US20210121430A1 - Omega-3 fatty acid supplementation for use in treating dry eye - Google Patents
Omega-3 fatty acid supplementation for use in treating dry eye Download PDFInfo
- Publication number
- US20210121430A1 US20210121430A1 US17/077,463 US202017077463A US2021121430A1 US 20210121430 A1 US20210121430 A1 US 20210121430A1 US 202017077463 A US202017077463 A US 202017077463A US 2021121430 A1 US2021121430 A1 US 2021121430A1
- Authority
- US
- United States
- Prior art keywords
- composition
- omega
- mammal
- fatty acids
- tear
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 235000020660 omega-3 fatty acid Nutrition 0.000 title claims abstract description 208
- 229940012843 omega-3 fatty acid Drugs 0.000 title claims abstract description 113
- 208000003556 Dry Eye Syndromes Diseases 0.000 title claims abstract description 68
- 206010013774 Dry eye Diseases 0.000 title claims abstract description 66
- 230000009469 supplementation Effects 0.000 title description 3
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 224
- 239000006014 omega-3 oil Substances 0.000 claims abstract description 111
- 210000004175 meibomian gland Anatomy 0.000 claims abstract description 80
- 241000124008 Mammalia Species 0.000 claims abstract description 62
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 claims abstract description 60
- 235000020673 eicosapentaenoic acid Nutrition 0.000 claims abstract description 59
- 229960005135 eicosapentaenoic acid Drugs 0.000 claims abstract description 59
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 46
- 125000005457 triglyceride group Chemical group 0.000 claims abstract description 35
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 32
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 27
- 230000006872 improvement Effects 0.000 claims abstract description 13
- 230000009467 reduction Effects 0.000 claims abstract description 8
- 239000000463 material Substances 0.000 claims abstract description 7
- 235000020665 omega-6 fatty acid Nutrition 0.000 claims abstract description 6
- 229940033080 omega-6 fatty acid Drugs 0.000 claims abstract description 6
- 238000005259 measurement Methods 0.000 claims abstract 36
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims description 52
- 235000020669 docosahexaenoic acid Nutrition 0.000 claims description 44
- 230000001965 increasing effect Effects 0.000 claims description 29
- 229940090949 docosahexaenoic acid Drugs 0.000 claims description 26
- 230000003247 decreasing effect Effects 0.000 claims description 22
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 claims description 18
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 claims description 18
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 claims description 18
- 230000007423 decrease Effects 0.000 abstract description 19
- 235000015872 dietary supplement Nutrition 0.000 description 54
- 208000024891 symptom Diseases 0.000 description 36
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 22
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 20
- 208000010217 blepharitis Diseases 0.000 description 17
- 210000001508 eye Anatomy 0.000 description 17
- 210000004369 blood Anatomy 0.000 description 16
- 239000008280 blood Substances 0.000 description 16
- 238000003287 bathing Methods 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 230000010534 mechanism of action Effects 0.000 description 15
- 206010065062 Meibomian gland dysfunction Diseases 0.000 description 14
- 229930003316 Vitamin D Natural products 0.000 description 12
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 12
- 235000019166 vitamin D Nutrition 0.000 description 12
- 239000011710 vitamin D Substances 0.000 description 12
- 150000003710 vitamin D derivatives Chemical class 0.000 description 12
- 229940046008 vitamin d Drugs 0.000 description 12
- 206010027137 Meibomianitis Diseases 0.000 description 11
- 230000004054 inflammatory process Effects 0.000 description 11
- 150000002632 lipids Chemical class 0.000 description 11
- 206010061218 Inflammation Diseases 0.000 description 10
- 235000021342 arachidonic acid Nutrition 0.000 description 10
- 229940114079 arachidonic acid Drugs 0.000 description 10
- 210000000744 eyelid Anatomy 0.000 description 10
- 230000006870 function Effects 0.000 description 8
- 230000008901 benefit Effects 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 210000003743 erythrocyte Anatomy 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- YUFFSWGQGVEMMI-JLNKQSITSA-N (7Z,10Z,13Z,16Z,19Z)-docosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCCC(O)=O YUFFSWGQGVEMMI-JLNKQSITSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 210000004087 cornea Anatomy 0.000 description 5
- 230000000378 dietary effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 150000004665 fatty acids Chemical group 0.000 description 5
- 235000016709 nutrition Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- 235000007882 dietary composition Nutrition 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 229930195729 fatty acid Natural products 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 210000004907 gland Anatomy 0.000 description 4
- 150000003180 prostaglandins Chemical class 0.000 description 4
- 238000010186 staining Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 3
- 235000021294 Docosapentaenoic acid Nutrition 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 230000001788 irregular Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 210000001732 sebaceous gland Anatomy 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- MJYQFWSXKFLTAY-OVEQLNGDSA-N (2r,3r)-2,3-bis[(4-hydroxy-3-methoxyphenyl)methyl]butane-1,4-diol;(2r,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O.C1=C(O)C(OC)=CC(C[C@@H](CO)[C@H](CO)CC=2C=C(OC)C(O)=CC=2)=C1 MJYQFWSXKFLTAY-OVEQLNGDSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 241000195493 Cryptophyta Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- OPGOLNDOMSBSCW-CLNHMMGSSA-N Fursultiamine hydrochloride Chemical compound Cl.C1CCOC1CSSC(\CCO)=C(/C)N(C=O)CC1=CN=C(C)N=C1N OPGOLNDOMSBSCW-CLNHMMGSSA-N 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004397 blinking Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 150000002066 eicosanoids Chemical class 0.000 description 2
- 230000003028 elevating effect Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 235000004426 flaxseed Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- JIWBIWFOSCKQMA-UHFFFAOYSA-N stearidonic acid Natural products CCC=CCC=CCC=CCC=CCCCCC(O)=O JIWBIWFOSCKQMA-UHFFFAOYSA-N 0.000 description 2
- 230000004489 tear production Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 241001474374 Blennius Species 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 241000238366 Cephalopoda Species 0.000 description 1
- 208000028006 Corneal injury Diseases 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 206010061842 Entropion Diseases 0.000 description 1
- 241000239366 Euphausiacea Species 0.000 description 1
- 208000020578 Eyelid movement disease Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 101000836150 Homo sapiens Transforming acidic coiled-coil-containing protein 3 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 206010052143 Ocular discomfort Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 208000023715 Ocular surface disease Diseases 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102100027048 Transforming acidic coiled-coil-containing protein 3 Human genes 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 101000942305 Zea mays Cytokinin dehydrogenase 1 Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000000607 artificial tear Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 230000005574 cross-species transmission Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 201000003079 ectropion Diseases 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 235000004626 essential fatty acids Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 229940013317 fish oils Drugs 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 231100001032 irritation of the eye Toxicity 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 235000021388 linseed oil Nutrition 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005461 lubrication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- -1 microgranules Substances 0.000 description 1
- 238000000199 molecular distillation Methods 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000011903 nutritional therapy Methods 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940127249 oral antibiotic Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000003904 phospholipids Chemical group 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 231100000719 pollutant Toxicity 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126703 systemic medication Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000004488 tear evaporation Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
- A61K31/232—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms having three or more double bonds, e.g. etretinate
-
- 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K31/593—9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/04—Artificial tears; Irrigation solutions
-
- 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
- This invention relates to methods for improving and enhancing the lipid layer of the tear and increasing tear breakup time by way of elevating the omega-3 index in patients suffering from symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction and, more specifically, to methods for administering a composition of omega-3 fatty acids to a patient having an inflamed meibomian gland so as to facilitate an increase in the amount of omega-3′s acting as an anti-inflammatory and, respectively, decrease the amount of omega-6′s acting as an inflammatory in the meibum composition, thereby normalizing the lipid layer of the tear and effectively reducing or eliminating the symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction.
- Dry eye is a condition in which there are insufficient tears to lubricate and nourish the eye. Tears are necessary for maintaining the health of the front surface of the eye and for providing clear vision. People with dry eyes either do not produce enough tears or have a poor quality of tears. With each blink of the eyelids, tears are spread across the cornea in order to provide lubrication, to wash away any foreign matter and to keep the surface of the eyes smooth and clear.
- Tears are produced by several glands in and around the eyelids. When the normal amount of tear production decreases or tears evaporate too quickly from the corneal surface, symptoms of dry eye can develop.
- tears are made up of oil, water and mucus. Each component serves a specified function in protecting and nourishing the front surface of the eye.
- a smooth oil layer helps to prevent evaporation of the water layer, while the mucin layer functions in spreading the tears evenly over the surface of the eye. If the tears evaporate too quickly or do not spread evenly over the cornea as a result of deficiencies with any of the three tear layers, symptoms of dry eye or posterior blepharitis may ensue.
- meibomian glands Along the margin of the eyelids are a series of small sebaceous glands called meibomian glands.
- the meibomian glands create and distribute a supply of meibum, an oily substance, that makes up the lipid layer of the tear.
- the supply of meibum functions to help keep the eye moist and tends to protect the tear film from evaporation.
- meibomian glands There are approximately twenty-five meibomian glands on the upper eyelids and twenty-five meibomian glands on the lower eyelids.
- Meibomianitis refers to inflammation or dysfunction of the meibomian glands which is also referred to in the art as meibomian gland dysfunction. Inflammation of the meibomian glands may occur because of the production of meibum which is pro-inflammatory in nature as a result of an increased composition of omega-6 essential fatty acids. Secondarily, bacteria have been found to invade the meibomian glands and colonize there. Once inflamed, the meibomian glands generally will not function in a manner sufficient to adequately produce the quantity and quality of oils necessary to properly lubricate the eye.
