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WO2024218722A2 - Compositions et procédés pour le traitement d'une déficience en coenzyme q10 - Google Patents

Compositions et procédés pour le traitement d'une déficience en coenzyme q10 Download PDF

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Publication number
WO2024218722A2
WO2024218722A2 PCT/IB2024/053816 IB2024053816W WO2024218722A2 WO 2024218722 A2 WO2024218722 A2 WO 2024218722A2 IB 2024053816 W IB2024053816 W IB 2024053816W WO 2024218722 A2 WO2024218722 A2 WO 2024218722A2
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WO
WIPO (PCT)
Prior art keywords
coenzyme
composition
parts
hpmc
weight
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Pending
Application number
PCT/IB2024/053816
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English (en)
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WO2024218722A3 (fr
Inventor
Yip Ching PUI
Yip Shu Pui
Hing Sang Pui
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Vellpharm Co Ltd
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Vellpharm Co Ltd
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Publication date
Priority claimed from AU2023901172A external-priority patent/AU2023901172A0/en
Application filed by Vellpharm Co Ltd filed Critical Vellpharm Co Ltd
Publication of WO2024218722A2 publication Critical patent/WO2024218722A2/fr
Publication of WO2024218722A3 publication Critical patent/WO2024218722A3/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

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    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug

Definitions

  • the present invention broadly relates to compositions comprising coenzyme Q10 and a water soluble excipient, such as, for example, PEG, polysorbate, docusate sodium, poloxamer, organic acid or HPMC.
  • a water soluble excipient such as, for example, PEG, polysorbate, docusate sodium, poloxamer, organic acid or HPMC.
  • the invention also broadly relates to methods of treating coenzyme Q10 deficiency in a subject by the invention.
  • Ubiquinone also known as coenzyme Q10 (abbreviated as CoQw)
  • CoQw coenzyme Q10
  • CoQw coenzyme Q10
  • CoQw coenzyme Q10
  • CoQw coenzyme Q10
  • mitochondria Coenzyme Q10
  • Coenzyme Q10 is naturally-occurring in the majority of aerobic organisms, ranging from bacteria to plants and animals. In mammals, coenzyme Q10 can be found in every organ. Most foods also contain coenzyme Q10. Vegetable oil and meat typically have higher concentrations of coenzyme Q10 than dairy products.
  • the solubility of coenzyme Q10 is 0.239 mg/mL, which means that to dissolve 150 mg of coenzyme Q10, more than 500 mL of water is required. However, it is difficult for a healthy human to retain 500 mL of water in the stomach for more than 10 minutes, as the water will pass from the stomach through the digestive system.
  • the pKa of coenzyme Q10 is -4.7.
  • Various techniques are used for the enhancement of the solubility of coenzyme Q10, including physical and chemical modifications of the drug, or other methods such as particle size reduction, crystal engineering, salt formation, solid dispersion, surfactant use, complexation, amongst others.
  • Oral bioavailability depends on several factors including, but not limited to, aqueous solubility, drug permeability, dissolution rate, first-pass metabolism and presystemic metabolism. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability of the drug.
  • the term "soluble" can also be used to describe materials that form colloidal suspensions of very fine solid particles in a liquid.
  • solubility of a water-insoluble drug is often related to drug particle size - as a particle becomes smaller, the surface area to volume ratio increases. A larger surface area allows greater interaction with the solvent, which increases the solubility of the drug in water.
  • Coenzyme Q10 is indicated for the treatment of heart failure.
  • administration of 30-100 mg/day of coenzyme Q10 was shown to result in 31% lower mortality.
  • Exercise capacity was also increased.
  • a 2018 meta-analysis concluded that there was preliminary evidence for oral coenzyme Q10 reducing statin-associated muscle symptoms, including muscle pain, muscle weakness, muscle cramps and muscle tiredness.
  • Coenzyme Q10 has a chemical formula of C59H90O4 and molar mass of 863.4 g/mol. Coenzyme Q10 has a yellow or orange appearance and is a solid at room temperature. Coenzyme Q10 is a component of the electron transport chain and participates in aerobic cellular respiration, which generates energy in the form of ATP. 95% of the human body's energy is generated in this way. There are three redox states of coenzyme Q10: fully oxidized (referred to as ubiquinone or coenzyme Q10), semiquinone (also referred to as ubisemiquinone), and fully reduced (referred to as ubiquinol).
  • coenzyme Q10 is well tolerated. However, some adverse effects, largely gastrointestinal, are reported with very high intakes of coenzyme Q10. The most common side effects are gastrointestinal symptoms including nausea, vomiting, appetite suppression, abdominal pain, rashes, and headaches.
  • the strength of coenzyme Q10 formulations on the market is in the range from 5 to 600 mg per capsule and the dosage is once or twice daily, as needed. Different manufacturers provide different strengths of coenzyme Q10 and the bioavailability of the preparations may vary.
  • Coenzyme Q10 is also used as a dietary supplement and can be prescribed or recommended by medical professional for preventing or treating the symptoms of heart failure.
  • the present invention relates generally to compositions comprising coenzyme Q10 and a water soluble excipient, and methods of treating coenzyme Q10 deficiency.
  • the present invention provides a composition comprising coenzyme Q10 and one or more water soluble excipients selected from HPMC, PEG, docusate sodium, poloxamer, organic acid and polysorbate, wherein the composition has a dissolution amount of coenzyme Q10 in an aqueous medium of greater than 60%.
  • the composition has a dissolution amount of coenzyme Q10 of greater than 60%, 70%, 80%, or 90%, in 1000 mL of an aqueous medium of 0.5% Triton of pH 4.5.
  • the composition is in the form of spheres comprising coenzyme Q10, a binder comprising HPMC of low molecular mass and a core comprising one or more excipients.
  • the HPMC is of a molecular mass equal to or lower than 26,000 g/mol.
  • the composition comprises a HPMC and coenzyme Q10 mixture coating on the surface of the core, wherein the core comprises sugar, microcrystalline cellulose or a mixture thereof.
  • the core comprises one or more of sugar, microcrystalline cellulose, lactose, starch, mannitol, sorbitol, fructose- 1,6-diphosphate, and cross-linked povidone, or a mixture thereof.
  • the composition comprises coenzyme Q10 and PEG 200 to 22000, wherein the composition is in the form of a liquid, granules, a tablet or a capsule.
  • the composition comprises 1 part of coenzyme Q10 and 1 to 4 parts of PEG 1000 to 22000 by weight.
  • the composition further comprises a filler, an expander and a lubricating excipient.
  • the composition comprises 1 part of coenzyme Q10 and 1 to 10 parts of PEG 200 to 600 by weight.
  • the composition is in the form of granules, tablets or capsules comprising coenzyme Q10 and poloxamer.
  • the composition comprises 1 part of coenzyme Q10 and 1 to 4 parts of poloxamer.
  • the composition comprises coenzyme Q10, PEG 1000 to 22000 and poloxamer, wherein the composition is in the form of granules, tablets or capsules.
  • the composition comprises 1 part of coenzyme Q10, 1 to 3 parts of PEG 1000 to 22000, 1 to 3 parts of poloxamer by weight.
  • the composition further comprises a filler, an expander and a lubricating excipient.
  • the composition comprises 1 part of coenzyme Q10 and 0.5 to 3 parts of docusate sodium by weight.
  • the composition further comprises a filler, an expander and a lubricating excipient.
  • the composition comprises 1 part of coenzyme Q10, 1 to 3 parts of PEG 1000 to 22000, 1 to 3 parts of poloxamer and 0.5 to 1 parts of docusate sodium by weight and the formulation further comprises a filler, an expander and a lubricating excipient.
  • the composition is in the form of a sphere comprising by weight 1 part of coenzyme Q10, 0.5 to 3 parts of HPMC of low molecular mass and 0.5 to 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof.
  • the composition comprises by weight 1 part of coenzyme Q10, 2 parts of HPMC and 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof.
  • the composition is in the form of granules or capsules comprising coenzyme Q10 and HPMC of low molecular mass, wherein the composition further comprises one or more of lactose, sugar, microcrystalline cellulose, and cross-linked povidone, or a mixture thereof.
  • the composition is a liquid solution comprising coenzyme Q10 and a PEG 200 to 600.
