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EP1865777A2 - Zusammensetzungen und verabreichung von stannsoporfin - Google Patents

Zusammensetzungen und verabreichung von stannsoporfin

Info

Publication number
EP1865777A2
EP1865777A2 EP06749109A EP06749109A EP1865777A2 EP 1865777 A2 EP1865777 A2 EP 1865777A2 EP 06749109 A EP06749109 A EP 06749109A EP 06749109 A EP06749109 A EP 06749109A EP 1865777 A2 EP1865777 A2 EP 1865777A2
Authority
EP
European Patent Office
Prior art keywords
stannsoporfin
pharmaceutical composition
solution
magnesium
calcium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP06749109A
Other languages
English (en)
French (fr)
Other versions
EP1865777A4 (de
Inventor
Philip C. Lang
George S. Drummond
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Infacare Pharmaceutical Corp
Original Assignee
Infacare Pharmaceutical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/096,359 external-priority patent/US20060222668A1/en
Application filed by Infacare Pharmaceutical Corp filed Critical Infacare Pharmaceutical Corp
Priority to EP10014149A priority Critical patent/EP2301548A1/de
Publication of EP1865777A2 publication Critical patent/EP1865777A2/de
Publication of EP1865777A4 publication Critical patent/EP1865777A4/de
Withdrawn legal-status Critical Current

