WO2018160154A1 - Iron oxide lotions for the treatment of anaemia - Google Patents
Iron oxide lotions for the treatment of anaemia Download PDFInfo
- Publication number
- WO2018160154A1 WO2018160154A1 PCT/TR2017/050311 TR2017050311W WO2018160154A1 WO 2018160154 A1 WO2018160154 A1 WO 2018160154A1 TR 2017050311 W TR2017050311 W TR 2017050311W WO 2018160154 A1 WO2018160154 A1 WO 2018160154A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oil
- iron
- iron oxide
- lotion according
- lotion
- Prior art date
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- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 title claims abstract description 67
- 239000006210 lotion Substances 0.000 title claims abstract description 32
- 238000011282 treatment Methods 0.000 title claims abstract description 23
- 208000007502 anemia Diseases 0.000 title description 8
- 239000003921 oil Substances 0.000 claims abstract description 21
- 206010022971 Iron Deficiencies Diseases 0.000 claims abstract description 14
- 239000004094 surface-active agent Substances 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 201000010099 disease Diseases 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 6
- 235000019198 oils Nutrition 0.000 claims description 20
- SZVJSHCCFOBDDC-UHFFFAOYSA-N iron(II,III) oxide Inorganic materials O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims description 12
- 229940031182 nanoparticles iron oxide Drugs 0.000 claims description 9
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 claims description 7
- 239000004006 olive oil Substances 0.000 claims description 6
- 235000008390 olive oil Nutrition 0.000 claims description 6
- 235000019489 Almond oil Nutrition 0.000 claims description 4
- 241000501711 Centaurium Species 0.000 claims description 4
- 235000019482 Palm oil Nutrition 0.000 claims description 4
- 235000019486 Sunflower oil Nutrition 0.000 claims description 4
- 244000299461 Theobroma cacao Species 0.000 claims description 4
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 claims description 4
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 claims description 4
- 239000008168 almond oil Substances 0.000 claims description 4
- 235000001046 cacaotero Nutrition 0.000 claims description 4
- 238000000975 co-precipitation Methods 0.000 claims description 4
- 239000002540 palm oil Substances 0.000 claims description 4
- 239000002600 sunflower oil Substances 0.000 claims description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 4
- 239000008158 vegetable oil Substances 0.000 claims description 4
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 3
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 3
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 3
- 239000005642 Oleic acid Substances 0.000 claims description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 3
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 3
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 3
- 235000019501 Lemon oil Nutrition 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 238000004945 emulsification Methods 0.000 claims description 2
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 claims description 2
- 239000010501 lemon oil Substances 0.000 claims description 2
- 238000005979 thermal decomposition reaction Methods 0.000 claims description 2
- 239000000341 volatile oil Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 62
- 229910052742 iron Inorganic materials 0.000 description 31
- 235000013980 iron oxide Nutrition 0.000 description 18
- 238000000034 method Methods 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 8
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 235000007144 ferric diphosphate Nutrition 0.000 description 4
- 239000011706 ferric diphosphate Substances 0.000 description 4
- CADNYOZXMIKYPR-UHFFFAOYSA-B ferric pyrophosphate Chemical compound [Fe+3].[Fe+3].[Fe+3].[Fe+3].[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O.[O-]P([O-])(=O)OP([O-])([O-])=O CADNYOZXMIKYPR-UHFFFAOYSA-B 0.000 description 4
- 229940036404 ferric pyrophosphate Drugs 0.000 description 4
- 229940082629 iron antianemic preparations Drugs 0.000 description 4
- 150000002506 iron compounds Chemical class 0.000 description 4
- VBMVTYDPPZVILR-UHFFFAOYSA-N iron(2+);oxygen(2-) Chemical class [O-2].[Fe+2] VBMVTYDPPZVILR-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 3
- 208000003455 anaphylaxis Diseases 0.000 description 3
- FWZTTZUKDVJDCM-CEJAUHOTSA-M disodium;(2r,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol;iron(3+);oxygen(2-);hydroxide;trihydrate Chemical compound O.O.O.[OH-].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[O-2].[Na+].[Na+].[Fe+3].[Fe+3].[Fe+3].[Fe+3].[Fe+3].O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FWZTTZUKDVJDCM-CEJAUHOTSA-M 0.000 description 3
