ITGE20110004A1 - OPHTHALMIC COMPOSITIONS FOR NUTRITION, MAINTAINING THE INTEGRITY OF THE EPITHELIUM OF THE EYE AND THE PROTECTION OF THEMSELVES FROM OXIDATION. - Google Patents
OPHTHALMIC COMPOSITIONS FOR NUTRITION, MAINTAINING THE INTEGRITY OF THE EPITHELIUM OF THE EYE AND THE PROTECTION OF THEMSELVES FROM OXIDATION. Download PDFInfo
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- ITGE20110004A1 ITGE20110004A1 IT000004A ITGE20110004A ITGE20110004A1 IT GE20110004 A1 ITGE20110004 A1 IT GE20110004A1 IT 000004 A IT000004 A IT 000004A IT GE20110004 A ITGE20110004 A IT GE20110004A IT GE20110004 A1 ITGE20110004 A1 IT GE20110004A1
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- Prior art keywords
- vitamin
- compositions according
- water dispersible
- sodium
- msm
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 38
- 235000016709 nutrition Nutrition 0.000 title description 7
- 210000000981 epithelium Anatomy 0.000 title description 5
- 230000035764 nutrition Effects 0.000 title description 5
- 230000003647 oxidation Effects 0.000 title description 5
- 238000007254 oxidation reaction Methods 0.000 title description 5
- 229940016409 methylsulfonylmethane Drugs 0.000 claims description 29
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 claims description 29
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 claims description 18
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 claims description 9
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 claims description 9
- 239000000017 hydrogel Substances 0.000 claims description 9
- 229940108325 retinyl palmitate Drugs 0.000 claims description 9
- 235000019172 retinyl palmitate Nutrition 0.000 claims description 9
- 239000011769 retinyl palmitate Substances 0.000 claims description 9
- 229940042585 tocopherol acetate Drugs 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 229940124274 edetate disodium Drugs 0.000 claims description 8
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 7
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 7
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 6
- VAZJLPXFVQHDFB-UHFFFAOYSA-N 1-(diaminomethylidene)-2-hexylguanidine Polymers CCCCCCN=C(N)N=C(N)N VAZJLPXFVQHDFB-UHFFFAOYSA-N 0.000 claims description 5
- 229920002413 Polyhexanide Polymers 0.000 claims description 5
- 229940093158 polyhexanide Drugs 0.000 claims description 5
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 5
- 229960003415 propylparaben Drugs 0.000 claims description 5
- 239000000872 buffer Substances 0.000 claims description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 229910021538 borax Inorganic materials 0.000 claims description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 claims description 3
- 239000004328 sodium tetraborate Substances 0.000 claims description 3
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- 235000010338 boric acid Nutrition 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 241000894006 Bacteria Species 0.000 claims 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims 1
- 235000015497 potassium bicarbonate Nutrition 0.000 claims 1
- 239000011736 potassium bicarbonate Substances 0.000 claims 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims 1
- 239000003755 preservative agent Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 1
- 239000001488 sodium phosphate Substances 0.000 claims 1
- 235000011008 sodium phosphates Nutrition 0.000 claims 1
- 230000003068 static effect Effects 0.000 claims 1
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- 238000009472 formulation Methods 0.000 description 13
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- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 8
- 229930003231 vitamin Natural products 0.000 description 8
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- 229910052717 sulfur Inorganic materials 0.000 description 7
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 6
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- 150000003722 vitamin derivatives Chemical class 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 229930003427 Vitamin E Natural products 0.000 description 5
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- 235000006708 antioxidants Nutrition 0.000 description 5
- 210000004087 cornea Anatomy 0.000 description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
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- 230000018109 developmental process Effects 0.000 description 4
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- 229940061607 dibasic sodium phosphate Drugs 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 230000004438 eyesight Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
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- 239000008213 purified water Substances 0.000 description 3
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- 208000005494 xerophthalmia Diseases 0.000 description 3
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229940087168 alpha tocopherol Drugs 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
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- 229930182817 methionine Natural products 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 230000004792 oxidative damage Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
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- 241000283690 Bos taurus Species 0.000 description 1
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- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
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- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
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- 230000035587 bioadhesion Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
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- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
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- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
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- 230000007613 environmental effect Effects 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960004452 methionine Drugs 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000037125 natural defense Effects 0.000 description 1
- 230000004297 night vision Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 229940093916 potassium phosphate Drugs 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
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- 239000000790 retinal pigment Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
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- 239000011573 trace mineral Substances 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
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Classifications
-
- 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
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
-
- 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
- A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
- A61K31/10—Sulfides; Sulfoxides; Sulfones
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
Description
DESCRIZIONE DELL'INVENZIONE DESCRIPTION OF THE INVENTION
Descrizione del brevetto per invenzione industriale avente per titolo: Description of the patent for industrial invention entitled:
"COMPOSIZIONI OFTALMICHE PER LA NUTRIZIONE, IL MANTENIMENTO DELL'INTEGRITA' DELL'EPITELIO DEI TESSUTI OCULARI E LA PROTEZIONE DEGLI STESSI DALL'OSSIDAZIONE" "OPHTHALMIC COMPOSITIONS FOR NUTRITION, MAINTENANCE OF THE INTEGRITY OF THE EPITHELIUM OF THE OCULAR TISSUES AND THE PROTECTION OF THE SAME FROM OXIDATION"
La presente invenzione si riferisce a composizioni oftalmiche<per la nutrizione, il mantenimento e la protezione dell'integrità >dell'epitelio dei tessuti oculari e la difesa degli stessi dai danni ossidativi dei radicali liberi a livello delle membrane cellulari di retina cornea e cristallino e di altri tessuti oculari. The present invention refers to ophthalmic compositions <for the nutrition, maintenance and protection of the integrity> of the epithelium of ocular tissues and the defense of the same from oxidative damage of free radicals at the level of the cell membranes of the cornea and crystalline retina and of other ocular tissues.