- the volume of oil produced from inflamed meibomian glands tends to decrease and the oils that are produced become thicker in composition, like toothpaste. These oils also become abnormal in their characteristics. Instead of spreading evenly across the aqueous layer, the oil coalesces leaving areas on the corneal surface in which the aqueous can evaporate and other areas in which the oil adheres to the cornea surface itself This creates a dry spot on the cornea for which the aqueous cannot penetrate. Such condition generally produces a foreign body sensation and if it persists may result in injury to the epithelium which is seen as corneal staining on examination. A reduction in oil production therefore inherently results in a quantitative decrease in the quality and quantity of the oily layer, thus causing tears to evaporate more rapidly.
- a person with inflamed meibomian glands may experience discomfort or problems with their eyes that may include, for example, but not by way of limitation: (1) dryness; (2) burning; (3) itching; (4) irritation and redness; (5) blurred vision; and/or (6) foreign body sensations.
- Some of the treatments for meibomianitis include: (1) the application of artificial tears; (2) cleaning the affected eyelid margins with a gentle baby shampoo; and (3) applying warm and moist compresses 5-10 minutes two to three times per day in an effort to promote normal eyelid glandular function.
- a physician may also prescribe a topical and/or oral antibiotic such as, for example, tetracycline, erythromycin, or doxycycline, to help eradicate the bacteria found in the glands and to facilitate a breakdown in the thickened lipid secretions from the meibomian glands.
- a mammal i.e., patient
- the composition consisting essentially of omega-3 fatty acids is administered in an effective amount sufficient to facilitate an increase in the resulting omega-3′s content of the treated meibomian glands, acting as an anti-inflammatory, and, respectively, in
- the present invention is directed to nutritional or dietary supplementation of a composition of omega-3 fatty acids for dry eye and methods for administering a composition of omega-3 fatty acids to a patient suffering from symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction or inflammation.
- composition of omega-3 fatty acids is administered in an amount formulated to change the composition of the oil (meibum) produced by meibomian glands from pro-inflammatory omega-6 to anti-inflammatory omega-3, whereby normalizing the oil production of the meibomian gland so as to improve or increase tear break up time, reduce tear osmolarity, and elevate the omega-3 index, thereby, consequently, eliminating or reducing the related symptoms of dry eye, posterior blepharitis or meibomianitis (meibomian gland dysfunction).
- the present invention provides for methods for treating and preventing dry eye associated with meibomian gland inflammation or dysfunction by way of administering a nutritional or dietary supplement composition comprising an effective amount of omega-3 fatty acids.
- the composition may include an effective amount of omega-3 fatty acids comprising a daily dosage that includes between about 600 mg and about 5,000 mg.
- the effective amount of omega-3′s may comprise the triglyceride or re-esterified triglyceride form.
- the effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA).
- EPA eicosapentaenoic acid
- the daily dosage of an effective amount of EPA may include an amount greater than 600 mg.
- the effective amount of omega-3 fatty acids may comprise an effective amount of docosahexaenoic acid (DHA).
- the daily dosage of an effective amount of DHA may include an amount greater than 500 mg.
- an effective amount of omega-3 fatty acids may be delivered in a daily dosage that includes between about 2,000 mg and about 3,000 mg.
- This effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA) and an effective amount of docosahexaenoic acid (DHA).
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the daily dosage of an effective amount of EPA may include an amount between about 1,600 mg and about 2,500 mg and the daily dosage of an effective amount of DHA may include an amount between about 500 mg and about 900 mg.
- omega-3 fatty acids may also be included in the administered composition. These additional omega-3 fatty acids may include a daily dosage amount of between about 400 mg and about 700 mg.
- the nutritional or dietary supplement composition of the present invention may include an effective amount of Vitamin D (as D3). Such effective amount of Vitamin D may comprise a daily dosage amount between about 500 IU and about 2,000 IU.
- the administration of the dietary or nutritional supplement composition of the present invention to effectively change the quality of the meibum composition of the meibomian glands may be delivered by means of softgel, tablet, liquids, granules, microgranules, powders, or any other delivery system deemed effective.
- composition of omega-3 fatty acids does not include any additional omega-6 fatty acids beyond the amount normally found in the source material of the omega-3 fatty acids, such as fish oil.
- the term “effective amount” includes the amount of omega-3 fatty acids in the triglyceride, esterified triglyceride or re-esterified triglyceride form which is capable of effectively changing the quality of the meibum concentration which has a direct correlation to improving the lipid layer of the tear, while eliminating or reducing the related symptoms of dry eye, posterior blepharitis and/or meibomianitis.
- the present invention provides for methods for treating and preventing dry eye associated with meibomian gland inflammation or dysfunction by way of administering a nutritional or dietary supplement composition comprising an effective amount of omega-3 fatty acids.
- the composition may include an effective amount of omega-3 fatty acids comprising a daily dosage that includes between about 600 mg and about 5,000 mg.
- This effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA).
- EPA eicosapentaenoic acid
- the daily dosage of an effective amount of EPA may include an amount greater than 600 mg.
- the effective amount of omega-3 fatty acids may comprise an effective amount of docosahexaenoic acid (DHA).
- the daily dosage of an effective amount of DHA may include an amount greater than 500 mg.
- the dietary or nutritional composition may include an effective amount of omega-3 fatty acids comprising a daily dosage including an effective amount between about 2,000 mg and about 3,000 mg.
- This effective amount of omega-3 fatty acids may be comprised of an effective amount of eicosapentaenoic acid (EPA) and an effective amount of docosahexaenoic acid (DHA).
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- the daily dosage of an effective amount of EPA may include an amount between about 1,600 mg and about 2,500 mg and the daily dosage of an effective amount DHA may include an amount between about 500 mg and about 900 mg.
- the dietary or nutritional supplement composition of the present invention includes omega-3 fatty acids that may comprise, for example, but not by way of limitation, the triglyceride form, re-esterified triglyceride concentrates, the ethyl ester form, the free fatty acid form, the phospholipids form, or any other suitable form sufficient to effectively change the quality of the meibum composition of the meibomian glands which has a direct correlation to improving the lipid layer of the tear, while eliminating or reducing the related symptoms of dry eye or meibomianitis. It is contemplated herein that the composition of the omega-3′s can be in a concentrated form, whereas up to 100% of the unit volume can be omega-3.
- the effective amount of eicosapentaenoic acid (EPA) and/or an effective amount of docosahexaenoic acid (DHA) included in the dietary or nutritional supplement of the present invention may be obtained from known sources, such as for example, and not by way of limitation, fish, algae, squid, yeast, and vegetable sources. It is further recognized that stearidonic acid is a precursor to EPA and DHA and that consuming a product rich in stearidonic acid may be used to achieve the benefits as disclosed herein.
- the nutritional or dietary supplement composition of the present invention may include an effective amount of Vitamin D (as D3).
- Such effective amount of Vitamin D may comprise a daily dosage amount of between about 500 IU and about 2,000 IU.
- the first visit included an initial base line analysis for inclusion in the study.
- the second visit involved a 4-week follow-up and the third visit was an 8-week follow-up.
- the parameters of the study protocol for the “inclusion” of participants included the following conditions: (1) the participant must be of the age of 18 to 60 at the time of signing the informed consent; (2) must understand, be willing and able, and likely to fully comply with study procedures, visit schedule, and restrictions; and (3) have symptoms of dry eye, posterior blepharitis, and/or meibomian gland dysfunction.
- the parameters of the study protocol for the “exclusion” of participants included the following conditions: (1) clinically significant eyelid deformity or eyelid movement disorder that is caused by conditions such as notch deformity, incomplete lid closure, entropion, ectropion, hordeola, or chalazia; (2) previous ocular disease leaving sequelae or requiring current topical eye therapy other than for DED, including, but not limited to: active corneal or conjunctival infection of the eye and ocular surface scarring; (3) active ocular or nasal allergy; (4) LASIK or PRK surgery that was performed within one (1) year of Visit 1 or at any time during the study; (5) ophthalmologic drop use within 2 hours of Visits 1, 2, or 3; (6) pregnancy or lactation at any time during the study; (7) abnormality of nasolacrimal drainage (by history); (8) previous Punctal plugs placement or cauterization; or (9) started or changed the dose of chronic systemic medication known to affect tear production including, but not limited to
- Ocular Surface Disease Index which is a survey based on an array of questions that are asked having a gradation scale for answers to score subjective symptoms and to distinguish between normal subjects and patients with dry eye disease (normal, mild to moderate, and severe) and effect on vision-related function
- Slit Lamp Examination which involves the use of a low-power microscope combined with a high-intensity light source that can be focused to shine in a thin beam so that the physician can examine the patient's eyes, especially the eyelids, cornea, conjunctiva, sclera and iris
- Corneal Staining which is an evaluation of epithelial integrity
- Tear Break Up Time (TBUT) which involves a method of determining the stability of the tear film and checking for evaporative dry eye by way of determining the time required for dry spots to appear on the corneal surface after blinking
- Tear Osmolarity TearLab®
- compositions of omega-3 fatty acids comprising a daily dosage amount of 2,668 mg in a re-esterified triglyceride form (rTG) dispensed in four 667 mg capsules, each containing 420 mg of EPA, 140 mg of DHA, 107 mg of other omega-3′s and 250 mg of Vitamin D (D3).
- rTG re-esterified triglyceride form
- the participant levels of arachidonic acid a direct precursor to pro-inflammatory eicosanoid derivatives, decreased significantly (p ⁇ 0.00004) from 12.2% at baseline to 10.3% at 8 weeks, as measured in the blood.
