WO2000061154A1 - Composition, containing sublimed sulphur, for altering plasma homodyst(e) levels in humans - Google Patents
Composition, containing sublimed sulphur, for altering plasma homodyst(e) levels in humans Download PDFInfo
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- WO2000061154A1 WO2000061154A1 PCT/CA1999/000892 CA9900892W WO0061154A1 WO 2000061154 A1 WO2000061154 A1 WO 2000061154A1 CA 9900892 W CA9900892 W CA 9900892W WO 0061154 A1 WO0061154 A1 WO 0061154A1
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- Prior art keywords
- atherosclerosis
- plasma homocysteine
- sublimed sulfur
- levels
- basal
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 29
- 239000000203 mixture Substances 0.000 title description 2
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims abstract description 27
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 claims abstract description 20
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960000304 folic acid Drugs 0.000 claims abstract description 10
- 235000019152 folic acid Nutrition 0.000 claims abstract description 10
- 239000011724 folic acid Substances 0.000 claims abstract description 10
- 229930003779 Vitamin B12 Natural products 0.000 claims abstract description 9
- 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 abstract description 9
- 235000019163 vitamin B12 Nutrition 0.000 claims abstract description 9
- 239000011715 vitamin B12 Substances 0.000 claims abstract description 9
- 206010003178 Arterial thrombosis Diseases 0.000 claims abstract description 5
- 230000007214 atherothrombosis Effects 0.000 claims abstract description 5
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 14
- 229940011671 vitamin b6 Drugs 0.000 claims description 7
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 claims description 4
- 235000019158 vitamin B6 Nutrition 0.000 claims description 4
- 239000011726 vitamin B6 Substances 0.000 claims description 4
- 206010047249 Venous thrombosis Diseases 0.000 claims description 3
- 201000006408 generalized atherosclerosis Diseases 0.000 claims description 3
- 208000003532 hypothyroidism Diseases 0.000 claims description 3
- 230000002989 hypothyroidism Effects 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 208000031845 Pernicious anaemia Diseases 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
- 208000022831 chronic renal failure syndrome Diseases 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 7
- 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 6
- 206010056677 Nerve degeneration Diseases 0.000 claims 3
- 235000000639 cyanocobalamin Nutrition 0.000 claims 3
- 239000011666 cyanocobalamin Substances 0.000 claims 3
- 229960002104 cyanocobalamin Drugs 0.000 claims 3
- 235000008160 pyridoxine Nutrition 0.000 claims 3
- 239000011677 pyridoxine Substances 0.000 claims 3
- 206010028980 Neoplasm Diseases 0.000 claims 2
- 208000010378 Pulmonary Embolism Diseases 0.000 claims 2
- 230000003143 atherosclerotic effect Effects 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 230000000306 recurrent effect Effects 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 claims 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 208000014882 Carotid artery disease Diseases 0.000 claims 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 1
- 208000002249 Diabetes Complications Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 208000005189 Embolism Diseases 0.000 claims 1
- 201000005569 Gout Diseases 0.000 claims 1
- 208000033463 Ischaemic neuropathy Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010034576 Peripheral ischaemia Diseases 0.000 claims 1
- 201000004681 Psoriasis Diseases 0.000 claims 1
- 201000004239 Secondary hypertension Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 208000001435 Thromboembolism Diseases 0.000 claims 1
- 208000032109 Transient ischaemic attack Diseases 0.000 claims 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims 1
- 230000032683 aging Effects 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 208000037876 carotid Atherosclerosis Diseases 0.000 claims 1
- 201000002676 cerebral atherosclerosis Diseases 0.000 claims 1
- 201000004559 cerebral degeneration Diseases 0.000 claims 1
- 208000029078 coronary artery disease Diseases 0.000 claims 1
- 208000026758 coronary atherosclerosis Diseases 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 230000007423 decrease Effects 0.000 claims 1
- 235000013305 food Nutrition 0.000 claims 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 230000009245 menopause Effects 0.000 claims 1
- 208000031225 myocardial ischemia Diseases 0.000 claims 1
