WO2023126537A1 - Compositions - Google Patents

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Publication number
WO2023126537A1
WO2023126537A1 PCT/EP2023/050012 EP2023050012W WO2023126537A1 WO 2023126537 A1 WO2023126537 A1 WO 2023126537A1 EP 2023050012 W EP2023050012 W EP 2023050012W WO 2023126537 A1 WO2023126537 A1 WO 2023126537A1
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Prior art keywords
composition
red yeast
yeast rice
caco
monacolin
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PCT/EP2023/050012
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French (fr)
Inventor
Elena GELFI
Manuel Roberto MOSCONI
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MEDA Pharma S.p.A.
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Publication of WO2023126537A1 publication Critical patent/WO2023126537A1/en

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    • 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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/16—Inorganic salts, minerals or trace elements
    • 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
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/062—Ascomycota
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/752—Citrus, e.g. lime, orange or lemon
    • 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)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10—Preparation or pretreatment of starting material
    • A61K2236/19—Preparation or pretreatment of starting material involving fermentation using yeast, bacteria or both; enzymatic treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria

Definitions

  • the invention relates to solid oral compositions, based on monascus fermented rice standardized in monacolin K (MK), using addition of calcium carbonate for improving monacolin K stability.
  • Monascus fermented rice also known as red yeast rice (RYR)
  • RYR red yeast rice
  • Monacolin K is considered the most efficacious compound to lower cholesterol in the plasma. It is structurally identical to lovastatin, and mevinolin (Klimek, Wang, and Ogunkanmi, P&T 2009, 34 No 6, 313-316).
  • monacolin K has poor stability in red yeast rice and in pharmaceutical dosage forms. Stability analyses have shown that monacolin K was unstable during prolonged storage of red yeast rice powder particularly at high storage temperature (40-50°C) especially under atmospheric storage conditions (Sani Jirasatid et al., Journal of Food Engineering 116 (2013) 436-443).
  • monacolins decreased significantly under the conditions of high humidity at high temperature (75% relative humidity (RH), 60°C) and sunlight.
  • Monacolin K and its hydroxyl acid form would be dehydrolyzed and turned to dehydromonacolin K at high temperature (80°C) while monacolin K, J and L would be transformed into their corresponding hydroxyl acid forms under the condition of high humidity (92.5% RH, 25°C).
  • the observations show the result that monacolins in red yeast rice powder are light-sensitive and thermal-sensitive (Yong-Guo Li,. Journal of Pharmaceutical and Biomedical Analysis 39 (2005) 82-90.
  • compositions comprising red yeast rice and CaCO 3 has improved stability showing a statistically significant effect.
  • the proportions of the various components of the combination are defined relative to other components.
  • Monascus fermented rice or red yeast rice is a traditional Chinese preparation of cooked white rice, being fermented with Monascus purpureus for a few days at room temperature, which results in the red colour.
  • the red yeast rice used in the context of the present invention can be standardized in Monacolin K from 0.5 to 2.0 % (w/w).
  • the invention provides a composition comprising red yeast rice and CaCO 3 (calcium carbonate).
  • the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO 3 in a weight ratio of 1 to 5 to 5 to 1 .
  • the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO 3 in a weight ratio of 2 to 1 .
  • the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO 3 in a weight ratio of 1 to 2.
  • the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO 3 in a weight ratio of 2 to 3.
  • compositions may additionally comprise one or more components selected from Berberis aristata, phytosterols and/or phytostanols, Cynara cardunculus extract, Citrus bergamia extract, Allium sativum, Salvia miltiorrhiza, policosanol, Camellia sinensis extract, Melannurca campana extract, Curcuma longa and curcuminoids, spirulina, chitosan, betaglucan, glucomannan, coenzyme Q10, astaxanthin, folic acid and orthosiphon.
  • aristata phytosterols and/or phytostanols
  • Cynara cardunculus extract Citrus bergamia extract
  • Allium sativum Salvia miltiorrhiza
  • policosanol Camellia sinensis extract
  • Melannurca campana extract Curcuma longa and curcuminoids
  • spirulina chitosan
  • the invention also provides the compositions disclosed herein for use in the treatment or prevention of hypercholesterolemia or hyperlipidemia.
  • the invention also provides the use of the compositions disclosed herein for the manufacture of a medicament for the treatment or prevention of hypercholesterolemia or hyperlipidemia.
