitamins, minerals, other plant extracts, excipients for microencapsulation, compression excipients, emollients, humectants, binders, rheology modifiers, pH regulators, water and similar. For example, the composition of the invention may include maltodextrin, microcrystalline cellulose, gum arabic, magnesium stearate, silica, and the like.

Non-limiting examples of vitamins that can be used in the composition of the present invention are vitamin D3 (cholecalciferol) and vitamin E (tocopherol) and its derivatives such as vitamin E acetate.

Non-limiting examples of minerals which can be used in the composition of the present invention are magnesium, in the form, for example but without limitation, of magnesium oxide, sodium, in the form, for example but without limitation, of sodium selenite, and the like.

Non-limiting examples of other plant extracts that can be used in the composition of the present invention are: a green tea extract (Camellia sinensis), a Boswellia serrata extract, a garlic extract (Allium sativum), a Serenoa repens extract, a blueberry extract (Vaccinium myrtillus), an extract of Capsicum sp. (e.g. Capsicum annuum), an essential oil of peppermint, an extract of Pygeum africanum, and the like.

A non-limiting example of an excipient for microencapsulation that can be used in the composition of the present invention is gelatin.

The composition may also contain further excipients or other active ingredients according to the type of formulation to be prepared.

In certain embodiments, the composition is a capsule.

In certain embodiments, the composition is a tablet.

In certain embodiments, the composition is a granulate.

Another object of the invention is a production process of the composition of the present invention. The manufacturing process includes the following steps (Scheme 1):

Scheme 1:

sorting of raw materials

mixing of the active ingredients containing polyphenols with chitosan

addition of the other active ingredients and mixing

addition of excipients and acceptable carriers e

mixing

bulk unloading and transfer

distribution and packaging

EXAMPLES

Example 1 - composition in capsules

By the process illustrated in Scheme 1, a composition was prepared using the following ingredients (Table 1):

Table 1.

RAW MATERIAL Quantity Vitamin D3 - cholecalciferol 0.05 mg Capsicumin powder 5 mg Prickly pear flower extract in oil of 150 mg serenoa microencapsulated

Sodium selenite 0.1 mg Dry extract of green coffee titrated in 240 mg chlorogenic acids at 50%

Chitosan 30 mg Excipients q.s. to 500 mg Total 500 mg

Example 2 - tablet composition

By the process illustrated in Scheme 1, a composition was prepared using the following ingredients (Table 2):

Table 2.

RAW MATERIAL Quantity Vitamin D3 0.025 mg Lycopene 20 mg Prickly pear flower extract in 300 mg serenoa microencapsulated oil

Zinc oxide 15 mg Microencapsulated mint essential oil 7 mg Pomegranate extract 100 mg Sodium selenite 0.05 mg Vitamin E acetate 12 mg Dry extract of green coffee titrated in 100 mg chlorogenic acids at 50%

Chitosan 50 mg Excipients q.s. at 800 mg Total 800 mg Example 3 - composition in tablets

By the process illustrated in Scheme 1, a composition was prepared using the following ingredients (Table 3):

Table 3.

RAW MATERIAL Quantity

Boswellia serrata dry extract titrated in 100 mg

65% boswellic acids

Vitamin D3 0.125 mg

Lycopene 10 mg

Prickly pear flower extract in 230 mg oil

microencapsulated serenoa

Dry extract of nettle (Urtica dioica) 75 mg

Capsicum powder 4 mg

Dry extract of bilberry (Vacciniummyrtillus) 10 mg

Dry extract of ginger (Zingiber officinale) 5 mg

titrated in gingerols at 20%

Dry extract of green tea (Camellia sinensis) 50 mg

titrated in epigallocatechin gallate (EGCG) al

95%

Sodium selenite 0.014 mg

Zinc oxide 3.5 mg

Vitamin E acetate 3 mg

Dry extract of green coffee titrated in acids 100 mg

50% chlorogenic

Chitosan 22.5 mg

Excipients q.s. at 800 mg Total 800

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

Claims (10)

CLAIMS 1. A composition comprising: prickly pear flower extract in microencapsulated Serenoa repens oil, green coffee extract containing chlorogenic acids, chitosan, acceptable excipients and carriers. 2. Composition according to claim 1, wherein the composition is such as to provide for a single administration dose a content of: - total polyphenols from 50 to 1000 mg - total fatty acids from 120 to 1000 mg, - total polysaccharides from 20 to 250 mg. 3. Composition according to claim 1 or 2, wherein the composition is such as to provide for a single administration dose a content of: - total polyphenols from 50 to 500 mg - total fatty acids from 120 to 500 mg, - total polysaccharides from 20 to 125 mg. Composition according to any one of claims 1-3 further comprising a dry green tea extract containing epigallocatechin gallate. 5. Composition according to any one of claims 1-4 further comprising Capsicumspp powder. A composition according to any one of claims 1-5 further comprising pomegranate extract. 7. Composition according to any one of claims 1-6 further comprising dry garlic extract. 8. Composition according to any one of claims 1-7 further comprising a dry extract of Boswellia serrata. Process for producing a composition according to any one of claims 1-8, the aforementioned process comprising the following steps: - sorting of raw materials, - mixing the active ingredients containing polyphenols with chitosan, - adding the other active ingredients and mixing, - adding the excipients and acceptable carriers and mixing, - bulk unloading and transfer, - distribution and packaging. 10. Composition according to any one of claims 1 to 8, for use in maintaining the functionality of the prostate.