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics

Definitions

  • Tin (IV) mesoporphyrin IX dichloride, or stannsoporfin, is a mesoporphyrin chemical compound having the following structure :
  • Stannsoporfin has been proposed for use, for example, as a medicament in the treatment of various diseases including, for example, psoriasis (U.S. Patent No. 4,782,049 to Kappas et al.) and infant jaundice (for example, in U.S. Patent Nos. 4,684,637, 4,657,902 and 4,692,440).
  • Stannsoporfin is also known to inhibit heme metabolism in mammals, to control the rate of tryptophan metabolism in mammals, and to increase the rate at which heme is excreted by mammals (U.S. Patent Nos. 4,657,902 and 4,692,440).
  • stannsoporfin is commonly used as starting material.
  • the hemin is generally hydrogenated to form an intermediate mesoporphyrin IX dihydrochloride, which is subsequently subjected to tin insertion, yielding stannsoporfin.
  • Methods for making stannsoporfin are disclosed in United States Patent No. 6,818,763 and United States Patent Application Serial No. 10/812,156, filed on March 29, 2004, the contents of both of which are incorporated herein by reference.
  • stannsoporfin One way of administering stannsoporfin is by an injectable solution. Although stannsoporfin has been provided in aqueous solutions in the past, it has been found that in stannsoporfin solutions having higher concentrations, the stannsoporfin does not adequately dissolve in the solution. It would be desirable to provide compositions, drug products and methods of manufacture that can include higher concentrations of stannsoporfin. It would further be desirable to provide compositions and drug products that include stannsoporfin that are stable and have an acceptable shelf life. DISCLOSURE OF THE INVENTION
  • One aspect of the present invention is directed towards a pharmaceutical composition or drug product comprising stannsoporfin in an aqueous solution, wherein the concentration of stannsoporfin in the solution is at least about 4 mg/ml, preferably at least about 4.5 mg/ml, and more preferably at least about 5 mg/ml.
  • a preferred range of stannsoporfin concentration is between about 5-40 mg/ml, including concentrations of 10 mg/ml, 15 mg/ml, 20 mg/ml, 25 mg/ml, 30 mg/ml, 35 mg/ml and 40 mg/ml.
  • the composition or drug product has a physiological osmolarity.
  • the composition or drug product is stable at room temperature for at least about one month.
  • the composition or drug product is stable at room temperature up to at least about two months
  • the solution or drug product is stable at room temperature up to at least about three months
  • the solution or drug product is stable at room temperature up to at least about six months.
  • room temperature includes, but is not limited to temperatures between about 68° F and 77° F.
  • Another aspect of the present invention is directed towards a drug product including a stannsoporfin solution, wherein the drug product includes a single dose of stannsoporfin in solution.
  • the solution may further comprise a base, an acid and a buffering agent .
  • Another aspect of the present invention is directed towards a method of making a pharmaceutical composition
  • a pharmaceutical composition comprising a stannsoporfin aqueous solution, wherein stannsoporfin is mixed with a buffering agent.
  • the stannsoporfin is then dissolved through the addition of a base which preferably raises the pH to at least about 10.
  • the pH is then lowered within a physiological pH range by the addition of an acid so that it can be administered to a patient.
  • physiological pH range refers to a pH range of less than about 8.
  • physiological pH range means a pH between about 7.2 and 7.9, and more preferably, a physiological pH means a pH between about 7.4 and 7.9.
  • Another aspect of this invention is directed towards a method of making a drug product comprising an aqueous solution of stannsoporfin in a concentration of at least about 4.5 mg/ml.
  • Still another aspect of the invention pertains to treatment of hyperbilirubinemia utilizing the compositions and drug products disclosed herein.
  • tin (IV) mesoporphyrin IX dichloride includes tin 4 + mesoporphyrin IX dichloride and stannsoporfin.
  • Tin (IV) mesoporphyrin IX dichloride can be obtained according to a variety of methods, for example, through the methods disclosed in United States Patent No. 6,818,763, and co-pending United States Patent Application Serial No. 10/812,156 (Publication No. 20040210048), which are incorporated herein by reference.
  • mesoporphyrin halides such as tin mesoporphyrin IX dichloride
  • present invention is not limited to a particular method of mesoporphyrin production.
  • a two-stage hydrogenation process can be used to prepare tin mesoporphyrin.
  • a reaction mixture of hemin and a hydrogenation catalyst are subjected to a first elevated temperature for a first period of time.
  • the first stage temperature can be in the range of about 85-95 0 C and the period of time is at least about one hour, for example, between about 1-3 hours.
  • the reaction mixture is cooled to a second temperature for a second period of time.
  • the second temperature can be in a range of about 45-5O 0 C and hydrogenated for a second period of time of about 3-6 hours, in order to convert substantially all hemin (protoporphyrin IX iron (III) chloride) to mesoporphyrin IX formate.
