WO2022185159A1 - Dietary supplement useful as an adjuvant in the treatment of chronic pain - Google Patents
Dietary supplement useful as an adjuvant in the treatment of chronic pain Download PDFInfo
- Publication number
- WO2022185159A1 WO2022185159A1 PCT/IB2022/051633 IB2022051633W WO2022185159A1 WO 2022185159 A1 WO2022185159 A1 WO 2022185159A1 IB 2022051633 W IB2022051633 W IB 2022051633W WO 2022185159 A1 WO2022185159 A1 WO 2022185159A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- supplement
- pain
- vitamin
- chronic pain
- coenzyme
- Prior art date
Links
- 208000002193 Pain Diseases 0.000 title claims abstract description 74
- 208000000094 Chronic Pain Diseases 0.000 title claims abstract description 29
- 238000011282 treatment Methods 0.000 title claims abstract description 22
- 235000015872 dietary supplement Nutrition 0.000 title claims abstract description 12
- 239000002671 adjuvant Substances 0.000 title claims abstract description 10
- 239000000419 plant extract Substances 0.000 claims abstract description 18
- 239000000203 mixture Substances 0.000 claims abstract description 17
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000017471 coenzyme Q10 Nutrition 0.000 claims abstract description 16
- 229940110767 coenzyme Q10 Drugs 0.000 claims abstract description 16
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 claims abstract description 16
- 229940088594 vitamin Drugs 0.000 claims abstract description 10
- 229930003231 vitamin Natural products 0.000 claims abstract description 10
- 235000013343 vitamin Nutrition 0.000 claims abstract description 10
- 239000011782 vitamin Substances 0.000 claims abstract description 10
- 235000007892 Spilanthes oleracea Nutrition 0.000 claims abstract description 4
- 244000273928 Zingiber officinale Species 0.000 claims abstract description 4
- 235000006886 Zingiber officinale Nutrition 0.000 claims abstract description 4
- 235000008397 ginger Nutrition 0.000 claims abstract description 4
- 239000001841 zingiber officinale Substances 0.000 claims abstract description 3
- 244000145321 Acmella oleracea Species 0.000 claims abstract 2
- 239000013589 supplement Substances 0.000 claims description 54
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 241000218236 Cannabis Species 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 8
- 229960003495 thiamine Drugs 0.000 claims description 8
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 8
- 229940011671 vitamin b6 Drugs 0.000 claims description 8
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 229930003451 Vitamin B1 Natural products 0.000 claims description 6
- 229930003779 Vitamin B12 Natural products 0.000 claims description 6
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 6
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 6
- 239000011691 vitamin B1 Substances 0.000 claims description 6
- 235000010374 vitamin B1 Nutrition 0.000 claims description 6
- 239000011715 vitamin B12 Substances 0.000 claims description 6
- 235000019163 vitamin B12 Nutrition 0.000 claims description 6
- 239000011726 vitamin B6 Substances 0.000 claims description 6
- 235000019158 vitamin B6 Nutrition 0.000 claims description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 5
- 235000010445 lecithin Nutrition 0.000 claims description 5
- 239000000787 lecithin Substances 0.000 claims description 5
- 229940067606 lecithin Drugs 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 3
- 235000010980 cellulose Nutrition 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000004615 ingredient Substances 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 239000005913 Maltodextrin Substances 0.000 claims description 2
- 229920002774 Maltodextrin Polymers 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000011666 cyanocobalamin Substances 0.000 claims description 2
- 235000000639 cyanocobalamin Nutrition 0.000 claims description 2
- 229960002104 cyanocobalamin Drugs 0.000 claims description 2
- 239000008298 dragée Substances 0.000 claims description 2
- 235000013305 food Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 2
- 229940035034 maltodextrin Drugs 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 235000008160 pyridoxine Nutrition 0.000 claims description 2
- 239000011677 pyridoxine Substances 0.000 claims description 2
- 239000007962 solid dispersion Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 235000019157 thiamine Nutrition 0.000 claims description 2
- 239000011721 thiamine Substances 0.000 claims description 2
- 239000008240 homogeneous mixture Substances 0.000 claims 1
- 239000007937 lozenge Substances 0.000 claims 1
- 230000036407 pain Effects 0.000 description 40
- 230000000694 effects Effects 0.000 description 11
- 208000019901 Anxiety disease Diseases 0.000 description 8
- 230000036506 anxiety Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000008901 benefit Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010021118 Hypotonia Diseases 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 150000001200 N-acyl ethanolamides Chemical class 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000002621 endocannabinoid Substances 0.000 description 3
- 230000036640 muscle relaxation Effects 0.000 description 3
- 239000005445 natural material Substances 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 244000139010 Spilanthes oleracea Species 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000013065 commercial product Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 229940005741 sunflower lecithin Drugs 0.000 description 2
- 241000521948 Acmella Species 0.000 description 1
- 206010002869 Anxiety symptoms Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 244000061944 Helianthus giganteus Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000037490 Medically Unexplained Symptoms Diseases 0.000 description 1
- 208000003926 Myelitis Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 241000234314 Zingiber Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000013523 data management Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000010490 psychological well-being Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000002747 voluntary effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4415—Pyridoxine, i.e. Vitamin B6
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A61K31/51—Thiamines, e.g. vitamin B1
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates generally to the field of dietary supplements, and more precisely to a supplement in the form of a composition of plant extracts and natural substances described below, to the process for the preparation thereof and to the supplement itself for use as an adjuvant in the treatment of chronic pain.