- participant levels of EPA increased significantly (p ⁇ 0.00000) in the RBCs from baseline and at 8 weeks (0.8% and 3.2%, respectfully) and levels of DHA increased (p ⁇ 0.00349) in the RBCs from baseline and 8 weeks (3.3% and 4.1%, respectfully), as shown in Table 2.
- the lid margins were graded on a scale of trace—4 for meibomian gland insipissation.
- the results of the participants of the clinical study are illustrated in Table 5.
- Corneal staining was graded on a scale of trace, 1+, 2+, 3+, and 4+. Improving one grade was considered clinically significant.
- Nine (9) of twenty-one (21) patients did not present with corneal staining at baseline, but the eleven (11) patients that did all had significant improvement by way of slit lamp examination at the four week exam.
- omega-3 RBC and meibum composition had a direct correlation to the improvement of tear break up time, reduction in tear osmolarity, and elevation of omega-3 index from the baseline.
- the study also demonstrated the new presence of omega-3 fatty acids within the meibum itself.
- a meibum sample was obtained from each of the participants using a Mastroda paddle at baseline and at 8-weeks. The samples were immediately frozen and shipped at a later date on dry ice to be analyzed by the OmegaQuant® system. The participants were placed on a supplementation of a composition of omega-3 fatty acids comprising a daily dosage amount of 2,668 mg in a re-esterified triglyceride form (rTG) dispensed in four 667 mg capsules, each containing 420 mg of EPA, 140 mg of DHA, 107 mg of other omega-3′s and 250 mg of Vitamin D (D3).
- rTG re-esterified triglyceride form
- bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3 in re-esterified triglyceride form, delivered in the dosage amounts disclosed herein, such that said composition improved the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example I, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example II, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- omega-3 fatty acids 2,000 mg-3,000 mg
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example III, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example IV, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- DHA docosahexaenoic acid
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example V, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VI, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- Vitamin D 500 IU-2,000 IU
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VIII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- Vitamin D 500 mg-900 mg Vitamin D (as D3) 500 IU-2,000 IU
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example IX, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- other omega-3 fatty acids 400 mg-700 mg Vitamin D (as D3) 500 IU-2,000 IU
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example X, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- EPA 1,600 mg-2,500 mg docosahexaenoic acid
- DHA docosahexaenoic acid
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XI, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- Vitamin D as D3
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- a daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
- EPA eicosapentaenoic acid
- DHA docosahexaenoic acid
- other omega-3 fatty acids 400 mg-700 mg Vitamin D (as D3) 334 IU
- composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XIII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3.
- the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- omega-3′s in the triglyceride, esterified or re-esterified triglyceride form has a three (3) phase affect in the inflamed meibomian gland.
- the level of omega-3 is increased which, respectively, competes with arachidonic acid (omega-6) for binding sites on cyclooxygenase.
- arachidonic acid omega-6
- the amount of arachidonic acid which leads to prostaglandin synthesis is reduced.
- the products of COX 1 & 2 enzymes working on omega-3 creates eicosanoids that compete with those in the prostaglandin pathway from the omega-6.
- the production of resolvin from the omega-3 may provide an even greater factor in the anti-inflammatory action within the meibomian glands. Consequently, the level of inflammatory fatty acids (omega-6′s) decreased about two (2) fold and the level of anti-inflammatory fatty acids (omega-3′s) increased nearly five (5) fold.
- certain embodiments of the present invention provide methods of composition of omega-3 fatty acids for treating dry eye by way of improving the quality of the meibum concentration of inflamed or dysfunctional meibomian glands, comprising the steps of: (1) administering a composition comprising an effective amount of omega-3 fatty acids; (2) increasing levels of omega-3′s in a composition of meibum of the treated meibomian glands; and (3) decreasing levels of omega-6′s in said composition of meibum.
- Bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum facilitates the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to eliminate or reduce the related symptoms of dry eye, posterior blepharitis, and/or meibomianitis, reduce tear osmolarity, improve or increase tear break up time, and/or elevate the omega-3 index.
Abstract
Description
- This is a continuation-in-part application that claims the benefit of U.S. patent application Ser. No. 16/926,022, filed on Jul. 10, 2020 and entitled “OMEGA-3 FATTY ACID SUPPLEMENTATION FOR USE IN TREATING DRY EYE,” which claims the benefit of U.S. patent application Ser. No. 15/910,661, filed on Mar. 2, 2018 and entitled “METHODS FOR TREATING DRY EYE” (now issued as U.S. Pat. No. 10,709,680), which claims the benefit of U.S. patent application Ser. No. 15/197,212, filed on Jun. 29, 2016 and entitled “COMPOSITIONS AND METHODS FOR USING SAME FOR REDUCING LEVELS OF ARACHIDONIC ACID IN TISSUE HAVING UNDERGONE AN INVASIVE PROCEDURE” (now abandoned), which claims the benefit of U.S. patent application Ser. No. 13/815,599, filed on Mar. 12, 2013 and entitled “METHODS FOR IMPROVING THE QUALITY OF THE MEIBUM COMPOSITION OF MEIBOMIAN GLANDS” (now issued as U.S. Pat. No. 9,381,183), which claims the benefit of U.S. patent application Ser. No. 13/507,673, filed on Jul. 18, 2012 and entitled “COMPOSITIONS FOR IMPROVING THE QUALITY OF THE MEIBUM COMPOSITION OF INFLAMED OR DYSFUNCTIONAL MEIBOMIAN GLANDS” (now issued as U.S. Pat. No. 9,115,078), which claims the benefit of U.S. Provisional Patent App. Ser. No. 61/572,574, filed on Jul. 18, 2011 and entitled “COMPOSITION AND METHODS FOR USING SAME FOR TREATING POSTERIOR BLEPHARITIS.”
- This invention relates to methods for improving and enhancing the lipid layer of the tear and increasing tear breakup time by way of elevating the omega-3 index in patients suffering from symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction and, more specifically, to methods for administering a composition of omega-3 fatty acids to a patient having an inflamed meibomian gland so as to facilitate an increase in the amount of omega-3′s acting as an anti-inflammatory and, respectively, decrease the amount of omega-6′s acting as an inflammatory in the meibum composition, thereby normalizing the lipid layer of the tear and effectively reducing or eliminating the symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction.
- Dry eye is a condition in which there are insufficient tears to lubricate and nourish the eye. Tears are necessary for maintaining the health of the front surface of the eye and for providing clear vision. People with dry eyes either do not produce enough tears or have a poor quality of tears. With each blink of the eyelids, tears are spread across the cornea in order to provide lubrication, to wash away any foreign matter and to keep the surface of the eyes smooth and clear.
- Tears are produced by several glands in and around the eyelids. When the normal amount of tear production decreases or tears evaporate too quickly from the corneal surface, symptoms of dry eye can develop.
- As appreciated, tears are made up of oil, water and mucus. Each component serves a specified function in protecting and nourishing the front surface of the eye. A smooth oil layer helps to prevent evaporation of the water layer, while the mucin layer functions in spreading the tears evenly over the surface of the eye. If the tears evaporate too quickly or do not spread evenly over the cornea as a result of deficiencies with any of the three tear layers, symptoms of dry eye or posterior blepharitis may ensue.
- Along the margin of the eyelids are a series of small sebaceous glands called meibomian glands. The meibomian glands create and distribute a supply of meibum, an oily substance, that makes up the lipid layer of the tear. The supply of meibum functions to help keep the eye moist and tends to protect the tear film from evaporation. There are approximately twenty-five meibomian glands on the upper eyelids and twenty-five meibomian glands on the lower eyelids. Upon blinking of the eye, the upper eyelid comes down, presses on the oily substance produced by the meibomian glands, and pulls a sheet of this oily substance upwards, thereby coating the tear layer beneath to keep it from evaporating. This oily substance or meibum (wherein lipids are a major component) which is created by the meibomian glands is therefore critical for healthy eyes and clear vision.
- Meibomianitis refers to inflammation or dysfunction of the meibomian glands which is also referred to in the art as meibomian gland dysfunction. Inflammation of the meibomian glands may occur because of the production of meibum which is pro-inflammatory in nature as a result of an increased composition of omega-6 essential fatty acids. Secondarily, bacteria have been found to invade the meibomian glands and colonize there. Once inflamed, the meibomian glands generally will not function in a manner sufficient to adequately produce the quantity and quality of oils necessary to properly lubricate the eye.
- The volume of oil produced from inflamed meibomian glands tends to decrease and the oils that are produced become thicker in composition, like toothpaste. These oils also become abnormal in their characteristics. Instead of spreading evenly across the aqueous layer, the oil coalesces leaving areas on the corneal surface in which the aqueous can evaporate and other areas in which the oil adheres to the cornea surface itself This creates a dry spot on the cornea for which the aqueous cannot penetrate. Such condition generally produces a foreign body sensation and if it persists may result in injury to the epithelium which is seen as corneal staining on examination. A reduction in oil production therefore inherently results in a quantitative decrease in the quality and quantity of the oily layer, thus causing tears to evaporate more rapidly. Because the thickened oil does not coat the eye properly, a person with inflamed meibomian glands may experience discomfort or problems with their eyes that may include, for example, but not by way of limitation: (1) dryness; (2) burning; (3) itching; (4) irritation and redness; (5) blurred vision; and/or (6) foreign body sensations.
- This inflammatory process can also spread throughout the lid margin and spill over to involve the ocular surface resulting in significant ocular discomfort. Inflammation of the meibomian glands in the upper and lower lids can further lead to vascularization and fibrosis, causing stenosis and then closure of the meibomian gland orifices. Deprived of the meibum or lipids that inhibit evaporation, tear film evaporation will generally increase. Similarly, a deficiency in tear film generally results in irritation of the eye, but can also cause damage to the surface of the eye. As appreciated, an irregular oil pattern disrupts tears and allows for increased exposure of the aqueous layer to the atmosphere and the increased evaporation of the aqueous. Unfortunately, this inflamed condition of the meibomian glands has often been found to be chronic.