  • the liquid solution is filled in a bottle or into a soft capsule.
  • the composition comprises 1 part of coenzyme Q10 and 1 to 10 parts of a PEG 200 to 600.
  • the composition is a liquid solution comprising coenzyme Q10 and a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80.
  • the composition is a liquid solution comprising coenzyme Q10, PEG 200 to 600 and a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80.
  • the liquid solution is filled in a bottle or into a soft capsule.
  • the composition comprises by weight 1 part of coenzyme Q10, 1 to 10 parts of a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80.
  • the composition comprises by weight 1 part of coenzyme Q10 and 1 to 10 parts of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid and ascorbic acid.
  • the present invention provides a method of producing a coenzyme Q10 composition in the form of a sphere, the method comprising the steps of: a) dissolving 1 part by weight of coenzyme Q10 in an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane, until the coenzyme Q10 is fully dissolved; b) dissolving 0.5 to 3 parts by weight of HPMC of low molecular mass in a solvent selected from ethanol, isopropyl alcohol or benzyl alcohol; c) mixing the solution of step a) and the solution of step b) together to form a solution comprising co
  • the present invention provides a method of producing a coenzyme Q10 composition, wherein the method comprises the steps of: a) dissolving 1 part by weight of coenzyme Q10 in an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane until the coenzyme Q10 is fully dissolved or dispersed; b) adding 1 to 3 parts of PEG 1000 to 22000, 1 to 3 part of poloxamer or 0.5 to 1 parts of docusate sodium by weight into the solution or dispersion of step a) until the PEG, poloxamer or docusate sodium is fully dissolved or dispersed; c) placing 1 part each of lactose, microcrystalline cellulose, cross-linked povidone in a fluidised bed; d) spraying the solution or dispersion of step b) onto the fluidised bed to form a powdered mixture;
  • the present invention provides the composition as described herein for use in providing heart nutrients to a patient with heart disease.
  • the present invention provides use of the composition as described herein in the manufacture of a medicament for treating coenzyme Q10 deficiency or a condition related to coenzyme Q10 deficiency, such as heart failure, cardiomyopathy or myopathy, wherein the composition is formulated for administration of 300 mg of coenzyme Q10 to a patient daily.
  • the present invention provides a method of treating coenzyme Q10 deficiency or a condition related to coenzyme Q10 deficiency, such as heart failure, cardiomyopathy or myopathy comprising administering to a subject the composition the invention as described herein, wherein the composition is formulated for administration of 300 mg of coenzyme Q10 to a patient daily.
  • terapéuticaally effective amount or “effective amount” means an amount that, when administered to an animal for treating a disease, disorder or condition, is sufficient to produce a desired therapeutic effect (e.g., to affect treatment for that disease).
  • composition and “formulation” are synonymous and are used interchangeably herein.
  • RPM rotations per minute
  • core refers to a small sphere.
  • PVP polyvinyl pyrrolidone
  • HPMC hydroxypropyl methylcellulose
  • hypromellose hydroxypropyl methylcellulose
  • An HPMC of low molecular mass refers to HPMC with molecular mass equal to or lower than 26,000 g/mol.
  • An HPMC of high molecular mass refers to HPMC with molecular mass equal or greater than 26,000 g/mol.
  • PEG refers to polyethylene glycol.
  • PEG of a molecular mass of 200 to 400 g/mol may be in the form of a liquid.
  • PEG of a molecular mass of 600 g/mol may be in the form of a semi-liquid.
  • PEG of a molecular mass of greater than 1 ,000 g/mol may be in the form of a solid.
  • Polysorbate is a surfactant, examples of which include Tween® 20, Tween® 40, Tween® 60 and Tween® 80.
  • the present invention relates to compositions comprising coenzyme Q10 and one or more water soluble excipients.
  • compositions comprising coenzyme Q10 and one or more water soluble excipients such as hydroxypropyl methylcellulose (HPMC), preferably low molecular mass HPMC, PEG 1000 to 22,000, PEG 200 to 600, docusate sodium, poloxamer (e.g., Pluronic®), polysorbate such as Tween® 20, Tween® 40, Tween® 60 or Tween® 80, a filler, an expander and a lubricating excipient.
  • HPMC hydroxypropyl methylcellulose
  • HPMC hydroxypropyl methylcellulose
  • PEG 1000 to 22,000 PEG 200 to 600
  • docusate sodium e.g., Pluronic®
  • polysorbate such as Tween® 20, Tween® 40, Tween® 60 or Tween® 80
  • the present invention further relates to methods of treating coenzyme Q10 deficiency in a subject comprising orally administering such compositions.
  • the composition may be in the form of spheres, granules, capsules, tablets, soft capsules or a liquid.
  • the composition is an immediate-release formulation with high dissolution in an aqueous medium.
  • the composition may be in the form of spheres to be administered orally.
  • the sphere comprises a coating on a core, wherein the coating comprises a mixture of coenzyme Q10 and HPMC, e.g., HPMC E5, over the core.
  • the composition may be in the form of granules which may be filled into a capsule or a granules bag, or compressed into tablets to be administered orally.
  • the granule composition comprises coenzyme Q10, PEG 1000 to 22,000, poloxamer, docusate sodium, HPMC of low molecular mass equal to or lower than 26,000 g/mol, and one or more other excipients such as a filler, expander and lubricating powder.
  • the composition comprises a mixture of coenzyme Q10 and a binder coating on a core, wherein the core comprises sugar, microcrystalline cellulose or a mixture thereof.
  • the binder is HPMC of a low molecular mass equal to or lower than 26,000 g/mol.
  • the formulation comprises coenzyme Q10, PEG of a molecular weight from 1000 to 22,000 g/mol and one or more other excipients such as a filler, expander and lubricating powder.
  • the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises coenzyme Q10, PEG of a molecular weight from 1000 to 22,000 g/mol, poloxamer and one or more other excipients such as a filler, expander and lubricating powder, wherein the formulation is preferably in the form of granules, tablets or capsules.
  • the formulation comprises coenzyme Q10, docusate sodium, and one or more other excipients such as a filler, expander and lubricating powder, wherein the formulation is preferably in the form of granules, tablets or capsules.
  • the formulation comprises coenzyme Q10, HPMC of low molecular mass and one or more other excipients such as a filler, expander and lubricating powder, wherein the formulation is preferably in the form of granules and capsules.
  • the formulation comprises coenzyme Q10, HPMC, poloxamer, wherein the formulation is preferably in the form of granules, tablets or capsules.
  • the formulation comprises coenzyme Q10, poloxamer and PEG 1000 to 22,000, wherein the formulation is preferably in the form of granules, tablets or capsules.
  • the formulation comprises coenzyme Q10, poloxamer, PEG 1000 to 22,000 and HPMC, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 1 part of poloxamer and 1 part of PEG 1000 to 22,000, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 1 part of PEG 1000 to 22000, 1 part of cross-linked povidone, and 1 part of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 2 parts of PEG 1000 to 22,000, 2 parts of cross-linked povidone, and 2 parts of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 10 parts of PEG 1000 to 22000, 2 parts of cross-linked povidone, and 3 parts of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10 and 1 to 10 parts of PEG 200 to 600, wherein the formulation may be in the form of a liquid or soft capsules.
  • the formulation comprises 1 part of coenzyme Q10 and 1 to 10 parts of a polysorbate such as Tween® 20, Tween® 40, Tween® 60 and Tween® 80, wherein the formulation may be in the form of a liquid or soft capsules.
  • a polysorbate such as Tween® 20, Tween® 40, Tween® 60 and Tween® 80, wherein the formulation may be in the form of a liquid or soft capsules.
  • the formulation comprises 1 part of coenzyme Q10, 1 to 2 parts of PEG 200 to 600 and 1 to 2 parts of a polysorbate such as Tween® 20, Tween® 40, Tween® 60 and Tween® 80, wherein the formulation may be in the form of a liquid or soft capsules.
  • the formulation comprises 1 part of coenzyme Q10, 1 part of poloxamer, 1 part of cross-linked povidone and 1 part of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 2 parts of poloxamer, 2 parts of cross-linked povidone and 2 parts of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 0.5 to 1 parts of docusate sodium, 1 part of cross-linked povidone and 1 part of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • the formulation comprises 1 part of coenzyme Q10, 1 part of docusate sodium, 1 part of PEG 1000 to 22000, 1 part of cross-linked povidone and 1 part of microcrystalline cellulose, wherein the formulation may be in the form of granules, tablets or capsules.