- 201000009925 nephrosclerosis Diseases 0.000 claims 1
- 208000015122 neurodegenerative disease Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000010875 transient cerebral ischemia Diseases 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 abstract description 5
- 230000000694 effects Effects 0.000 abstract description 4
- 210000003743 erythrocyte Anatomy 0.000 abstract description 4
- 238000013101 initial test Methods 0.000 abstract description 4
- 210000002966 serum Anatomy 0.000 abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 150000002632 lipids Chemical class 0.000 abstract description 2
- 206010048707 Homocystinaemia Diseases 0.000 abstract 1
- 201000010538 Lactose Intolerance Diseases 0.000 abstract 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 201000009030 Carcinoma Diseases 0.000 description 2
- 208000034991 Hiatal Hernia Diseases 0.000 description 2
- 206010020028 Hiatus hernia Diseases 0.000 description 2
- 208000033892 Hyperhomocysteinemia Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 230000003225 hyperhomocysteinemia Effects 0.000 description 2
- 102000011848 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Human genes 0.000 description 1
- 108010075604 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
- 102100034976 Cystathionine beta-synthase Human genes 0.000 description 1
- 108010073644 Cystathionine beta-synthase Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 208000027771 Obstructive airways disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 235000021152 breakfast Nutrition 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229940037395 electrolytes Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/04—Sulfur, selenium or tellurium; Compounds thereof
Definitions
- Elevated plasma homocysteine concentrations have been reported in chronic renal failure, 14"15 hypothyroidism, pernicious anemia, 16 advancing age and several types of carcinoma, including breast, ovarian and pancreatic, 17 and in deficiencies of vitamin B12, folic acid, 18"19 vitamin B6, 20 methionine synthase
- Elemental sulfur an integral component of the sulfur-containing essential ammo acids and sulfur-containing enzymes, was considered to be a possible
- pecto s peripheral vascular disease
- coronary angioplasty diabetes mellitus
- hyperlipidemia hypothyroidism
- past history of carcinoma hiatus hernia, osteoarthritis and osteoporosis
- depression obstructive airways disease
- bronchial asthma essential tremour
- hiatus hernia and the postmenopausal
- erythrocyte folic acid and serum levels of vitamin B12 and lipids The subjects did not receive betaine, vitamin B12, folic acid and vitamin B6 during the course of the study.
- Sublimed Sulfur varied according to the initial basal plasma homocysteine concentration; low basal plasma homocysteine levels generally increased and high basal plasma homocysteine levels usually decreased after completion of
- Sublimed Sulfur is an effective treatment for the alteration of plasma homocysteine in medical conditions associated with abnormal plasma homocysteine levels.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Plasma homocysteine values > 10.2νmol per litre are associated with an increased risk of atherothrombosis, but normal values are considered to be 4 to 15 νmol per litre. An initial test subject with Hyper-homocystinemia and lactose intolerance was treated with Sublimed Sulfur 300 mg orally twice daily for 45 days. An additional 46 randomly selected subjects were treated with Sublimed Sulfur 200 mg orally daily for 30 days. Basal control plasma homocysteine, erythrocyte folic acid and serum vitamin B12 and lipids were compared with follow-up results obtained 24 hours and 30 days after discontinuation of Sublimed Sulfur. In the initial test subject, basal plasma homocysteine of 77 νmol per litre decreased by 95.7 percent. In the 46 patients, the effect of Sublimed Sulfur varied according to the initial basal plasma homocysteine concentration; basal levels of 2.3 to 7 νmol per litre increased by 58.5 percent (p < 0.001) 24 hours after discontinuation of treatment, and by 85.4 percent 30 days later; basal levels of 7.1 to 9.9 νmol per litre showed no consistent changes, and basal levels of 9.9 to 22.1 νmol per litre decreased to 63.9 percent (p < 0.005) of basal levels 24 hours after discontinuation of Sublimed Sulfur, and to 70.7 percent of basal levels 30 days later. Sublimed Sulfur therapy eliminated the initial plasma homocysteine differences between low, intermediate and high basal levels. Sublimed Sulfur therapy normalized plasma homocysteine by causing a regression towards the mean of basal plasma homocysteine levels.