- VRIVJOXICYMTAG-IYEMJOQQSA-L iron(ii) gluconate Chemical compound [Fe+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O VRIVJOXICYMTAG-IYEMJOQQSA-L 0.000 description 3
- 239000002159 nanocrystal Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000001027 hydrothermal synthesis Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229940032961 iron sucrose Drugs 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- 208000012866 low blood pressure Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000009897 systematic effect Effects 0.000 description 2
- 208000020154 Acnes Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 239000005569 Iron sulphate Substances 0.000 description 1
- 229910021577 Iron(II) chloride Inorganic materials 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 1
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000008133 cognitive development Effects 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940076449 dexferrum Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 230000009365 direct transmission Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 229940086604 feraheme Drugs 0.000 description 1
- 229940042644 ferrlecit Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229940090441 infed Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000004698 iron complex Chemical class 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000008132 psychomotor development Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- MQBDAEHWGRMADS-XNHLMZCASA-M sodium;(2r,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol;iron(3+);oxygen(2-);(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate Chemical compound [O-2].[O-2].[O-2].[Na+].[Fe+3].[Fe+3].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1.O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1.O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1.O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1.O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 MQBDAEHWGRMADS-XNHLMZCASA-M 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000004227 thermal cracking Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Definitions
- the invention relates to a lotion containing iron oxide nano crystals to be used in transdermal treatment of anaemia.
- the invention particularly relates to a lotion containing nano-size iron oxide nano-particles which can be used in treatment of diseases arising from iron deficiency or protection against such diseases, and treatment method.
- Iron is a transitional metal existing every where. Use of iron for healing purposes dates back to ancient times. For instance, ancient Greeks used iron powders in diets to treat muscle weakness of the injured warriors. It is reported that iron is used in treatment of baldness and acnes in dermatology. The important role of iron in human physiology is that it carries oxygen and controls other metabolic processes in the system. Iron acts as catalyser in various biological processes taking part in oxidization and reduction reactions.
- Iron deficiency is the most common nutrition deficiency in the world. If iron deficiency anaemia is not treated, it may cause diseases and even fatality. More than one billion people suffer from anaemia in the world, most of which are from underdeveloped and low income countries. Most of patient population suffering from iron deficiency anaemia are children and women. Iron deficiency causes premature or low weight infants, cognitive and psycho-motor development defects in children and reduction in working capacity in adults. Furthermore, anaemia patients are more vulnerable to infections. For that reason, ways of protection against disease as well as treatments should be developed.
- Iron deficiency anaemia can be prevented or treated by means of taking iron containing preparations orally, which is the easiest way for patients. However, it should not be forgotten that the orally taking oral preparations might cause digestive disorders and bioavailability of iron preparations is low. Furthermore, since orally applied treatments take longer times (3 - 6 months), most patients leave the treatment uncompleted.
- a shorter way to increase iron quantity in the blood is to administer the preparations containing iron by syringe (parenteral).
- Simple iron compounds used orally (iron sulphate, iron ascorbate etc.) are not good for parenteral application because release of free iron of high quantity leads to lipid peroxidation and oxidative stress. Since easy availability of iron in hemoglobin synthesis, little local or systematic side effects and half life, the need for adequate storing stability should be met.
- Current parenteral iron preparations consist of iron dextrane approved in USA (for instance, InFed, Dexferrum), iron - gluconate complex (Ferrlecit), iron succrose (Venoferrum) etc.