  • compositions prepared according to the methods described herein can provide higher dissolution rates of coenzyme Q10 in an aqueous medium, thereby enabling a lower amount of coenzyme Q10 to be administered to provide a therapeutic effect.
  • an advantage of particularly preferred embodiments of the present invention is that compositions may comprise less coenzyme Q10 per unit dosage than the dosage of currently available soft capsule compositions. This provides a benefit of reducing side effects from having high levels of coenzyme Q10 in the alimentary system, while providing the same or better efficacy.
  • Coenzyme Q10 is currently available in the form of soft capsules.
  • coenzyme Q10 formulations on the market are in the form of soft capsules containing vegetable oil and coenzyme Q10.
  • the soft capsules of the present invention comprises water soluble excipients and do not comprise oil-based excipients, thereby helping to improve in vivo solubility.
  • CN 101703477 A describes the preparation of a coenzyme Q10 pellet formulation and a method of production thereof.
  • the coenzyme Q10 pellet was prepared from coenzyme Q10 and pharmaceutical excipients, and is characterised in that the pharmaceutical excipients are excipients and binders, wherein the weight of coenzyme Q10 in the pellet preparation is from 2- 80%, the weight percentage content of the excipient is from 12-97%, and the weight percentage content of the binder is from 1-8%.
  • the pellet preparations can be prepared as sustained-release or enteric-coated preparations as required.
  • the coenzyme Q10 pellet was produced by (1) mixing the coenzyme Q10 and the excipient together and grinding the mixture to micronisation-grade; (2) dissolving a binder in water, a dehydrated alcohol or hydrous ethanol; and (3) using micropill-forming technology to make a micropill.
  • the degree of pulverisation of medicinal materials or extracts provides coarse powders (for oral use, having a particle diameter of 850 pm ⁇ 70 pm, and capable of passing through 24 mesh sieves), medium powder (for oral use, having a particle diameter of 250 pm ⁇ 9.9 pm, and capable of passing through 65 mesh sieves), fine powder (for wound trauma use, having a particle diameter of 150 pm ⁇ 6.6 pm, and capable of passing through 100 mesh sieves), finer powder (for use in eye drops, having a particle diameter of 125 pm ⁇ 5.8 pm, and capable of passing through 120 mesh sieves) and very fine powder (having a particle diameter of 75 pm ⁇ 4 pm, and capable of passing through 200 mesh sieves).
  • the coenzyme Q10 composition of the present invention may be in the form of a sphere which comprises in its outer layer a mixture of coenzyme Q10 and hydroxypropyl methylcellulose (HPMC).
  • the sphere may comprise a core which comprises sugar, microcrystalline cellulose or a mixture thereof.
  • the outer layer comprising coenzyme Q10 and HPMC may be formed from numerous layers of coenzyme Q10 and HPMC. After the diameter of the sphere reaches about 1 mm, the coating process may be stopped. The resultant coated spheres may be filled into a capsule or a granule bag.
  • the composition described herein may further comprise magnesium stearate as a lubricating agent.
  • the amount of dissolution of coenzyme Q10 of a composition of the invention in the form of spheres comprising 150 mg coenzyme Q10 when subjected to the conditions of 1000 mL of 0.5% Triton as the dissolution medium may be more than 60%, 70%, 80%, 90% or 95%.
  • An embodiment of the invention may comprise an amount of 5 mg, 10 mg, 20 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg of coenzyme Q10.
  • the amount of coenzyme Q10 in compositions as described herein is a reduced dose amount relative to dosage forms in the prior art.
  • the present invention provides a composition as described herein, wherein the composition has a dissolution amount of coenzyme Q10 in a 1% Triton aqueous medium of greater than 60%, or greater than 65%, or greater than 70%, or greater than 75%, or greater than 80%, or greater than 85%, or greater than 90%, or greater than 95%.
  • composition as described herein may be used to treat a subject with coenzyme Q10 deficiency, or conditions related to coenzyme Q10 deficiency, such as for example, heart failure, cardiomyopathy or myopathy.
  • the present invention provides an oral composition which may be in the form of spheres, granules, tablets or capsules.
  • the spheres or granules may be filled into a capsule or a granules bag, or the granules may be compressed into a tablet.
  • the composition of the invention in the form of spheres or pellets may comprise coenzyme Q10, HPMC and a core comprising sugar or microcrystalline cellulose.
  • the outer layer of the sphere composition may comprise coenzyme Q10 and HPMC, while the core comprises sugar, starch, lactose, mannitol, sorbitol, fructose- 1,6-diphosphate, microcrystalline cellulose, or a mixture thereof.
  • HPMC is an abbreviation for hydroxypropyl methylcellulose (also referred to as hypromellose) which is a methyl and hydroxypropyl mixed ether having a molecular mass equal to or lower than about 26,000 g/mol.
  • the coenzyme Q10 sphere of the invention is an immediate-release formulation.
  • the method of production of coenzyme Q10 sphere comprises the following steps: a) dissolving an amount of coenzyme Q10 in a ketone selected from acetone, butanone or pentanone, b) dissolving an amount of a HPMC of low molecular mass in an alcohol selected from ethanol, isopropanol, benzyl alcohol or a combination thereof, c) mixing together the coenzyme Q10 ketone solution of step a) and the HPMC alcohol solution of step b) to form a solution comprising coenzyme Q10 and HPMC which is sprayed into a fluidised bed containing cores, wherein the cores comprise one or more excipients such as starch, lactose, sugar, mannitol, sorbitol, fructose-1 ,6-diphosphate, microcrystalline cellulose, cross-linked povidone, sodium croscarmellose, or a mixture thereof, d) drying the sphere
  • the coenzyme Q10 spheres of the invention comprise about 1 part of coenzyme Q10 by weight, about 0.5 to 3 parts of HPMC of low molecular mass by weight, and about 0.5 to 2 parts of cores by weight, wherein the smaller the size of the sphere, the smaller the amount of core is used.
  • the core may comprise starch, lactose, sugar, mannitol, sorbitol, fructose-1 ,6-diphosphate, microcrystalline cellulose, or a mixture thereof.
  • the coenzyme Q10 dissolution amount of the sphere when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate, is greater than 60%, 80% or 90%.
  • the greater the amount of HPMC the higher the dissolution amount.
  • a coenzyme Q10 composition of the invention comprises a therapeutically effective amount of coenzyme Q10 and a binder comprising HPMC of low molecular mass, and the amount of the binder may be from 1 to 3 times the weight of coenzyme Q10 of the composition.
  • the amount of dissolution of the coenzyme Q10 spheres, when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate is in the range of 60% to 95%.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 0.5 parts by weight of HPMC, and about 0.5 parts by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • the dissolution amount of the coenzyme Q10 sphere of the invention when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate, is greater than 60%.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 1 part by weight of HPMC, and about 0.5 parts by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • the amount of dissolution of the coenzyme Q10 sphere, when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate is greater than 80%.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 1 part by weight of HPMC, and about 1 part by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 1.5 parts by weight of HPMC, and about 1 part by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 2 parts by weight of HPMC, and about 1 part by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 3 parts by weight of HPMC, and about 1 part by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 2 parts by weight of HPMC, and about 2 parts by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 sphere of the invention comprises 1 part by weight of coenzyme Q10, 3 parts by weight of HPMC, and about 2 parts by weight of the core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • a coenzyme Q10 composition of the invention in the form of granules comprises coenzyme Q10, HPMC of low molecular mass, a filler, an expander, starch, lactose, sugar, mannitol, sorbitol, fructose- 1 ,6-diphosphate, microcrystalline cellulose, crosslinked povidone, or a mixture thereof.
  • the core is a small sphere of about 0.3 mm to about 1 mm diameter, and comprises sugar, starch, microcrystalline cellulose, lactose, mannitol, sorbitol, fructose-1 ,6-diphosphate, cross-linked povidone and sodium croscarmellose.
  • the reduced dose coenzyme Q10 composition of the invention comprises a coenzyme Q10 coating on the core, wherein the composition may be filled into a capsule or granule bag.