- Some of the treatments for meibomianitis that have been contemplated by those skilled in the art include: (1) the application of artificial tears; (2) cleaning the affected eyelid margins with a gentle baby shampoo; and (3) applying warm and moist compresses 5-10 minutes two to three times per day in an effort to promote normal eyelid glandular function. A physician may also prescribe a topical and/or oral antibiotic such as, for example, tetracycline, erythromycin, or doxycycline, to help eradicate the bacteria found in the glands and to facilitate a breakdown in the thickened lipid secretions from the meibomian glands. These various treatments, however, can often take months before a treated patient notices any significant improvement.
- Although the elimination of bacteria or anti-inflammatory effects of the antibiotics resulted in a temporary change, none of the known treatment methodologies have brought long-lasting relief to patients. Hoping to provide a form of sustainable relief to the ongoing symptoms associated with dry eye, with or without meibomian gland dysfunction, that are suffered by patients, a study was conducted by those skilled in the art to investigate the effects of dietary composition of a combination of flaxseed and fish oils on the tear film and the ocular surface. At the baseline, all patients in the study had a history of dry eye or one or more symptoms of posterior blepharitis. At the end of the study, the clinical results did not achieve any statistical significance, wherein the lipid composition of the samples collected from the omega-3 supplemented group was found to be very similar to that collected from the placebo group. Thus, the study concluded that dietary composition of flaxseed oil and omega-3 fatty acids for treating dry eye or meibomianitis showed no significant effect on meibum composition or aqueous tear evaporation rate.
- Consistent with the foregoing, in order to control or resolve the long term effects of dry eye, posterior blepharitis, or meibomian gland dysfunction, the characteristics or nature of the oil (meibum) that is produced by the meibomian glands must be normalized. Thus, what is needed are nutritional or dietary supplement compositions and treatment methodologies using the same that effectively change the quality of the meibum composition, thereby resulting in a meibum composition having a direct correlation to enhancing and improving the function and/or composition of the lipid layer of the tear which reduces the symptoms associated with dry eye, posterior blepharitis and/or meibomian gland dysfunction.
- In view of the foregoing, it is a primary object of the present invention to provide nutritional or dietary composition of omega-3 fatty acids for dry eye and methods for administering a composition consisting essentially of omega-3 fatty acids to a mammal (i.e., patient) suffering from dry eye, wherein the composition consisting essentially of omega-3 fatty acids is administered in an effective amount sufficient to facilitate an increase in the resulting omega-3′s content of the treated meibomian glands, acting as an anti-inflammatory, and, respectively, in a decrease in the amount of resulting omega-6′s (i.e., arachidonic acid), acting as an inflammatory, thereby having a direct affect on the normalization of the lipid layer of the tear and a corresponding reduction in the symptoms associated with dry eye.
- It is a further object of the present invention to provide methods for administering a composition consisting essentially of omega-3 fatty acids to a patient suffering from symptoms of dry eye, posterior blepharitis or meibomian gland dysfunction or inflammation, wherein the composition of omega-3 fatty acids may be in the triglyceride, esterified triglyceride or re-esterified triglyceride form in an effective amount sufficient to effectively change the quality of the meibum composition resulting in a meibum composition that improves by way of increasing tear breakup time, reducing tear osmolarity and/or elevating the omega-3 index, while eliminating or reducing the symptoms of dry eye or posterior blepharitis.
- It is a still further object of the present invention to provide nutritional or dietary composition consisting essentially of omega-3 fatty acids and methods for administering said composition to a patient suffering from symptoms of meibomianitis, wherein the composition consisting essentially of omega-3 fatty acids may be in the triglyceride, esterified triglyceride or re-esterified triglyceride form in an amount sufficient to effectively change the quality of the meibum composition resulting in a meibum composition that improves or increases tear breakup time, reduces tear osmolarity, and/or elevates the omega-3 index, while eliminating or reducing the related symptoms of meibomianitis.
- Additionally, it is an object of the present invention to provide a method for affecting the composition of the oil produced by sebaceous glands that are found in the body from pro-inflammatory omega-6s to anti-inflammatory omega-3s, whereby normalizing the oil production of the treated glands by way of administering the composition of omega-3 fatty acids as taught by the present invention.
- It is a further object of the present invention to provide a nutritional or dietary supplementation of a composition of omega-3 fatty acids for dry eye and methods for changing the composition of the oil (meibum) produced by meibomian glands from pro-inflammatory omega-6 to anti-inflammatory omega-3, whereby normalizing the oil production of the meibomian gland by way of administering a a of omega-3 fatty acids as taught by the present invention, wherein the composition of the present invention does not include any additional omega-6 fatty acids beyond an amount normally found in a source material of said omega-3 fatty acids.
- It is also an object of the present invention to provide a method for treating acne by way of changing the composition of the oil (sebum) produced by sebaceous glands found in the skin from pro-inflammatory omega-6 to anti-inflammatory omega-3, whereby normalizing the oil production of the gland by way of administering an embodiment of a nutritional or dietary supplement composition as taught by the present invention.
- It is a still further object of the present invention to provide a method for treating post surgical inflammation by preoperatively administering an embodiment of a nutritional or dietary supplement composition as taught by the present invention, whereby increasing the omega-3 level and decreasing the omega-6 (arachidonic acid) level within the cell wall thereby reducing post surgical inflammation by reducing the prostaglandin precursors and increasing the anti-inflammatory and resolvins available at the surgical site.
- Consistent with the foregoing objects, the present invention is directed to nutritional or dietary supplementation of a composition of omega-3 fatty acids for dry eye and methods for administering a composition of omega-3 fatty acids to a patient suffering from symptoms of dry eye, posterior blepharitis and/or meibomian gland dysfunction or inflammation. The composition of omega-3 fatty acids is administered in an amount formulated to change the composition of the oil (meibum) produced by meibomian glands from pro-inflammatory omega-6 to anti-inflammatory omega-3, whereby normalizing the oil production of the meibomian gland so as to improve or increase tear break up time, reduce tear osmolarity, and elevate the omega-3 index, thereby, consequently, eliminating or reducing the related symptoms of dry eye, posterior blepharitis or meibomianitis (meibomian gland dysfunction).
- In an embodiment of the present invention, the present invention provides for methods for treating and preventing dry eye associated with meibomian gland inflammation or dysfunction by way of administering a nutritional or dietary supplement composition comprising an effective amount of omega-3 fatty acids. The composition may include an effective amount of omega-3 fatty acids comprising a daily dosage that includes between about 600 mg and about 5,000 mg. The effective amount of omega-3′s may comprise the triglyceride or re-esterified triglyceride form.
- The effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA). In one embodiment of the present invention, the daily dosage of an effective amount of EPA may include an amount greater than 600 mg.
- In yet another embodiment of the present invention, the effective amount of omega-3 fatty acids may comprise an effective amount of docosahexaenoic acid (DHA). The daily dosage of an effective amount of DHA may include an amount greater than 500 mg.
- In certain embodiments of the present invention, an effective amount of omega-3 fatty acids may be delivered in a daily dosage that includes between about 2,000 mg and about 3,000 mg. This effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA) and an effective amount of docosahexaenoic acid (DHA). Similarly, in one embodiment of the present invention, the daily dosage of an effective amount of EPA may include an amount between about 1,600 mg and about 2,500 mg and the daily dosage of an effective amount of DHA may include an amount between about 500 mg and about 900 mg.
- An additional amount of omega-3 fatty acids may also be included in the administered composition. These additional omega-3 fatty acids may include a daily dosage amount of between about 400 mg and about 700 mg. Furthermore, the nutritional or dietary supplement composition of the present invention may include an effective amount of Vitamin D (as D3). Such effective amount of Vitamin D may comprise a daily dosage amount between about 500 IU and about 2,000 IU.
- As contemplated herein, the administration of the dietary or nutritional supplement composition of the present invention to effectively change the quality of the meibum composition of the meibomian glands may be delivered by means of softgel, tablet, liquids, granules, microgranules, powders, or any other delivery system deemed effective.
- It will be readily understood that the components of the present invention, as generally described herein, could be modified, arranged and designed in a wide variety of different formulas. Thus, the following more detailed description of the embodiments of the composition and systems and methods of the present invention is not intended to limit the scope of the invention. The scope of the invention is as broad as claimed herein.
- As used herein, the term “omega-3 fatty acids” may be selected from the group consisting of fish, krill, mollusks, crustaceans, seaweed, algae, flaxseed, nuts, plants, microbial organisms, transgenic organisms, and/or combinations of one or more of the foregoing.
- It is important to note that the composition of omega-3 fatty acids, as taught by the present invention, does not include any additional omega-6 fatty acids beyond the amount normally found in the source material of the omega-3 fatty acids, such as fish oil.
- As appreciated, omega-3 fatty acids obtained from marine sources are usually present in the ethyl ester or triglyceride form. Omega-3 fatty acids obtained from marine sources may undergo purification by the use of absorbents and molecular distillation to remove mercury and other heavy metals and pollutants that are usually prevalent in these sources. This purification process generally results in the omega-3′s being in the ethyl ester form, which is how the vast majority of OTC omega-3 products are sold. The omega-3′s derived from marine sources, as used in the studies and as contemplated by the present invention, underwent a further re-esterification step to restore the triglyceride group to the omega-3′s (rTG). Consequently, this further step of re-esterification of the omega-3′s greatly increased the body′s ability to absorb the omega-3′s as illustrated in the studies.
