WO2018160154A1 - Iron oxide lotions for the treatment of anaemia - Google Patents

Iron oxide lotions for the treatment of anaemia Download PDF

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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
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Prior art keywords
oil
iron
iron oxide
lotion according
lotion
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PCT/TR2017/050311
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French (fr)
Inventor
Berna Bülbül
Seda Beyaz
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Buelbuel Berna
Seda Beyaz
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Publication of WO2018160154A1 publication Critical patent/WO2018160154A1/en

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    • 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)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Dispersion Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (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.
Figure imgf000006_0001
Table. 1 : Lotion 1
Acid HCI or HNOs or HCI04
Iron oxide: Fe304, Fe203, FeO (< 10 nm)
Table 2: Lotion 2
Figure imgf000006_0002
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
Figure imgf000007_0001
Iron oxide: Fe3O4, Fe2O3,FeO (< 10 nm)
Oil : Non-refined acidic olive oil is used. Table 4: Lotion 4
Figure imgf000007_0002
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
Figure imgf000007_0003
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
Figure imgf000007_0004
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.
PCT/TR2017/050311 2017-03-03 2017-07-07 Iron oxide lotions for the treatment of anaemia WO2018160154A1 (en)

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

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Citations (4)

* Cited by examiner, † Cited by third party
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
WO2012092628A2 (en) * 2010-12-31 2012-07-05 Incube Labs, Llc Patches and methods for the transdermal delivery of agents to treat hair loss
WO2012092305A2 (en) * 2010-12-27 2012-07-05 Incube Labs, Llc Nanonized iron compositions and methods of use thereof
EP3090750A1 (en) 2013-12-30 2016-11-09 Hanwha Chemical Corporation Pharmaceutical composition for preventing or treating iron deficiency, comprising iron oxide nanoparticles

Patent Citations (5)

* Cited by examiner, † Cited by third party
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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