Senza voler essere legati ad alcuna teoria, ma sulla base dei dati della letteratura scientifica, l'inventore ritiene che le composizioni oftalmiche descritte nella presente invenzione siano assolutamente originali e non mai descritte in precedenza, né in letteratura, né in altri brevetti. Without wishing to be tied to any theory, but on the basis of the data of the scientific literature, the inventor believes that the ophthalmic compositions described in the present invention are absolutely original and never described previously, neither in literature, nor in other patents.
Infatti l'originalità della presente invenzione consiste nell'aver associato per la prima volta, in una soluzione per uso topico oftalmico, quattro sostanze che presentano caratteristiche di sinergismo: nutrizionale-vitaminico, antiossidante, protettivo dell' integrità epiteliale a livello dei tessuti oculari. In fact, the originality of the present invention consists in having associated for the first time, in a solution for topical ophthalmic use, four substances which have synergistic characteristics: nutritional-vitamin, antioxidant, protective of the epithelial integrity at the level of the ocular tissues.
Le sostanze in oggetto sono: The substances in question are:
1) Metilsulfonilmetano (MSM) 1) Methylsulfonylmethane (MSM)
Sostanza presente in natura e nei tessuti dell'uomo ,che fornisce zolfo biologicamente attivo, per la biosintesi di aminoacidi solforati (metionina, cistina, cisterna, taurina) indispensabili a loro volta per la biosintesi delle proteine costituenti del tessuto connettivo e della membrana cellulare dei tessuti oculari (cornea, retina, cristallino ecc.) ed inoltre elementi essenziali degli enzimi ad azione antiossidante, che devono la loro azione cosiddetti ponti disolfuro. Substance present in nature and in human tissues, which provides biologically active sulfur, for the biosynthesis of sulfur amino acids (methionine, cystine, cistern, taurine) which are in turn indispensable for the biosynthesis of the constituent proteins of the connective tissue and cell membrane of ocular tissues (cornea, retina, lens, etc.) and also essential elements of the enzymes with antioxidant action, which owe their action to so-called disulfide bridges.
MSM svolge pertanto una duplice funzione: quale nutriente apportatore di zolfo e quale antagonista dei radicali liberi. MSM therefore has a dual function: as a nutrient that brings sulfur and as an antagonist of free radicals.
2) Vitamina A (axeroftolo) 2) Vitamin A (axerophtol)
Vitamina essenziale per la crescita, lo sviluppo e il mantenimento del tessuto epiteliale dell'occhio (retina particolare) e per una corretta visione, specialmente in condizioni di ridotta luminosità . Vitamin essential for the growth, development and maintenance of the epithelial tissue of the eye (particular retina) and for correct vision, especially in conditions of reduced brightness.
Deficit di vitamina A può portare alla sindrome dell'occhio secco (xeroftalmia). Vitamin A deficiency can lead to dry eye syndrome (xerophthalmia).
Tale vitamina svolge inoltre una efficace azione antiossidante. 3) Vitamina E (alfa tocoferolo) This vitamin also has an effective antioxidant action. 3) Vitamin E (alpha tocopherol)
Tale vitamina ha la specifica funzione di prevenire l'ossidazione degli acidi polinsaturi, indispensabili per il metabolismo cellulare, inibendo in tal modo la formazione dei radicali liberi, responsabili dei danni ossidativi alla membrana cellulare dei tessuti oculari. La Vitamina E viene utilizzata nella prevenzione e nel trattamento della retinopatia, causata da un eccesso di ossidazione della retina. This vitamin has the specific function of preventing the oxidation of polyunsaturated acids, essential for cellular metabolism, thus inhibiting the formation of free radicals, responsible for oxidative damage to the cell membrane of eye tissues. Vitamin E is used in the prevention and treatment of retinopathy, caused by an excess of oxidation of the retina.
4) Disodio edetato 4) Disodium edetate
Tale sostanza ha la funzione di complessare (sequestrare) gli ioni metallici, indispensabili per la biosintesi e la proliferazione dei radicali liberi nei tessuti oculari, facilitando l'eliminazione di tali radicali, attraverso il flusso sanguigno e l'emuntorio renale, rallentando in tal modo le patologie ossidative a livello di retina, cristallino, cornea e di altri tessuti dell'occhio. This substance has the function of complexing (sequestrating) the metal ions, essential for the biosynthesis and proliferation of free radicals in the ocular tissues, facilitating the elimination of these radicals, through the blood flow and the renal emunctory, thus slowing down oxidative pathologies in the retina, lens, cornea and other tissues of the eye.
La composizione à ̈ stata approvata dal Centro per la Ricerca Clinica e Sperimentazione delle Malattie della Superficie Oculare di Genova (Prof. Maurizio Rolando). The composition has been approved by the Center for Clinical Research and Experimentation of Ocular Surface Diseases of Genoa (Prof. Maurizio Rolando).