  • This second stage can also be conducted in the presence of formic acid.
  • the same catalyst may be used as in the first step described above, so that the two stages of the process may be conducted in the same reactor.
  • a further charge of hydrogen may be supplied to the reactor prior to commencing the second stage.
  • the second hydrogenation stage increases the yield of the mesoporphyrin IX formate, while reducing the amount of impurities in the final metal mesoporphyrin halide. (See the following Figure) .
  • the mesoporphyrin IX intermediate compound in the present invention is not isolated as a dihydrochloride, but rather as a formate salt. It will be understood, of course, that other processes can be used for the preparation of tin (IV) mesoporphyrin intermediates.
  • the mesoporphyrin IX formate may be isolated from a formic acid solution by the addition of a solvent such as ether or another organic solvent, leading directly to the mesoporphyrin IX formate intermediate, which is further subjected to drying.
  • a solvent such as ether or another organic solvent
  • Ethers such as, for example, methyl tert-butyl ether, diethyl ether or di-isopropyl ether, among others, may be used.
  • tin mesoporphyrin IX formate is utilized to create tin mesoporphyrin.
  • mesoporphyrin IX formate is subjected to heating with a tin (II) carrier in an acid such as acetic acid, buffered with an acetate ion, in the presence of an oxidant, at reflux.
  • Tin (II) carriers such as tin (II) halides or tin (II) acetate can be used.
  • Suitable acetate counter ions include ammonium, sodium or potassium ions. Oxidants such as oxygen from air or in pure form as well as hydrogen peroxide can also be used.
  • Mesoporphyrin IX formate can be subjected to heating with tin (II) chloride in acetic acid, buffered with ammonium acetate, and the reaction is conducted in the presence of air, at reflux. During this process, tin mesoporphyrin dichloride is isolated from the reaction mixture by the addition of water, followed by filtration to provide a filter cake. Prior to drying at about 90-100 0 C, the filter cake is triturated into hot, dilute hydrochloric acid, for example, at a concentration of about 0.1N-6N, at about 90-100 0 C.
  • the crude, substantially pure tin mesoporphyrin chloride (crude tin (IV) mesoporphyrin IX dichloride) is obtained with a yield of about 75-95% and a purity of about 95%, as judged by HPLC analysis. (See the following Figure) .
  • the tin mesoporphyrin IX dichloride obtained by the above-described process may be further purified by dissolving the product in an aqueous inorganic base solution, for example, dilute ammonium hydroxide, followed by treatment with charcoal. The product is then re-precipitated by addition to an acid solution, such as acetic acid, hydrochloric acid or a mixture thereof.
  • an acid solution such as acetic acid, hydrochloric acid or a mixture thereof.
  • the above dissolving, charcoal treatment and re-precipitation steps may be repeated a number of times, typically about 1-3 times in order to ensure the desired purity.
  • tin mesoporphyrin chloride product (tin (IV) mesoporphyrin IX dichloride or stannsoporfin) is obtained in a yield of about 50-70%, with an HPLC purity of about or greater than 97%.
  • tin mesoporphyrin chloride tin (IV) mesoporphyrin IX dichloride or stannsoporfin
  • large scale quantities such as quantities exceeding about 0.1kg through and including multiple kilogram amounts
  • Temperature and pressure times likewise can be modified as needed.
  • tin mesoporphyrin chloride product (tin (IV) mesoporphyrin IX dichloride or stannsoporfin) is obtained in the large scale production process in a yield of about 60-90%, with an HPLC purity of about 97%.
  • stannsoporfin can be obtained by the methods disclosed in co-pending and United States Patent Application Serial No. 10/812,156, filed on March 29, 2004, the entire contents of which is incorporated herein by reference.
  • stannsoporfin can be produced by isolating a mesoporphyrin formate and converting the mesoporphyrin formate to a tin mesoporphyrin halide.
  • the mesoporphyrin formate can be converted directly to a metal mesoporphyrin halide, or alternatively, the mesoporphyrin formate can first be converted to mesoporphyrin dihydrochloride and the mesoporphyrin dihydrochloride can then be converted to the metal mesoporphyrin halide.
  • the compositions of the present invention can be prepared and administered in a wide variety of parenteral dosage forms.
  • the compositions of the present invention can be administered by injection, that is, intravenously, intramuscularly, intrathecally, intracutaneously, subcutaneously, intraduodenally, or intraperitoneally. Additionally, the compositions of the present invention can be administered transdermally.
  • Liquid form preparations can include solutions, suspensions, and emulsions, for example, water or water propylene glycol solutions.
  • liquid preparations can be formulated in solution in aqueous solutions as described herein.
  • the pharmaceutical preparation is preferably in unit dosage form. In such form, the preparation is subdivided into unit doses containing appropriate quantities of the active component.
  • the unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packeted in vials or ampules.