- As used herein, the term “effective amount” includes the amount of omega-3 fatty acids in the triglyceride, esterified triglyceride or re-esterified triglyceride form which is capable of effectively changing the quality of the meibum concentration which has a direct correlation to improving the lipid layer of the tear, while eliminating or reducing the related symptoms of dry eye, posterior blepharitis and/or meibomianitis.
- As used herein, the terms “dry eye, meibomianitis, meibomian gland dysfunction, posterior blepharitis and blepharitis” are to be considered as synonyms.
- The present invention provides for methods for treating and preventing dry eye associated with meibomian gland inflammation or dysfunction by way of administering a nutritional or dietary supplement composition comprising an effective amount of omega-3 fatty acids. The composition may include an effective amount of omega-3 fatty acids comprising a daily dosage that includes between about 600 mg and about 5,000 mg.
- This effective amount of omega-3 fatty acids may comprise an effective amount of eicosapentaenoic acid (EPA). In one embodiment of the present invention, the daily dosage of an effective amount of EPA may include an amount greater than 600 mg.
- In yet another embodiment of the present invention, the effective amount of omega-3 fatty acids may comprise an effective amount of docosahexaenoic acid (DHA). The daily dosage of an effective amount of DHA may include an amount greater than 500 mg.
- In certain embodiments, the dietary or nutritional composition may include an effective amount of omega-3 fatty acids comprising a daily dosage including an effective amount between about 2,000 mg and about 3,000 mg. This effective amount of omega-3 fatty acids may be comprised of an effective amount of eicosapentaenoic acid (EPA) and an effective amount of docosahexaenoic acid (DHA). In an embodiment of the present invention, the daily dosage of an effective amount of EPA may include an amount between about 1,600 mg and about 2,500 mg and the daily dosage of an effective amount DHA may include an amount between about 500 mg and about 900 mg.
- As appreciated by those skilled in the art, the dietary or nutritional supplement composition of the present invention includes omega-3 fatty acids that may comprise, for example, but not by way of limitation, the triglyceride form, re-esterified triglyceride concentrates, the ethyl ester form, the free fatty acid form, the phospholipids form, or any other suitable form sufficient to effectively change the quality of the meibum composition of the meibomian glands which has a direct correlation to improving the lipid layer of the tear, while eliminating or reducing the related symptoms of dry eye or meibomianitis. It is contemplated herein that the composition of the omega-3′s can be in a concentrated form, whereas up to 100% of the unit volume can be omega-3. In certain embodiments of the present invention, the dietary or nutritional supplement omega-3 composition administered for treating dry eye, posterior blepharitis, meibomianitis for changing the quality of the meibum concentration of inflamed or dysfunctional meibomian glands in order to improve or increase tear break up time, reduce tear osmolarity, and elevate the omega-3 index may comprise omega-3 fatty acids in the re-esterified triglyceride form.
- The effective amount of eicosapentaenoic acid (EPA) and/or an effective amount of docosahexaenoic acid (DHA) included in the dietary or nutritional supplement of the present invention may be obtained from known sources, such as for example, and not by way of limitation, fish, algae, squid, yeast, and vegetable sources. It is further recognized that stearidonic acid is a precursor to EPA and DHA and that consuming a product rich in stearidonic acid may be used to achieve the benefits as disclosed herein.
- In selected embodiments of the nutritional or dietary supplement composition of the present invention, an effective amount of EPA/DHA may be administered in one or more softgel capsules containing an amount in the range of between about 800 mg and 1,250 mg and between about 250 mg and about 450 mg, respectively. For purposes of dosage, in certain embodiments of the present invention, the daily dosage amount may include an effective amount of EPA/DHA comprising the amounts of 840 mg and 280 mg, respectively.
- In certain embodiments, this effective amount of EPA/DHA form may comprises a ratio of EPA/DHA of 3:1. Whereas, in selected embodiments, the ratio of EPA/DHA in each capsule may be in the range of between about 800 mg and 1,250 mg of EPA and between about 250 mg and 450 mg of DHA, whereby two capsules would comprise a daily effective dosage range.
- An additional amount of omega-3 fatty acids may also be included in the administered composition. These additional omega-3 fatty acids may include a daily dosage amount of between about 400 mg and about 700 mg.
- Furthermore, the nutritional or dietary supplement composition of the present invention may include an effective amount of Vitamin D (as D3). Such effective amount of Vitamin D may comprise a daily dosage amount of between about 500 IU and about 2,000 IU.
- A clinical study was conducted based on the following parameters:
- To evaluate the clinical effect of the oral administration of a composition of omega-3 fatty acids in the re-esterified triglyceride form to a patient suffering from symptoms of dry eye and meibomian gland dysfunction.
- A total of twenty-one (21) subjects or participants, between the ages of 18-60 years of age inclusive, who voluntarily provided written informed consent and who were capable of complying with the study visit schedule, were enrolled.
- There were three (3) scheduled visits with an attending physician. The first visit included an initial base line analysis for inclusion in the study. The second visit involved a 4-week follow-up and the third visit was an 8-week follow-up.
- The parameters of the study protocol for the “inclusion” of participants included the following conditions: (1) the participant must be of the age of 18 to 60 at the time of signing the informed consent; (2) must understand, be willing and able, and likely to fully comply with study procedures, visit schedule, and restrictions; and (3) have symptoms of dry eye, posterior blepharitis, and/or meibomian gland dysfunction.
- The parameters of the study protocol for the “exclusion” of participants included the following conditions: (1) clinically significant eyelid deformity or eyelid movement disorder that is caused by conditions such as notch deformity, incomplete lid closure, entropion, ectropion, hordeola, or chalazia; (2) previous ocular disease leaving sequelae or requiring current topical eye therapy other than for DED, including, but not limited to: active corneal or conjunctival infection of the eye and ocular surface scarring; (3) active ocular or nasal allergy; (4) LASIK or PRK surgery that was performed within one (1) year of Visit 1 or at any time during the study; (5) ophthalmologic drop use within 2 hours of Visits 1, 2, or 3; (6) pregnancy or lactation at any time during the study; (7) abnormality of nasolacrimal drainage (by history); (8) previous Punctal plugs placement or cauterization; or (9) started or changed the dose of chronic systemic medication known to affect tear production including, but not limited to antihistamines, antidepressants, diuretics, corticosteroids or immuno-modulators within 30 days of Visit 1, 2, or 3.
- This is a single-center study of participants with signs and symptoms of dry eye undergoing nutritional therapy treatment with an amount of omega-3 fatty acids delivered in re-esterified triglyceride form over the course of three (3) visits with approximately 4-week intervals between each visit.
- The following clinical tests were performed on each participant at baseline: (1) Ocular Surface Disease Index (OSDI) which is a survey based on an array of questions that are asked having a gradation scale for answers to score subjective symptoms and to distinguish between normal subjects and patients with dry eye disease (normal, mild to moderate, and severe) and effect on vision-related function; (2) Slit Lamp Examination which involves the use of a low-power microscope combined with a high-intensity light source that can be focused to shine in a thin beam so that the physician can examine the patient's eyes, especially the eyelids, cornea, conjunctiva, sclera and iris; (3) Corneal Staining which is an evaluation of epithelial integrity; (4) Tear Break Up Time (TBUT) which involves a method of determining the stability of the tear film and checking for evaporative dry eye by way of determining the time required for dry spots to appear on the corneal surface after blinking; (5) Tear Osmolarity (TearLab®) that involves measuring the concentration of the osmotic solution of the tear; (6) EPA and DHA red blood cell saturation using the HS Omega-3 Index (OmegaQuant®) performed by probing the meibomian glands with a Maskin probe for a meibum sample; and (7) blood omega-3 levels were obtained to ensure patient compliance with composition given.
- The participants were placed on a composition of omega-3 fatty acids comprising a daily dosage amount of 2,668 mg in a re-esterified triglyceride form (rTG) dispensed in four 667 mg capsules, each containing 420 mg of EPA, 140 mg of DHA, 107 mg of other omega-3′s and 250 mg of Vitamin D (D3).
- The participants were reevaluated at the 4-week visit with all the baseline testing except the (1) HS Omega-3 Index (OmegaQuant®) and meibum analysis. At 8-weeks, the participants were reevaluated with all the testing conducted at the baseline and, in addition, a the Mastroda paddle was used to collect meibomian gland secretions from each participant.
- Based on OSDI which was taken at baseline, all twenty-one (21) participants reported a reduction of their primary complaint and fourteen (14) of the twenty-one (21) patients became completely asymptomatic.
- As illustrated in Table 1, the participant levels of arachidonic acid, a direct precursor to pro-inflammatory eicosanoid derivatives, decreased significantly (p<0.00004) from 12.2% at baseline to 10.3% at 8 weeks, as measured in the blood.