L'Istituto Superiore di Sanità sta svolgendo le pratiche per il rilascio della certificazione Ce del prodotto Oftyvit® che avremmo a breve. The Istituto Superiore di Sanità is carrying out the procedures for the release of the Ce certification of the Oftyvit® product that we will soon have.
Oltre al razionale del sinergismo nutrizionale,antiossidante dei quattro componenti sopra indicati, risulta particolarmente originale l'attività del metilsulfonilmetano che, oltre a fornire zolfo biologicamente attivo, aumenta la permeabilità cellulare e facilita l'assorbimento intraoculare della stessa sostanza e degli altri tre componenti attivi. In addition to the rationale of the nutritional synergism, antioxidant of the four components indicated above, the activity of methylsulfonylmethane is particularly original which, in addition to providing biologically active sulfur, increases cell permeability and facilitates the intraocular absorption of the same substance and of the other three active components. .
Secondo l'invenzione, risulta che al presente siano presenti in commercio in diversi Paesi preparazioni per uso oftalmico contenenti metilsulfonilmetano, altri colliri contenenti vitamina A e/o vitamina E, molti colliri con disodio edetato, ma non risulta attualmente in commercio in nessun Paese nessun collirio contenente l'associazione di tutte le sostanze attive indicate nella presente invenzione, con le finalità e il sinergismo specificati, che saranno più estesamente illustrate in seguito. According to the invention, it appears that preparations for ophthalmic use containing methylsulfonylmethane, other eye drops containing vitamin A and / or vitamin E, many eye drops with edetate disodium, are currently available on the market in various countries, but none are currently on the market in any country. eye drops containing the association of all the active substances indicated in the present invention, with the specified purposes and synergism, which will be more fully illustrated below.
Si può pertanto validamente affermare l'assoluta originalità e innovatività delle formulazioni oftalmiche descritte e illustrate nella presente invenzione The absolute originality and innovativeness of the ophthalmic formulations described and illustrated in the present invention can therefore be validly affirmed.
Secondo l'invenzione le sostanze sopra citate,associate per la prima volta tutte insieme, vengono incorporate in un idrogel acquoso a base di carbossimetilcellulosa. According to the invention, the substances mentioned above, associated for the first time all together, are incorporated in an aqueous hydrogel based on carboxymethylcellulose.
Tale veicolo, che presenta caratteristiche di pH, viscosità , osmolarità molto simili a quelle del liquido lacrimale, risulta perfettamente tollerato dalle mucose oculari, e per le sue caratteristiche reologiche e viscoelastiche, assicura un efficace contatto delle sostanze attive sulla cornea e sulle altre mucose oculari, ed inoltre, per la presenza dell'MSM, attivatore della permeabilità cellulare, facilita la penetrazione intraoculare delle quattro sostanze attive. This vehicle, which has pH, viscosity, osmolarity characteristics very similar to those of tear fluid, is perfectly tolerated by the ocular mucous membranes, and due to its rheological and viscoelastic characteristics, ensures effective contact of the active substances on the cornea and other ocular mucous membranes. , and moreover, due to the presence of MSM, activator of cellular permeability, it facilitates the intraocular penetration of the four active substances.
Oggetto della presente invenzione à ̈ la messa a punto originale di una preparazione per uso topico oftalmico ad azione: The object of the present invention is the original development of a preparation for topical ophthalmic use with action:
I) nutriente -vitaminica; I) nutrient-vitamin;
2) protettiva antiossidante,antiradicali liberi; 2) protective antioxidant, anti-free radicals;
3) rallentante la degenerazione delle proteine dei tessuti oculari, agevolando il processo di riparazione, in tutti i casi di stress ossidativi dovuti ad avverse condizioni ambientali (smog, irradiazione solare o da luce artificiale, radiazioni UV,videoterminali) senescenza, uso di fermaci ad azione ossidante. 3) slowing down the degeneration of ocular tissue proteins, facilitating the repair process, in all cases of oxidative stress due to adverse environmental conditions (smog, solar irradiation or artificial light, UV radiation, video terminals) senescence, use of fasteners to oxidizing action.
Tutte condizioni che sovente comportano alterazioni che possono essere reversibili e di lieve entità o anche più significative. All conditions that often involve alterations that can be reversible and of slight entity or even more significant.
RAZIONALE DELLA SCELTA DEI COMPONENTI DELL'INVENZIONE E LORO CARATTERISTICHE 1) La scelta del metilsulfonilmetano (MSM) nelle formulazioni oftalmiche della presente invenzione à ̈ correlata con l'effetto nutritivo e antiossidante di tale sostanza. RATIONALE OF THE SELECTION OF THE COMPONENTS OF THE INVENTION AND THEIR CHARACTERISTICS 1) The choice of methylsulfonylmethane (MSM) in the ophthalmic formulations of the present invention is correlated with the nutritional and antioxidant effect of this substance.
Trattasi di una molecola contenente zolfo biologicamente attivo, che si trova molto diffusa in natura ,nei mammiferi e nell'uomo (nel sangue di un uomo adulto circa 0.2 mg/ kg ) It is a molecule containing biologically active sulfur, which is found very widespread in nature, in mammals and in humans (in the blood of an adult man about 0.2 mg / kg)
I tessuti oculari richiedono un costante apporto di zolfo per la biosintesi degli aminoacidi solforati (metionina, cisteina, cistina, taurina) indispensabili per la biosintesi delle proteine costituenti del tessuto connettivo e della membrana cellulare di tali tessuti (comea,cristallino,retina,congiuntiva ecc.) e costituenti essenziali dei numerosi enzimi ad azione antiossidante ed antagonisti dei radicali liberi per la presenza dei cosiddetti ponti disolfuro(-S_S). Ocular tissues require a constant supply of sulfur for the biosynthesis of sulfur amino acids (methionine, cysteine, cystine, taurine) essential for the biosynthesis of the constituent proteins of the connective tissue and cell membrane of these tissues (comea, crystalline, retina, conjunctiva, etc. .) and essential constituents of the numerous enzymes with antioxidant action and antagonists of free radicals due to the presence of the so-called disulfide bridges (-S_S).
