WO2020160620A1 - An epigenetic drift attenuating composition and method of use thereof - Google Patents

An epigenetic drift attenuating composition and method of use thereof Download PDF

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Publication number
WO2020160620A1
WO2020160620A1 PCT/AU2020/050095 AU2020050095W WO2020160620A1 WO 2020160620 A1 WO2020160620 A1 WO 2020160620A1 AU 2020050095 W AU2020050095 W AU 2020050095W WO 2020160620 A1 WO2020160620 A1 WO 2020160620A1
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composition
formulated
curcumin
administration
subject
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PCT/AU2020/050095
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French (fr)
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Raymond Denis PALMER
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Helium 3 Biotech Pty Ltd
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Publication of WO2020160620A1 publication Critical patent/WO2020160620A1/en

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Definitions

  • the present disclosure relates to an epigenetic drift attenuating composition and a method of use thereof.
  • epigenetic changes to the DNA lead to methylation of the cytosines in the CpG islands, but also methylation of other nucleotides.
  • Epigenetic changes are associated with the development of ageing- related cell and tissue dysfunction, and patient morbidities within the ageing populations world-wide.
  • compositions that will attenuate epigenetic drift when administered in a therapeutically effective dose to a subject in need thereof and a method of using such a composition.
  • Epigenetic changes particularly methylation of nucleotides, accumulate in multicellular organisms, such as humans, with the passage of time. Accumulation of such methylation is associated with deleterious effects that are typically termed “ageing”. These deleterious effects, including a deterioration of cell function, lead to an increase of ageing-related pathologies and inevitably accelerate mortality. A reduction in the epigenetic drift may delay onset of ageing-related negative effects on the health of an individual and contribute to economic benefits insofar as the costs associated with an increase in the ageing populations world-wide may be diminished.
  • composition including a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12, the composition formulated to attenuate epigenetic drift in a cell of a subject.
  • the present disclosure in another aspect sets forth a method of attenuating epigenetic drift in a cell of a subject, the method including administering to a subject in need thereof a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
  • a green tea extract apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
  • the present disclosure is directed to a composition that attenuates epigenetic drift in one or more cell of a multicellular organism, such as humans, that may arise with the passage of time.
  • the present disclosure also relates to a method of use of the composition.
  • the term“epigenetic drift” should be understood for the purposes herein to define not only methylation of the cytosines in the CpG islands, but also methylation other nucleotides.
  • composition formulated to attenuate epigenetic drift in a cell of a subject.
  • the composition including a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
  • a therapeutically effective dose refers to an amount of a composition administered to a subject, either as a single dose or as part of a series of doses, which is effective to produce a desired therapeutic effect. It will be appreciated that the amount of green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 will depend on a preferred route of administration, the rate and expected duration of release of the composition, and the nature of the condition, disease or disorder to be treated or prevented.
  • each of the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 20 - 150 mg.
  • each of the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 40 mg.
  • composition herein disclosed may be delivered to a subject in need thereof by any one of several routes.
  • the composition may be delivered via buccal, infusion (e.g., a bolus infusion), inhalation, intracranial injection, enteral, intradermal, intramuscular, intranasal, intraocular, intraperitoneally, intravenously, orally, rectal, rectal, subcutaneously, sublingual, topically, transdermal, vaginal, or any combination thereof.