-
TABLE 1 RBC Hemoglobin - Omega-6 (Arachidonic Acid/Docosapentaenoic Acid) ARA DPA C20:4n6/ C20:4n6/ C22:5n6/ C22:5n6/ Patient Visit 1 Visit 2 Visit 1 Visit 2 1 9.03% 8.63% 0.23% 0.14% 2 10.48% 10.56% 0.40% 0.51% 3 12.55% 10.35% 0.45% 0.27% 4 13.81% 10.63% 0.38% 0.37% 5 11.98% 11.09% 0.32% 0.27% 6 12.35% 11.16% 0.68% 0.42% 7 13.04% 10.54% 0.65% 0.33% 8 13.48% 11.13% 0.30% 0.26% 9 11.01% 8.93% 0.45% 0.24% 10 10.79% 9.80% 0.22% 0.11% 11 11.41% 10.95% 0.30% 0.20% 12 14.40% 11.14% 0.73% 0.41% 13 12.92% 10.33% 0.46% 0.14% 14 12.64% 10.38% 0.57% 0.30% 15 14.68% 10.78% 0.53% 0.19% 16 10.84% 8.48% 0.37% 0.25% 17 11.15% 8.33% 0.36% 0.17% 18 12.61% 10.74% 0.28% 0.26% 19 12.25% 10.59% 0.27% 0.18% 20 10.83% 8.63% 0.31% 0.27% 21 14.70% 13.30% 0.43% 0.22%
(ARA=Arachidonic Acid; C20:4n6=Arachidonic Acid; DPA=Docosapentaenoic Acid; C22:5n6=Docosapentaenoic Acid) - The participant levels of EPA increased significantly (p<0.00000) in the RBCs from baseline and at 8 weeks (0.8% and 3.2%, respectfully) and levels of DHA increased (p<0.00349) in the RBCs from baseline and 8 weeks (3.3% and 4.1%, respectfully), as shown in Table 2.
-
TABLE 2 RBC Hemoglobin - Omega-3 (Docosahexaenoic Acid/Eicosapentaenoic Acid) DHA EPA C22:6n3/ C22:6n3/ C20:5n3/ C20:5n3/ Patient # Visit 1 Visit 2 Visit 1 Visit2 1 3.39% 5.23% 0.49% 3.76% 2 2.92% 3.53% 0.23% 1.04% 3 2.65% 3.67% 0.30% 3.56% 4 3.06% 4.32% 0.75% 2.63% 5 3.04% 3.80% 1.13% 2.49% 6 2.69% 3.97% 0.43% 3.22% 7 4.08% 5.80% 0.51% 3.46% 8 5.52% 5.31% 1.68% 3.78% 9 2.03% 3.17% 0.70% 2.49% 10 2.35% 3.46% 0.55% 3.27% 11 3.87% 4.35% 1.64% 3.22% 12 2.48% 4.19% 0.31% 3.41% 13 2.01% 3.11% 0.44% 3.15% 14 2.59% 3.36% 0.49% 2.95% 15 3.05% 4.43% 1.78% 4.69% 16 3.24% 3.70% 0.45% 2.55% 17 4.03% 3.70% 0.46% 4.97% 18 2.88% 4.20% 0.62% 3.92% 19 5.27% 5.13% 1.77% 3.78% 20 4.45% 3.67% 1.16% 1.91% 21 3.41% 4.08% 1.52% 2.51%
(DHA=Docosahexaenoic Acid; C22:6n3=Docosahexaenoic Acid; EPA=Eicosapentaenoic Acid; C20:5n3=Eicosapentaenoic Acid) - Referring now to Table 3, the HS Omega-3 Index Scores are provided for each of the twenty-one (21) participants.
-
TABLE 3 HS Omega-3 Index Scores HS Omega 3/Visit 1 HS Omega 3/Visit 2 Patient # Index Percentage Index Percentage 1 4.34% 9.52% 2 3.60% 5.05% 3 3.42% 7.74% 4 4.28% 7.46% 5 4.65% 6.78% 6 3.58% 7.70% 7 5.07% 9.79% 8 7.71% 9.63% 9 3.19% 6.15% 10 3.36% 7.24% 11 6.00% 8.08% 12 3.26% 8.11% 13 2.91% 6.76% 14 3.54% 6.81% 15 5.32% 9.65% 16 4.16% 6.76% 17 4.97% 9.20% 18 3.97% 8.64% 19 7.55% 9.44% 20 6.10% 6.08% 21 5.41% 7.09%
(HS-Omega-3 Index percentage=Red Blood Cell Membrane Saturation of Omega-3s) - Tear osmolarity decreased on average seventeen percent (17%) at the eight week exam period, as illustrated in Table 4.
-
TABLE 4 Tear Osmolarity Patient # Visit 1 Visit 2 Visit 3 1 300/300 325/303 300/289 2 284/298 Px missed appt 315, 299 OD, 298 OS 3 290/307 305/293 286/300 4 307/303 309/288 303/309 5 345/318 302/292 292/308 6 349/305 301/306 310/317 7 305/301 330, 302/292 305/303 8 337, 323/297 320/334 below range, 311 9 308/298 300/315, 285 308/303 10 298/292 289/288 275/296 11 279/280 276/ 300/280 below range x2 12 311/302 309/292 312/298 13 307/321 306/287 309/309 14 301/304 301/319 300/305 15 282/295 Px missed appt Unable gtts instilled 16 325/301 304/303 312/291 17 327/296, 301 290/282 295/299 18 280/295 294/299 303/302 19 305/303 309/300 314/306 20 282/285 285/276 280/286 21 297/291 294/294 281/292
(The osmolarity of the right eye/left eye in milliosmols)
As shown, there were variations in starting osmolarities among patients. The use of topical drops within two (2) hours of checking osmolality disqualified participant 15′s test as it may have had a dilution effect on the tears. - The lid margins were graded on a scale of trace—4 for meibomian gland insipissation. The results of the participants of the clinical study are illustrated in Table 5.
-
TABLE 5 Lid Margins Patient # Visit 1 Visit 2 Visit 3 1 irregular irreg slight irreg 2 1+ missed appt trace 3 tr − 1 trace cl-tr 4 trace+ clear-trace clear 5 irreg less irreg tr irreg 6 trace trace cl-tr 7 tr+ trace tr 8 tr − 1 tr OD, tr − 1 OS tr OU 9 tr+ w/foam tr+ w/foam tr no foam 10 irreg irreg mild irreg 11 1+ tr+ tr 12 tr − 1 tr − 1 tr − 1 w/foam 13 tr cl-tr cl OD, tr OS 14 irreg irreg slight irreg 15 3 + OD, 4 + OS missed appt 1 + OU 16 tr Tr cl-tr 17 tr OD, cl-tr OS cl-tr/irreg tr irreg 18 Tr/irreg tr/irreg mild irreg 19 tr − 1 tr OD, cl-tr OS irreg 20 1+ tr − 1 tr+ 21 tr OD, tr − 1 OS tr OD, tr − 1 OS cl-tr OD, tr OS
(Grading of meibomian gland appearance with reference to inspissation) - As shown, some patients did not have insipisation, but their lid margins were irregular versus smooth due to previous inflammation.
- Referring now to Table 6, the improvement of Tear Break Up Time (TBUT) at eight weeks was statistically significant (p<0.00027).
-
TABLE 6 Tear Breakup Time Patient # Visit 1 Visit 2 Visit 3 1 2-3 sec OD, OS 3-4 sec OD, OS 4-5 OD, 3-4 OS 2 3 OD, OS, SPK OS > OD missed appt 4 OD, OS no SPK OD, tr OS 3 3 sec OD, OS 3-4 OD, 2-3 OS 3 sec OU no SPK on any visit 4 3 sec OU, SPK OD 3 OD, 4 OS, tr SPK OD 4-5 OU, no SPK 5 not noted, SPK OS > OD 4 OD, 5 OS tr SPK OU 4-5 sec OU no SPK 6 3 sec OU 3 sec OU 4-5 OD, 4 OS no SPK on any visit 7 3 OU, tr SPK OU 3 OD, 4 OS, tr SPK OU 3 OU, minimal SPK OU 8 3 OU, SPK OD/denseOS 2-3 OU, Inf SPK OU 3-4 OD, 3 OS, minimal SPK inf OU 9 not noted, SPK OU sec ou, no SPK 4 sec OD, OS, no SPK 10 3-4 OD, 2 OS, SPKOD > OD 4 OD, 2-3 OS, tr SPK OS 4 OD, 3 OS, tr SPK OS 11 2-3 OD, 3 OS, no SPK not noted, no SPK 3 OU, minimal SPK OU 12 not noted 3 sec OU 4-5 sec OU 13 3-4 OD, 2-3 OS, SPK OS 4 OD, 3 OS, no SPK 4 OU, no SPK 14 1-2 OU, inf SPK OU 4 OD, 3 OS, Inf SPK OU 2-3 OD, 3 OS, tr SPK OU 15 Corneal Abrasions OU missed appt OD clear, Lt irreg 16 3 OU, tr SPK OU 4 OU, tr SPK OU 4 sec OU, no SPK OD, tr OS 17 3 OU, Inf SPK OU 3 OU, tr SPK OU 4 OD, 3-4 OS, sm tr SPK OU 18 3 OU, dense SPK OU 4 OU, no SPK OU 3 OU, tr inf SPK OU 19 3-4 OD, 3 OS no SPK OU 3 OD, 4-5 OS, tr SPK OD 3-4 OU, tr inf SPK OU 20 3 OU, no SPK 4-5 OU, mild SPK OU 4 OU, no SPK 21 2 OU, no SPK 2-3 OU, no SPK OU 3-4 OU, tr inf SPK OU
(Tear breakup time in seconds)
As shown, fifteen (15) of nineteen (19) participants demonstrated a lengthening of their TBUT from baseline. - As illustrated in Tables 7 and 8, meibum analysis from the initial samples from the study participants revealed that thirteen (13) participants had insufficient quantity of oil to analyze. Of the seven (7) that were readable, none of the participants exhibited omega-3 fatty acids in the meibum. Bacterial components comprised 10 to 15% of the oils present. Oleic acid (18:1 w9c) comprised between 34% and 60%.
- (Iso and anti-iso represent bacterial components)
- At the eight weeks exam period, fourteen (14) of the twenty-one (21) meibum samples had sufficient quantity to analyze. All fourteen (14) meibum samples had DHA (22:6n-3) present. The DHA was present as approximately 2% to 3% of the meibum composition.