L'MSM rappresenta una valida risposta a tali esigenze e svolge pertanto una duplice funzione: nutriente nei casi di deficit carenziali e antiossidante, per assicurare il corretto funzionamento dei naturali processi di difesa dei tessuti dall' aggressione dei radicali liberi. MSM represents a valid response to these needs and therefore performs a double function: nourishing in cases of deficiency and antioxidant, to ensure the correct functioning of the natural defense processes of the tissues from the aggression of free radicals.
Inoltre I'MSM migliora la permeabilità delle membrane cellulari favorendo l'assorbimento intraoculare di oligoelementi ,vitamine e dello stesso MSM. (Richmond VL. Life Sci. I986.Jul.21 ;39(3):263-8.; Magnuson BA et al. J Agric Food Chem. 2007,Feb.55 (3):1033-38.) Furthermore, the MSM improves the permeability of cell membranes by promoting the intraocular absorption of trace elements, vitamins and the same MSM. (Richmond VL. Life Sci. I986. Jul. 21; 39 (3): 263-8 .; Magnuson BA et al. J Agric Food Chem. 2007, Feb.55 (3): 1033-38.)
<La tossicità dell'MSM à ̈ molto bassa ,sia in dosi singole che ripetute.Alcuni studi (Horvath K et al. Food Chem. Toxicol.2002,Oct.40(1 0): 1459-62) hanno dimostrato che dosi di>g.1.5/kg/die somministrate per os per 90 gg. non hanno provocato nessun effetto tossico.Altri studi (Magnusson BA et al. Food Chem. Toxicol. 2007Jun.45 (6);977-84) hanno confermato l'assenza di tossicità con dosi di g.l/kg/die sulla fertilità ,la gravidanza e lo sviluppo neonatale nel ratto. Studi sul metabolismo dell'MSM harmo rivelato un rapido assorbimento ed una rapida eliminazione urinaria di tale sostanza ( A et al. Toxicol.Letter.2001, 123:169-177. Magnuson BA et al .Agric. Food. Chem. 2007,55 (3):1033-38) <The toxicity of MSM is very low, both in single and repeated doses. Studies (Horvath K et al. Food Chem. Toxicol. 2002, Oct.40 (1 0): 1459-62) have shown that doses of > 1.5 g / kg / day administered orally for 90 days. did not cause any toxic effects. Other studies (Magnusson BA et al. Food Chem. Toxicol. 2007Jun.45 (6); 977-84) confirmed the absence of toxicity with doses of g.l / kg / day on fertility, the pregnancy and neonatal development in the rat. Studies on the metabolism of MSM revealed a rapid absorption and urinary elimination of this substance (A et al. Toxicol.Letter.2001, 123: 169-177. Magnuson BA et al. Agricultural. Food. Chem. 2007,55. (3): 1033-38)
2) La presenza della vitamina A palmitato (axeroftolo) nelle formulazioni oftalmiche della presente invenzione à ̈ dovuta al fatto che tale vitamina à ̈ essenziale per la crescita, lo sviluppo e il mantenimento del tessuto epiteliale dell'occhio, in particolare della retina, ed à ̈ indispensabile per una corretta visione, particolarmente in condizioni di scarsa illuminazione. 2) The presence of vitamin A palmitate (axerophtol) in the ophthalmic formulations of the present invention is due to the fact that this vitamin is essential for the growth, development and maintenance of the epithelial tissue of the eye, in particular of the retina, and It is essential for correct vision, particularly in low light conditions.
Deficienze prolungate di apporto di vitamina A con la dieta, o per particolari disfunzioni, possono provocare la sindrome dell'occhio secco (xeroftalmia), della quale il sintomo iniziale à ̈ la scarsa visione notturna, che può progredire fino a gravi lesioni della retina. Altri sintomi carenziali sono le alterazioni delle membrane oculari. Prolonged deficiencies in dietary vitamin A, or due to particular dysfunctions, can cause dry eye syndrome (xerophthalmia), of which the initial symptom is poor night vision, which can progress to severe retinal lesions. Other deficiency symptoms are changes in the ocular membranes.
La vitamina A viene usata come riepitelizzante nella profilassi della xeroftalmia e come coadiuvante nel trattamento della retinite pigmentosa,patologia degenerativa e progressiva della retina. Vitamin A is used as a restorative in the prophylaxis of xerophthalmia and as an adjuvant in the treatment of retinitis pigmentosa, a degenerative and progressive pathology of the retina.