  • the reduced dose coenzyme Q10 composition of the invention is in the form of granules comprising coenzyme Q10 and a water soluble excipient selected from one or more of HPMC of low molecular mass, PEG 1000 to 22000, poloxamer, docusate sodium, and one or more of a filler and expander selected from microcrystalline cellulose, crosslinked povidone, sodium croscarmellose, or a mixture thereof.
  • the granules are filled into a capsule or granule bag, or the granules may be compressed into a tablet.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 0.5 parts of HPMC of low molecular mass,1 to 3 parts of PEG 100 to 22000, 1 to 2 parts of poloxamer, 0.5 to 1 parts of docusate sodium, 10% microcrystalline cellulose, 1 part of cross-linked povidone and, 1 part of sodium croscarmellose, or a mixture thereof, and wherein the formulation may be in the form of granules, tablets or capsules.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 1 to 2 parts of PEG 1000 to 22000, 1 part of poloxamer, 10% microcrystalline cellulose, 1 part of cross-linked povidone and 1 part of sodium croscarmellose, or a mixture thereof, and wherein the formulation may be in the form of granules, tablets or capsules.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 1 to 10 parts of PEG 1000 to 22000, 10% microcrystalline cellulose, 1 part of cross-linked povidone and 1 part of sodium croscarmellose, or a mixture thereof.
  • the coenzyme Q10 composition of the invention comprises coenzyme Q10, poloxamer, microcrystalline cellulose, cross-linked povidone and sodium croscarmellose, or a mixture thereof.
  • the coenzyme Q10 composition of the invention comprises coenzyme Q10 and docusate sodium.
  • the coenzyme Q10 composition of the invention comprises coenzyme Q10 and PEG 200 to 600.
  • the coenzyme Q10 composition of the invention comprises coenzyme Q10 and a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, wherein the formulation may be in the form of a liquid or soft capsules.
  • the coenzyme Q10 composition of the invention comprises coenzyme Q10 and PEG 1000 to 22000.
  • the composition of the invention is in the form of a sphere comprising a core, the core comprising sugar, microcrystalline cellulose, or a mixture thereof, and an outer layer comprising coenzyme Q10 and HPMC of low molecular mass surrounding the core.
  • the sphere has a diameter of about 0.3 mm to about 2 mm, or preferably wherein the diameter is from about 0.5 mm to 1.2 mm.
  • the spheres may be filled into a hard capsule or a sphere bag, wherein the composition is preferably an immediate-release product.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 1 to 2 parts of poloxamer, 10% microcrystalline cellulose, 1 part of cross-linked povidone and 1 part of sodium croscarmellose, or a mixture thereof.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 0.5 to 1 parts of docusate sodium, 10% microcrystalline cellulose, 1 part of cross-linked povidone and 1 part of sodium croscarmellose, or a mixture thereof.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 0.5 to 1 parts of docusate sodium, 1 to 10 parts of PEG 1000 to 22000, 10% microcrystalline cellulose, 1 part of cross-linked povidone and 1 part of sodium croscarmellose, or a mixture thereof.
  • the ratio of HPMC of low molecular mass to coenzyme Q10 is in the range from 0.5:1 to 3:1 by weight. Preferably, the ratio is from 1 :1 to 2:1 by weight.
  • HPMC Hydroxypropyl methylcellulose
  • the HPMC has a low molecular mass.
  • HMPC is used as a binder.
  • HPMC polymers are available in various viscosity grades ranging from 4,000-100,000 mPas. The viscosity of the polymer affects the diffusion pathway.
  • High molecular mass HPMC may be employed as a matrix for controlling the release of both hydrophilic and hydrophobic drugs and is a critical excipient of sustained-release formulations. In slow-release tablets, the HPMC may act as a retarding agent.
  • the low molecular mass HPMC acts as a binder only.
  • a coenzyme Q10 composition of the invention is produced by following method: a) 1 part of coenzyme Q10 powder by weight is placed in a tank and mixed with about 6 parts by weight of a ketone selected from acetone, butanone or pentanone until the powder is fully dissolved; b) 0.5 to 3 parts by weight of HPMC of low molecular mass is placed in the tank with about 1 to 18 parts by weight of an alcohol selected from ethanol, isopropanol or benzyl alcohol until the HPMC is fully dissolved; c) 1 part by weight of cores having a diameter of 0.4 mm to 1.0 mm are placed in a fluidised bed, wherein the cores comprise sugar, microcrystalline cellulose, or a mixture thereof; d) the solutions of step a) and b) are mixed together; e) the solution of step d) is sprayed onto the fluidised bed, wherein the solution adheres and dries on the surface of the cores, coating the
  • the coenzyme Q10 composition of the invention may be produced by the following method: a) 1 part by weight of coenzyme Q10 powder is placed in a tank with about 3 to 6 parts by weight of a ketone selected from acetone, butanone or pentanone until the powder is fully dissolved; b) 0.5 to 3 parts by weight of HPMC of low molecular mass is dissolved or dispersed in 1 to 18 parts by weight of water; c) the aqueous HPMC solution or mixture of step b) is mixed with the coenzyme Q10 ketone solution of step a) to form a suspension; d) 1 part by weight of cores having a diameter of 0.4 mm to 1.0 mm is placed in a fluidised bed, wherein the cores comprise sugar, microcrystalline cellulose, or a mixture thereof; e) the resultant suspension of step c) is sprayed onto the fluidised bed, wherein the suspension adheres and dries on the surface of the cores
  • the coenzyme Q10 composition of the invention may be in the form of granules and may be produced according to the following method: a) 1 part by weight of coenzyme Q10 powder is placed in a tank with about 6 parts by weight of a ketone selected from acetone, butanone or pentanone until the powder is fully dissolved; b) 0.5 to 3 parts by weight of HPMC of low molecular mass is dissolved in about 3 to 18 parts by weight of water; c) 1 to 3 parts by weight of a filler and expander is placed in a fluidised bed, wherein the filler and expander comprises sugar, microcrystalline cellulose, lactose, crosslinked povidone, or a mixture thereof; d) a mixture of the solutions from a) and b) is sprayed onto the fluidised bed; wherein the mixture adheres and dries with the filler and expander, forming granules which are allowed to increase in size until the granules are about
  • the coenzyme Q10 composition of the invention may be produced according to the following method: a) 1 part by weight of coenzyme Q10 powder is placed in a tank with about 6 parts by weight of a ketone selected from acetone, butanone or pentanone until the powder is fully dissolved; b) 1 to 3 parts by weight of PEG 1000 to 22000 is dissolved in the solution of step a); c) 1 to 3 parts by weight of a filler and expander is placed in a fluidised bed, wherein the filler and expander comprises microcrystalline cellulose, lactose, cross-linked povidone, or a mixture thereof; d) the solution of step b) is sprayed onto the fluidised bed; wherein the mixture adheres and dries with the filler and expander, forming granules which are allowed to increase in size until the granules are about 24 mesh; e) an aqueous solution of PVPK30 is sprayed onto the fluidised bed,
  • the ratio of HPMC of low molecular mass to coenzyme Q10 is 0.5:1 by weight. In another embodiment, the ratio of HPMC to coenzyme Q10 is 1 :1 by weight. In another embodiment, the ratio of HPMC to coenzyme Q10 is 2:1 by weight. In another embodiment, the ratio of HPMC to coenzyme Q10 is 3:1 by weight. Preferably, the ratio of HPMC of low molecular mass to coenzyme Q10 is from 1:1 to 2:1 by weight.
  • the dissolution of coenzyme Q10 is much higher than the dissolution of prior art coenzyme Q10 soft capsules of the same strength.
  • this increases the absorption of coenzyme Q10 in the alimentary system and reduces side effects from elevated coenzyme Q10 levels compared with the prior art soft capsules.
  • Coenzyme Q10 may have a variety of adverse reactions which are infrequent and generally mild. These may include decreased appetite, diarrhea, dizziness, dyspepsia, nausea and vomiting. However, decreasing the amount of coenzyme Q10 in the alimentary system may reduce the frequency and/or severity of these side effects.