  • the composition may be formulated for enteral administration.
  • composition herein disclosed may be formulated for delayed release (also termed sustained or slow release, timed release, delayed release, or controlled release).
  • delayed release also termed sustained or slow release, timed release, delayed release, or controlled release.
  • Such compositions may generally be prepared using well known technology and administered by, for example, oral, rectal, intradermal, or subcutaneous implantation, or by implantation at the desired target site in a delayed release manner.
  • Delayed-release formulations may contain the compound dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling barrier.
  • a particularly preferred embodiment of the composition may be formulated in an enteric coating layer.
  • the enteric coating layer may include one or more of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, and water-based polymer solutions or dispersions of acrylates.
  • composition disclosed herein may be formulated with a buffering agent to protect the compound from low pH of the gastric environment and/or an enteric coating.
  • the composition may, when administer orally, buccally, or sublingually, may be formulated with a flavouring agent, e.g., in a liquid, solid or semi-solid formulation.
  • Preferred embodiments may include one or more pharmaceutically acceptable dispersant, excipient, pH-buffering compound, and pigment.
  • Preferred embodiments will include at least one excipient that is biocompatible and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release.
  • the excipient facilitates absorption.
  • the excipient enhances solubility.
  • the composition may be a tablet formulation.
  • the composition may be a powder formulation.
  • the powder formulation may be in a capsule.
  • the composition may be a liquid formulation.
  • the composition may be formulated for parenteral administration.
  • the composition may be formulated for subcutaneous administration.
  • the composition may be formulated for intramuscular administration.
  • the composition may be formulated for intravenous administration.
  • the composition may be formulated for intradermal administration.
  • the composition may be formulated for transdermal administration.
  • composition disclosed herein will be administered for a sufficient amount of time to selectively purge senescent cells from one or more tissue in a subject, wherein the purging of such cells does not lead to a cancer.
  • purging of senescent cells may ameliorate at least one symptom associated with a number of pathologies.
  • Such pathologies may include age-related loss of pulmonary function, Alzheimer's disease, angina, aortic aneurysm, arrhythmia, arteriosclerosis, asthma, atherosclerosis, atopic dermatitis, brain aneurysm, bronchiectasis, cardiac diastolic dysfunction, a cancer, cardiac fibrosis, cardiac stress resistance, cardiomyopathy, carotid artery disease, cataracts, chronic obstructive pulmonary disease, chronic renal failure, congestive heart failure, coronary artery disease, coronary thrombosis, cutaneous lupus, cutaneous lymphomas, cystic fibrosis, dementia, diabetes, diabetic ulcer, diseases and disorders related to photosensitivity or photoaging, dysesthesia, eczema, eczematous eruptions, emphysema, endocarditis, eosinophilic dermatosis, fibrohistocytic proliferations of skin, frailty, glaucoma,
  • a method of attenuating epigenetic drift in a cell of a subject including administering to a subject in need thereof a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
  • the method may include a treatment course no longer than (a) one month, or (b) no longer than two months, or (c) no longer than three months.
  • each treatment course is no longer than (a) five days, (b) seven days, (c) ten days, (d) fourteen days, or (e) twenty-one days.
  • the composition is administered every second day or every third day of each treatment course.
  • the composition is administered once daily during each treatment course.
  • the composition is administered twice daily during each treatment course. Suitable interval periods between treatments will be known to a person skilled in the art.
  • the subject may be a multicellular animal.
  • the multicellular animal is a human.

