Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/06—Antihyperlipidemics
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
  • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
  • A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
  • A61K31/47—Quinolines; Isoquinolines
  • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
  • A61K31/51—Thiamines, e.g. vitamin B1
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
  • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
  • A61K36/18—Magnoliophyta (angiosperms)
  • A61K36/185—Magnoliopsida (dicotyledons)
  • A61K36/67—Piperaceae (Pepper family), e.g. Jamaican pepper or kava
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2009—Inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2013—Organic compounds, e.g. phospholipids, fats
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2013—Organic compounds, e.g. phospholipids, fats
  • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/2004—Excipients; Inactive ingredients
  • A61K9/2022—Organic macromolecular compounds
  • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
  • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
  • A61K9/2846—Poly(meth)acrylates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/20—Pills, tablets, discs, rods
  • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
  • A61K9/2806—Coating materials
  • A61K9/2833—Organic macromolecular compounds
  • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
  • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

• the present invention relates to a composition, in particular a nutraceutical formulation for the treatment of the metabolic syndrome.
• berberine chloride an alkaloid extracted from plants of the genus Berberis, characterized by the following formula, is certainly worth of consideration
• BERC pharmacological synergies in terms of reduction of plasma cholesterol fractions, in particular LDL and fasting glycaemia and to favour the restoration of a trophic state of the hepatic parenchyma, reducing steatosis and normalizing the secretion of intracellular enzymes such as GOT and GPT, indicators of hepatocytic cell damage during exotoxic liver diseases.
• the black pepper pipeline acts as an inhibitor of the metabolization of pharmacological and nutraceutical active ingredients, in particular by inhibiting the enzyme UDP-glucuronyl transferase, responsible for enterocytic and hepatic glucuronidation
• PS 80 polyoxyethylene sorbitan ester with oleic acid
• WO 2014/044744 Al describes compositions for the treatment of the metabolic syndrome containing, as essential ingredients, the Cynara scolimus extract with a content of 30-45% in caffeoylquinic acid, extracts of Coffea spp with a content of caffeoylquinic acids ranging from 40 to 80% by weight and finally an Olea europaea extract.
• JP 2013 237656 A reports that pipeline is used as an anti-dyslipidaemic agent, as it prevents the differentiation and maturation of cells in adipocytes.
• US 2016/106793 Al describes a composition containing a combination of at least 3 extracts (including Cynara Scolimus , Chrysanttellum indicum and Vaccinium myrtillus) together with pipeline for the treatment of metabolic disorders.
• EP 2 810 941 Al describes piperine derivatives having anti-dyslipidaemic activity, PANAHI YUNES ET AL in "Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: Results of a randomized controlled t", COMPLEMENTARY THERAPIES IN MEDICINE, vol. 22, no. 5, pages 851-857, XP029080004,ISSN: 0965-2299, DOI:
• NOMIKOS ET Al in "Boiled wild artichoke reduces postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients", NUTRITION RESEARCH, ELSEVIER INC, XX, vol. 27, no. 12, 26 November 2007 (2007-11-26), pages 741-749, XP022361961, ISSN: 0271-5317, DOI: 10.1016/J.NUTRES.2007.09 .009 reports the activity of Cynara cardiunculus extracts (thistle or wild artichoke) in reducing blood glucose and postprandial insulin only on healthy subjects but not on individuals with metabolic syndrome.
• JURGONSKI ADAM ET AL in "Caffeoylquinic acid-rich extract from chicory seeds improves glycaemia, atherogenic index, and antioxidant status in rats", NUTRI, vol. 28, no. 3, 1 March 2012 (2012-03-01), pages 300-306,
• XP009166712, ISSN: 1873-1244, DOI: 10.1016/J.NUT.2011.06.010 [retrieved on 2011-10-19] report that chicory extracts rich in caffeoylquinic acids are effective in the treatment of metabolic syndrome together with rutin, a quercetin derivative.
• WO 2018/189672 Al describes the association of the Cynara cordiunculus extract that, as noted above, is the common thistle, with an extract of another plant, Citrus aurantium bergamia, in the treatment of hepatic steatosis and in the treatment of dyslipidaemia.