  • Coenzyme Q10 as a food supplement or drug is available in single capsule doses of 30, 60, 100, 200, 300, 400 and 600 mg. Generally, the dose required for attaining a therapeutic plasma concentration of >2.5 pg/mL is 200 mg administered twice daily with a meal. In subjects with heart disease, daily doses of 100 to 400 mg have been used, while in neurodegenerative diseases, maximum doses of 3,000 mg have been used. Coenzyme Q10 may also reduce statin-associated muscle symptoms and death rates from heart failure. [0126]
  • the coenzyme Q10 composition of the invention may comprise different amounts of coenzyme Q10 in the range of from 20 mg to 600 mg. Preferably, the composition may be in the form of spheres, granules, tablets, capsules, a liquid or soft capsules.
  • the composition of the invention comprises 1 part by weight of coenzyme Q10, 0.5 to 3 parts by weight of HPMC of low molecular mass, and 0.5 to 1 parts by weight of a core, the core comprising sugar, microcrystalline cellulose, or a mixture thereof.
  • the composition of the invention in the form of spheres comprises 20 to 150 mg of coenzyme Q10, 20 to 300 mg of HPMC of low molecular mass, and 20 to 150 mg of a sugar core.
  • the coenzyme Q10 dissolution amount of the spheres when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution buffered at pH
  • the spheres may be filled into a capsule or a pellet bag.
  • composition of the invention is in the form of a sphere comprising 150 mg of coenzyme Q10, 150 mg of HPMC of low molecular mass, and 150 mg of a core comprising sugar, microcrystalline cellulose or a mixture thereof.
  • the composition of the invention is in the form of a sphere, comprising 120 mg of coenzyme Q10, 240 mg of HPMC of low molecular mass, and 100 mg of a sugar core.
  • the amount of dissolution of coenzyme Q10 of the spheres in 1000 mL of 0.5% Triton aqueous solution of pH 4.5 when stirred at 75 RPM for 2 hours is greater than 80%.
  • the composition of the invention is in the form of a sphere comprising 100 mg of coenzyme Q10, 200 mg of HPMC of low molecular mass and 100 mg of a core comprising a mixture of sugar and microcrystalline cellulose.
  • the composition of the invention is in the form of a sphere comprising 100 mg of coenzyme Q10, 150 mg of HPMC of low molecular mass and 100 mg of a core comprising a mixture of sugar and microcrystalline cellulose.
  • the composition of the invention is in the form of a sphere comprising 75 mg of coenzyme Q10, 75 to 150 mg of HPMC of low molecular mass and 50 to 100 mg of a core comprising a mixture of sugar and microcrystalline cellulose.
  • the composition of the invention is in the form of a sphere comprising 45 mg of coenzyme Q10, 45 to 90 mg of HPMC of low molecular mass and 45 to 90 mg of a core comprising a mixture of sugar and microcrystalline cellulose.
  • composition of the invention is in the form of a tablet comprising 45 mg of coenzyme Q10, 45 to 135 mg of PEG 1000 to 22000 and 45 to 90 mg of poloxamer and cross-linked povidone, cross-linked sodium carboxymethyl cellulose, lactose and microcrystalline cellulose.
  • the composition of the invention is in the form of a tablet comprising 100 mg of coenzyme Q10, 100 to 300 mg of PEG 1000 to 22000 and 100 to 200 mg of poloxamer.
  • the formulation further comprises cross-linked povidone, cross-linked sodium carboxymethyl cellulose, lactose and microcrystalline cellulose.
  • a method of producing the coenzyme Q10 composition of the invention comprises the following steps: a) 1 part of coenzyme Q10 by weight is mixed with about 2 parts of acetone by weight until the coenzyme Q10 is fully dissolved; b) 0.5 to 3 parts by weight of HPMC of low molecular mass is mixed with 1.5 to 18 parts by weight of ethanol; c) the coenzyme Q10 acetone solution of step a) and the HPMC ethanol solution of step b) are mixed together; d) 1 part by weight of cores comprising sugar, microcrystalline cellulose, or a mixture thereof is placed in a fluidised bed; e) the solution of step c) is sprayed onto the fluidised bed; wherein the solution adheres and dries on the surface of the cores, coating the cores and increasing their size to give spheres; and f) the resultant spheres are mixed with magnesium stearate, and are filled into a capsule or granule bag.
  • the present invention provides a Q10 composition as described herein for use in providing heart nutrients to a patient with heart disease.
  • the present invention provides a method of treating coenzyme Q10 deficiency or conditions related to coenzyme Q10 deficiency, such as heart failure, cardiomyopathy or myopathy, the method comprising administering to a patient the decomposition as described herein, wherein less than 300 mg of coenzyme Q10 is administered to the patient once daily.
  • the present invention provides use of the Q10 composition as described herein for treating coenzyme Q10 deficiency or conditions related to coenzyme Q10 deficiency, such as heart failure, cardiomyopathy or myopathy, wherein the composition is formulated for administration of 300 mg of coenzyme Q10 to a patient once daily.
  • the composition of the invention is used to treat subjects with coenzyme Q10 deficiency, heart failure, myopathy or cardiomyopathy in a dosage from 5 mg to 600 mg per day.
  • the daily dosage is 600 mg of coenzyme Q10 per day.
  • the daily dosage is 500 mg of coenzyme Q10 per day.
  • the daily dosage is 400 mg of coenzyme Q10 per day.
  • the daily dosage is 300 mg of coenzyme Q10 per day.
  • the daily dosage is 200 mg of coenzyme Q10 per day.
  • the daily dosage is 150 mg of coenzyme Q10 per day.
  • the daily dosage is 100 mg of coenzyme Q10 per day. In some embodiments, the daily dosage is 50 mg of coenzyme Q10 per day. In some embodiments, the daily dosage is 10 mg of coenzyme Q10 per day. In some embodiments, the daily dosage is 5 mg of coenzyme Q10 per day.
  • the amount of coenzyme Q10 in the composition of the invention is from 5 mg to 150 per capsule and is used to treat subjects with coenzyme Q10 deficiency, heart failure, myopathy and cardiomyopathy in a dosage from 5 mg to 600 mg per day. In some embodiments, the amount of coenzyme Q10 is 5 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 10 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 20 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 50 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 100 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 120 mg per capsule. In some embodiments, the amount of coenzyme Q10 is 150 mg per capsule.
  • the capsules comprise spheres comprising a coenzyme Q10 and HPMC coating on the core, wherein the core comprises sugar and microcrystalline cellulose, or a mixture thereof.
  • Coenzyme Q10 is a water-insoluble chemical and its dissolution is low in an aqueous medium. When testing the amount of dissolution of coenzyme Q10 of the coenzyme Q10 soft capsules and API, the amount of dissolution of coenzyme Q10 is about the same in both coenzyme Q10 API, or coenzyme Q10.
  • the composition of the invention is in the form of a sphere comprising water-insoluble coenzyme Q10 and a water-soluble HPMC of low molecular mass, both of which are coated on the outside of a core comprising sugar, microcrystalline cellulose or a mixture thereof.
  • This composition may be in the form of spheres or a hard capsule comprising said spheres.
  • the spheres or hard capsules comprising said spheres have a higher coenzyme Q10 dissolution amount in an aqueous medium than the coenzyme Q10 raw material or coenzyme Q10 soft capsules, when subject to the same dissolution conditions.
  • the composition of the invention is in the form of granules, a tablet or a capsule.
  • the granules may comprise water-insoluble coenzyme Q10 and a water- soluble HPMC of low molecular mass, wherein the granules further comprise excipients such as microcrystalline cellulose, lactose and cross-linked povidone.
  • the granules may be compressed into a tablet or filled into a hard capsule.
  • the granules or tablets of the invention have a higher coenzyme Q10 dissolution amount in an aqueous medium than the coenzyme Q10 raw material or coenzyme Q10 soft capsules, when subjected to the same dissolution conditions.
  • the composition of the invention is in the form of granules, a tablet or a capsule.
  • the granules may comprise coenzyme Q10, PEG 1000 to 22000, poloxamer and docusate sodium, HPMC, wherein the granules may further comprise one or more excipients such as microcrystalline cellulose, lactose and cross-linked povidone and crosslinked sodium carboxymethyl cellulose.
  • the granules may be compressed into a tablet or filled into a hard capsule.
  • the granules or tablets of the invention have a higher coenzyme Q10 dissolution amount in an aqueous medium than the coenzyme Q10 raw material or coenzyme Q10 soft capsules, when subjected to the same dissolution conditions.