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Abstract

As animals, including humans, age, epigenetic changes to the DNA lead to methylation of the cytosines in the CpG islands, but also methylation of other nucleotides. Epigenetic changes are associated with the development of ageing-related cell and tissue dysfunction, and patient morbidities within the ageing populations world-wide. Given the afore-mentioned dysfunction and morbidities within the ageing populations around the world, a need exists for a composition that will attenuate epigenetic drift when administered in a therapeutically effective dose to a subject in need thereof and a method of using such a composition. The present disclosure relates to an epigenetic drift attenuating composition comprising green tea extract, apigenin, betaine, choline, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 and a method of use thereof.

Description

AN EPIGENETIC DRIFT ATTENUATING COMPOSITION AND METHOD OF USE
THEREOF
Field of Invention
The present disclosure relates to an epigenetic drift attenuating composition and a method of use thereof.
Background of Invention
As animals, including humans, age, epigenetic changes to the DNA lead to methylation of the cytosines in the CpG islands, but also methylation of other nucleotides. Epigenetic changes are associated with the development of ageing- related cell and tissue dysfunction, and patient morbidities within the ageing populations world-wide.
Given the afore-mentioned dysfunction and morbidities within the ageing populations around the world, a need exists for a composition that will attenuate epigenetic drift when administered in a therapeutically effective dose to a subject in need thereof and a method of using such a composition.
Summary
Epigenetic changes, particularly methylation of nucleotides, accumulate in multicellular organisms, such as humans, with the passage of time. Accumulation of such methylation is associated with deleterious effects that are typically termed “ageing”. These deleterious effects, including a deterioration of cell function, lead to an increase of ageing-related pathologies and inevitably accelerate mortality. A reduction in the epigenetic drift may delay onset of ageing-related negative effects on the health of an individual and contribute to economic benefits insofar as the costs associated with an increase in the ageing populations world-wide may be diminished.
The present disclosure in one aspect sets forth composition including a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12, the composition formulated to attenuate epigenetic drift in a cell of a subject.
The present disclosure in another aspect sets forth a method of attenuating epigenetic drift in a cell of a subject, the method including administering to a subject in need thereof a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12. The reference to any prior art in this specification is not and should not be taken as an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge in Australia or in any other country.
It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed, unless otherwise stated. In the present specification and claims, the word“comprising” and its derivatives including“comprises” and“comprise” include each of the stated integers but does not exclude the inclusion of one or more integers. The claims as filed with this application are hereby incorporated by reference in the description.
Detailed Description
The present disclosure is directed to a composition that attenuates epigenetic drift in one or more cell of a multicellular organism, such as humans, that may arise with the passage of time. The present disclosure also relates to a method of use of the composition. The term“epigenetic drift” should be understood for the purposes herein to define not only methylation of the cytosines in the CpG islands, but also methylation other nucleotides.
In a preferred embodiment, there is provided a composition formulated to attenuate epigenetic drift in a cell of a subject. The composition including a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
Without wishing to be bound by theory, a therapeutically effective dose refers to an amount of a composition administered to a subject, either as a single dose or as part of a series of doses, which is effective to produce a desired therapeutic effect. It will be appreciated that the amount of green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 will depend on a preferred route of administration, the rate and expected duration of release of the composition, and the nature of the condition, disease or disorder to be treated or prevented. In a preferred embodiment, each of the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 20 - 150 mg. In a particularly preferred embodiment, each of the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 40 mg.
A person skilled in the art will appreciate that the composition herein disclosed may be delivered to a subject in need thereof by any one of several routes. By way of non-limiting example, the composition may be delivered via buccal, infusion (e.g., a bolus infusion), inhalation, intracranial injection, enteral, intradermal, intramuscular, intranasal, intraocular, intraperitoneally, intravenously, orally, rectal, rectal, subcutaneously, sublingual, topically, transdermal, vaginal, or any combination thereof. Preferably, the composition may be formulated for enteral administration.
It will be appreciated that the composition herein disclosed may be formulated for delayed release (also termed sustained or slow release, timed release, delayed release, or controlled release). Such compositions may generally be prepared using well known technology and administered by, for example, oral, rectal, intradermal, or subcutaneous implantation, or by implantation at the desired target site in a delayed release manner. Delayed-release formulations may contain the compound dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling barrier.