  • the invention also provides a method for the treatment or prevention of hypercholesterolemia or hyperlipidemia comprising administration of the compositions disclosed herein to a patient in need thereof.
  • Hypercholesterolemia (and hyperlipidemia) is a well-known risk factor for coronary artery, cerebrovascular and peripheral artery diseases. In fact, any reduction of basal cholesterol in plasma levels is correlated to a proportionally reduced incidence of cardiovascular complications (myocardial infarction, stroke, peripheral obstructive arterial disease). The correlation already exists before the first clinical event, relevant for primary prevention, as well as for the cardiovascular events that follow the first clinical vent, relevant for secondary prevention.
  • compositions of the invention are useful in the treatment or prevention of hypercholesterolemia, and hyperlipidemia.
  • compositions are generally administered to a subject in need of such administration, for example a human or animal, typically a human.
  • the compositions will typically be administered in amounts that are therapeutically or prophylactically useful.
  • compositions may be administered over a prolonged term to maintain beneficial therapeutic effects or may be administered for a short period only.
  • a typical daily dose of each components of the combination can be in the range from 100 pg to 100 mg per kg of body weight, more typically 5 ng to 25 mg per kg of bodyweight, and more usually 10 ng to 15 mg per kg (e.g. 10 ng to 10 to 20 mg, and more typically 1 pg per kg to 20 mg per kg, for example 1 pg to 10 mg per kg) per kg of bodyweight although higher or lower doses may be administered where required.
  • compositions may be administered orally in a range of doses, for example 0.1 to 1000 mg, 1 to 800 mg, 5 to 700 mg, 10 to 500 mg, 25 to 400 mg, or 50 to 350 mg.
  • compositions of red yeast rice standardized in monacolin K to 1 .75% w/w typically corresponds to a daily dose of monacolin K of between 0.2 mg to about 35 mg.
  • the daily dose may be administered in a single daily dose, or multiple doses spread throughout the day e.g. once-daily, twice-daily or three-times daily.
  • the red yeast rice composition according to the invention e.g. a pharmaceutical composition is provided as an oral dosage form.
  • Oral dosage forms include tablets (coated or uncoated), capsules (hard or soft shell), caplets, pills, lozenges, syrups, solutions, powders, granules, elixirs and suspensions, sublingual tablets, wafers or patches such as buccal patches. Therefore, in one embodiment of the invention, the red yeast rice composition according to the invention is presented in a tablet.
  • the tablet includes one or more pharmaceutically acceptable excipient.
  • the pharmaceutically acceptable excipient can be selected from, for example, carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents, fillers or bulking agents, granulating agents, coating agents, release-controlling agents, binding agents, disintegrants, lubricating agents, preservatives, antioxidants, buffering agents, suspending agents, thickening agents, flavouring agents, sweeteners, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions.
  • composition of the invention is formulated with one or more pharmaceutically acceptable fillers or bulking agents.
  • excipients examples include magnesium stearate, silicon dioxide, carboxymethylcellulose, crospovidone, and hydroxypropyl cellulose and maltodextrin.
  • the red yeast rice composition is provided in capsules.
  • the capsule includes one or more pharmaceutically or nutraceutically acceptable excipient.
  • the pharmaceutically or nutraceutically acceptable excipient can be selected from, for example, carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents, fillers or bulking agents, granulating agents, coating agents, release-controlling agents, binding agents, disintegrants, lubricating agents, preservatives, antioxidants, buffering agents, suspending agents, thickening agents, flavouring agents, sweeteners, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions.
  • carriers e.g. a solid, liquid or semi-solid carrier
  • adjuvants e.g. a solid, liquid or semi-solid carrier
  • granulating agents e.g. a solid, liquid or semi-solid carrier
  • coating agents e.g. a solid, liquid or semi-solid carrier
  • release-controlling agents e.g., granulating agents
  • excipients examples include magnesium stearate, silicon dioxide, maltodextrin, carboxymethylcellulose, crospovidone, and hydroxypropyl cellulose.
  • Formulation example EXAMPLES STABILITY ANALYSIS OF RED YEAST RICE COMPOSITIONS The aim of the stability study was to compare the effect of different ratios of RYR and CaCO3 on the stability profiles of monacolin K comprising composition. Tablet preparation was done in the usual way.
  • compositions comprising RYR and CaCO 3 have an improved stability, with respect to monacolin K concentration, compared to the composition comprising RYR and CaHPO 4 .
  • compositions comprising RYR and CaCO 3 in a ratio of 2 to 3 and 1 to 2.

Abstract

The invention relates to solid oral compositions, comprising monascus fermented rice stabilized by adding CaCO3.