• the oral composition that is the object of the present invention and comprises Berberis aristata extract with a minimum titre of 50% in BERC, Cynara scolimus extract with a minimum title of 2.5% in caffeoylquinic acids, dispersed in a suspension of polysorbate 80 and Piper Nigrum extract with a minimum titre of 80% in piperine, shows a high efficacy, clinically documented, in normalizing the lipidic, glucidic and hepatic profile in patients with moderate hypercholesterolemia and compatible with the initial clinical signs of metabolic syndrome.
• the object of the present invention is an oral composition comprising
• the association of polysorbate 80 - piperine has not been described yet, at least in the form of intimate mixing of the second in the first, as foreseen in the process to prepare the aforementioned formulation in order to obtain an enteric absorption promoter capable of simultaneously improving the diffusion of the active ingredient through the UWP and the inhibition of UDP-glucuronyl transferase in the enterocyte.
• the further object of the present invention namely the industrial method for the preparation of the aforementioned oral composition, preferably in the form of a gastro-resistant tablet, comprises in particular the following steps:
• step b) wetting the powder coming from step b) with the liquid suspension of step a);
• step c) merging the obtained wet powder coming from step c) with possible excipients such as calcium phosphate, microcrystalline cellulose and magnesium stearate in order to obtain a dry, smooth and compressible powder;
• step d compressing the powder obtained in step d;
• This process is characterized by the wetting of the powder mixture composed of Berberis aristata extract and Cynara scolimus extract titrated in caffeoylquinic acids into the suspension of the polyoxyethylenate sorbitan ester and Piperine, prepared in step a.
• the intimate mixing of the two active principles with the aforementioned absorption promoters achieved in the step c of the process of the invention allows obtaining a final powder, which is subsequently compressed and coated with a film that ensures the overcoming of the gastric transit and the subsequent disaggregation in the first enteric tract (3 hours), considerably increases the effectiveness of the absorption promotion system thus favouring an increased clinical response compared to the mere association of the active ingredients.
• Cynara scolimus titrated in caffeoylquinic acids is responsible for a cholesterol-lowering effect synergistic to that of BERC and of a hepato-trophic and detoxifying effect, responsible for the normalization of the plasma enzyme profile (GOT, GPT).
• the definition "comprising" before a list of components, as in the case of the oral composition object of the invention or of steps as in the process, further object of the invention, does not exclude the presence of further components or steps besides those listed.
• the Berberis aristata extract preferably has a titre of 98% in berberine chloride.
• the Berberis aristata is present in the formulations object of the invention in such a content that the berberine chloride is present in a variable amount between 250 and 500 mg.
• the Cynara scolimus extract is present in amounts such as to have a caffeoylquinic acid content of between 0.5 and 5 mg.
• Polysorbate 80 also known as PS80, is preferably used as sorbitan polyoxyethylenate ester.
• the sorbitan polyoxyethylenate ester content can vary from a minimum of 1% to a maximum of 10% by weight of the weight of the oral composition.
• the Piper nigrum extract has a piperine titre between 95 and 98%.
• the Piper nigrum is present in such amounts that the piperine content varies between a minimum of 0.1% by weight to a maximum of 2% of the total weight of said composition.
• Oral compositions may also contain as an active ingredient a vitamin belonging to B vitamins and a pharmaceutically acceptable chromium salt to further promote the normalization of glycaemia.
• the oral composition object of the present invention comprises picolinate chromium as pharmaceutically acceptable chromium salt, and as B vitamins, the oral composition object of the invention contains vitamin Bl and folic acid to assist the hypoglycaemic effect.
• the oral composition according to the present invention comprises chromium picolinate, vitamin Bl and folic acid.
• the oral compositions object of the present invention can be in the form of granulates or gastro-resistant tablets, even if as mentioned above, the latter are particularly preferred.
• compositions according to the present invention are preferably in the form of nutraceutical formulations and are in particular suitable for the treatment of the metabolic syndrome.
• a nutraceutical is, in its original definition, a food, or part of a food with proven beneficial and protective effects on both the physical and psychological health of the individual, according to what reported in the review entitled NUTRACEUTICA: DEFINIZIONE, REGOL AMENT AZIONE E APPLICAZIONI by A. Pirillo and A.L. Catapano and published in Giornale Italiano di Farmacoeconomia e Farmacoutilizzaée 2014; 6 (4): 23-30.