A particularly preferred embodiment of the composition may be formulated in an enteric coating layer. In a preferred embodiment, the enteric coating layer may include one or more of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, and water-based polymer solutions or dispersions of acrylates.
A skilled person will appreciate that the composition disclosed herein may be formulated with a buffering agent to protect the compound from low pH of the gastric environment and/or an enteric coating. Furthermore, the composition may, when administer orally, buccally, or sublingually, may be formulated with a flavouring agent, e.g., in a liquid, solid or semi-solid formulation. Preferred embodiments may include one or more pharmaceutically acceptable dispersant, excipient, pH-buffering compound, and pigment. Preferred embodiments will include at least one excipient that is biocompatible and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. In a particularly preferred embodiment, the excipient facilitates absorption. In yet a further particularly preferred embodiment, the excipient enhances solubility.
In a further preferred embodiment, the composition may be a tablet formulation.
In a further preferred embodiment, the composition may be a powder formulation. In a particularly preferred embodiment, the powder formulation may be in a capsule.
In a further preferred embodiment, the composition may be a liquid formulation. Preferably, the composition may be formulated for parenteral administration. In a particularly preferred embodiment, the composition may be formulated for subcutaneous administration. In a further particularly preferred embodiment, the composition may be formulated for intramuscular administration. In a further particularly preferred embodiment, the composition may be formulated for intravenous administration. In a further particularly preferred embodiment, the composition may be formulated for intradermal administration. In a further particularly preferred embodiment, the composition may be formulated for transdermal administration.
A skilled person will appreciate that the composition disclosed herein will be administered for a sufficient amount of time to selectively purge senescent cells from one or more tissue in a subject, wherein the purging of such cells does not lead to a cancer. A skilled person will also appreciated that such purging of senescent cells may ameliorate at least one symptom associated with a number of pathologies. Such pathologies may include age-related loss of pulmonary function, Alzheimer's disease, angina, aortic aneurysm, arrhythmia, arteriosclerosis, asthma, atherosclerosis, atopic dermatitis, brain aneurysm, bronchiectasis, cardiac diastolic dysfunction, a cancer, cardiac fibrosis, cardiac stress resistance, cardiomyopathy, carotid artery disease, cataracts, chronic obstructive pulmonary disease, chronic renal failure, congestive heart failure, coronary artery disease, coronary thrombosis, cutaneous lupus, cutaneous lymphomas, cystic fibrosis, dementia, diabetes, diabetic ulcer, diseases and disorders related to photosensitivity or photoaging, dysesthesia, eczema, eczematous eruptions, emphysema, endocarditis, eosinophilic dermatosis, fibrohistocytic proliferations of skin, frailty, glaucoma, hearing loss, herniated intervertebral disc, Huntington's disease, hypercholesterolemia, hyperlipidemia, hyperpigmentation, hypertension, hypertension, immunobullous dermatosis, impaired angiogenesis, impaired endothelium-dependent vasodilation, inflammatory bowel disease, vitamin D metabolic abnormalities, kyphosis, liver fibrosis, macular degeneration, metabolic syndrome, mild cognitive impairment, mitral valve prolapse, motor neuron dysfunction, muscle fatigue, myocardial infarction, nevi, rashes, obesity, oral mucositis, oral submucosa fibrosis, osteoarthritis, osteoarthritis, osteoporosis, osteoporosis, pathologies associated with the cardiovascular system through endothelium-derived NO production, pancreatic fibrosis, Parkinson's disease, pathologies associated with cellular calcium homeostasis, pathologies associated with perturbed TRPV5, i.e., transient receptor potential cation channel subfamily v member 5, pathologies of the skin, pemphigoid, pemphigus, peripheral vascular disease, presbyopia, pruritis, psoriasis, pulmonary fibrosis, pulmonary fibrosis, reactive neutrophilic dermatosis, renal disease, renal failure, rhytides, sarcopenia, skin conditions, skin wound healing, stroke, urticaria, and vision loss.
In another embodiment, there is provided a method of attenuating epigenetic drift in a cell of a subject. The method including administering to a subject in need thereof a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
In preferred embodiments of the method disclosed herein, the method may include a treatment course no longer than (a) one month, or (b) no longer than two months, or (c) no longer than three months. In further preferred embodiments, each treatment course is no longer than (a) five days, (b) seven days, (c) ten days, (d) fourteen days, or (e) twenty-one days. In further preferred embodiments, the composition is administered every second day or every third day of each treatment course. In another specific embodiment, the composition is administered once daily during each treatment course. In another preferred embodiment, the composition is administered twice daily during each treatment course. Suitable interval periods between treatments will be known to a person skilled in the art.
In a preferred embodiment, the subject may be a multicellular animal. Preferably, the multicellular animal is a human.
The features described with respect to one embodiment may be applied to other embodiments, or combined with, or interchanged with, the features of other embodiments without departing from the scope of the present invention.
Other embodiments of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.