Description

COMPOSITIONS
The invention relates to solid oral compositions, based on monascus fermented rice standardized in monacolin K (MK), using addition of calcium carbonate for improving monacolin K stability.
BACKGROUND OF THE INVENTION
Monascus fermented rice, also known as red yeast rice (RYR), has traditionally been used as a natural food colorant and food preservative of meat and fish for centuries. It has recently become a popular dietary supplement because many of its bioactive constituents, including a series of active drug compounds, monacolins (indicated as 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) have been discovered as being capable of reducing serum cholesterol levels (Lin et al., Appl Microbiol Biotechnol 2008; 77, 965 - 973).
Among the bioactive compounds found in red yeast rice, monacolins are well known for their pharmacological effects to control hyperlipidemia. Monacolin K is considered the most efficacious compound to lower cholesterol in the plasma. It is structurally identical to lovastatin, and mevinolin (Klimek, Wang, and Ogunkanmi, P&T 2009, 34 No 6, 313-316).
It is well known that monacolin K has poor stability in red yeast rice and in pharmaceutical dosage forms. Stability analyses have shown that monacolin K was unstable during prolonged storage of red yeast rice powder particularly at high storage temperature (40-50°C) especially under atmospheric storage conditions (Sani Jirasatid et al., Journal of Food Engineering 116 (2013) 436-443).
Further studies exhibited that monacolins decreased significantly under the conditions of high humidity at high temperature (75% relative humidity (RH), 60°C) and sunlight. Monacolin K and its hydroxyl acid form would be dehydrolyzed and turned to dehydromonacolin K at high temperature (80°C) while monacolin K, J and L would be transformed into their corresponding hydroxyl acid forms under the condition of high humidity (92.5% RH, 25°C). The observations show the result that monacolins in red yeast rice powder are light-sensitive and thermal-sensitive (Yong-Guo Li,. Journal of Pharmaceutical and Biomedical Analysis 39 (2005) 82-90.
Accordingly, it is an object of the present invention to provide monacolin K in a red yeast rice formulation which shows an increased stability
SUMMARY OF THE INVENTION
The invention provides a composition comprising red yeast rice and CaCO3. Surprisingly the applicant has found that compositions comprising red yeast rice and CaCO3 has improved stability showing a statistically significant effect. DEFINITIONS
The proportions of the various components of the combination are defined relative to other components. The wt% (weight percent) of a particular component, based on the other components, is the weight (mass) of the particular component, divided by the weight (mass) of based on weight of the composition, times 100 i.e. wt% single component X (based on weight of the composition Y) =
Figure imgf000003_0001
x 100
Figure imgf000003_0002
Monascus fermented rice or red yeast rice is a traditional Chinese preparation of cooked white rice, being fermented with Monascus purpureus for a few days at room temperature, which results in the red colour. The red yeast rice used in the context of the present invention can be standardized in Monacolin K from 0.5 to 2.0 % (w/w).
Particularly preferred is a red yeast rice standardized in Monacolin K 1.75%.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a composition comprising red yeast rice and CaCO3 (calcium carbonate).
In one embodiment, the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO3 in a weight ratio of 1 to 5 to 5 to 1 .
Preferably the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO3 in a weight ratio of 2 to 1 .
More preferably, the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO3 in a weight ratio of 1 to 2.
More preferably, the invention provides a composition of red yeast rice standardized in monacolin K to 1 .75% w/w and CaCO3 in a weight ratio of 2 to 3.
In a further embodiment, the aforementioned compositions may additionally comprise one or more components selected from Berberis aristata, phytosterols and/or phytostanols, Cynara cardunculus extract, Citrus bergamia extract, Allium sativum, Salvia miltiorrhiza, policosanol, Camellia sinensis extract, Melannurca campana extract, Curcuma longa and curcuminoids, spirulina, chitosan, betaglucan, glucomannan, coenzyme Q10, astaxanthin, folic acid and orthosiphon. Uses of the invention
The invention also provides the compositions disclosed herein for use in the treatment or prevention of hypercholesterolemia or hyperlipidemia.
The invention also provides the use of the compositions disclosed herein for the manufacture of a medicament for the treatment or prevention of hypercholesterolemia or hyperlipidemia.
The invention also provides a method for the treatment or prevention of hypercholesterolemia or hyperlipidemia comprising administration of the compositions disclosed herein to a patient in need thereof.