  • the present invention broadly relates to a convenient drug delivery system, and methods of producing the drug delivery system, preferably using common excipients via a simple method and at low cost.
  • the method of producing the coenzyme Q10 composition in the form of spheres comprises the following steps: a) 1 part by weight of coenzyme Q10 is mixed in an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropanol, benzyl alcohol, dichloromethane or trichloromethane until the coenzyme Q10 is fully dissolved; b) 0.5 to 3 parts by weight of HPMC of low molecular mass is dissolved in 1.5 to 9 parts by weight of an alcohol; c) the coenzyme Q10 solution of step a) and the HPMC solution of step b) are mixed together to form a solution; d) 1 part by weight of cores comprising sugar, microcrystalline cellulose, or a mixture thereof is placed in a fluidised bed; e) the solution of step c) comprising coenzyme Q10 and HPMC is sprayed onto the fluidised bed containing the cores and coating the cores and increasing their size until
  • the method of producing a composition of the invention in the form of granules comprises the following steps: a) 1 part by weight of coenzyme Q10 is mixed into an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane until the coenzyme Q10 is fully dissolved; b) 1 to 3 parts by weight of HPMC of low molecular mass is dissolved in 3 to 18 parts by weight of an alcohol selected from ethanol, benzyl alcohol or isopropyl alcohol; c) the solutions of steps a) and b) are mixed together to form a solution comprising HPMC and coenzyme Q10; d) a filler and expander comprising 1 part by weight of microcrystalline cellulose, 1 part by weight of lactose and 1 part by weight of cross-linked povidone is placed in a fluidised bed; e) the solution of step c) comprising
  • the method of producing a composition of the invention in the form of granules comprises the following steps: a) 1 part by weight of coenzyme Q10 is mixed into an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane until the coenzyme Q10 is fully dissolved; b) 1 to 3 parts by weight of HPMC of low molecular mass is mixed with 3 to 18 parts by weight of water to form a suspension; c) the coenzyme Q10 solution of step a) and the HPMC suspension of step b) are mixed together to form a suspension comprising coenzyme Q10 and HPMC; d) 1 part by weight of cores comprising sugar, microcrystalline cellulose or a mixture thereof is placed in a fluidised bed; e) the suspension of step c) comprising coenzyme Q10 and HPMC is sprayed onto the fluidised bed; and
  • the solid composition of the invention can be produced by wet granulator.
  • the higher coenzyme Q10 dissolution amount of the present invention compared with prior art coenzyme Q10 soft capsules or tablets may reduce the amount of coenzyme Q10 needed to be administered to treat heart disease, which will in turn reduce the alimentary side effects of excessive coenzyme Q10 in the gastrointestinal system.
  • the weight ratio of HPMC of low molecular mass to coenzyme Q10 in compositions of the invention is in the range of from 0.5:1 to 3:1, or preferably from 1 :1 to 2:1.
  • the coenzyme Q10 composition of the invention comprises
  • the amount of dissolution of coenzyme Q10 of the composition when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution of pH 4.5 is greater than 80%.
  • the coenzyme Q10 composition of the invention is in the form of a sphere which comprises 150 mg of coenzyme Q10, 150 mg to 300 mg of HPMC, and 100 to 150 mg of a core, wherein the core comprises sugar, microcrystalline cellulose, or a mixture thereof.
  • the composition is in the form of spheres, or a capsule comprising said spheres.
  • the amount of dissolution of the coenzyme Q10 composition is greater than 80% when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution at pH 4.5.
  • the coenzyme Q10 composition of the invention comprises 120 mg of coenzyme Q10 and 120 mg to 240 mg of HPMC, wherein the composition is in the form of spheres or a capsule comprising said spheres.
  • the amount of dissolution of coenzyme Q10 of the composition is greater than 80% when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution at pH 4.5.
  • the coenzyme Q10 composition of the invention comprises 50 mg of coenzyme Q10 and 50 mg to 150 mg of HPMC, wherein the composition is in the form of spheres, or a capsule comprising said spheres.
  • the amount of dissolution of coenzyme Q10 of the composition is greater than 80% when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution at pH 4.5.
  • the coenzyme Q10 composition of the invention comprises 30 mg of coenzyme Q10 and 60 mg to 90 mg of HPMC, wherein the composition is in the form of spheres or a capsule comprising said spheres.
  • the amount of dissolution of coenzyme Q10 of the composition is greater than 80% when stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton aqueous solution at pH 4.5.
  • the coenzyme Q10 composition of the invention comprises 30 mg of coenzyme Q10, 30 mg to 90 mg of PEG 1000 to 22000, and 30 to 60 mg of poloxamer, wherein the composition is in the form of granules, capsule or tablets.
  • the coenzyme Q10 composition of the invention comprises 30 mg to 150 mg of coenzyme Q10, 30 mg to 450 mg of PEG 1000 to 22000, and 30 to 450 mg of poloxamer, wherein the composition is in the form of capsule or tablets.
  • the coenzyme Q10 composition of the invention comprises 200 mg of coenzyme Q10, 600 mg of PEG 1000 to 22000, 200 mg of poloxamer, 100 mg of microcrystalline cellulose, and 200 mg of cross-linked povidone, wherein the composition is in the form of granules or tablets.
  • the coenzyme Q10 composition of the invention comprises 150 mg of coenzyme Q10, 300 mg of PEG 1000 to 22000, 300 mg of poloxamer, 100 mg of microcrystalline cellulose, and 150 mg cross-linked povidone, wherein the composition is in the form of granules or tablets.
  • the coenzyme Q10 composition of the invention comprises 30 mg to 150 mg of coenzyme Q10, 30 mg to 300 mg of PEG 1000 to 22000, 30 to 300 mg of poloxamer, 30 to 75 mg of docusate sodium, 30 to 75 mg of HPMC and 30 to 300 mg of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid, or ascorbic acid, wherein the composition is in the form of granules, capsules or tablets.
  • the coenzyme Q10 composition of the invention comprises 30 mg to 150 mg of coenzyme Q10, 30 mg to 300 mg of PEG 1000 to 22000, 30 to 300 mg of poloxamer, 30 to 150 mg of HPMC and 30 to 300 mg of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid or ascorbic acid, wherein the composition is in the form of granules, capsules or tablets.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10 and 1 to 3 parts of PEG 1000 to 22000, and 1-3 parts of poloxamer wherein the composition is in the form of capsules or tablets.
  • the coenzyme Q10 composition of the invention comprises 30 mg to 150 mg of coenzyme Q10, 30 mg to 150 mg of PEG 1000 to 22000, 30 to 150 mg of poloxamer, 30 to 75 mg of docusate sodium and 30 to 150 mg of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid or ascorbic acid, wherein the composition is in the form of granules, capsules or tablets.
  • the coenzyme Q10 composition of the invention comprises 1 part of coenzyme Q10, 1 to 3 parts of HPMC of low molecular mass, 1 to 3 parts of PEG 1000 to 22000, 1 to 3 parts of poloxamer, 1 part of docusate sodium and 1 to 3 parts of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid or ascorbic acid, or a mixture thereof; wherein the composition is in the form of granules, capsules or tablets.
  • the coenzyme Q10 composition of the invention comprises 30 mg to 150 mg of coenzyme Q10, 30 mg to 450 mg of PEG 1000 to 22000, 30 to 450 mg of poloxamer, 30 to 150 mg of docusate sodium, 30 to 150 mg of HPMC and 30 to 450 mg of an organic acid selected from malic acid, maleic acid, tartaric acid, succinic acid, citric acid or ascorbic acid, wherein the composition is in the form of granules, capsules or tablets.
  • the composition of the invention may be a liquid solution or a solid dosage form comprising coenzyme Q10, a water soluble excipient such as HPMC, PEG, docusate sodium, poloxamer or Pluronics, and polysorbate, wherein the composition has a high amount of dissolution of coenzyme Q10 of greater than 60% in an aqueous medium, wherein the composition may be used for treating coenzyme Q10 deficiency in a subject.
  • the composition may have a high amount of dissolution of coenzyme Q10 in an aqueous medium of 0.5% Triton of pH 4.5 of greater than 70%, 80%, or 90%
  • the liquid composition of the invention may be in the form of soft capsules comprising coenzyme Q10, PEG 200 to 600 and a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, or a mixture thereof.