Description
COMPOSITION, CONTAINING SUBLIMED SULPHUR, FOR ALTERING PLASMA HOMODYST(E) LEVELS IN HUMANS
DESCRIPTION
Background Hyper-homocysteinemia is a risk factor for venous thrombosis
and atherothrombosis of the coronary, carotid, cerebral, central and peripheral arteries 1"13 Elevated plasma homocysteine concentrations have been reported in chronic renal failure,14"15 hypothyroidism, pernicious anemia,16 advancing age and several types of carcinoma, including breast, ovarian and pancreatic,17 and in deficiencies of vitamin B12, folic acid,18"19 vitamin B6,20 methionine synthase
and cystathionine-Beta-synthase 21 The complications due to atherothrombosis are reported to be associated with plasma homocysteine concentrations > 10.2
μmol per litre22 but the normal laboratory values are considered to be 4 to 15
μmol per litre.23 The apparent contradiction between plasma homocysteine
concentrations reported to be normal and the values associated with an increased risk of atherothrombosis suggested that one or more additional factors
may be necessary for alteration of plasma homocysteine concentrations
Elemental sulfur, an integral component of the sulfur-containing essential ammo acids and sulfur-containing enzymes, was considered to be a possible
necessary factor, and a clinical study was undertaken to determine the effect of
orally administered elemental Sulfur on the Sulfur -containing essential ammo
acid, homocysteine Orally administered Sublimed Sulfur USP, and also precipitated sulfur, has been mixed with molasses and used as a laxative 24'26
Methods An initial test subject with hyper-homocysteinemia of 77 μmol per
litre was treated with Sublimed Sulfur. An additional 46 subjects, 31 men and 15 women were randomly selected. The subjects had single or multiple diagnoses of generalized atherosclerosis, hypertension, myocardial infarction, angina
pecto s, peripheral vascular disease, coronary angioplasty, diabetes mellitus, hyperlipidemia, hypothyroidism, past history of carcinoma, hiatus hernia, osteoarthritis and osteoporosis, depression, obstructive airways disease, bronchial asthma, essential tremour, hiatus hernia and the postmenopausal
state. A 30 day course of Sublimed Sulfur 200 mg, 1 capsule orally pc breakfast daily, was added to existing medical therapy which was continued unchanged for
the duration of the study. Each subject's basal plasma homocysteine was compared with results obtained 24 hours and 30 days after discontinuation of Sublimed Sulfur. Basal and follow-up comparisons were also made for
erythrocyte folic acid and serum levels of vitamin B12 and lipids. The subjects did not receive betaine, vitamin B12, folic acid and vitamin B6 during the course of the study.
The Wilcoxon T test was used to evaluate the quantitative data. Numerical
values indicate the mean and standard error of the mean.
Results The initial test subject's basal plasma homocysteine of 77 μmol per litre
decreased by 95.7 percent. In the 46 additional subjects, the effect of the
Sublimed Sulfur varied according to the initial basal plasma homocysteine concentration; low basal plasma homocysteine levels generally increased and
high basal plasma homocysteine levels usually decreased after completion of
the 30 day course of Sublimed Sulfur; basal levels of 2.3 to 7 μmol per litre
(N=15) increased by 58.5 percent (P<0.001 ) 24 hours after discontinuation of
treatment, and by 85.4 percent 30 days later; basal levels of 7.1 to 9.9 μmol per
litre (N=15) showed no consistent changes, and the basal levels of 9.9 to 22J
μmol per litre (N= 16) decreased to 63.9 percent (P <0.005) 24 hours after
discontinuation of Sublimed Sulfur, and to 70.7 percent of basal levels 30 days later.
There were no adverse effects on the pulse rate and rhythm, blood pressure and electrocardiograms. There were no significant changes of the complete blood count, urinalysis, erythrocyte folic acid and serum levels of vitamin B12, creatinine, electrolytes, uric acid, glucose, aspartate transaminase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and calculated levels of low-density lipoprotein cholesterol and total cholesterol/high-density
lipoprotein cholesterol ratio. There were no reports of adverse effects by the subjects.
Conclusions Sublimed Sulfur therapy caused a regression towards the mean of basal plasma homocysteine levels and normalized plasma homocysteine to
between 7.5 and 8.5 μmol per litre in subjects with normal levels of erythrocyte
folic acid and serum vitamin B12. Sublimed Sulfur is an effective treatment for the alteration of plasma homocysteine in medical conditions associated with abnormal plasma homocysteine levels.
References
1. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J. Pathol 1969;56:111-28.
2. McCully KS. Homocysteine and vascular disease. Nat Med 1996;2:386-9.
3. Ueland PM, Refsum H, Brattstrom L. Plasma homocysteine and cardiovascular disease. In: Francis RB Jr, ed. Atherosclerotic cardiovascular disease, hemostasis, and endothelial function. New York: Marcel Dekker, 1992:183-236.
4. Stampfer MJ, Malinow MR. Can lowering homocysteine levels reduce cardiovascular risk? N Engl J Med 1995; 332:328-9.
5. Boers GHJ, Smals AGH, Trijbels FJM, et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. N Engl J Med 1985;313:709-15.
6. Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991 ;324:1149-55.