  • the quantity of active component in a unit dose preparation may be varied or adjusted from about 0.1 to about 50 mg, preferably 0.1 to about 40 mg, and more preferably 0.1 to about 20 mg according to the particular application and the potency of the active component and size of the patient.
  • the composition can, if desired, also contain other compatible therapeutic agents.
  • the compounds utilized in the pharmaceutical methods of this invention are administered at the initial dosage of about 0.1 mg to about 20 mg per kilogram body weight (IM) daily.
  • Specific exemplary embodiments involve the use of about 0.5 mg to about 6 mg per kilogram body weight (IM) for the treatment of neonatal hyperbilirubinemia.
  • the dosages may be varied depending upon the requirements of the patient, the severity of the condition being treated and the compound being employed. Determination of the proper dosage for a particular situation is within the skill of the art. In one embodiment, generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small increments until the optimum effect under the circumstance is reached.
  • One aspect of the present invention is directed towards a pharmaceutical composition that comprises stannsoporfin, where it is in an aqueous solution and the concentration of stannsoporfin in the solution is between about 4.5 and 40 mg/ml, and preferably between about 4.5 and 25 mg/ml.
  • the components of the stannsoporfin composition comprise an acid, a base and a buffering agent mixed in an aqueous solution.
  • the composition is preferably sterile and has a physiological osmolarlity.
  • the compositions or drug products are preferably packaged in amber glass vials.
  • the pharmaceutical composition containing stannsoporfin can be a component of a drug product, wherein the product is contained in a single dose unit.
  • a single dose unit includes at least about 0.5 ml of solution, and more preferably, at least about 1 ml of solution.
  • the solution may be provided in a drug product form by containing the solution in a suitable container such as an ampule or vial.
  • a suitable container such as an ampule or vial.
  • the solution is stable and has a shelf life of at least about 3 months. In other embodiments, the solution has a shelf life of at least about 6 months.
  • Another aspect of this invention is directed towards a method of making a pharmaceutical composition comprising large quantities of stannsoporfin.
  • the stannsoporfin is present in an amount of at least about 4.5 mg/ml.
  • a pre-determined amount of stannsoporfin is mixed with a buffering agent in aqueous solution.
  • buffering agent There are numerous buffers which may be suitable for creating the pharmaceutical composition.
  • buffers include: an alkali earth metal buffering agent, a calcium buffering agent, a magnesium buffering agent, an aluminum buffering agent, sodium bicarbonate, potassium bicarbonate, magnesium hydroxide, magnesium lactate, magnesium gluconate, magnesium oxide, magnesium aluminate, magnesium carbonate, magnesium silicate, magnesium citrate, aluminum hydroxide, aluminum hydroxide/magnesium carbonate, aluminum hydroxide/sodium bicarbonate coprecipitate, aluminum glycinate, aluminum magnesium hydroxide, aluminum phosphate, sodium citrate, calcium citrate, sodium tartrate, sodium acetate, sodium carbonate, sodium polyphosphate, sodium dihydrogen phosphate, potassium pyrophosphate, sodium polyphosphate, potassium pyrophosphate, disodium hydrogenphosphate, tribasic sodium phosphate dodecahydrate, dipotassium hydrogen phosphate, trisodium phosphate, tripotassium phosphate, potassium carbonate, potassium metaphosphate, calcium acetate, calcium glycerophosphate,
  • the buffer used should be able to be used in a concentration effective to raise the pH of the solution to about 10 or above, when base is added to the solution.
  • the buffer must be pharmaceutically acceptable.
  • the method of making a pharmaceutical composition further comprises adjusting the pH of the solution to a pH of at least about 10 to facilitate dissolution of the stannsoporfin in the solution. This can be accomplished through the addition of a strong base to the solution. Strong bases with low pK b values facilitate the dissolution of large quantities of stannsoporfin.
  • the base used in this method can be any pharmaceutically acceptable strong base such as a metal hydroxide or other hydroxide bases. Presently preferred bases include pharmaceutically acceptable Group I and Group II metal hydroxides.
  • Sodium hydroxide has been demonstrated to be suitable.
  • Other suitable bases may include potassium hydroxide, calcium hydroxide, ammonium hydroxide, tetraethyl ammonium hydroxide, 10% ethanolamine or magnesium hydroxide.
  • the base should be pharmaceutically acceptable and effective to raise the pH of the solution to about 10 or above.
  • the pH of the solution is adjusted to a pH range of less than 8, for example between about 7.2 and 7.9, more preferably to a pH of between about 7.4 to 7.9.
  • a pharmaceutically effective strong acid in a dilute concentration to the solution corresponding to the base used to raise the pH.
  • suitable acid is 0.3 N. hydrochloric acid.
  • suitable acids may include niric acid, perchloric acid or hydroiodic acid.
  • the pH range of the stannsoporfin solution should be in a form that can be administered so the pH range is preferably between about 7.4 and 7.9.