- Chronic pain is defined as a pain that has been ongoing, afflicting a patient for at least six months or that has persisted for at least one month after healing that should have ended it. This is a condition that, unlike acute pain, can occur even in the absence of an obvious cause and does not appear to have a useful function; it can also persist for a long time, even for years, and is extremely difficult to recognise and diagnose, but also to treat once diagnosed.
- the Applicant has now found a dietary supplement based on natural substances and titrated plant extracts, thus in a controlled dosage of the active ingredients contain therein, which solves the problems described above in that it has proved to be an effective adjuvant in the therapeutic treatment of chronic pain, both alone and in combination with known products already used for these therapies.
- the supplement in the form of composition of this invention has been shown to be effective as an adjuvant in patients suffering from chronic pain, under treatment with Cannabis Medica.
- this supplement had a positive effect both on the intensity of chronic pain and on aspects related to patients' psychological well-being and improved quality of life.
- the supplement of the invention is also palatable to the patient, due to the convenience of taking the product in tablet form, and also due to the absence of major side effects.
- the object of the invention is therefore a dietary supplement, the essential characteristics of which are defined in the first of the appended claims. Further important characteristics of the supplement according to the invention are defined in the dependent claims of the first one.
- a further object of the invention is a process for the preparation of the aforesaid supplement, the essential features of which are defined by the respective independent claim appended hereto.
- Still a further object of the invention is the aforesaid supplement for use as an adjuvant in the therapeutic treatment of chronic pain.
- Figure 1 graph in the form of histograms showing the percentage of patients with decreased pain for the different diseases tested in the study described in the experimental part below;
- Figure 2 graph showing the trend over time of the decrease in pain for the subjects subjected to the study described in the experimental part below, in the time interval between 10 and 30 days after the start of the study;
- DVAS1 indicates the average of the pain values declared by the subjects according to the visual analogue scale of pain after 10 days from the start of the study,
- DVAS2 indicates the average of the pain values declared after 20 days and
- DVAS3 indicates the average of the pain values declared after 30 days from the start of the study;
- Figure 3 graph in the form of histograms showing the number of patients, among those recruited for the study, who dropped out before the end, with the relative reasons.
- the term “dosage unit” herein means a single tablet, pill, capsule, or other available form that can be administered to a subject as a single unit.
- the term “phytosomal preparation” referring to an active substance means a preparation in which the active substance is in the form of a complex with phospholipids to reduce the polarity thereof and improve the bioavailability thereof, according to a technology known as Phytosome ® patented by Indena SpA (see Petrangolini G. et al. “A new Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers” in Current drug Delivery 2019, 16(8):759-767).
- the term “standardized” with reference in particular to natural substances or plant extracts means a titrated product, for which the exact quantity of active ingredient present in the substance or extract respectively is known.
- DVAS refers to pain according to the Visual Analogue Scale (VAS), which is one of the internationally recognised methods of algometry or pain measurement, which is extremely simple and understandable for patients of all ages, perfectly reproducible and has high correlation with other algometric methods (see Scott-Huskisson E.C. “Graphic Representation of Pain” in Pain 1976; 2:175-84).
- VAS Visual Analogue Scale
- This scale ranges from 0 for no pain to 100 for severe or very severe pain, and is based on the subjective graphic response of the patient who must indicate a value on the scale to give a measure of the pain experienced.
- HADS in the present invention means the Hospital Anxiety and Depression Scale. This is a self-assessment scale developed to detect states of depression, anxiety and distress in chronically ill patients; it consists of 14 points, 7 for anxiety and 7 for depression, and allows discrimination between psychopathological and somatic symptoms.
- the dietary supplement according to the invention comprises a combination of plant extracts of Zingiber officinale and Acmella Oleracea, coenzyme Q10, and one or more vitamins of group B.
- the above-mentioned combination of plant extracts comprises the two extracts, with a high degree of standardization.
- the plant extracts present in the supplement of the invention are obtained by extraction with supercritical carbon dioxide.
- the combination of plant extracts of the present supplement is a combination of standardized botanical extracts of ginger and Acmella oleracea, originally in oil form, formulated in powder form by addition of lecithin, e.g. sunflower lecithin.
- the coenzyme Q10 is in the form of a phytosomal preparation, wherein the coenzyme Q10 is in the form of a complex with lecithin, for example sunflower lecithin, to form a solid dispersion of the active ingredient in a lecithin matrix.
- lecithin for example sunflower lecithin
- the combination of plant extracts and/or the phytosomal preparation further comprise food grade excipients, selected for example from maltodextrin, silica dioxide, cellulose and derivatives thereof, such as hydroxypropylcellulose, hydroxypropylmethylcellulose and microcrystalline cellulose, and mixtures thereof.
- food grade excipients selected for example from maltodextrin, silica dioxide, cellulose and derivatives thereof, such as hydroxypropylcellulose, hydroxypropylmethylcellulose and microcrystalline cellulose, and mixtures thereof.