7. Malinow MR. Hyperhomocyst(e)inemia: a common and easily reversible risk factor of occlusive atherosclerosis. Circulation 1990;81:2004-6.
8. Kang SS, Wong PWK, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annu Rev Nutr 1992;12:279-98.
9. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57.
10. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27.
11. Duell PB, Malinow MR. Plasma homocyst(e)ine: an important risk factor for atherosclerosis vascular disease. Curr Opin Lipidol 1997;8:28-34.
12. Malinow MR, Kang SS, Taylor LM, et al. Prevalence of hyperhomocyt(e)inemia in patients with peripheral arterial occlusive disease. Circulation 1989;79:1180-8.
13. Malinow MR, Sexton G, Averbuch M, Grossman M, Wilson D, Upson B. Homocyst(e)inemia in daily practice: levels in coronary heart disease. Coronary Artery Dis 1990;1 :215-20.
14. Wilcken DE, Gupta VJ. Sulphur containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixed disulphide. Eur J Clin Invest 1979;9:301-7.
References
15. Chauveau P, Chadefaux B, Coύde M, et al. Hyperhomocysteinemia, a risk factor for atherosclerosis in chronic uremic patients. Kidney Int Suppl 1993;41 :S72-S77.
16. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinants for diagnosing cobalamin and folate deficiencies. Am J Med 1994;96:239-46.
17. Mayer EL, Jacobsen DW, Robinson K. Homocysteine and coronary atherosclerosis. J Am Coll Cardiol 1996;27:517-27.
18. Brattstrom LE, Israelsson B, Jeppsson JO, Hultberg BL. Folic acid an innocuous means to reduce plasma homocysteine. Scand J Clin Laboratory Invest 1988;48:215- 21.
19. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyt(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009-15.
20. Saltzman E, Mason JB, Jacques PF, et al. B vitamin supplementation lowers homocysteine levels in heart disease. Clin Res 1994;42:172A. Abstract.
21. Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 7th ed. Vol. 1. New York: McGraw-Hill, 1995; 1279-327.
22. Ueland PM, Refsum H, Stabler SP, Malinow MR, Andersson A, Allen RH. Total homocysteine in plasma or serum: methods and clinical applications. Clin Chem 1993;39:1764-79.
23. Jacobsen DW, Gatautis VJ, Green R, et al. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clin Chem 1994;40:873- 81.
24. Cushny AR, Grollman A, Slaughter D. Pharmacology and Therapeutics. Thirteenth Edition. 1947;245.
25. Goodman L, Gilman A. The Pharmacological Basis of Therapeutics. Fifteenth Printing April 1947. 1941 ;870-71.
26. Gaddum JH, Parmacology. Fifth Edition, Oxford University Press. 1959;274.
Claims
1. A regimen of treatment with Sublimed Sulfur alters plasma homocysteine levels.
2. Treatment with Sublimed Sulfur as defined in claim 1 increases low levels of plasma homocysteine and decreases high levels of plasma homocysteine.
3. Treatment with Sublimed Sulfur as defined in claim 1 and claim 2 causes plasma homocysteine levels to be maintained within the normal range.
4. Sublimed Sulfur alters plasma homocysteine levels as defined in Claim 1 , Claim 2 and Claim 3 when administered together with: folic acid, folic acid and vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin) and folic acid, vitamin B12 (cyanocobalamin), folic acid and vitamin B6 (pyridoxine), multi-vitamins, and foods.