I fotorecettori, bastoncelli e coni, presenti nel fondo della retina, sono i primi ad essere colpiti dalla patologia con conseguente diminuzione della visione, specie notturna. (Maurin JF, Renard JP.Rev.Int.Trach ..Pathol. Ocul. Trop Subtrop Santà ̈ Publique 1997;74:21-42.) La somministrazione anche topica di vitamina A può rallentare il manifestarsi di tale patologia. (Tseng SC et al. Ophthalmology .1985;Jun.92 (6):717-27.- Basti S et aI.Cornea.2008;Sept.;27 (8):973) The photoreceptors, rods and cones, present in the bottom of the retina, are the first to be affected by the disease with a consequent decrease in vision, especially at night. (Maurin JF, Renard JP.Rev.Int.Trach ..Pathol. Ocul. Trop Subtrop Santà ̈ Publique 1997; 74: 21-42.) The topical administration of vitamin A can also slow down the onset of this pathology. (Tseng SC et al. Ophthalmology. 1985; Jun. 92 (6): 717-27.- Basti S et aI. Cornea. 2008; Sept.; 27 (8): 973)
3) La vitamina E acetato (alfa tocoferolo) à ̈ stata inserita nelle formulazioni a motivo della sua funzione svolta a livello dei tessuti oculari. Tale vitamina infatti à ̈ presente nell'occhio e in molti altri tessuti del corpo umano con la funzione di prevenire l'ossidazione degli acidi polinsaturi, indispensabili per il metabolismo cellulare, inibendo la formazione dei radicali liberi, responsabili dei danni ossidati vi alla membrana cellulare dei tessuti retinici e di altri tessuti oculari. 3) Vitamin E acetate (alpha tocopherol) has been included in the formulations due to its function carried out in the ocular tissues. In fact, this vitamin is present in the eye and in many other tissues of the human body with the function of preventing the oxidation of polyunsaturated acids, essential for cellular metabolism, inhibiting the formation of free radicals, responsible for oxidized damage to the cell membrane. retinal tissues and other ocular tissues.
Alcuni studiosi (Wiegand RD et al. Invest. Ophthalmol. Vis Sci 1986.May.27 (5) :727-33) hanno dimostrato un'azione protettiva della vitamina E a livello del metabolismo degli acidi grassi polinsaturi nei bastoncelli e coni della retina, durante l'azione danneggiante della luce. Tale azione protettiva si svolge nei Some scholars (Wiegand RD et al. Invest. Ophthalmol. Vis Sci 1986.May.27 (5): 727-33) have demonstrated a protective action of vitamin E at the level of the metabolism of polyunsaturated fatty acids in rods and cones of the retina , during the damaging action of light. This protective action takes place in the
confronti<di diverse patologie della retina: degenerazione>macul are , ossidativi pigmentosa, distrofia epiteliale dei pigmenti retinici, stress ossidativi retinico, danni retinici da irradiazione luminosa UV Ylmaz T et al .Ophthalmologica.2007 ;221(3):159-66 - Goss -Sampson MA et al. Free Radic. Biol. Med. 1998 Sept.;25 (4-5):457-62.) - Robison WG et al. Invest Ophthalmol Vis Sci. 1979 Jul;18 (7):683-90. Kagan VE et al. Biul. Exp .Biol .Med.1977 Apr.83 (4) :411-13. - Berson EL et al..Arch.Ophthalmo1.1993 Jun.lll (6) :761-72. - EI-Hifnawi el S .et al. Nutrition. 1995 Sept.Oct. Il (5 Suppl.) :576-81.) comparisons of different retinal pathologies: macular degeneration, oxidative pigments, epithelial dystrophy of retinal pigments, retinal oxidative stress, retinal damage from UV light irradiation Ylmaz T et al. Ophthalmologica. 2007; 221 (3): 159-66 - Goss -Sampson MA et al. Free Radic. Biol. Med. 1998 Sept.; 25 (4-5): 457-62.) - Robison WG et al. Invest Ophthalmol Vis Sci. 1979 Jul; 18 (7): 683-90. Kagan VE et al. Biul. Exp .Biol .Med.1977 Apr.83 (4): 411-13. - Berson EL et al. Arch. Ophthalmo 1.1993 Jun.lll (6): 761-72. - EI-Hifnawi el S .et al. Nutrition. 1995 Sept Oct. Il (5 Suppl.): 576-81.)
Nelle formulazioni oftalmiche della presente invenzione l'apporto della vitamina E completa il razionale di un'azione topica nutriente e antiossidante di tale vitamina con un evidente sinergismo con la vitamina A, il metilsulfonilmetano e il disodio edetato. In the ophthalmic formulations of the present invention the contribution of vitamin E completes the rationale of a topical nourishing and antioxidant action of this vitamin with an evident synergism with vitamin A, methylsulfonylmethane and edetate disodium.