- the above-mentioned combination of plant extracts may be present for example in amount comprised between 50 mg and 1000 mg per dosage unit; preferably in amount equal to about 350 mg.
- the amount of coenzyme Q10 in this supplement may for example be comprised between about 10 mg and about 200 mg per dosage unit, and between about 10 mg and about 1000 mg per dosage unit when the coenzyme Q10 is present in the supplement in the form of a phytosomal preparation. According to a preferred embodiment of this supplement, it comprises about 150 mg per dosage unit of a phytosomal preparation of coenzyme Q10.
- the supplement of the invention may comprise, for example, as a combination of the plant extracts mentioned above, a product having the following composition shown in Table 1 for a 350 mg unit dosage form, like in the commercial product known as Mitidol®.
- Table 1
- the supplement of the invention may comprise, for example, as a phytosomal preparation of coenzyme Q10 standardized to 18-22% for a 150 mg unit dosage form, a product having the following composition shown in Table 2 and obtainable using ethyl acetate as a solvent, like in the commercial product known as Ubiqsome®.
- “Vitamins of group B” preferably means the vitamins selected from the group consisting of vitamin B1 or thiamine, vitamin B6 or pyridoxine, vitamin B12 or cyanocobalamin, and mixtures thereof.
- the supplement comprises more vitamins of group B, preferably a mixture of vitamin B1, vitamin B6 and vitamin B12.
- vitamin B1 may be present for example in amount from about 0.50 to about 12.5 mg, vitamin B6 in amount from about 0.7 to about 5 mg and vitamin B12 in amount from about 1.25 mg to about 500 mg, independently of each other.
- the supplement comprises, per dosage unit, about 350 mg of the combination of plant extracts, about 150 mg of coenzyme Q10, about 0.55 mg of vitamin B1, about 0.7 mg of vitamin B6 and about 1.25 mg of vitamin B12.
- the components of the supplement according to the invention may be formulated according to conventional methods, such as those described for example in “Remington’s Pharmaceutical Handbook”, Mack Publishing Co., N.Y., USA.”
- the present supplement may be formulated according to conventional formulation techniques for lipophilic ingredients suitable for oral administration, mainly in the form of tablets, hard or soft gelatine capsules, cellulose capsules, dragees, and similar.
- a process for the preparation of the supplement comprising the steps of mixing the above-described combination of plant extracts with one or more vitamins of Group B and with the coenzyme Q10, and formation of the dosage units for oral administration, is part of the present invention.
- this process comprises a preliminary step of formulating the combination of plant extracts and of the coenzyme Q10 in the form of a phytosomal preparation, prior to mixing.
- the supplement of this invention has shown remarkable efficacy in reducing chronic pain in particular in certain diseases. It can be used alone, or administered to patients already receiving traditional medications for treating chronic pain such as opioids or even Cannabis medica. Particularly in patients already undergoing treatment with Cannabis medica, the supplement of this invention has made it possible to significantly reduce pain, allowing in some cases a reduction in the daily dose of cannabis and thus also the relative side effects.
- the dietary supplement described above for use as an adjuvant in the therapeutic treatment of chronic pain, alone or in combination with one or more conventional pain-relieving drugs, in particular therapeutic cannabis, is also an object of the present invention, as is a method for therapeutic treatment of chronic pain comprising administering an effective dose of the aforesaid supplement, alone or in combination with one or more conventional pain-relieving drugs, to a subject in need thereof.
- a supplement for use or method of treatment preferably comprises oral administration of the supplement, possibly combined with the administration of one or more of the above drugs.
- this supplement has no significant side effects (there were only a few cases of nausea in those taking Cannabis at high THC concentrations, at the time when the dosage of this conventional therapy had not yet been reduced, contrary to the recommendation given in the study described below, demonstrating the mechanism of action on the receptors of the endocannabinoid system of this supplement and the efficacy thereof).
- the present supplement therefore also helps in this sense to improve the conditions of the patient and increase his or her compliance with the therapy; it also reduces the administration of any conventional drugs which on the contrary have important side effects.
- this supplement has also been shown to induce muscle relaxation, increased activation and greater energy in daily activities.
- Another advantage of this supplement is its formulation based on natural products and plant extracts, which are, however, standardized and titrated for an exact and constant dosage in the final product.
- the Study also aimed to demonstrate that taking the supplement of this invention can enable the dosage of conventional medication to be reduced even in subjects who have been treated for some time with this drug therapy.
- -psychological variables comprise symptoms of anxiety and depressive psychopathology as measured by the Hospital Anxiety and Depression Scale (HADS);
- VAS Visual Analogue Scale
- VAS scale VAS scale
- HADS scale -Anxiety and depression
Abstract
The present invention relates to a dietary supplement in the form of a composition comprising: a combination of standardized plant extracts of Zingiber officinale and Acmella Oleracea, coenzyme Q10, and one or more vitamins of group B, useful as an adjuvant in the treatment of chronic pain.
Description
DIETARY SUPPLEMENT
USEFUL AS AN ADJUVANT IN THE TREATMENT OF CHRONIC PAIN
DESCRIPTION
Field of the invention The present invention relates generally to the field of dietary supplements, and more precisely to a supplement in the form of a composition of plant extracts and natural substances described below, to the process for the preparation thereof and to the supplement itself for use as an adjuvant in the treatment of chronic pain.