- Iron dextrane is parenteral iron preparations firstly marketed in USA and anaphylactic reactions (dyspnea, asthma coughing, chest pain, low blood pressure, rash, angio oedema) are seen at high rates. Iron dextrane frequently causes serious and life threatening reactions as well as symptoms such as joint pains, back pains, low blood pressure, temperature, muscle pains, itching, dizziness and nausea. The high anaphylactic reactions rate is believed to arise from formation of antibodies against dextrane. Although these negative incidents are not of the extent threatening life, in several cases they are obstacle before several practices.
- ferrumoxitol (commercial name Feraheme) based on iron oxide nano particles not iron complex is developed as a preparate containing iron for parenteral application.
- Ferumoxitol has a relatively big size and average particle size of iron oxide crystal therein is about 7 nm and molecular weight is 731 kDa.
- ferrumoxitol Because of having higher stability in comparison to other parenteral iron preparations such as iron dextrane, iron-sucrose, iron gluconate etc.,ferrumoxitol has a low free iron concentration. In a typical ferumoxitol treatment, 1 g iron is administered twice a week and such administration mode increases hospital costs such as tube and infusion and causes inconvenience for patients.
- Transdermal drug release imitates intravenous infusion and provides administration of drugs for long time. There is no device on the patient and drug can be given to the most non - submissive patient in this way. However, transdermal transfer of drugs is limited to dermal barrier feature. Iron compounds that can be given parentally can also be given transdermally. However, transdermal absorption of colloidal iron products used parentally is considerably weak due to big molecular sizes. For that reason, it is urgently needed to identify safe, low molecular weight iron compounds for successful transdermal treatment. The most important compound whose use in iron deficiency treatment given transdermally is searched is ferric pyrophosphate (FPP).
- FPP ferric pyrophosphate
- FPP has high stability constant (log Kstab 22.3) and therefore, it does not cause free- iron-decomposition and release in physiological fluids. In addition, it may affirmatively affect the direct transmission of iron into transferring protein.
- passive transdermal absorption is very poor due to high molecular weight and low lipid dissolution of the compound (only by putting on skin).
- methods such as iontophoresis, micro-syringe and sonophoresis have been used to enhance the FPP absorption. Electric current is needed for iontophoresis, while sound waves are needed for sonophoresis and special apparatus is needed for micro-syringe. All of those are highly challenging and are not economical methods for anaemia patients needing long-time treatment. Not-toxic, stabile iron lotions allowing iron feeding into blood circulation by putting onto skin are needed.
- Iron oxide nano particles approved by FDA for parental use can also be used transdermally. Although there are studies indicating that iron oxides with size less than 10 nm can be diffused towards inner layers of skin, no studies on use of them for iron deficiency treatment have been seen.
- Iron oxide nano particles that can be applied to various nano- bio areas such as magnetic resonance imaging (MRI), cell separation, hyperthermia, drug release, bio sensors and contrast agents etc. can be prepared by co-precipitation, hydrothermal synthesis, thermal cracking etc.
- co-precipitation and hydrothermal synthesis are precipitation methods which iron (II) chloride and iron (III) chloride react directly in the solution and they are used to prepare iron oxide nano particles easily.
- the purpose of the invention is to use it in transdermal treatment of anaemia.
- Another purpose of the invention is to give iron to body slowly and in a longer time. Thus many side effects caused by too much iron loading are eliminated.
- the invention is a lotion composed of individuals or combinations of compounds selected from a group consisting of acid, iron oxide, water, oil, surfactant for treatment of diseases arising from iron deficiency.
- the invention is a lotion consisting of nano - sized iron oxide nano particles that can be used in treatment or prevention of diseases arising from iron deficiency, and treatment method.
- Iron oxide nano particles to be used in drug absorption dermally should be smaller than 10 nm. The smaller the size the better the absorption is. Iron oxide nano particles of such sizes can be synthesized by coprecipitation, thermal decomposition or mini emulsion methods known in the literature. The characteristics and chemical ingredients of the lotions to be prepared based on the selected method are given in the table below.