  • the liquid solution may be filled into a bottle for oral use.
  • composition of the invention may be in the form of spheres comprising coenzyme Q10, a core comprising one or more excipients, and a binder comprising HPMC of low molecular mass.
  • the molecular mass of HPMC is equal to or lower than 26,000 g/mol.
  • composition of the invention may be in the form of spheres comprising a mixture of HPMC and coenzyme Q10 coating on the surface of a core, wherein the core comprises sugar, microcrystalline cellulose or a mixture thereof.
  • the core of spheres of the composition may comprise one or more of sugar, microcrystalline cellulose, lactose, starch, mannitol, sorbitol, fructose-1 ,6-diphosphate, and cross-linked povidone, or a mixture thereof.
  • the composition of the invention may comprise coenzyme Q10, PEG 1000 to 22000, poloxamer, and polysorbate, wherein the composition may be in the form of granules, tablets, capsules or a liquid.
  • the composition of the invention may comprise: a) 1 part of coenzyme Q10, 10 parts of PEG 1000 to 22000, wherein the composition may be in the form of granules, tablets or capsules further comprising a filler, an expander and a lubricant; b) 1 part of coenzyme Q10, 2 parts of PEG 1000 to 22000, wherein the composition may be in the form of granules, tablets or capsules further comprising a filler, an expander and a lubricant; c) 1 part of coenzyme Q10, 3 parts of PEG 1000 to 22000, wherein the composition may be in the form of granules, tablets or capsules further comprising a filler, an expander and a lubricant;
  • composition of the invention may be in the form of a sphere comprising by weight: a) 1 part of coenzyme Q10, 0.5 to 3 parts of HPMC of low molecular mass and 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof; b) 1 part of coenzyme Q10, 1 parts of HPMC of low molecular mass and 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof; c) 1 part of coenzyme Q10, 2 parts of HPMC of low molecular mass and 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof; or d) 1 part of coenzyme Q10, 3 parts of HPMC of low molecular mass and 1 part of a core comprising sugar, microcrystalline cellulose or a mixture thereof.
  • the composition of the invention comprises coenzyme Q10 and PEG 200 to 600, preferably wherein the composition is in the form of a liquid or soft capsules.
  • the composition of the invention may be a liquid solution comprising coenzyme Q10, PEG 200 to 600 and a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, or a mixture thereof, wherein the composition may be in the form of a soft capsule.
  • the composition of the invention may be a liquid solution comprising 1 part of coenzyme Q10, 1 part of PEG 200 to 600 and 1 part of a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, or a mixture thereof, wherein the composition may be in the form of a soft capsule.
  • the composition of the invention may be a liquid solution comprising 1 part of coenzyme Q10, 2 parts of PEG 200 to 600 and 1 to 2 parts of a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, or a mixture thereof, wherein the liquid may be filled into a soft capsule or a bottle.
  • the composition of the invention comprises by weight 1 part of coenzyme Q10, 1 to 10 parts of a polysorbate selected from Tween® 20, Tween® 40, Tween® 60 and Tween® 80, wherein the composition may be in the form of a soft capsule.
  • a method of producing a coenzyme Q10 composition in the form of spheres comprises the steps of: a) dissolving 1 part by weight of coenzyme Q10 in an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane, until the coenzyme Q10 is fully dissolved; b) dissolving 1 to 3 parts by weight of HPMC of low molecular mass in a solvent selected from ethanol, isopropyl alcohol or benzyl alcohol; c) mixing the solution of step a) and the solution of step b) together to form a solution comprising coenzyme Q10 and HPMC; and d) spraying the coenzyme Q1O and HPMC solution of step c) onto cores on a fluidised bed, wherein the cores comprise sugar, microcrystalline cellulose or a mixture thereof, to form spheres.
  • a method of producing a coenzyme Q10 composition comprises the steps of: a) dissolving 1 part by weight of coenzyme Q10 in an organic solvent selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane or trichloromethane; b) adding 1 to 3 parts of PEG 1000 to 22000, 1 to 3 parts of poloxamer or 0.5 parts of docusate sodium by weight into the solution of step a) until the PEG, poloxamer or docusate sodium is fully dissolved or dispersed; c) 1 part each of lactose, microcrystalline cellulose, and cross-linked povidone, are placed in the fluidised bed; d) spraying the mixture of step b) comprising coenzyme Q10 onto the cores on a fluidised bed to form a powder mixture; e) spraying a PVP K30 solution into the fluidised bed of step d) to
  • composition of invention may be used to provide heart nutrients to a patient with heart disease.
  • the invention provides use of the composition of the invention in the manufacture of a medicament for treating coenzyme Q10 deficiency or a condition related to coenzyme Q10 deficiency, such as heart failure, cardiomyopathy or myopathy, wherein the composition is formulated for the administration of 300 mg of coenzyme Q10 to a patient once daily.
  • the composition of the invention comprises coenzyme Q10, HPMC of low molecular mass, and a core comprising sugar, microcrystalline cellulose, or a mixture thereof.
  • the coenzyme Q10 and HPMC are mixed together as a layer of coating on the surface of the core.
  • the weight ratio of HPMC to coenzyme Q10 is in the range from about 0.5:1 to 3:1.
  • coenzyme Q10 compositions in the form of spheres or a capsule comprising spheres according to the invention have a higher coenzyme Q10 dissolution amount in an aqueous medium or in the alimentary system, increasing absorption in a human body if ingested compared with coenzyme Q10 soft capsules of the prior art.
  • the coenzyme Q10 composition of the invention is in the form of granules comprising coenzyme Q10, PEG 1000 to 22000, poloxamer and HPMC of low molecular mass, and a filler and expander comprising microcrystalline cellulose, lactose and cross-linked povidone and crosslinked sodium carboxymethyl cellulose.
  • a solution comprising HPMC and coenzyme Q10 is mixed with microcrystalline cellulose, lactose and cross-linked povidone in a fluidised bed.
  • the composition of the invention may be in the form of granules, tablets or capsules comprising said granules.
  • formulation of the invention may be prepared in a variety of ways known to those skilled in the art.
  • composition of the invention including in the form of spheres and capsules in accordance with the present invention.
  • a coenzyme Q10 composition of the invention in the form of spheres is produced using the following method: a) 1 part by weight of coenzyme Q10 raw material is dissolved in 2 to 6 parts by weight of an organic solvent, wherein the organic solvent is selected from acetone, butanone, pentanone, ethanol, isopropyl alcohol, benzyl alcohol, dichloromethane and trichloromethane; b) 1 to 3 parts by weight of HPMC is dissolved in 2 to 18 parts by weight of an alcohol selected from ethanol, benzyl alcohol, and isopropyl alcohol, or dispersed in a large amount of water; c) 1 part by weight of cores comprising sugar, microcrystalline cellulose, or a mixture thereof are placed in a fluidised bed; d) the solution of step a) and the solution or suspension of step b) are mixed together and sprayed onto the fluidised bed comprising the cores; e) the resultant spheres of step
  • the following embodiments illustrate methods for manufacturing the composition of the invention including in the form of granules and tablets in accordance with the present invention.
  • 1 to 3 parts by weight of PEG 1000 to 22000, 1 to 3 parts by weight of poloxamer, and 1 part by weight of docusate sodium are dissolved in 3 to 10 parts by weight of an alcohol selected from ethanol, isopropanol or benzyl alcohol until fully dissolved;
  • the coenzyme Q10 solution of step a) and the resultant solution of step b) are mixed together;
  • the following embodiments illustrate methods for manufacturing the composition of the invention including in the form of granules, tablets and capsules in accordance with the present invention.
  • 1 to 3 parts by weight of PEG 1000 to 22000 and 1 to 2 parts by weight of poloxamer are dissolved in 3 to 12 parts by weight of an alcohol selected from ethanol, isopropanol or benzyl alcohol until fully dissolved;
  • the coenzyme Q10 solution of step a) and the PEG/poloxamer solution of step b) are mixed together;
  • d) 1 to 2 parts by weight of crosslinked sodium carboxymethyl cellulose, 1 to 2 parts by weight of cross-linked povidone are placed in a fluid
  • An embodiment of the invention relates to administration of compositions of the invention as disclosed herein to treat coenzyme Q10 deficiency, or conditions related to coenzyme Q10 deficiency, including e.g. heart failure, cardiomyopathy or myopathy.