Background of the Invention Chronic pain is defined as a pain that has been ongoing, afflicting a patient for at least six months or that has persisted for at least one month after healing that should have ended it. This is a condition that, unlike acute pain, can occur even in the absence of an obvious cause and does not appear to have a useful function; it can also persist for a long time, even for years, and is extremely difficult to recognise and diagnose, but also to treat once diagnosed.
An epidemiological study of the situation in Europe indicates that 95 million European adults in the 15-64 age group suffer from chronic pain, which is far more than the 60 million European citizens suffering from diabetes (see Brevik et al. “Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment” Eur. J. Pain 2006; 10:287-333).
This and other similar studies highlight how chronic pain can result from a disease or trauma from which one has now recovered, or it can develop for no apparent reason, also affecting any part of the body, arms, legs, hands or feet, with a prevalence however reported by European patients for back pain. The physical consequences and the emotional and social impact of this disease can be devastating, with a strong impact on the patient's daily life and work. Depending on the severity of the chronic pain and how well the patient can manage it, it can in fact reduce the patient's mobility to the point of making him or her non-self-sufficient, and also reduce his or her ability to cope with stress and anxiety, leading to social isolation and depression.
By its very nature, chronic pain, even when correctly diagnosed, can be very
difficult to treat by doctors and have enormous costs on public health systems and society. The drugs available, particularly for severe chronic pain, are those based on opioids, which in the vast majority of cases cause severe side effects in patients, such as nausea, vomiting, migraine, etc., as well as addiction if used for a long time. It is clear from the above that there is a strong need to have effective products available to improve, if not eliminate, the conditions of chronic pain of the many subjects who are affected.
Summary of the invention
The Applicant has now found a dietary supplement based on natural substances and titrated plant extracts, thus in a controlled dosage of the active ingredients contain therein, which solves the problems described above in that it has proved to be an effective adjuvant in the therapeutic treatment of chronic pain, both alone and in combination with known products already used for these therapies.
In particular, the supplement in the form of composition of this invention has been shown to be effective as an adjuvant in patients suffering from chronic pain, under treatment with Cannabis Medica. As illustrated below, this supplement had a positive effect both on the intensity of chronic pain and on aspects related to patients' psychological well-being and improved quality of life.
At the same time, the supplement of the invention is also palatable to the patient, due to the convenience of taking the product in tablet form, and also due to the absence of major side effects.
The object of the invention is therefore a dietary supplement, the essential characteristics of which are defined in the first of the appended claims. Further important characteristics of the supplement according to the invention are defined in the dependent claims of the first one.
A further object of the invention is a process for the preparation of the aforesaid supplement, the essential features of which are defined by the respective independent claim appended hereto.
Still a further object of the invention is the aforesaid supplement for use as an adjuvant in the therapeutic treatment of chronic pain.
Other important features of the supplement, of the process for the preparation
thereof and of the supplement for use according to the invention are given in the following detailed description, also with reference to the figures.
Brief description of the drawings
Figure 1: graph in the form of histograms showing the percentage of patients with decreased pain for the different diseases tested in the study described in the experimental part below;
Figure 2: graph showing the trend over time of the decrease in pain for the subjects subjected to the study described in the experimental part below, in the time interval between 10 and 30 days after the start of the study; DVAS1 indicates the average of the pain values declared by the subjects according to the visual analogue scale of pain after 10 days from the start of the study, DVAS2 indicates the average of the pain values declared after 20 days and DVAS3 indicates the average of the pain values declared after 30 days from the start of the study;
Figure 3: graph in the form of histograms showing the number of patients, among those recruited for the study, who dropped out before the end, with the relative reasons.
Detailed description of the invention
Definitions
Within the scope of the present invention, unless otherwise specified, when a % by weight of a single component of a composition or combination is indicated, it is to be understood as a % by weight with respect to the total weight of the composition or combination of components.
The term “dosage unit” herein means a single tablet, pill, capsule, or other available form that can be administered to a subject as a single unit. The term “phytosomal preparation” referring to an active substance means a preparation in which the active substance is in the form of a complex with phospholipids to reduce the polarity thereof and improve the bioavailability thereof, according to a technology known as Phytosome® patented by Indena SpA (see Petrangolini G. et al. “A new Food-grade Coenzyme Q10 Formulation Improves Bioavailability: Single and Repeated Pharmacokinetic Studies in Healthy Volunteers” in Current drug Delivery 2019, 16(8):759-767).
The term “standardized” with reference in particular to natural substances or plant extracts means a titrated product, for which the exact quantity of active ingredient present in the substance or extract respectively is known.
The term “DVAS” in the present invention refers to pain according to the Visual Analogue Scale (VAS), which is one of the internationally recognised methods of algometry or pain measurement, which is extremely simple and understandable for patients of all ages, perfectly reproducible and has high correlation with other algometric methods (see Scott-Huskisson E.C. “Graphic Representation of Pain” in Pain 1976; 2:175-84). This scale ranges from 0 for no pain to 100 for severe or very severe pain, and is based on the subjective graphic response of the patient who must indicate a value on the scale to give a measure of the pain experienced.