Claims

What is claimed is:
1 . A composition comprising a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12, the composition formulated to attenuate epigenetic drift in a cell of a subject.
2. The composition of claim 1 , wherein each of the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 20 - 150 mg.
3. The composition of either claim 1 or claim 2, wherein the green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12 is present in an amount of 40 mg
4. The composition of any one of claim 1 to 3, formulated for enteral administration.
5. The composition of claim 4, formulated for delayed release.
6. The composition of claim 5, formulated in an enteric coating layer.
7. The composition of claim 6, wherein the enteric coating layer includes one or more of cellulose acetate phthalate, cellulose acetate trimellitate, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, and water-based polymer solutions or dispersions of acrylates.
8. The composition of any one of claims 1 to 7, further comprising one or more pharmaceutically acceptable dispersant, excipient, pH-buffering compound, and pigment.
9. The composition of claim 8, wherein the excipient facilitates absorption.
10. The composition of claim 8, wherein the excipient enhances solubility.
1 1 . The composition of any one of claims 1 to 10, wherein the composition is a tablet formulation.
12. The composition of any one of claims 1 to 1 1 , wherein the composition is a powder formulation.
13. The composition of claim 12, wherein the powder formulation is in a capsule.
14. The composition of any one of claims 1 to 1 1 , wherein the composition is a liquid formulation.
15. The composition of any one of claims 1 to 10 and 14, formulated for parenteral administration.
16. The composition of claim 15, formulated for subcutaneous administration.
17. The composition of claim 15, formulated for intramuscular administration.
18. The composition of claim 15, formulated for intravenous administration.
19. The composition of claim 15, formulated for intradermal administration.
20. The composition of claim 15, formulated for transdermal administration.
21 . A method of attenuating the epigenetic drift in a cell of a subject, the method comprising administering to a subject in need thereof a therapeutically effective dose of each of a green tea extract, apigenin, betaine, choline, curcumin, curcumin, epigallocatechin, folic acid, genistein, lycopene, quercetin, resveratrol, selenium, sulforaphane, and vitamin B12.
22. The method of claim 21 , wherein the subject is a human.
PCT/AU2020/050095 2019-02-05 2020-02-05 An epigenetic drift attenuating composition and method of use thereof WO2020160620A1 (en)

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Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ATHANASOPOULOS, D. ET AL.: "Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics", ADVANCES IN NUTRITION, vol. 7, 2016, pages 917 - 927, XP055728632 *
BEKDASH, R.A.: "Choline, the brain and neurodegeneration: insights from epigenetics", FRONTIERS IN BIOSCIENCE, vol. 23, 2018, Landmark, pages 1113 - 1143, XP055728631 *
MEERAN, S.M. ET AL.: "Epigenetic targets of bioactive dietary components for cancer prevention and therapy", CLINICAL EPIGENETICS, vol. 1, 2010, pages 101 - 116, XP055728630 *
PARK, L.K. ET AL.: "70th Anniversary Conference on ‘Vitamins in early development and healthy aging: impact on infectious and chronic disease’ Symposium 4: Vitamins, infectious and chronic disease during adulthood and aging Nutritional influences on epigenetics and age-related disease", PROCEEDINGS OF THE NUTRITION SOCIETY (2012), vol. 71, 2012, pages 75 - 83, XP055728629 *
POINTNER, A. ET AL.: "EGCG Containing Combined Dietary Supplement Affects Telomeres and Epigenetic Regulation", JOURNAL OF NUTRITION & FOOD SCIENCES, vol. 7, no. 1, 2017, pages 3, XP055728633 *

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