- Corneal staining was graded on a scale of trace, 1+, 2+, 3+, and 4+. Improving one grade was considered clinically significant. Nine (9) of twenty-one (21) patients did not present with corneal staining at baseline, but the eleven (11) patients that did all had significant improvement by way of slit lamp examination at the four week exam.
- By end of the study, all participants showed improvement. Consequently, an increase in omega-3 RBC and meibum composition had a direct correlation to the improvement of tear break up time, reduction in tear osmolarity, and elevation of omega-3 index from the baseline. The study also demonstrated the new presence of omega-3 fatty acids within the meibum itself.
- An additional clinical study was conducted based on the following parameters:
- To evaluate the clinical effect of the oral administration of a composition of omega-3 fatty acids in re-esterified triglyceride form on the meibum in patients suffering from symptoms of dry eye and meibomian gland dysfunction.
- Patients with meibomian gland dysfunction were selected from the clinic and a meibum sample was obtained from each of the participants using a Mastroda paddle at baseline and at 8-weeks. The samples were immediately frozen and shipped at a later date on dry ice to be analyzed by the OmegaQuant® system. The participants were placed on a supplementation of a composition of omega-3 fatty acids comprising a daily dosage amount of 2,668 mg in a re-esterified triglyceride form (rTG) dispensed in four 667 mg capsules, each containing 420 mg of EPA, 140 mg of DHA, 107 mg of other omega-3′s and 250 mg of Vitamin D (D3).
- Of the eighteen (18) available participant samples (three (3) samples appeared to be contaminated), twelve (12) showed an increase in the level of anti-inflammatory fatty acids (omega-3′s) of almost five (5) fold and, more specifically, 4.85. The level of inflammatory fatty acids (omega-6′s) decreased about two (2) fold. The results of the second study confirm the findings of the first study showing an increase in omega-3 in the meibum with the more accurate analytic system facilitated with by use of the OmegaQuant® system.
- Furthermore, the findings of these studies indicate that on each blink a bath of inflammatory material, namely arachidonic acid (an omega-6) flows over the entire ocular surface. Here, lipases and other enzymes such as cyclooxygenase have the opportunity to break this chemical down into its prostaglandin derivatives, which are very potent inflammatory agents. When treated with oral composition of omega-3 in the re-esterified triglyceride form, the meibum is changed from an inflammatory bath with each blink to an anti-inflammatory bath. Reducing the inflammatory components about 2.5 fold would have a profound effect on the tissues continually bathed by the meibum, changing to an almost five (5) fold increase in anti-inflammatory would further stabilize the ocular surface. As taught by the present invention, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3 in re-esterified triglyceride form, delivered in the dosage amounts disclosed herein, such that said composition improved the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega.
- The following examples will illustrate several embodiments of the present invention in further detail. It will be readily understood that the nutritional or dietary supplement composition of the present invention, as generally described and illustrated in the Examples herein, could be synthesized in a variety of formulations and dosage forms. Thus, the following more detailed description of the embodiments of the methods, formulations and compositions of the present invention, as represented in the Examples are not intended to limit the scope of the invention, as claimed, but it is merely representative of various contemplated embodiments of the present invention.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
Omega-3 fatty acids 600 mg-5,000 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example I, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
Omega-3 fatty acids 1,000 mg-3,000 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example II, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
omega-3 fatty acids 2,000 mg-3,000 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example III, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) ≥600 mg docosahexaenoic acid (DHA) ≥500 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example IV, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
docosahexaenoic acid (DHA) ≥500 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example V, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) ≥600 mg docosahexaenoic acid (DHA) ≥500 mg other omega-3 fatty acids 400 mg-700 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VI, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) 1,600 mg-2,500 mg docosahexaenoic acid (DHA) 500 mg-900 mg other omega-3 fatty acids 400 mg-700 mg - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) ≥600 mg docosahexaenoic acid (DHA) ≥500 mg Vitamin D (as D3) 500 IU-2,000 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example VIII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) 1,600 mg-2,500 mg docosahexaenoic acid (DHA) 500 mg-900 mg Vitamin D (as D3) 500 IU-2,000 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example IX, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) ≥600 mg docosahexaenoic acid (DHA) ≥500 mg other omega-3 fatty acids 400 mg-700 mg Vitamin D (as D3) 500 IU-2,000 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example X, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) 1,600 mg-2,500 mg docosahexaenoic acid (DHA) 500 mg-900 mg other omega-3 fatty acids 400 mg-700 mg Vitamin D (as D3) 500 IU-2,000 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XI, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) 1,650 mg-1,750 mg docosahexaenoic acid (DHA) 500 mg-600 mg other omega-3 fatty acids 400 mg-500 mg Vitamin D (as D3) 600 IU-800 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- A daily dosage formulation of an embodiment of the nutritional or dietary supplement composition of the present invention administered for an increase in the omega-3 level and a decrease in the omega-6 in the meibum composition of the meibomian glands is set forth as comprising:
-
eicosapentaenoic acid (EPA) 1,680 mg docosahexaenoic acid (DHA) 560 mg other omega-3 fatty acids 400 mg-700 mg Vitamin D (as D3) 334 IU - In certain embodiments of the present invention, composition comprising omega-3 fatty acids for use in treating dry eye in a mammal by improving the quality of the meibum composition of inflamed of dysfunctional meibomian glands comprises the steps of administering a composition of omega-3 fatty acids as disclosed in Example XIII, wherein increasing levels of omega-3′s and, respectively, decreasing levels of omega-6′s in the meibum composition. Consequently, bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum is the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to improve the resolution of dry eye symptoms, tear osmolarity, tear break up time, and blood saturation of omega-3. In certain embodiments, the omega-3 fatty acids comprise the triglyceride, esterified or re-esterified triglyceride form.
- As concluded from the studies conducted, the composition of omega-3′s in the triglyceride, esterified or re-esterified triglyceride form has a three (3) phase affect in the inflamed meibomian gland. First, the level of omega-3 is increased which, respectively, competes with arachidonic acid (omega-6) for binding sites on cyclooxygenase. Secondly, the amount of arachidonic acid which leads to prostaglandin synthesis is reduced. The products of COX 1 & 2 enzymes working on omega-3 creates eicosanoids that compete with those in the prostaglandin pathway from the omega-6. Thirdly, the production of resolvin from the omega-3 may provide an even greater factor in the anti-inflammatory action within the meibomian glands. Consequently, the level of inflammatory fatty acids (omega-6′s) decreased about two (2) fold and the level of anti-inflammatory fatty acids (omega-3′s) increased nearly five (5) fold.
- Consistent with the foregoing, certain embodiments of the present invention provide methods of composition of omega-3 fatty acids for treating dry eye by way of improving the quality of the meibum concentration of inflamed or dysfunctional meibomian glands, comprising the steps of: (1) administering a composition comprising an effective amount of omega-3 fatty acids; (2) increasing levels of omega-3′s in a composition of meibum of the treated meibomian glands; and (3) decreasing levels of omega-6′s in said composition of meibum. Bathing the ocular surface in an anti-inflammatory meibum instead of an inflammatory meibum facilitates the mechanism of action of the composition of the omega-3′s delivered in the dosage amounts disclosed herein so as to eliminate or reduce the related symptoms of dry eye, posterior blepharitis, and/or meibomianitis, reduce tear osmolarity, improve or increase tear break up time, and/or elevate the omega-3 index.
- The present invention may be embodied in other specific forms without departing from its fundamental functions or essential characteristics. The described embodiments are to be considered in all respects only as illustrative, and not restrictive. All changes which come within the meaning and range of equivalency of the illustrative embodiments are to be embraced within their scope.