The term “HADS” in the present invention means the Hospital Anxiety and Depression Scale. This is a self-assessment scale developed to detect states of depression, anxiety and distress in chronically ill patients; it consists of 14 points, 7 for anxiety and 7 for depression, and allows discrimination between psychopathological and somatic symptoms.
Detailed description
The dietary supplement according to the invention comprises a combination of plant extracts of Zingiber officinale and Acmella Oleracea, coenzyme Q10, and one or more vitamins of group B.
In one aspect of the invention, the above-mentioned combination of plant extracts comprises the two extracts, with a high degree of standardization. Preferably the plant extracts present in the supplement of the invention are obtained by extraction with supercritical carbon dioxide. In a preferred aspect of the invention, the combination of plant extracts of the present supplement is a combination of standardized botanical extracts of ginger and Acmella oleracea, originally in oil form, formulated in powder form by addition of lecithin, e.g. sunflower lecithin.
In a preferred aspect of the invention, the coenzyme Q10 is in the form of a phytosomal preparation, wherein the coenzyme Q10 is in the form of a complex with
lecithin, for example sunflower lecithin, to form a solid dispersion of the active ingredient in a lecithin matrix.
In another aspect of the invention, the combination of plant extracts and/or the phytosomal preparation further comprise food grade excipients, selected for example from maltodextrin, silica dioxide, cellulose and derivatives thereof, such as hydroxypropylcellulose, hydroxypropylmethylcellulose and microcrystalline cellulose, and mixtures thereof.
In this supplement, the above-mentioned combination of plant extracts may be present for example in amount comprised between 50 mg and 1000 mg per dosage unit; preferably in amount equal to about 350 mg. The amount of coenzyme Q10 in this supplement may for example be comprised between about 10 mg and about 200 mg per dosage unit, and between about 10 mg and about 1000 mg per dosage unit when the coenzyme Q10 is present in the supplement in the form of a phytosomal preparation. According to a preferred embodiment of this supplement, it comprises about 150 mg per dosage unit of a phytosomal preparation of coenzyme Q10.
The supplement of the invention may comprise, for example, as a combination of the plant extracts mentioned above, a product having the following composition shown in Table 1 for a 350 mg unit dosage form, like in the commercial product known as Mitidol®. Table 1
The supplement of the invention may comprise, for example, as a phytosomal preparation of coenzyme Q10 standardized to 18-22% for a 150 mg unit dosage form,
a product having the following composition shown in Table 2 and obtainable using ethyl acetate as a solvent, like in the commercial product known as Ubiqsome®.
“Vitamins of group B” according to the invention preferably means the vitamins selected from the group consisting of vitamin B1 or thiamine, vitamin B6 or pyridoxine, vitamin B12 or cyanocobalamin, and mixtures thereof. In one aspect of the invention, the supplement comprises more vitamins of group B, preferably a mixture of vitamin B1, vitamin B6 and vitamin B12. In the supplement of the present invention, vitamin B1 may be present for example in amount from about 0.50 to about 12.5 mg, vitamin B6 in amount from about 0.7 to about 5 mg and vitamin B12 in amount from about 1.25 mg to about 500 mg, independently of each other.
In a particularly preferred embodiment of this invention, the supplement comprises, per dosage unit, about 350 mg of the combination of plant extracts, about 150 mg of coenzyme Q10, about 0.55 mg of vitamin B1, about 0.7 mg of vitamin B6 and about 1.25 mg of vitamin B12.
The components of the supplement according to the invention may be formulated according to conventional methods, such as those described for example in “Remington’s Pharmaceutical Handbook”, Mack Publishing Co., N.Y., USA.” In particular, the present supplement may be formulated according to conventional formulation techniques for lipophilic ingredients suitable for oral administration, mainly in the form of tablets, hard or soft gelatine capsules, cellulose capsules, dragees, and similar.
A process for the preparation of the supplement, comprising the steps of mixing the above-described combination of plant extracts with one or more vitamins of Group B and with the coenzyme Q10, and formation of the dosage units for oral administration, is part of the present invention. Optionally, this process comprises a preliminary step of formulating the combination of plant extracts and of the coenzyme Q10 in the form of a phytosomal preparation, prior to mixing.
As described in the experimental part below, the supplement of this invention has shown remarkable efficacy in reducing chronic pain in particular in certain diseases. It can be used alone, or administered to patients already receiving traditional medications for treating chronic pain such as opioids or even Cannabis medica. Particularly in patients already undergoing treatment with Cannabis medica, the supplement of this invention has made it possible to significantly reduce pain, allowing in some cases a reduction in the daily dose of cannabis and thus also the relative side effects.
The efficacy in reducing chronic pain shown by the present supplement has exceeded all expectations of the inventor starting from the knowledge of the individual components, whose anti-inflammatory activity has also been described and the use in pain management has been proposed.
The combination of the plants Zingiber and Acmella, known for their anti inflammatory and analgesic activity, was studied by the inventor in relation to their activity on the endocannabinoid system, testing it on patients responding to Cannabis Medica therapies, and combining it with the bioavailable Coenzyme Q10, known to reduce oxidative stress and inflammatory cytokines, and vitamins of Group B. Patients treated with Cannabis Medica in pain therapy had chronic diseases with a major neurodegenerative component. The combination of natural active ingredients with cannabis has proven to be more effective than traditional treatments. Without wishing to be bound by a theory, this could be linked to the completeness of the action of the painkiller with the supplement of this invention: anti-inflammatory, modulatory of the endocannabinoid system and neuroprotective.