Hypercholesterolemia (and hyperlipidemia) is a well-known risk factor for coronary artery, cerebrovascular and peripheral artery diseases. In fact, any reduction of basal cholesterol in plasma levels is correlated to a proportionally reduced incidence of cardiovascular complications (myocardial infarction, stroke, peripheral obstructive arterial disease). The correlation already exists before the first clinical event, relevant for primary prevention, as well as for the cardiovascular events that follow the first clinical vent, relevant for secondary prevention.
Dosage
The compositions of the invention are useful in the treatment or prevention of hypercholesterolemia, and hyperlipidemia.
The compositions are generally administered to a subject in need of such administration, for example a human or animal, typically a human. The compositions will typically be administered in amounts that are therapeutically or prophylactically useful.
The compositions may be administered over a prolonged term to maintain beneficial therapeutic effects or may be administered for a short period only.
A typical daily dose of each components of the combination can be in the range from 100 pg to 100 mg per kg of body weight, more typically 5 ng to 25 mg per kg of bodyweight, and more usually 10 ng to 15 mg per kg (e.g. 10 ng to 10 to 20 mg, and more typically 1 pg per kg to 20 mg per kg, for example 1 pg to 10 mg per kg) per kg of bodyweight although higher or lower doses may be administered where required.
The compositions may be administered orally in a range of doses, for example 0.1 to 1000 mg, 1 to 800 mg, 5 to 700 mg, 10 to 500 mg, 25 to 400 mg, or 50 to 350 mg.
Particular examples of daily doses of the composition are 100, 200, 300, 600, 900, 1200, 1500 and 1800 mg. For a composition of red yeast rice standardized in monacolin K to 1 .75% w/w, this dosage range typically corresponds to a daily dose of monacolin K of between 0.2 mg to about 35 mg.
The daily dose may be administered in a single daily dose, or multiple doses spread throughout the day e.g. once-daily, twice-daily or three-times daily.
Formulations
In one embodiment, the red yeast rice composition according to the invention e.g. a pharmaceutical composition is provided as an oral dosage form. Oral dosage forms include tablets (coated or uncoated), capsules (hard or soft shell), caplets, pills, lozenges, syrups, solutions, powders, granules, elixirs and suspensions, sublingual tablets, wafers or patches such as buccal patches. Therefore, in one embodiment of the invention, the red yeast rice composition according to the invention is presented in a tablet.
Typically, the tablet includes one or more pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient can be selected from, for example, carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents, fillers or bulking agents, granulating agents, coating agents, release-controlling agents, binding agents, disintegrants, lubricating agents, preservatives, antioxidants, buffering agents, suspending agents, thickening agents, flavouring agents, sweeteners, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions.
Preferably, the composition of the invention is formulated with one or more pharmaceutically acceptable fillers or bulking agents.
Examples of excipients include magnesium stearate, silicon dioxide, carboxymethylcellulose, crospovidone, and hydroxypropyl cellulose and maltodextrin.
In one embodiment, the red yeast rice composition is provided in capsules.
Typically, the capsule includes one or more pharmaceutically or nutraceutically acceptable excipient. The pharmaceutically or nutraceutically acceptable excipient can be selected from, for example, carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents, fillers or bulking agents, granulating agents, coating agents, release-controlling agents, binding agents, disintegrants, lubricating agents, preservatives, antioxidants, buffering agents, suspending agents, thickening agents, flavouring agents, sweeteners, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions.
Examples of excipients include magnesium stearate, silicon dioxide, maltodextrin, carboxymethylcellulose, crospovidone, and hydroxypropyl cellulose.
Formulation example
Figure imgf000006_0001
EXAMPLES STABILITY ANALYSIS OF RED YEAST RICE COMPOSITIONS The aim of the stability study was to compare the effect of different ratios of RYR and CaCO3 on the stability profiles of monacolin K comprising composition. Tablet preparation was done in the usual way. The following tablet compositions were analysed: 10 A RYR/CaCO3 in a ratio of 2 to 3 B RYR/CaCO3 in a ratio of 2 to 1 C RYR/CaCO3 in a ratio of 1 to 2 D RYR/CaHPO4 in a ratio of 1 to 2 Storage conditions were 25°C 65%RH, 30°C 75%RH, 40°C 75%RH Samples were analysed after 0, 3, 6, 12, 18 and 24 months 5 Results
Figure imgf000007_0001
Figure imgf000007_0002
Figure imgf000007_0003
Figure imgf000007_0004
Figure imgf000007_0005
Figure imgf000007_0006
Figure imgf000008_0001
Figure imgf000008_0002
The results demonstrate that the compositions comprising RYR and CaCO3 have an improved stability, with respect to monacolin K concentration, compared to the composition comprising RYR and CaHPO4.
Especially stable are the compositions comprising RYR and CaCO3 in a ratio of 2 to 3 and 1 to 2.