  • Another aspect of this invention is directed towards a method of lowering bilirubin levels in a mammal comprising parenterally administering a stannsoporfin solution that has a concentration of stannsoporfin greater than 4.5 mg/ml. While the intended recipients of this medication to treat hyperbilirubinemia are humans, particularly infants, the stannsoporfin solution may also be effective in other mammals.
  • Another aspect of this invention is directed towards a method of making a drug product comprised of an aqueous solution of stannsoporfin in a concentration of at least about 4.5 mg/ml.
  • This aqueous solution can further comprise an acid, a base and a buffering agent.
  • One way in which this aqueous solution can be packaged is in a vial.
  • the vial is a Type 1 amber glass tubing vial to protect the composition from light.
  • the drug product is stable and has a shelf life of at least about 1 month, and preferably at least about 3 months. In other embodiments, the product has a shelf life of at least about 6 months at room temperature.
  • the drug product or compositions exhibits a physiological osmolarity.
  • physiological osmolarity means the drug product or composition, when administered to a patient does not cause irritation or an adverse reaction. Previous formulations did not exhibit a physiological osmolarity, and administration of the composition caused irritation to the patient.
  • a suitable range for the osmolarity according to certain embodiments is between about 270 and 328 mOsmol/L, and more preferably between about 280-300 mOsmol/L osmolarity.
  • a desired volume of the batch for the solution was determined.
  • the amount of stannsoporfin required for the batch was calculated and recorded.
  • An empty mixing vessel was purged with nitrogen NF for a minimum of 15 minutes. Purging continued throughout the formulation process.
  • Water for injection was added to the vessel.
  • the temperature of the mixing vessel was measured and adjusted to between about 15 0 C to 30 °C.
  • the mixing vessel was maintained within this temperature range throughout the process.
  • Mixing began at 400 to 600 rpm, and the mixing was maintained at this rate throughout the process.
  • a buffering agent for example, tribasic sodium phosphate dodecahydrate
  • Stannsoporfin was added to the mixing vessel. The contents of the vessel were now mixed for approximately 30 to 35 minutes.
  • a 10 ml sample of the bulk solution was withdrawn and its pH was measured. If the pH was below about 10, small increments of IN sodium hydroxide solution was added to aid in the dissolution of the stannsoporfin.
  • the pH was increased to above about 10 and any amount of added sodium hydroxide was recorded. The solution was then observed to determine if the stannsoporfin was dissolved. The contents of the vessel were mixed for approximately 30 to 35 minutes. Another 10 ml sample of the bulk solution was withdrawn, and its pH was measured.
  • a 23 L stannsoporfin solution was prepared in accordance with Example 1 including the following components: Component Amount/ml Amount/23L
  • Samples produced in accordance with EXAMPLES 1 and 2 were subjected to stability testing as follows.
  • the stability samples were stored at 3 conditions (4°C ⁇ 2 0 C, 25°C ⁇ 2°C/60% ⁇ 5%RH and, 40 0 C ⁇ 2°C/75% + 5%RH) , and were monitored as follows: 4°C + 2°C for 0, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months; 25°C ⁇ 2°C/60% ⁇ 5%RH for 0, 3, 6, 9, 12, 18, 24, 36, 48, and 60 months; 40 0 C ⁇ 2°C/75% + 5%RH 0, 1, 2, 3, 4, 5, and 6 months.
  • Volume in Container Not less than 1.5 ml per vial withdrawable.
  • a formulation was prepared in accordance with the having the following components therein: Component Amount/ml Amount/25ml
  • Osmolality was measured using a Wescore 5500 Vapor Pressure Osmometer. Prior to measuring the osmolality of the samples, the osmometer was calibrated using osmolality standards of 290 mmol/kg, 1000 mmol/kg and 100 mmol/kg. The osmolality values were 255, 252 and 256 mmol/kg, and the average value was 254 mmol/kg.
  • a formulation was prepared having the following components therein: Component Amount/ml Amount/25ml
  • Osmolality was measured using a Wescore 5500 Vapor Pressure Osmometer, Prior to measuring the osmolality of the samples, the osmometer was calibrated using osmolality standards of 290 mmol/kg, 1000 mmol/kg and 100 mmol/kg. The osmolality values were 292, 289 and 284 mmol/kg, and the average value was 288 mmol/kg.
  • Urinary excretion of two stannsoporfin formulations differing in osmolarity was measured as a marker of drug absorption from the muscle compartment into the central circulatory compartment.
  • Forty mg of a prior art formulation having a non-physiological osmolarity of 400 mOsmol/L or a formulation having a physiological osmolarity of 270-328 mOsmol/L prepared according to the present invention were administered intramuscularly to healthy adult volunteers.
  • Urine samples were collected up to 48 hrs after administration and excreted tin mesoporphyrin measured fluorometrically and expressed as % of dose administered.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
EP06749109A 2005-04-01 2006-03-31 Zusammensetzungen und verabreichung von stannsoporfin Withdrawn EP1865777A4 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP10014149A EP2301548A1 (de) 2005-04-01 2006-03-31 Stannsoporfin-Zubereitungen und ihre Anwendungen