The dietary supplement described above for use as an adjuvant in the therapeutic treatment of chronic pain, alone or in combination with one or more conventional pain-relieving drugs, in particular therapeutic cannabis, is also an object
of the present invention, as is a method for therapeutic treatment of chronic pain comprising administering an effective dose of the aforesaid supplement, alone or in combination with one or more conventional pain-relieving drugs, to a subject in need thereof. Such a supplement for use or method of treatment preferably comprises oral administration of the supplement, possibly combined with the administration of one or more of the above drugs.
As mentioned above, this supplement has no significant side effects (there were only a few cases of nausea in those taking Cannabis at high THC concentrations, at the time when the dosage of this conventional therapy had not yet been reduced, contrary to the recommendation given in the study described below, demonstrating the mechanism of action on the receptors of the endocannabinoid system of this supplement and the efficacy thereof). The present supplement therefore also helps in this sense to improve the conditions of the patient and increase his or her compliance with the therapy; it also reduces the administration of any conventional drugs which on the contrary have important side effects.
In addition, this supplement has also been shown to induce muscle relaxation, increased activation and greater energy in daily activities.
Another advantage of this supplement is its formulation based on natural products and plant extracts, which are, however, standardized and titrated for an exact and constant dosage in the final product.
The following experimental part is given by way of illustration and not limitation of the present invention.
Experimental part A pilot study was carried out in order to evaluate the efficacy of the supplement subject-matter of this invention as an adjuvant in the treatment of chronic pain, in subjects already being treated with conventional drugs for such therapy. In particular, the Study was aimed at assessing the influence of this supplement on the reduction of chronic pain and the improvement in quality of life, compared to therapy with the conventional painkiller alone.
The Study also aimed to demonstrate that taking the supplement of this invention
can enable the dosage of conventional medication to be reduced even in subjects who have been treated for some time with this drug therapy.
Study design, data management and ethical considerations This open-ended pilot Study lasted four weeks. The variables investigated were measured at baseline, and during periodic follow-up meetings held once a week during the 4 weeks of the Study, to highlight correlations and possible changes over time.
All subjects joined the Study on a voluntary basis after having given their free and informed written consent to join the Study and after having received the necessary and due explanations as well as a detailed and comprehensive description of the Study. Each subject was free to withdraw their consent to participate in the Study at any time.
All data collected has been handled with the utmost attention to the protection of privacy, in accordance with current legal provisions, and has been stored with the help of Excel platforms. Patients' names were anonymised through the automatic generation of a code on the basis of the origin and sequence number. The Study was carried out in compliance with and according to the basic principles, guiding principles and supplementary guidelines of the 6th and final 2008 version of the Declaration of Helsinki of 1975. The opinion of the relevant Ethics Committee has also been sought.
Enrolment and inclusion/exclusion criteria The procedures for enrolling the volunteers in the Study took place at the
POLIPAIN CLINIC Pain Therapy Clinic in Cascina, Pisa, Italy.
The existence of the following criteria for inclusion in the Study were ascertained for each subject recruited:
-presence of chronic pain; -use of pain-relieving drugs of the conventional pharmacopoeia, for at least 3 months, without achieving full efficacy;
-ability to fully and consciously understand the research process and sufficient ability to provide informed consent; and the absence of the following exclusion criteria: -presence of organic or psychiatric disorders that might interfere with the ability to judge and understand;
-presence of pain for less than 3 months;
-patients with an allergy to the ingredients of the dietary supplement of the invention;
-pregnant or breast-feeding patients;
-patients with arrhythmia or ischaemic heart disease.
Materials and Methods Population in the Study
The Study population consisted of 48 subjects (mean age = 58.56 years), of which 10 males (22.91% of the total population) and 38 females (79.16% of the total population), all under treatment with Cannabis medica for chronic pain of different types: 4 subjects (8.3%) were suffering from headaches and migraines, 9 subjects (18.7%) were suffering from Central Nervous System disorders, 26 subjects (54.1%) were suffering from fibromyalgia, and 9 subjects (18.7%) from neuropathic pain.
Study outcome Physiological variables
The main physiological variables measured within the Study were:
-the intensity of the pain;
-the presence/absence of a range of benefits (reduction/disappearance of pain, muscle relaxation, mental relaxation, increased activation, improved quality of sleep, overall improvement in quality of life); and
-the presence/absence of a range of side effects (lack of concentration, mental blankness/disorientation; tachycardia, dry mouth, drowsiness, multiple side effects, increased appetite, hyperactivity/agitation).
Psychological variables
The main psychological variables measured within the Study were:
-clinical characteristics of pain (Italian Pain Questionnaire, QUID);
-psychological variables comprise symptoms of anxiety and depressive psychopathology as measured by the Hospital Anxiety and Depression Scale (HADS);
- pain intensity is measured with the Visual Analogue Scale (VAS).
Discussion of the results of the Study
At the end of the 4 weeks of data collection, the evaluation was carried out:
Primary Endpoints:
-Pain intensity (VAS scale); and
-Type and quality of pain (Italian Pain Questionnaire, QUID); and
Secondary Endpoints:
-Anxiety and depression (HADS scale).