• the possible excipients are selected from at least one of the following: calcium phosphate, microcrystalline cellulose and magnesium stearate in order to obtain a dry, smooth and compressible powder.
• an oral composition according to the present invention in the form of a gastro-resistant tablet is reported below for illustrative purposes.
• cardiovascular diseases Despite the progress in scientific knowledge about the prevention of cardiovascular diseases, they still represent the most frequent cause of death in the world today, causing the death of about 4 million people every year in Europe alone. In particular, cardiovascular diseases related to atherosclerosis are responsible for 42% of deaths in women and 38% in men under 75 [12]
• cardiovascular diseases Several known risk factors contribute to the development of cardiovascular diseases; classically they are divided into factors that can be modified with lifestyle changes or a pharmacological treatment (e.g. hypercholesterolemia, hypertension, smoking, diabetes mellitus) and non-modifiable factors (age, male sex, familiarity).
• pharmacological treatment e.g. hypercholesterolemia, hypertension, smoking, diabetes mellitus
• non-modifiable factors e.g. hypercholesterolemia, hypertension, smoking, diabetes mellitus
• non-modifiable factors e.g. hypercholesterolemia, hypertension, smoking, diabetes mellitus
• non-modifiable factors e.g. hypertension, smoking, diabetes mellitus
• high concentrations of LDL cholesterol represent one of the main independent cardiovascular risk factors [13]
• the lipid-lowering nutraceuticals described in the literature are numerous and their use is supported by different levels of scientific evidence and efficacy [15]
• the single most effective (and even best-selling) nutraceutical is fermented red rice extract, whose active ingredient is monacolin K, a substance produced by fermentation of common rice by the fungus Monascus purpureus.
• Monacolin K is very effective, as it has the same chemical structure as synthetic lovastatin [16]
• this analogy has its disadvantages, because it is associated with the same side effects of statins (although attenuated by the dosage limitations provided for by the law) and the same risk of drug interactions, for which some European Union states are proposing employment restrictions.
• the aim of this study was the evaluation of the short-term metabolic effect of the combination of other cholesterol-lowering nutraceuticals with a different action from statins such as dry extracts of artichoke and berberis in patients suffering from moderate hypercholesterolemia in primary prevention for cardiovascular diseases.
• Example 1 placebo (indistinguishable in shape and volume), for a duration of 8 weeks, in association with a standardized Mediterranean diet.
• the combined nutraceutical significantly reduced levels of total cholesterol, LDL (calculated and dosed) and non-HDL cholesterol, triglycerides, basal glycaemia, GOT and GPT compared to baseline, while cholesterolaemia HDL has increased compared to baseline (Table 2).
• the values of total cholesterol, LDL (calculated and dosed) and non-HDL cholesterol decreased significantly even compared to placebo (Table 2).
• Table 1- Baseline clinical and laboratory values in the two treatment groups
• Li -Blatter X Nervi P, Seelig A. Detergents as intrinsic P-glycoprotein substrates and inhibitors. Biochim Biophys Acta. 2009 Oct;l788(lO):2335-44;
• EACPR Cardiovascular Prevention & Rehabilitation
• 2016 ESC/EAS Guidelines for the management of dyslipidaemias The task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J 2016; 37:2999-3058
• Cicero AFG Red yeast rice, monacolin K, and pleiotropic effects. Recenti Prog Med. 20l8;l09(2): l54e-l57e.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Natural Medicines & Medicinal Plants (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biotechnology (AREA)
• Alternative & Traditional Medicine (AREA)
• Botany (AREA)
• Medical Informatics (AREA)
• Microbiology (AREA)
• Mycology (AREA)
• Molecular Biology (AREA)
• Biophysics (AREA)
• Emergency Medicine (AREA)
• Inorganic Chemistry (AREA)
• Diabetes (AREA)
• Hematology (AREA)
• Obesity (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Cosmetics (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=63965880

Family Applications (1)

Country Status (3)

Families Citing this family (3)

Family Cites Families (5)

• 2018
  • 2018-08-01 IT IT102018000007746A patent/IT201800007746A1/it unknown
• 2019
  • 2019-08-01 EP EP19758812.2A patent/EP3829714A1/de active Pending
  • 2019-08-01 WO PCT/IB2019/056566 patent/WO2020026186A1/en unknown

Also Published As

Similar Documents

Legal Events