Claims (20)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17/077,463 US20210121430A1 (en) | 2011-07-18 | 2020-10-22 | Omega-3 fatty acid supplementation for use in treating dry eye |
US17/687,485 US11648227B2 (en) | 2011-07-18 | 2022-03-04 | Omega-3 fatty acid supplementation for use in treating dry eye |
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161572574P | 2011-07-18 | 2011-07-18 | |
US13/507,673 US9115078B2 (en) | 2011-07-18 | 2012-07-18 | Compositions for improving the quality of the meibum composition of inflamed or dysfunctional meibomian glands |
US13/815,599 US9381183B2 (en) | 2012-07-18 | 2013-03-12 | Methods for improving the quality of the meibum composition of meibomian glands |
US15/197,212 US20160310456A1 (en) | 2013-03-12 | 2016-06-29 | Compositions and methods for using same for reducing levels of arachidonic acid in tissue having undergone an invasive procedure |
US15/910,661 US10709680B2 (en) | 2011-07-18 | 2018-03-02 | Methods for treating dry eye |
US17/077,463 US20210121430A1 (en) | 2011-07-18 | 2020-10-22 | Omega-3 fatty acid supplementation for use in treating dry eye |
Related Parent Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/910,661 Continuation-In-Part US10709680B2 (en) | 2011-07-18 | 2018-03-02 | Methods for treating dry eye |
US202016926022A Continuation | 2011-07-18 | 2020-07-10 | |
US202016926022A Continuation-In-Part | 2011-07-18 | 2020-07-10 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/687,485 Continuation US11648227B2 (en) | 2011-07-18 | 2022-03-04 | Omega-3 fatty acid supplementation for use in treating dry eye |
Publications (1)
Publication Number | Publication Date |
---|---|
US20210121430A1 true US20210121430A1 (en) | 2021-04-29 |
Family
ID=75585409
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/077,463 Abandoned US20210121430A1 (en) | 2011-07-18 | 2020-10-22 | Omega-3 fatty acid supplementation for use in treating dry eye |
US17/687,485 Active US11648227B2 (en) | 2011-07-18 | 2022-03-04 | Omega-3 fatty acid supplementation for use in treating dry eye |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/687,485 Active US11648227B2 (en) | 2011-07-18 | 2022-03-04 | Omega-3 fatty acid supplementation for use in treating dry eye |
Country Status (1)
Country | Link |
---|---|
US (2) | US20210121430A1 (en) |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI225398B (en) | 1999-07-14 | 2004-12-21 | R Tech Ueno Ltd | Composition for treatment of external secretion disorders |
PL355998A1 (en) | 1999-11-09 | 2004-05-31 | Alcon Inc. | Compositions containing hydroxyeicosatetraenoic acid derivatives and methods of use in treating dry eye disorders |
US6506412B2 (en) | 2000-11-29 | 2003-01-14 | Sciencebased Health | Treatment of dry eye syndrome |
US20060127505A1 (en) | 2002-01-16 | 2006-06-15 | David Haines | Anti-inflammatory formulations |
US20040048926A1 (en) | 2002-03-15 | 2004-03-11 | Hoffman Dennis Robert | Use of docosahexaenoic acid and arachidonic acid to enhance the visual development of term infants breast-fed up to the age of six months |
US20040076695A1 (en) | 2002-07-08 | 2004-04-22 | Advanced Vision Research | EPA and DHA enriched omega-3 supplement for the treatment of dry eye, meibomianitis and xerostomia |
US6649195B1 (en) | 2002-07-11 | 2003-11-18 | Vitacost.Com, Inc. | Eyesight enhanced maintenance composition |
US7041840B2 (en) | 2002-12-18 | 2006-05-09 | Alberta Research Council Inc. | Antioxidant triacylglycerols and lipid compositions |
US9192586B2 (en) | 2003-03-10 | 2015-11-24 | Zeavision Llc | Zeaxanthin formulations with additional ocular-active nutrients, for protecting eye health and treating eye disorders |
US20070265341A1 (en) | 2004-07-01 | 2007-11-15 | The Schepens Eye Research Institute Inc. | Compositions and methods for treating eye disorders and conditions |
US8541413B2 (en) | 2004-10-01 | 2013-09-24 | Ramscor, Inc. | Sustained release eye drop formulations |
DE202004015931U1 (en) | 2004-10-13 | 2005-01-05 | Dr. Gerhard Mann Chem.-Pharm. Fabrik Gmbh | Composition containing omega-3 fatty acids and omega-6 fatty acids |
BRPI0620210A2 (en) | 2005-12-20 | 2011-11-01 | Alcon Res Ltd | composition and processes for inhibiting the progression of macular degeneration and promoting healthy vision |
WO2008143642A2 (en) | 2006-11-09 | 2008-11-27 | Children's Medical Center Corporation | Methods of treating and preventing ocular neovascularization with omega-3 polyunsaturated fatty acids |
EP1932520A1 (en) | 2006-12-15 | 2008-06-18 | Novartis AG | Nutritional supplement composition for treatment of ocular diseases |
EP1932521A1 (en) | 2006-12-15 | 2008-06-18 | Novartis AG | Nutritional supplement composition for treatment of ocular diseases |
US20090226547A1 (en) | 2008-03-05 | 2009-09-10 | Gilbard Jeffrey P | Dietary Supplement For Eye Health |
WO2010040232A1 (en) | 2008-10-09 | 2010-04-15 | Waratah Pharmaceuticals Inc. | Use of scyllo-inositols for the treatment of macular degeneration-related disorders |
US20130011469A1 (en) | 2009-07-23 | 2013-01-10 | U.S. Nutraceuticals, Llc D/B/A Valensa International | Krill oil and carotenoid composition, associated method and delivery system |
WO2011057183A1 (en) | 2009-11-06 | 2011-05-12 | Alcon Research, Ltd. | Nutritional supplements for relief of dry eye |
CN103221041B (en) | 2010-11-19 | 2016-08-03 | 日本水产株式会社 | For corneal epithelium pathological changes and/or the therapeutic agent of conjunctival epithelium pathological changes or preventive |
CA2738357C (en) | 2011-04-07 | 2019-08-06 | Amerisciences, Lp | Methods and compositions to promote ocular health |
US9115078B2 (en) | 2011-07-18 | 2015-08-25 | Physicians Recommended Nutriceuticals, Llc | Compositions for improving the quality of the meibum composition of inflamed or dysfunctional meibomian glands |
US9381183B2 (en) | 2012-07-18 | 2016-07-05 | Physicians Recommended Nutriceuticals, Llc | Methods for improving the quality of the meibum composition of meibomian glands |
US10709680B2 (en) * | 2011-07-18 | 2020-07-14 | Physicians Recommended Nutriceuticals, Llc | Methods for treating dry eye |
ES2565402T3 (en) | 2011-09-12 | 2016-04-04 | Tassos GEORGIOU | Use of omega fatty acids for the treatment of diseases |
-
2020
- 2020-10-22 US US17/077,463 patent/US20210121430A1/en not_active Abandoned
-
2022
- 2022-03-04 US US17/687,485 patent/US11648227B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20220184018A1 (en) | 2022-06-16 |
US11648227B2 (en) | 2023-05-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9381183B2 (en) | Methods for improving the quality of the meibum composition of meibomian glands | |
US9115078B2 (en) | Compositions for improving the quality of the meibum composition of inflamed or dysfunctional meibomian glands | |
Deinema et al. | A randomized, double-masked, placebo-controlled clinical trial of two forms of omega-3 supplements for treating dry eye disease | |
Thode et al. | Current and emerging therapeutic strategies for the treatment of meibomian gland dysfunction (MGD) | |
Chinnery et al. | Omega‐3 supplementation is neuroprotective to corneal nerves in dry eye disease: a pilot study | |
Kangari et al. | Short-term consumption of oral omega-3 and dry eye syndrome | |
Barabino et al. | The role of systemic and topical fatty acids for dry eye treatment | |
US20100080768A1 (en) | Compositions and Methods for the Treatment of Inflammatory Dermatosis and Other Pathological Conditions of the Skin | |
Romeo Villadóniga et al. | Effects of oral supplementation with docosahexaenoic acid (DHA) plus antioxidants in pseudoexfoliative glaucoma: A 6-month open-label randomized trial | |
US20160067204A1 (en) | Therapeutic or prophylactic agent for corneal epithelium disorders and/or conjunctival epithelium disorders | |
NO20180849A1 (en) | Composition for treatment of dry eye disease and meibomianitis | |
Downie et al. | An artificial tear containing flaxseed oil for treating dry eye disease: A randomized controlled trial | |
Sandford et al. | Therapeutic potential of castor oil in managing blepharitis, meibomian gland dysfunction and dry eye | |
Tellez-Vazquez | Omega-3 fatty acid supplementation improves dry eye symptoms in patients with glaucoma: results of a prospective multicenter study | |
EP1904044B1 (en) | Use of a combination comprising l-carnitine or alkanoyl l-carnitine, lipid solubl benzoquinone and omega-3-polyunsaturated fatty acid for the preparation of a dietary supplement or medicament for the treatment of corneal diseases | |
US10709680B2 (en) | Methods for treating dry eye | |
US11648227B2 (en) | Omega-3 fatty acid supplementation for use in treating dry eye | |
Silva et al. | Comparison between fish and linseed oils administered orally for the treatment of experimentally induced keratoconjunctivitis sicca in rabbits | |
US20160310456A1 (en) | Compositions and methods for using same for reducing levels of arachidonic acid in tissue having undergone an invasive procedure | |
WO2018005685A1 (en) | Compositions and methods for using same for reducing levels of arachidonic acid in tissue having undergone an invasive procedure | |
Hsu et al. | Effects of Supplementation with Lutein Plus Docosahexaenoic Acid Oral Complex on Eye Dryness, Visual Function, and Memory Function in Healthy Subjects: A Single‐Arm Clinical Trial | |
Jain et al. | Role of Omega-3 fatty acids in meibomian gland dysfunction | |
Zabell | Advancing your practice: OMG it's MGD! The basics of meibomian gland dysfunction and how you can help in the pharmacy | |
Franke et al. | Neuromodulation for Treatment of Dry Eye | |
Zabell | OMG it's MGD! The basics of meibomian gland dysfunction and how you can help in the pharmacy. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: PRN PHYSICIAN RECOMMENDED NUTRICEUTICALS LLC, PENNSYLVANIA Free format text: NUNC PRO TUNC ASSIGNMENT;ASSIGNORS:SMITH, S GREGORY;GROSS, MICHAEL B.;SANDNES, OLAV B;SIGNING DATES FROM 20200424 TO 20200506;REEL/FRAME:054291/0813 |
|
AS | Assignment |
Owner name: PRN PHYSICIAN RECOMMENDED NUTRICEUTICALS LLC, PENNSYLVANIA Free format text: NUNC PRO TUNC ASSIGNMENT;ASSIGNORS:SMITH, S GREGORY;GROSS, MICHAEL B;SANDNES, OLAV E;SIGNING DATES FROM 20200424 TO 20200506;REEL/FRAME:054858/0672 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: APPLICATION DISPATCHED FROM PREEXAM, NOT YET DOCKETED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
AS | Assignment |
Owner name: CAPITAL ONE, NATIONAL ASSOCIATION, AS AGENT, MARYLAND Free format text: SECURITY INTEREST;ASSIGNOR:PRN PHYSICIAN RECOMMENDED NUTRICEUTICALS, LLC;REEL/FRAME:057339/0669 Effective date: 20210831 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER |
|
STCB | Information on status: application discontinuation |
Free format text: EXPRESSLY ABANDONED -- DURING EXAMINATION |