Claims

1 . A composition comprising red yeast rice and CaCO3.
2. The composition as claimed in claim 1 , characterized in that the ratio of red yeast rice and
CaCO3 is between 1 to 5 and 5 to 1 .
3. The composition as claimed in claim 1 , characterized in that the ratio of red yeast rice and
CaCO3 is between 1 to 2 and 2 to 3.
The composition as claimed in claim 1 , characterized in that the ratio of red yeast rice and
CaCO3 is 2 to 3.
5. The composition as claimed in claim 1 , characterized in that the ratio of red yeast rice and
CaCO3 is 1 to 2.
6. The composition as claimed in claims 1 to 5, characterized in that the red yeast rice is standardized in monacolin K from 0.5 to 2.0 % w/w.
7. The composition as claimed in claims 1 to 6, characterized in that the red yeast rice is standardized in monacolin K 1 .75 % w/w.
8. The composition as claimed in any of claims 1 to 7 for use in the treatment or prevention of hypercholesterolemia or hyperlipidemia.
9. The composition as claimed in any of claims 1 to 8, additionally comprising one or more components selected from Berbens aristata, phytosterols and/or phytostanols, Cynara cardunculus extract, Citrus bergamia extract, Allium sativum, Salvia miltiorrhiza, policosanol, Camellia sinensis extract, Melannurca campana extract, Curcuma longa and curcuminoids, spirulina, chitosan, betaglucan, glucomannan.
10. The composition as claimed in any of claims 1 to 9, additionally comprising one or more components selected from coenzyme Q10, astaxanthin, folic acid, orthosiphon.
PCT/EP2023/050012 2022-01-01 2023-01-02 Compositions WO2023126537A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120219619A1 (en) * 2007-06-01 2012-08-30 Joar Opheim Substances for reducing occurrence of major cardiac events in humans
EP2719287A1 (en) * 2012-10-09 2014-04-16 DDF Group di Damiani Luciano Marco & C. S.A.S. Compositions for the treatment of hyperlipidemia
US20140314729A1 (en) * 2013-04-12 2014-10-23 Creative Medical Health Inc. Nutraceutical formulation for treatment of elevated cholesterol and cardiovascular disease
EP3064200A1 (en) * 2015-03-03 2016-09-07 AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO - A.C.R.A.F. - S.p.A. Composition comprising natural substances and/or extracts
EP3169322A1 (en) * 2014-07-18 2017-05-24 BERLIN-CHEMIE Aktiengesellschaft Dietetic composition with antidyslipidemic activity
CN109123643A (en) * 2018-09-29 2019-01-04 中科和素（天津）医药科技有限公司 A kind of preparation method of cereal generation meal ball

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120219619A1 (en) * 2007-06-01 2012-08-30 Joar Opheim Substances for reducing occurrence of major cardiac events in humans
EP2719287A1 (en) * 2012-10-09 2014-04-16 DDF Group di Damiani Luciano Marco & C. S.A.S. Compositions for the treatment of hyperlipidemia
US20140314729A1 (en) * 2013-04-12 2014-10-23 Creative Medical Health Inc. Nutraceutical formulation for treatment of elevated cholesterol and cardiovascular disease
EP3169322A1 (en) * 2014-07-18 2017-05-24 BERLIN-CHEMIE Aktiengesellschaft Dietetic composition with antidyslipidemic activity
EP3064200A1 (en) * 2015-03-03 2016-09-07 AZIENDE CHIMICHE RIUNITE ANGELINI FRANCESCO - A.C.R.A.F. - S.p.A. Composition comprising natural substances and/or extracts
CN109123643A (en) * 2018-09-29 2019-01-04 中科和素（天津）医药科技有限公司 A kind of preparation method of cereal generation meal ball

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
KLIMEKWANGOGUNKANMI, P&T, vol. 34, no. 6, 2009, pages 313 - 316
LIN ET AL., APPL MICROBIOL BIOTECHNOL, vol. 77, 2008, pages 965 - 973
SANI JIRASATID ET AL., JOURNAL OF FOOD ENGINEERING, vol. 116, 2013, pages 436 - 443
YONG-GUO LI, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, vol. 39, 2005, pages 82 - 90
ZHANG JIE ET AL: "Stability, Microstructure, and Rheological Properties of CaCO3 S/O/W Calcium-Lipid Emulsions", FOODS, vol. 10, no. 9, 18 September 2021 (2021-09-18), pages 2216, XP055890277, DOI: 10.3390/foods10092216 *

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