5. Treatment with Sublimed Sulfur as defined in claim 1 , claim 2, claim 3 and claim 4 normalizes plasma homocysteine concentrations in generalized atherosclerosis, accelerated atherosclerosis, atherothrombosis, coronary atherosclerosis, ischemic heart disease, angina pectoris, coronary thrombosis, myocardial infarction, atrial arrhythmias, ventricular arrhythmias, cardiac nerve degeneration due to atherosclerosis, carotid atherosclerosis, recurrent cerebral embolisation, cerebral atherosclerosis, transient ischemic attacks, stroke, atherosclerotic cerebral degeneration, peripheral atherosclerosis, peripheral ischemia, nerve degeneration due to atherosclerosis in peripheral ischemic neuropathy, hypertension secondary to generalized atherosclerosis, atherosclerotic complications of diabetes mellitus, nerve degeneration due to atherosclerosis in diabetic neuropathy, recurrent thromboembolism, deep vein thrombosis and pulmonary embolism, recurrent pulmonary embolism, venous thrombosis in cancer, gout,
Alzheimer's disease, nephrosclerosis, chronic renal failure, menopause, hypothyroidism, pernicious anemia, psoriasis, leukemias, cancer, breast cancer, ovarian cancer, pancreatic cancer, osteoporosis due to atherosclerosis, and the aging process due to atherosclerosis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU58447/99A AU5844799A (en) | 1999-04-08 | 1999-09-27 | Composition, containing sublimed sulphur, for altering plasma homodyst(e) levelsin humans |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12836099P | 1999-04-08 | 1999-04-08 | |
| CA 2265926 CA2265926C (en) | 1999-04-08 | 1999-04-08 | Method of altering plasma homocysteine levels in humans |
| CA2,265,926 | 1999-04-08 | ||
| US60/128,360 | 1999-04-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2000061154A1 true WO2000061154A1 (en) | 2000-10-19 |
Family
ID=25680849
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CA1999/000892 WO2000061154A1 (en) | 1999-04-08 | 1999-09-27 | Composition, containing sublimed sulphur, for altering plasma homodyst(e) levels in humans |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU5844799A (en) |
| WO (1) | WO2000061154A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1696938A1 (en) * | 2003-12-23 | 2006-09-06 | Abdalla Magd Ahmed Kotb | Element sulfur as an oral or parental medical product |
| EP2451299A4 (en) * | 2009-07-10 | 2012-12-19 | Iii Linzy O Scott | METHODS AND COMPOSITIONS FOR TREATING THYROID MEDICAL DISEASES USING REDUCED FOLASES |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2228470A1 (en) * | 1973-05-09 | 1974-12-06 | Degemont Marguerite | Therapeutic compsn. contg. vitamin A, sulphur and live yeast - for treatment of disorders of the ear, nose and throat |
| US4976970A (en) * | 1989-02-24 | 1990-12-11 | Landy Wady N | Pharmaceutical composition and method for treatment of digestive disorders |
| EP0581972A1 (en) * | 1989-02-06 | 1994-02-09 | Verde, Giancarlo U. | Hemorrhoidal composition flaves of sulphur and cream of tartar |
| EP0615757A1 (en) * | 1993-03-18 | 1994-09-21 | Georges Serge Grimberg | New therapeutic composition having an immunostimulant effect |
-
1999
- 1999-09-27 AU AU58447/99A patent/AU5844799A/en not_active Abandoned
- 1999-09-27 WO PCT/CA1999/000892 patent/WO2000061154A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2228470A1 (en) * | 1973-05-09 | 1974-12-06 | Degemont Marguerite | Therapeutic compsn. contg. vitamin A, sulphur and live yeast - for treatment of disorders of the ear, nose and throat |
| EP0581972A1 (en) * | 1989-02-06 | 1994-02-09 | Verde, Giancarlo U. | Hemorrhoidal composition flaves of sulphur and cream of tartar |
| US4976970A (en) * | 1989-02-24 | 1990-12-11 | Landy Wady N | Pharmaceutical composition and method for treatment of digestive disorders |
| EP0615757A1 (en) * | 1993-03-18 | 1994-09-21 | Georges Serge Grimberg | New therapeutic composition having an immunostimulant effect |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1696938A1 (en) * | 2003-12-23 | 2006-09-06 | Abdalla Magd Ahmed Kotb | Element sulfur as an oral or parental medical product |
| EP2451299A4 (en) * | 2009-07-10 | 2012-12-19 | Iii Linzy O Scott | METHODS AND COMPOSITIONS FOR TREATING THYROID MEDICAL DISEASES USING REDUCED FOLASES |
| JP2012532891A (en) * | 2009-07-10 | 2012-12-20 | リンジー オー． ザ サード スコット， | Methods and compositions for treating thyroid-related medical conditions with reduced folic acid |
| US8575171B2 (en) | 2009-07-10 | 2013-11-05 | Linzy O. Scott, III | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
| AU2010271178B2 (en) * | 2009-07-10 | 2015-10-22 | Linzy O. Scott Iii | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
| US9248130B2 (en) | 2009-07-10 | 2016-02-02 | Linzy O. Scott, III | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
| IL256966B1 (en) * | 2009-07-10 | 2023-08-01 | O Scott Linzy Iii | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
| IL256966B2 (en) * | 2009-07-10 | 2023-12-01 | O Scott Linzy Iii | Methods and compositions for treating thyroid-related medical conditions with reduced folates |
Also Published As
| Publication number | Publication date |
|---|---|
| AU5844799A (en) | 2000-11-14 |
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