4) La presenza del disodio edetato nelle formulazioni oftalmiche della presente invenzione à ̈ legata al significativo ruolo svolto da tale sostanza complessante, non citotossica, nella rimozione dei siti attivi dell’enzima metalloproteinasi a livello dei tessuti oculari. L’EDTA disodico infatti sequestra il nucleo metallico dell’enzima, inattivando in tal modo la metalloproteinasi e rallentando o inibendo la degenerazione dei complessi proteici oculari. Inoltre, tale azione complessante (sequestrante) gli ioni metallici dei sistemi proteici, indispensabili per la formazione e la proliferazione dei radicali liberi nei tessuti oculari, comporta una riduzione della produzione dei radicali liberi ossigenati, riducendo la patologica iperossidazione lipidica delle membrane cellulari. (Chintala SK et al.Exp.Eye Res.2005 Oct.;81 (4):429-36. -Guttman C et al. Ophthalmology Times, 2005, Oct. 1. - Fong D et al. Curr.Eye Res.1987 Feb,6 (2) :357-61. - Kaur IP et al. Int J Pharm 2000 Apr.20;199 (2): 119-27.) Pertanto, la presente invenzione ha per oggetto una composizione oftalmica originale comprendente i seguenti principi attivi: 4) The presence of edetate disodium in the ophthalmic formulations of the present invention is linked to the significant role played by this complexing substance, not cytotoxic, in the removal of the active sites of the metalloproteinase enzyme in the ocular tissues. In fact, disodium EDTA sequestrates the metal nucleus of the enzyme, thus inactivating the metalloproteinase and slowing or inhibiting the degeneration of ocular protein complexes. Furthermore, this complexing (sequestering) action of the metal ions of the protein systems, essential for the formation and proliferation of free radicals in the ocular tissues, leads to a reduction in the production of oxygenated free radicals, reducing the pathological lipid hyperoxidation of cell membranes. (Chintala SK et al. Exp.Eye Res. 2005 Oct.; 81 (4): 429-36. -Guttman C et al. Ophthalmology Times, 2005, Oct. 1. - Fong D et al. Curr.Eye Res. 1987 Feb, 6 (2): 357-61. - Kaur IP et al. Int J Pharm 2000 Apr. 20; 199 (2): 119-27.) Therefore, the present invention relates to an original ophthalmic composition comprising the following active ingredients:
• metilsulfonilmetano (MSM) â € ¢ methylsulfonylmethane (MSM)
• vitamina A palmitato â € ¢ Vitamin A palmitate
• vitamina E acetato â € ¢ Vitamin E acetate
• disodio edetato â € ¢ edetate disodium
Le composizioni oftalmiche dell’invenzione presentano, come già specificato, requisiti ideali per soluzioni oftalmiche assolutamente originali, con azioni: nutriente-vitaminica, antiossidante, protettiva dell'endotelio, coadiuvante il processo di riparazione cellulare dopo i danni da stress ossidativi. The ophthalmic compositions of the invention have, as already specified, ideal requirements for absolutely original ophthalmic solutions, with actions: nourishing-vitamin, antioxidant, endothelial protective, assisting the cellular repair process after damage from oxidative stress.
Tali azioni sono dovute ad un effetto sinergico delle attività dei componenti attivi, venendo a colmare una vera e propria lacuna nell'ambito del trattamento topico oculare delle particolari condizioni precedentemente indicate, che richiedano un'efficace nutrizione e protezione dei tessuti oculari (retina in particolare) dagli effetti dannosi dei radicali liberi. These actions are due to a synergistic effect of the activities of the active components, filling a real gap in the topical ocular treatment of the particular conditions previously indicated, which require effective nutrition and protection of the ocular tissues (retina in particular ) from the harmful effects of free radicals.
Secondo l'invenzione, le composizioni in oggetto sono veicolate in un idrogel acquoso contenente un opportuna concentrazione (preferita tra 0.400% e 0.600%) di carbossimetilcellulosa, che per le sue caratteristiche viscoelastiche e mucomimetiche assicura un'efficace bioadesione delle sostanze attive sulle mucose oculari. La carbosimetilcellulosa può essere sostituita, senza inficiare l'originalità dell'invenzione, con altre sostanze polimeriche ad azione viscosizzante quali l'alcool polivinilico, carbopolimeri od altre sostanze polimeriche in grado di formare idrogeli vscosizzanti. La presenza del metilsulfonilmetano, che oltre alle proprietà nutrienti - vitaminiche - antiossidanti, presenta la ben nota attività di aumentare la permeabilità cellulare, favorisce la penetrazione dei principi attivi, incluso l'MSM stesso, nei tessuti oculari. According to the invention, the compositions in question are conveyed in an aqueous hydrogel containing an appropriate concentration (preferred between 0.400% and 0.600%) of carboxymethylcellulose, which due to its viscoelastic and mucomimetic characteristics ensures an effective bioadhesion of the active substances on the ocular mucous membranes. . The carboxy-methylcellulose can be replaced, without affecting the originality of the invention, with other polymeric substances with a viscosifying action such as polyvinyl alcohol, carbopolymers or other polymeric substances capable of forming vascosifying hydrogels. The presence of methylsulfonylmethane, which in addition to its nourishing - vitamin - antioxidant properties, has the well-known activity of increasing cell permeability, favors the penetration of active ingredients, including MSM itself, into the ocular tissues.