25 subjects reported a decrease in pain with an average of 0.46 Dvasl in the first 10 days; an average of 0.66 Dvas2 after 20 days and 0.96 Dvas3 after 30 days showing a decrease in pain after about 30 days of treatment.
Of these 25 subjects, 13 perceived a decrease in pain at the level of the sensory component, which supports the hypothesis of a real effect of the supplement of this invention on pain. 9 subjects perceived an improvement in the affective component of pain; and 10 subjects in the evaluative component. The latter two values indicate the level of perceived tolerability, which is also related to the mood.
Of the 25 subjects who reported a decrease in pain, only 7 made changes in the Cannabis dosage; 2 subjects decreased the THC dosages and increased the CBD dosages, whereas 5 subjects decreased the CBD dosages and increased the THC dosages.
The decrease in pain referred to the diseases they were suffering from was as follows:
-2 subjects with migraine reported a decrease in pain intensity by 50%;
-5 subjects with Central Nervous System diseases (myelitis, multiple sclerosis, SLA) perceived a 55.5% decrease in pain;
-13 subjects suffering from rheumatological and autoimmune diseases experienced a 50% decrease in pain;
-5 subjects with neuropathic pain perceived a decrease in pain of 55.5%.
23 subjects reported no change in pain perception. Of them, 3 patients dropped out of the Study in the first 20 days due to poor adherence to therapy; 3 patients dropped out of the Study due to nausea; and 1 patient dropped out of the Study due to worsening of underlying symptoms. Figure 3 shows the schematic representation of these drop-outs and their reasons. There was no correlation between psychological factors related to anxiety and depression and drop-out from treatment. None of the
patients who decided to drop out of the Study had anxiety and/or depressive symptoms.
Of the 16 subjects who did not perceive a decrease in pain, but continued till the end of the 30-day treatment period, 4 subjects still perceived other benefits, such as muscle relaxation, increased activation, and greater energy in daily activities. Conclusions
The index of 0.96 Dvas3 after only 30 days of treatment is suggestive of the validity of using this supplement in patients suffering from chronic pain.
Of the 41 subjects who completed the Study, 60.97% showed an improvement in their pain symptoms. The verified synergy among the components of this supplement is supported by the percentage data obtained which lead the inventor to believe that the combination of active ingredients in this supplement may lead to further benefits in relieving chronic pain in the medium/long term.
In addition, interactions between Cannabis medica and the supplement of this invention are demonstrated by a variation, in some of the subjects of the Study, in the dosage of the active ingredients of the Cannabis, while using the supplement.
The present invention has been described herein with reference to a preferred embodiment. It is to be understood that there may be other embodiments that relate to the same inventive nucleus, all falling within the scope of protection of the claims provided below.
Claims
1. A dietary supplement comprising: a combination of plant extracts of Zingiber officinale and Acmella Oleracea, coenzyme Q10, and one or more vitamins of group B.
2. The supplement according to claim 1, wherein said plant extracts are standardized in the form of a solid dispersion of the oil extracts in lecithin.
3. The supplement according to claims 1 or 2, wherein said coenzyme Q10 is in the form of a phytosomal preparation, in the form of a complex with lecithin.
4. The supplement according to any one of the preceding claims, wherein said vitamins of group B are selected from the group consisting of vitamin B1 (thiamine), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin), and mixtures thereof.
5. The supplement according to any one of the preceding claims, further comprising food grade excipients, selected for example from among maltodextrin, silica dioxide, cellulose and derivatives thereof, such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose and microcrystalline cellulose, and mixtures thereof.
6. The supplement according to any one of the preceding claims, comprising said combination of plant extracts in amount comprised between 50 mg and 1000 mg per dosage unit; preferably in amount equal to 350 mg; said coenzyme Q10 in amount comprised between 10 mg and 200 mg per dosage unit, and one or more vitamins of Group B selected from Vitamin B1 in amount comprised between 0.50 mg and 12.5 mg, Vitamin B6 in amount comprised between 0.7 mg and 5 mg, and Vitamin B12 in amount comprised between 1.25 mg and 500 m9·
7. The supplement according to any one of the preceding claims, in a form suitable for oral administration selected from tablets, pills, lozenges, capsules, dragees, and similar.
8. A process for the preparation of a dietary supplement as defined in any one of the claims 1-7, comprising a step of mixing of all ingredients until a homogeneous mixture is obtained.
9. The process according to claim 8, wherein said step of mixing is followed by a step of formulation of the mixture to obtain single dosage units suitable for oral administration.
10. A dietary supplement as defined in any one of claims 1-7 for the use as adjuvant in the therapeutic treatment of chronic pain in a subject in need thereof.
11. The supplement for use according to claim 10, wherein said subject is subjected to a concomitant therapeutic treatment with one or more drugs for the treatment of chronic pain.