- Iron oxide Fe304, Fe203, FeO ( ⁇ 10 nm)
- Iron oxide Fe3O4, Fe2O3, FeO ( ⁇ 10 nm)
- Oil (%) All vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil can be used. Table 3: Lotion 3
- Iron oxide Fe3O4, Fe2O3,FeO ( ⁇ 10 nm)
- Iron oxide Fe3O4, Fe2O3,FeO ( ⁇ 10 nm)
- Oil All vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil.
- Iron oxide Fe3O4, Fe2O3,FeO ( ⁇ 10 nm)
- oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil can be used.
- surfactant All surface active agents preventing combination and growth of iron oxide nano crystals in the lotion and having molecular weight under 400 Da can be used.
- Iron oxide Fe3O4, Fe2O3, FeO ( ⁇ 10 nm)
- surfactant All surface active agents preventing combination and growth of iron oxide nano crystals in the solution and having molecular weight under 400 Da can be used.
- volatile oils such as lemon oil, camomile oil lavender oil can be added to the lotions.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a lotion composed of individuals or combinations of compounds selected from a group consisting of acid, iron oxide, water, oil, surfactant for treatment of diseases arising from iron deficiency.
Description
IRON OXIDE LOTIONS FOR THE TREATMENT OF ANAEMIA
The Related Art
The invention relates to a lotion containing iron oxide nano crystals to be used in transdermal treatment of anaemia.
The invention particularly relates to a lotion containing nano-size iron oxide nano-particles which can be used in treatment of diseases arising from iron deficiency or protection against such diseases, and treatment method.
Background of the Invention
Today Iron is a transitional metal existing every where. Use of iron for healing purposes dates back to ancient times. For instance, ancient Greeks used iron powders in diets to treat muscle weakness of the injured warriors. It is reported that iron is used in treatment of baldness and acnes in dermatology. The important role of iron in human physiology is that it carries oxygen and controls other metabolic processes in the system. Iron acts as catalyser in various biological processes taking part in oxidization and reduction reactions.
Iron deficiency is the most common nutrition deficiency in the world. If iron deficiency anaemia is not treated, it may cause diseases and even fatality. More than one billion people suffer from anaemia in the world, most of which are from underdeveloped and low income countries. Most of patient population suffering from iron deficiency anaemia are children and women. Iron deficiency causes premature or low weight infants, cognitive and psycho-motor development defects in children and reduction in working capacity in adults. Furthermore, anaemia patients are more vulnerable to infections. For that reason, ways of protection against disease as well as treatments should be developed.
Anaemia arising from iron deficiency is known as one of the most frequently seen pathological cases in humans. Iron deficiency anaemia can be prevented or treated by means of taking iron containing preparations orally, which is the easiest way for patients.
However, it should not be forgotten that the orally taking oral preparations might cause digestive disorders and bioavailability of iron preparations is low. Furthermore, since orally applied treatments take longer times (3 - 6 months), most patients leave the treatment uncompleted.
A shorter way to increase iron quantity in the blood is to administer the preparations containing iron by syringe (parenteral). Simple iron compounds used orally (iron sulphate, iron ascorbate etc.) are not good for parenteral application because release of free iron of high quantity leads to lipid peroxidation and oxidative stress. Since easy availability of iron in hemoglobin synthesis, little local or systematic side effects and half life, the need for adequate storing stability should be met. Current parenteral iron preparations consist of iron dextrane approved in USA (for instance, InFed, Dexferrum), iron - gluconate complex (Ferrlecit), iron succrose (Venoferrum) etc.