Secondo la presente invenzione, le composizioni oftalmiche comprendono i vari componenti entro le seguenti concentrazioni percentuali in peso, sulla base del peso totale della composizione: • metilsulfonilmetano (MSM) :da 1.000% a 5.000% According to the present invention, the ophthalmic compositions comprise the various components within the following percentage concentrations by weight, based on the total weight of the composition: â € ¢ methylsulfonylmethane (MSM): from 1,000% to 5,000%
• vitamina A palmitato :da 0.100% a 1.000% â € ¢ Vitamin A palmitate: from 0.100% to 1.000%
• vitamina E acetato :da 0.010% a 0.100% â € ¢ Vitamin E acetate: from 0.010% to 0.100%
• disodio edetato :da 0.010% a 0.120% â € ¢ edetate disodium: from 0.010% to 0.120%
Secondo un aspetto preferito della presente invenzione, le composizioni oftalmiche comprenderanno i vari componenti entro le seguenti concentrazioni percentuali in peso: According to a preferred aspect of the present invention, the ophthalmic compositions will comprise the various components within the following weight percent concentrations:
• metilsulfonilmetano (MSM) :da 2.000% a 4.000% â € ¢ methylsulfonylmethane (MSM): from 2,000% to 4,000%
• vitamina A palmitato :da 0.400% a 0.600% • vitamina E acetato : da 0.010 % a 0.030% â € ¢ vitamin A palmitate: from 0.400% to 0.600% â € ¢ vitamin E acetate: from 0.010% to 0.030%
• disodio edetato :da 0.080% a 0.120% Il pH della soluzione oftalmica della presente invenzione deve essere compreso tra 6.0 e 8.0,preferibilmente tra 6.8 e7.8,tale valore di pH può essere aggiustato mediante aggiunta di acido cloridrico o sodio idrossido sol. concentrate, o preferibilmente aggiungendo un sistema tampone al fine di mantenere il pH entro i valori richiesti. Esempi di sistemi tampone adatti sono: la combinazione di fosfato monobasico e bibasico di sodio o potassio, i sistemi tampone di sodio tetraborato e acido borico, sodio bicarbonato, sodio citrato e acido citrico, ed altri ancora. Le formulazioni dell'invenzione possono inoltre contenere correttori di osmolarità come il sodio cloruro o altri simili, per rendere le soluzioni con osmolarità simile a quella del liquido lacrimale. â € ¢ disodium edetate: from 0.080% to 0.120% The pH of the ophthalmic solution of the present invention must be between 6.0 and 8.0, preferably between 6.8 and 7.8, this pH value can be adjusted by adding hydrochloric acid or sodium hydroxide sol. concentrated, or preferably by adding a buffer system in order to keep the pH within the required values. Examples of suitable buffer systems are: the combination of monobasic and dibasic sodium or potassium phosphate, sodium tetraborate and boric acid buffer systems, sodium bicarbonate, sodium citrate and citric acid, and others. The formulations of the invention can also contain osmolarity correctors such as sodium chloride or other similar ones, to make the solutions with osmolarity similar to that of the tear fluid.
Le formulazioni dell'invenzione possono inoltre comprendere altri additivi convenzionali, comunemente usati nelle composizioni oftalmiche, purchà ̈ essi non interferiscano con le attività dei principi attivi: nutritive-vitaminiche, protettive dagli effetti antiossidanti, riepitelizzanti a livello dei tessuti oculari, né con l'attivazione della permeabilità cellulare. The formulations of the invention can also comprise other conventional additives, commonly used in ophthalmic compositions, as long as they do not interfere with the activities of the active ingredients: nutritive-vitamin, protective from antioxidant effects, re-epithelizing at the level of ocular tissues, nor with the activation of cell permeability.
Le formulazioni dell'invenzione possono inoltre comprendere composti ad azione batteriostatica ed antisettica, comunque utili ai fini dell'invenzione per garantire le condizioni di sterilità delle soluzioni oftalmiche in oggetto, all'interno del contenitore sigillato durante il periodo di validità stabilito, e dopo la prima apertura del contenitore per la durata di 30 giorni. The formulations of the invention can also comprise compounds with bacteriostatic and antiseptic action, however useful for the purposes of the invention to guarantee the sterile conditions of the ophthalmic solutions in question, inside the sealed container during the established validity period, and after the first opening of the container for the duration of 30 days.
Esempi di tali composti sono l'associazione di metile e propile idrossibenzoato,e la poliesanide (poliesametilenbiguanide) cloridrato,utilizzata per la sua azione battericida a concentrazione molto bassa ma efficace. Examples of such compounds are the combination of methyl and propyl hydroxybenzoate, and polyhexanide (polyhexamethylene glycol) hydrochloride, used for its bactericidal action at a very low but effective concentration.
Secondo l'invenzione, una o due gocce delle soluzioni delle composizioni oggetto dell'invenzione, possono essere istillate nel sacco congiuntivale di ciascun occhio 2-4 volte al giorno o più frequentemente se necessario. According to the invention, one or two drops of the solutions of the compositions object of the invention can be instilled into the conjunctival sac of each eye 2-4 times a day or more frequently if necessary.
Le composizioni della presente invenzione possono essere usate sia negli esseri umani che negli animali quali, senza essere limitati ad essi, cani, gatti, equini e bovini. The compositions of the present invention can be used in both humans and animals such as, but not limited to, dogs, cats, horses and cattle.
Le composizioni dell'invenzione possono essere formulate sotto forma di soluzione colloidale moderatamente viscosa, microemulsione, o idrogel più<viscoso>e possono essere presentate sotto forma di collirio o pomata per la somministrazione oculare, non escludendo altre forme di somministrazione quali inserti oculari a struttura polimerica a lenta cessione di sostanze attive .. The compositions of the invention can be formulated in the form of a moderately viscous colloidal solution, microemulsion, or more viscous hydrogel and can be presented in the form of eye drops or ointment for ocular administration, not excluding other forms of administration such as ocular structure inserts polymer with slow release of active substances ..