  • the amount of coenzyme Q10 in the composition of the invention, when used to treat coenzyme Q10 deficiency is from about 5 mg to 150 mg per tablet. In some embodiments, the dosage amount of coenzyme Q10 in the composition of the invention, when used to treat heart failure, cardiomyopathy or myopathy is from about 5 mg to 150 mg daily.
  • a capsule containing 150 mg of coenzyme Q10 was subject to a dissolution test.
  • the dissolution amount from stirring the composition at 75 RPM at 2 hours in 1000 mL of 0.5% Triton (surfactant) aqueous solution was 26 mg or 17.3%.
  • Another prior art composition is BLACKMORES 150 mg coenzyme Q10 soft capsule, which was also subject to dissolution.
  • the dissolution amount (using batch number 31185) from stirring at 75 RPM at 2 hours in 1000 mL of 0.5% Triton buffered at pH 4.5 with sodium acetate was 14 mg or 9.3%. At 3 hour of stirring, the dissolution amount was about 26 mg, indicating that the soft capsules do not improve the dissolution of coenzyme Q10.
  • a representative dissolution protocol that may be used in accordance with the present invention is as follows: a composition comprising 150 mg coenzyme Q10 spheres is stirred at 75 RPM for 2 hours in 1000 mL of 0.5% Triton buffered at pH 4.5 with sodium acetate and provided a dissolution amount of 145 mg.
  • EXAMPLE 1 Formulation and dissolution of coenzyme Q10 spheres in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate
  • a coenzyme Q10 capsule comprising 150 mg of coenzyme Q10 was prepared according to the following method: a) 1500 g of coenzyme Q10 raw material was dissolved in 3000 g of acetone; b) 1500 g of HPMC (E5) was dissolved in 4950 g of ethanol; c) the solution of step a) and the solution of step b) were mixed together to form a solution; d) 3000 g of sucrose cores (of 0.5 mm to 0.71 mm diameter) were placed into a fluidised bed; e) the mixture of step c) was sprayed onto the fluidised bed; f) the material on the fluidised bed was cooled until the temperature was ⁇ 35°C to give a product in the form of spheres or pellets; g) the sphere or pellets of step f) are filled into a capsules or pellet bag.
  • EXAMPLE 2 Formulation of coenzyme Q10 granules and 90 mg tablet using fluidised bed granulation:
  • Coenzyme Q10 granules and 90 mg tablets were prepared according to the following procedure: a) 540 g of coenzyme Q10 raw material was dissolved in 1080 g of acetone; b) 1080 g of HPMC was dispersed in 7200 g of water; c) the solution of step a) and the mixture of step b) were mixed together to form a mixture; d) 180 g of lactose, 720 g of cross-linked povidone and 360 g of microcrystalline cellulose were placed in a fluidised bed; e) the mixture of step c) comprising coenzyme Q10 and HPMC was sprayed onto the fluidised bed; f) 8% PVPK30 solution was sprayed onto the fluidised bed to give granules; g) the granules of step f) were mixed with magnesium stearate; and the resulting granules were pressed into a tablet, wherein the tablet comprises 90 mg of coenzyme
  • Coenzyme Q10 granules and tablets (each comprising 90 mg of coenzyme Q10) were subjected to a dissolution test by stirring at 75 RPM in 1000 mL of 0.5% Triton aqueous solution buffered at pH 4.5 with sodium acetate to provide the following results:
  • EXAMPLE 3 Formulation of 45 mg coenzyme Q10 granules and tablet
  • Coenzyme Q10 tablets and granules (each comprising 45 mg of coenzyme Q10) were subjected to a dissolution test by stirring at 75 RPM in 1000 mL of 0.5% Triton aqueous solution to provide the following results:
  • EXAMPLE 4 Formulation of granules and a tablet comprising 45 mg coenzyme Q10 and 90 mg
  • Coenzyme Q10 tablets and granules (each comprising 45 mg of coenzyme Q10) were subjected to a dissolution test by stirring at 75 RPM in 1000 mL of 0.5% Triton aqueous solution to provide the following results:
  • EXAMPLE 5 Formulation and dissolution of coenzyme Q10 tablets in 1000 mL of 0.5% Triton and 0. 1% Tween 80 agueous solution
  • a coenzyme Q10 tablet comprising 30 mg of coenzyme Q10 was prepared according to the following method: a) 300 g of coenzyme Q10 raw material, 900 g sorbitol, 120 g egg lecithin, and 900 g malic acid were dissolved in 7800 g of acetone; b) 300 g cross-linked povidone, 300 g croscarmellose sodium, and 300 g lauryl sodium sulfate were placed into a fluidised bed; c) the solution of step a) was sprayed onto the fluidised bed; d) 3% PVPK30 solution was sprayed onto the fluidised bed to give granules; e) the granules of step d) were mixed with magnesium stearate and talcum powder; and the resulting granules were pressed into a tablet, wherein the tablet comprises 30 mg of coenzyme Q10.
  • Coenzyme Q10 granules and tablets (each comprising 30 mg of coenzyme Q10) were subjected to a dissolution test by stirring at 75 RPM in 1000 mL of 0.5% Triton and 0.1% Tween 80 aqueous solution to provide the following results:
  • EXAMPLE 6 Formulation and dissolution of coenzyme Q10 capsules in 1000 mL of 0.5% Triton aqueous solution
  • a coenzyme Q10 capsule comprising 150 mg of coenzyme Q10 was prepared according to the following method: a) 1500 g of coenzyme Q10 raw material and 1500g citric acid were dissolved in 39000 g of acetone; b) HPMC (E5) was dissolved in 5000 g of ethanol; c) the solution of step a) and the solution of step b) were mixed together to form a solution; d) 700 g lactose, 600 g microcrystalline cellulose, and 700 g sorbitol were placed into a fluidised bed; e) the mixture of step c) was sprayed onto the fluidised bed; f) 2.4% PVPK30 solution was sprayed onto the fluidised bed to give granules; g) the material on the fluidised bed was cooled until the temperature was ⁇ 35°C to give a product in the form of spheres or pellets; h) spheres or pellets of g) were mixed with magnesium stearate and
  • Coenzyme Q10 capsules (each comprising 150 mg of coenzyme Q10) were subjected to a dissolution test by stirring at 75 RPM in 1000 mL of 0.5% Triton aqueous solution to provide the following results:

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Abstract

L'invention concerne des compositions comprenant la coenzyme Q10 et un excipient soluble dans l'eau et des procédés de traitement d'une déficience en coenzyme Q10 chez un sujet comprenant l'administration orale de ladite composition. La composition peut se présenter sous la forme d'un dosage solide ou liquide tel que des sphères, des granules, des comprimés, des capsules, une solution orale et des capsules molles à administrer par voie orale. La composition peut comprendre un mélange de coenzyme Q10 et un revêtement de liant sur un noyau, le noyau comprenant du sucre, de la cellulose microcristalline ou un mélange de ceux-ci. La composition est une formulation à libération immédiate à dissolution élevée dans un milieu aqueux.
PCT/IB2024/053816 2023-04-20 2024-04-19 Compositions et procédés pour le traitement d'une déficience en coenzyme q10 Pending WO2024218722A2 (fr)

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CN119385957A (zh) * 2024-10-29 2025-02-07 广东润和生物科技有限公司 一种高生物利用度的辅酶q10的片剂及其制备方法

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CN101703477A (zh) 2009-11-20 2010-05-12 天津市弗兰德医药科技发展有限公司 一种辅酶q10微丸及其制备方法

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US20090060993A1 (en) * 2007-09-04 2009-03-05 Joseph Schwarz Solid pharmaceutical composition for enhanced delivery of coenzyme q-10 and ubiquinones
KR100982130B1 (ko) * 2007-11-09 2010-09-14 씨제이제일제당 (주) 코엔자임 ｑ10을 함유하는 안정화된 제제 및 이의 제조방법

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CN101703477A (zh) 2009-11-20 2010-05-12 天津市弗兰德医药科技发展有限公司 一种辅酶q10微丸及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN119385957A (zh) * 2024-10-29 2025-02-07 广东润和生物科技有限公司 一种高生物利用度的辅酶q10的片剂及其制备方法

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