Iron dextrane is parenteral iron preparations firstly marketed in USA and anaphylactic reactions (dyspnea, asthma coughing, chest pain, low blood pressure, rash, angio oedema) are seen at high rates. Iron dextrane frequently causes serious and life threatening reactions as well as symptoms such as joint pains, back pains, low blood pressure, temperature, muscle pains, itching, dizziness and nausea. The high anaphylactic reactions rate is believed to arise from formation of antibodies against dextrane. Although these negative incidents are not of the extent threatening life, in several cases they are obstacle before several practices. Other parenteral iron preparates (for example iron-sucrose and iron - gluconate) are products not containing dextrane and use of such products shows an incredibly low anaphylaxis rate. On the other hand, iron binding capacity of such compounds is low and for that reason, products contain high free iron quantities. As a result thereof, the applied dosage and rate is restricted. There is also a disadvantage where injectable high molecular weighed materials cause more allergic reactions than low molecular weighted materials.
Accordingly, ferrumoxitol (commercial name Feraheme) based on iron oxide nano particles not iron complex is developed as a preparate containing iron for parenteral application. Information about its effectiveness and application is available in the literature (US Patent No. 6,599,498). Ferumoxitol has a relatively big size and average particle size of iron oxide crystal therein is about 7 nm and molecular weight is 731 kDa. Because of having higher stability in comparison to other parenteral iron
preparations such as iron dextrane, iron-sucrose, iron gluconate etc.,ferrumoxitol has a low free iron concentration. In a typical ferumoxitol treatment, 1 g iron is administered twice a week and such administration mode increases hospital costs such as tube and infusion and causes inconvenience for patients.
Phosphate polyethylenglycol coated 1 1 - 12 nm nano particles having 3-4 nm iron oxide nucleus were synthesized and when given to rats as parenteral, considerable increase in haemoglobin values was observed and the product was published under patent number EP 3090750. However, the steps of synthesizing method used therein caused difficulties in commercialization of the product.
An intellectual patent disclosing nano - size iron compounds can be used in iron deficiency treatment (US2012/0177700) was also granted but claims have remained considerably limited.
If iron is given to body slowly and for long time, extreme saturation of "transferring" protein and free iron accumulation in systematic circulation may be avoided. Transdermal drug release imitates intravenous infusion and provides administration of drugs for long time. There is no device on the patient and drug can be given to the most non - submissive patient in this way. However, transdermal transfer of drugs is limited to dermal barrier feature. Iron compounds that can be given parentally can also be given transdermally. However, transdermal absorption of colloidal iron products used parentally is considerably weak due to big molecular sizes. For that reason, it is urgently needed to identify safe, low molecular weight iron compounds for successful transdermal treatment. The most important compound whose use in iron deficiency treatment given transdermally is searched is ferric pyrophosphate (FPP).
FPP has high stability constant (log Kstab 22.3) and therefore, it does not cause free- iron-decomposition and release in physiological fluids. In addition, it may affirmatively affect the direct transmission of iron into transferring protein. However, passive transdermal absorption is very poor due to high molecular weight and low lipid dissolution of the compound (only by putting on skin). In literature, methods such as iontophoresis, micro-syringe and sonophoresis have been used to enhance the FPP absorption. Electric current is needed for iontophoresis, while sound waves are needed for sonophoresis and special apparatus is needed for micro-syringe. All of
those are highly challenging and are not economical methods for anaemia patients needing long-time treatment. Not-toxic, stabile iron lotions allowing iron feeding into blood circulation by putting onto skin are needed.
Iron oxide nano particles approved by FDA for parental use can also be used transdermally. Although there are studies indicating that iron oxides with size less than 10 nm can be diffused towards inner layers of skin, no studies on use of them for iron deficiency treatment have been seen. Iron oxide nano particles that can be applied to various nano- bio areas such as magnetic resonance imaging (MRI), cell separation, hyperthermia, drug release, bio sensors and contrast agents etc. can be prepared by co-precipitation, hydrothermal synthesis, thermal cracking etc. Among these methods, co-precipitation and hydrothermal synthesis are precipitation methods which iron (II) chloride and iron (III) chloride react directly in the solution and they are used to prepare iron oxide nano particles easily.