12. The supplement for use according to claim 10 or 11, wherein said subject is treated with Cannabis medica.
13. The supplement for use according to any one of claims 10-12, which is orally administered to said subject.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT102021000004682A IT202100004682A1 (en) | 2021-03-01 | 2021-03-01 | FOOD SUPPLEMENT USEFUL AS AN ADJUVANT IN THE TREATMENT OF CHRONIC PAIN |
IT102021000004682 | 2021-03-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022185159A1 true WO2022185159A1 (en) | 2022-09-09 |
Family
ID=75769930
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2022/051633 WO2022185159A1 (en) | 2021-03-01 | 2022-02-24 | Dietary supplement useful as an adjuvant in the treatment of chronic pain |
Country Status (2)
Country | Link |
---|---|
IT (1) | IT202100004682A1 (en) |
WO (1) | WO2022185159A1 (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190151396A1 (en) * | 2016-06-29 | 2019-05-23 | Indena S.P.A. | Compositions useful in the prevention and/or treatment of osteoarticular inflammation and pain and cartilage damage |
US20190209491A1 (en) * | 2018-01-10 | 2019-07-11 | Robert Firger | Compositions of ketogenic sources, micronutrients and phytochemicals for prophylaxis and mitigation of migraine headache |
-
2021
- 2021-03-01 IT IT102021000004682A patent/IT202100004682A1/en unknown
-
2022
- 2022-02-24 WO PCT/IB2022/051633 patent/WO2022185159A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20190151396A1 (en) * | 2016-06-29 | 2019-05-23 | Indena S.P.A. | Compositions useful in the prevention and/or treatment of osteoarticular inflammation and pain and cartilage damage |
US20190209491A1 (en) * | 2018-01-10 | 2019-07-11 | Robert Firger | Compositions of ketogenic sources, micronutrients and phytochemicals for prophylaxis and mitigation of migraine headache |
Non-Patent Citations (2)
Title |
---|
ANONYMUS: "Mitidol Zingiber and Acmella standardized extracts combination", 6 January 2020 (2020-01-06), pages 1 - 1, XP055861610, Retrieved from the Internet <URL:https://www.indena.com/indena_files/2019/12/mitidol_ss_int-1.pdf> [retrieved on 20211115] * |
RONDANELLI MARIANGELA ET AL: "Acmella oleracea for pain management", FITOTERAPIA, IDB HOLDING, MILAN, IT, vol. 140, 6 November 2019 (2019-11-06), XP085964976, ISSN: 0367-326X, [retrieved on 20191106], DOI: 10.1016/J.FITOTE.2019.104419 * |
Also Published As
Publication number | Publication date |
---|---|
IT202100004682A1 (en) | 2022-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zhu et al. | A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer's disease: A pilot study | |
ES2681996B2 (en) | COMPOSITIONS TO REDUCE APPETITE AND ANSIA, STRENGTHEN SATIETY, IMPROVE MOOD AND REDUCE STRESS. | |
MX2013001298A (en) | Use of salvia miltiorrhiza composition in preparing drugs for secondary prevention of coronary heart disease. | |
Bernstein et al. | Evaluation of the clinical efficacy and safety of grapeseed extract in the treatment of fall seasonal allergic rhinitis: a pilot study | |
US9375463B2 (en) | Compositions and methods for improving sleep using a nutraceutical formulation | |
Hauner et al. | Efficacy and safety of cathine (nor-pseudoephedrine) in the treatment of obesity: a randomized dose-finding study | |
WO2019185439A1 (en) | Natural base composition for use in the treatment of chronical stress characterized by mood and/or anxiety disorders | |
Hesami et al. | Randomized, double-blind, placebo-controlled clinical trial studying the effects of Turmeric in combination with mefenamic acid in patients with primary dysmenorrhoea | |
Inoue et al. | Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized, double-blind, placebo-controlled study | |
Kunugi | Depression and lifestyle: Focusing on nutrition, exercise, and their possible relevance to molecular mechanisms | |
Bellanger et al. | Safety of complementary and alternative medicine treatments and practices | |
WO2022185159A1 (en) | Dietary supplement useful as an adjuvant in the treatment of chronic pain | |
US20240016875A1 (en) | Shan-zha for the treatment of depression and anxiety disorders | |
US10568920B2 (en) | Pharmaceutical compositions containing cannabis, uses thereof and methods for improving energy levels and/or alleviating fatigue | |
Hussein | A closer look at the risks vs. benefits of kava (Piper methysticum) | |
Ayati et al. | Advances in treatment of mild cognitive impairment (MCI) and dementia: A review of promising non-pharmaceutical modalities | |
US20220160808A1 (en) | Anti-Psychotic Composition and Treatment Methods | |
Jain | Study of Herbal Drugs for the treatment of Sexual Dysfunction | |
US20200246414A1 (en) | Compositions and methods for the treatment of constipation and other ailments of the gastrointestinal system | |
US20210379134A1 (en) | Synergistic herbal composition for sexual disorders | |
Gruner et al. | Stress and fatigue | |
Diamond et al. | Complementary, alternative, and integrative medicine in the treatment and management of dementia | |
EP3485894A1 (en) | Combination of officinal plants and their use in the treatment and/or prevention of sleep disorders | |
WO2022027122A1 (en) | Compositions with cannabinoids of cannabis sativa for treating erectile and sexual dysfunction | |
Saifi | Motor Neurone Disease: Treatment by Modern and Conventional Medicines |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22710440 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 22710440 Country of ref document: EP Kind code of ref document: A1 |