Una formulazione adatta contiene vantaggiosamente i seguenti ingredienti nelle seguenti percentuali in peso: A suitable formulation advantageously contains the following ingredients in the following percentages by weight:
• metilsulfonilmetano 3.000% • vitamina A palmitato 100 (idrodispersibile) 0.500% • vitamina E acetato 50% CWS (idrodispersibile) 0.020% • disodio edetato 0.100% • carbossimetilcellulosa (bassa viscosità ) 0.500% • metile idrossibenzoato 0.030% • propile idrossibenzoato 0.012% • poliesanide cloridrato 0.0001% • sodio fosfato bibasico12H2O 0.300% • potassio fosfato monobasico 0.050% • sodio cloruro 0.050% • acqua depurata q.b. a g 100 â € ¢ methylsulfonylmethane 3.000% â € ¢ vitamin A palmitate 100 (water dispersible) 0.500% â € ¢ vitamin E acetate 50% CWS (water dispersible) 0.020% â € ¢ disodium edetate 0.100% â € ¢ carboxymethylcellulose (low viscosity) 0.500% â € ¢ methyl hydroxybenzoate 0.030% â € ¢ propyl hydroxybenzoate 0.012% â € ¢ polyhexanide hydrochloride 0.0001% â € ¢ dibasic sodium phosphate 12H2O 0.300% â € ¢ monobasic potassium phosphate 0.050% â € ¢ sodium chloride 0.050% â € ¢ purified water q.b. to g 100
---ESEMPI DI FORMULAZIONE------ESEMPIO l-Composizione oftalmica acquosa colloidale (idrogel) --- FORMULATION EXAMPLES ------ EXAMPLE l-Colloidal aqueous ophthalmic composition (hydrogel)
Ingrediente quantità in grammi • acqua depurata 975.000 • metilsulfonilmetano 30.000 • vitamina A palmitato 100 (idrodispersibile) 5.000 • vitamina E acetato 50%CWS (idrodispersibile) 0.200 • disodio edetato 1.000 • carbossimetilcellulosa (bassa viscosità ) 5.000 • metile idrossibenzoato 0.300 • propile idrossibenzoato 0.120 • poliesanide cloridrato 0.00 I • sodio fosfato bibasico 12 H20 3.000 • potassio fosfato monobasico 0.500 • sodio cloruro 0.500 Totale 1020.621 --ESEMPIO 2- Composizione oftalmica acquosa colloidale (idrogel) Ingredient quantity in grams â € ¢ purified water 975,000 â € ¢ methylsulfonylmethane 30,000 â € ¢ vitamin A palmitate 100 (water dispersible) 5,000 â € ¢ vitamin E acetate 50% CWS (water dispersible) 0,200 â € ¢ edetate disodium 1,000 â € ¢ carboxymethylcellulose ( low viscosity) 5,000 â € ¢ methyl hydroxybenzoate 0.300 â € ¢ propyl hydroxybenzoate 0.120 â € ¢ polyhexanide hydrochloride 0.00 I â € ¢ dibasic sodium phosphate 12 H20 3.000 â € ¢ monobasic potassium phosphate 0.500 â € ¢ sodium chloride 0.500 Total 1020.621 --EXAMPLE 2- Colloidal aqueous ophthalmic composition (hydrogel)
Ingrediente quantità in grammi • acqua depurata 975.000 • metilsulfonilmetano 30.000 • vitamina A palmitato 100 (idrodispersibile) 5.000 • vitamina E acetato 50% CWS (idrodispersibile) 0.200 • disodio edetato 1.000 • carbossimetilcellulosa (bassa viscosità ) 5.000 • metile idrossibenzoato 0.300 • propile idrossibenzoato 0.120 • poliesanide cloridrato 0.001 • sodio tetraborato 1.500 • acido borico 0.300 Totale 1018.421 N:B. In entrambe le formulazioni il pH sarà eventualmente aggiustato con acido cloridrico o sodio idrossido sol. concentrate, ad un valore compreso tra 6.5 e 7.8. Ingredient quantity in grams â € ¢ purified water 975,000 â € ¢ methylsulfonylmethane 30,000 â € ¢ vitamin A palmitate 100 (water dispersible) 5,000 â € ¢ vitamin E acetate 50% CWS (water dispersible) 0,200 â € ¢ edetate disodium 1,000 â € ¢ carboxymethylcellulose ( low viscosity) 5,000 â € ¢ methyl hydroxybenzoate 0.300 â € ¢ propyl hydroxybenzoate 0.120 â € ¢ polyhexanide hydrochloride 0.001 â € ¢ sodium tetraborate 1,500 â € ¢ boric acid 0.300 Total 1018,421 N: B. In both formulations the pH will eventually be adjusted with hydrochloric acid or sodium hydroxide sol. concentrated, to a value between 6.5 and 7.8.
La formulazione dell'esempio 1) à ̈ stata sottoposta al controllo dell'osmolarità ed à ̈ risultato un valore di circa 300 (250-350) m Osmol /kg, perfettamente compatibile con i valori del liquido lacrimale, confermando un ottima miscibilità con tale liquido ed una perfetta tollerabilità da parte dei tessuti oculari. The formulation of example 1) was subjected to the osmolarity control and the result was a value of about 300 (250-350) m Osmol / kg, perfectly compatible with the tear fluid values, confirming an excellent miscibility with this liquid and perfect tolerability on the part of ocular tissues.
La viscosità à ̈ risultata di circa 1.4-1.8 cStokes, leggermente superiore ai valori medi del liquido lacrimai e, poiché finalizzata ad una particolarmente utile mucoadesività dell'idrogel sulle superfici delle mucose oculari. The viscosity was found to be about 1.4-1.8 cStokes, slightly higher than the average values of the tear fluid and, since it is aimed at a particularly useful mucoadhesion of the hydrogel on the surfaces of the ocular mucous membranes.
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