However, it is not so easy to prepare a colloidal stable that is not flaked and not precipitating iron oxide solution. It is needed to modify the surfaces of particles electrostatically or sterically very well. Surface charge of iron oxides is positive in low pH and negative in high pH. Considering that the skin is negative and provides better absorption against positive agents, iron oxide acidic solutions can be prepared. However, lyophilise fatty layer on the external layer of skin may slow down such passing. For that reason, surfaces of iron oxides may be made more compatible for skin by hydrophobicity by means of absorption enhancing chemicals such as oleic acid. Thus, in the light of these ideas, it is aimed to develop a new nano iron oxide solution to eliminate the iron deficiency transdermally.
Purpose of the Invention
In order to eliminate the disadvantages experienced in the related art, the purpose of the invention is to use it in transdermal treatment of anaemia.
Another purpose of the invention is to give iron to body slowly and in a longer time. Thus many side effects caused by too much iron loading are eliminated.
Since the passive absorption of iron by skin is advanced, the methods such as iontophoresis, micro-syringe etc. causing difficulties and costs for patient are no more needed. Thus a further purpose of the invention is to make iron deficiency treatment much easier and cheaper.
Since the lotion can be applied to the patient very easily, long time taking treatments do not cause problem and therefore another purpose of the invention is to decrease number of diseases arising from iron deficiency.
In order to achieve the above advantages, the invention is a lotion composed of individuals or combinations of compounds selected from a group consisting of acid, iron oxide, water, oil, surfactant for treatment of diseases arising from iron deficiency.
Detailed Description of the Invention
The invention is a lotion consisting of nano - sized iron oxide nano particles that can be used in treatment or prevention of diseases arising from iron deficiency, and treatment method.
Iron oxide nano particles to be used in drug absorption dermally should be smaller than 10 nm. The smaller the size the better the absorption is. Iron oxide nano particles of such sizes can be synthesized by coprecipitation, thermal decomposition or mini emulsion methods known in the literature. The characteristics and chemical ingredients of the lotions to be prepared based on the selected method are given in the table below.
Table. 1 : Lotion 1
Acid HCI or HNOs or HCI04
Iron oxide: Fe304, Fe203, FeO (< 10 nm)
Table 2: Lotion 2
Iron oxide: Fe3O4, Fe2O3, FeO (< 10 nm)
Oil (%) All vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower
oil, cacao oil can be used. Table 3: Lotion 3
Iron oxide: Fe3O4, Fe2O3,FeO (< 10 nm)
Oil : Non-refined acidic olive oil is used. Table 4: Lotion 4
Iron oxide: Fe3O4, Fe2O3,FeO (< 10 nm)
Oil : All vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil.
Table 5: Lotion 5
Iron oxide: Fe3O4, Fe2O3,FeO (< 10 nm)
Oil: All vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil can be used.
As surfactant : All surface active agents preventing combination and growth of iron oxide nano crystals in the lotion and having molecular weight under 400 Da can be used.
Table 6: Lotion 6
Iron oxide: Fe3O4, Fe2O3, FeO (< 10 nm)
As surfactant : All surface active agents preventing combination and growth of iron oxide nano crystals in the solution and having molecular weight under 400 Da can be used. In addition, in order to prevent unpleased smell, volatile oils such as lemon oil, camomile oil lavender oil can be added to the lotions.
Claims
1. The invention is a lotion composed of individuals or combinations of compounds selected from group consisting of acid, iron oxide, water, oil, surfactant for treatment of diseases arising from iron deficiency.
2. A lotion according to claim 1 and it is characterized in that iron oxide (Fe304, Fe203, FeO) nano particles are less than 10 nm.
3. A lotion according to claim 2 and it is characterized in that iron oxide nano particles are synthesized by means of coprecipitation, thermal decomposition or mini emulsion methods.
4. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of, 1 - 2 % acid, 1 - 5 % iron oxide, 93 - 98 % water.