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US11/096,359 US20060222668A1 (en) 2005-04-01 2005-04-01 Stannsoporfin compositions, drug products and methods of manufacture
US11/239,769 US20060222669A1 (en) 2005-04-01 2005-09-30 Stannsoporfin compositions and administration
PCT/US2006/012185 WO2006107806A2 (en) 2005-04-01 2006-03-31 Stannsoporfin compositions and administration

Publications (2)

Publication Number Publication Date
EP1865777A2 true EP1865777A2 (de) 2007-12-19
EP1865777A4 EP1865777A4 (de) 2008-07-16

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EP (1) EP1865777A4 (de)
KR (1) KR20080004531A (de)
AU (1) AU2006232330A1 (de)
CA (1) CA2602794A1 (de)
NO (1) NO20075508L (de)
WO (1) WO2006107806A2 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7375216B2 (en) 2002-06-04 2008-05-20 Infacare Pharmaceutical Corporation Preparation of metal mesoporphyrin compounds
EP2079472B1 (de) 2006-10-04 2011-09-14 InfaCare Pharmaceutical Corporation Herstellung grosser mengen von hochreinem stannsoporfin
WO2012135686A1 (en) 2011-03-30 2012-10-04 Infacare Pharmaceutical Corporation Methods for synthesizing metal mesoporphyrins

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4692440A (en) * 1985-03-25 1987-09-08 The Rockefeller University Therapeutic use of tin mesoporphyrin

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4657902A (en) * 1985-03-25 1987-04-14 The Rockefeller University Therapeutic use of tin mesoporphyrin
US7375216B2 (en) * 2002-06-04 2008-05-20 Infacare Pharmaceutical Corporation Preparation of metal mesoporphyrin compounds
US20040097481A1 (en) * 2002-11-20 2004-05-20 Benjamin Levinson Water-soluble mesoporphyrin compounds and methods of preparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4692440A (en) * 1985-03-25 1987-09-08 The Rockefeller University Therapeutic use of tin mesoporphyrin

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
See also references of WO2006107806A2 *
SHENOUDA MAGDY ET AL: "The pharmacokinetics (PK) of stannsoporfin in healthy adult volunteers are dose-proportionate" JOURNAL OF CLINICAL PHARMACOLOGY, vol. 44, no. 10, October 2004 (2004-10), page 1186, XP008092154 & 33RD ANNUAL MEETING OF THE AMERICAN-COLLEGE-OF-CLINICAL-PHARMACOLOGY; PHOENIX, AZ, USA; OCTOBER 03 -05, 2004 ISSN: 0091-2700 *

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Publication number Publication date
WO2006107806A3 (en) 2007-07-12
CA2602794A1 (en) 2006-10-12
AU2006232330A1 (en) 2006-10-12
EP1865777A4 (de) 2008-07-16
NO20075508L (no) 2007-10-31
WO2006107806A2 (en) 2006-10-12
KR20080004531A (ko) 2008-01-09

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