5. A lotion according to claim 4 and it is characterized in that the said acid is: HCI or HNOs or HCI04.
6. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of 1 - 5 % oleic acid, 1 - 5 % iron oxide, 90 - 98 % water.
7. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of 1 - 5 % iron oxide, 95 - 99 % water.
8. A lotion according to claim 7 and it is characterized in that the said oil is non - refined acidic olive oil.
9. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of 1 - 2 % oleic acid oleat, 1 - 5 % iron oxide, 93 - 98 % oil.
10. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of 1 - 5 % surfactant, 1 - 5 % iron oxide, 90 - 98 % oil.
11. A lotion according to claims 6, 9 and 10 and it is characterized in that the said oil is all vegetable oils such as olive oil, almond oil, centaury oil, palm oil, sunflower oil, cacao oil.
12. A lotion according to claims 1 , 2 and 3 and it is characterized in that it consists of 1 - 5 % surfactant, 1 - 5 % iron oxide, 90 - 98 % water.
13. A lotion according to claims 10 and 12 and it is characterized in that the said surfactant is all surface active agents having molecular weight under 400 Da.
A lotion according to claim 1 and it is characterized in that it consists of volatile oils such as lemon oil, camomile oil, lavender oil.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2017/03251A TR201703251A2 (en) | 2017-03-03 | 2017-03-03 | A SOLUTION CONTAINING IRON OXIDE NANOCRISTALS TO BE USED IN THE TREATMENT OF THE ANIMALITY BY TRANSDERMAL |
| TR2017/03251 | 2017-03-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2018160154A1 true WO2018160154A1 (en) | 2018-09-07 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/TR2017/050311 WO2018160154A1 (en) | 2017-03-03 | 2017-07-07 | Iron oxide lotions for the treatment of anaemia |
Country Status (2)
| Country | Link |
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| TR (1) | TR201703251A2 (en) |
| WO (1) | WO2018160154A1 (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6599498B1 (en) | 1999-04-09 | 2003-07-29 | Advanced Magnetics, Inc. | Heat stable colloidal iron oxides coated with reduced carbohydrates and carbohdrate derivatives |
| WO2012092305A2 (en) * | 2010-12-27 | 2012-07-05 | Incube Labs, Llc | Nanonized iron compositions and methods of use thereof |
| WO2012092628A2 (en) * | 2010-12-31 | 2012-07-05 | Incube Labs, Llc | Patches and methods for the transdermal delivery of agents to treat hair loss |
| EP3090750A1 (en) | 2013-12-30 | 2016-11-09 | Hanwha Chemical Corporation | Pharmaceutical composition for preventing or treating iron deficiency, comprising iron oxide nanoparticles |
-
2017
- 2017-03-03 TR TR2017/03251A patent/TR201703251A2/en unknown
- 2017-07-07 WO PCT/TR2017/050311 patent/WO2018160154A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6599498B1 (en) | 1999-04-09 | 2003-07-29 | Advanced Magnetics, Inc. | Heat stable colloidal iron oxides coated with reduced carbohydrates and carbohdrate derivatives |
| WO2012092305A2 (en) * | 2010-12-27 | 2012-07-05 | Incube Labs, Llc | Nanonized iron compositions and methods of use thereof |
| US20120177700A1 (en) | 2010-12-27 | 2012-07-12 | Imran Mir A | Nanonized Iron Compositions and Methods of Use Thereof |
| WO2012092628A2 (en) * | 2010-12-31 | 2012-07-05 | Incube Labs, Llc | Patches and methods for the transdermal delivery of agents to treat hair loss |
| EP3090750A1 (en) | 2013-12-30 | 2016-11-09 | Hanwha Chemical Corporation | Pharmaceutical composition for preventing or treating iron deficiency, comprising iron oxide nanoparticles |
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| Publication number | Publication date |
|---|---|
| TR201703251A2 (en) | 2017-07-21 |
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