EP0000253B1 - Dispositif diagnostique pour la visualisation d'hématomes - Google Patents

Dispositif diagnostique pour la visualisation d'hématomes Download PDF

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Publication number
EP0000253B1
EP0000253B1 EP78300048A EP78300048A EP0000253B1 EP 0000253 B1 EP0000253 B1 EP 0000253B1 EP 78300048 A EP78300048 A EP 78300048A EP 78300048 A EP78300048 A EP 78300048A EP 0000253 B1 EP0000253 B1 EP 0000253B1
Authority
EP
European Patent Office
Prior art keywords
stannous
salt
chloride dihydrate
glucoheptonate
solution
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.)
Expired
Application number
EP78300048A
Other languages
German (de)
English (en)
Other versions
EP0000253A1 (fr
Inventor
Paul-Emile Bonneau
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.)
Merck Sharp and Dohme IA Corp
Original Assignee
Merck Sharp and Dohme IA Corp
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Filing date
Publication date
Application filed by Merck Sharp and Dohme IA Corp filed Critical Merck Sharp and Dohme IA Corp
Publication of EP0000253A1 publication Critical patent/EP0000253A1/fr
Application granted granted Critical
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Definitions

  • One of the methods employed in the past to image the blood pool for diagnostic purposes involves the intravenous administration of 99m Tc serum albumin which is available commercially and is a sterile pyrogen-free solution of albumin labelled with Technetium 99m having an activity of greater than 100 micro- curies/ml.
  • Another method used in the past for imaging blood pools is the in vitro labelling of red blood cells (outside the host animal) followed by reinjection of the cells into the vascular system of the selected animal.
  • this method it is possible to visualize both heart blood pools plus major peripheral vessels up to 3 hours after injection of the labelled cells. As can be seen, this is a complicated procedure, and therefore is a more time-consuming and expensive method.
  • Still another procedure for imaging blood involves the injection of stannous pyrophosphate followed by injection of 99m Tc-pertechnetate. This technique is reported as successful in producing satisfactory imaging of blood pools.
  • US Patent Specification No. 4 027 005 discloses inter alia an in vitro prepared radioactive diagnostic composition comprising a pertechnetate, stannous chloride dihydrate and a glucoheptonate salt, the preferred minimum weight of glucoheptonate being 200 times that of the stannous compound. This composition is primarily for use in examination of the kidneys.
  • a diagnostic kit suitable for the radioactive labelling of red blood cells in vivo, thus making possible the imaging of blood pools within the circulatory system of the patient being examined.
  • a novel chemical composition comprising a lyophilized mixture of a glucoheptonate salt and a pharmaceutically acceptable stannous salt in the ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt measured as calcium glucoheptonate and stannous chloride dihydrate or approximately 22.9 parts of glucoheptonate ion to 1.32 parts of tin calculated as available stannous ion.
  • An important feature of the present invention is the provision of an individual diagnostic kit containing a non-toxic stannous salt capable of supplying an amount of stannous ion equivalent to at least 2.5 mg and no more than 4.0 mg of stannous chloride dihydrate. Less than 2.5 mg of the stannous chloride does not provide sufficient stannous ion to effect a satisfactory degree of labelling of red blood cells. Because of the known toxicity of stannous salts, no more than 4 mg of stannous chloride dihydrate or a stannous salt containing an equivalent amount of stannous ion should be incorporated in an individual dosage kit.
  • the present invention also includes the process for the preparation of the novel chemical composition and the diagnostic method for imaging blood pools in patients suspected of having abnormalities in the circulatory system.
  • a sterile solution of a non-toxic pharmaceutically acceptable salt of glucoheptonic acid e.g., calcium glucoheptonate
  • a non-toxic stannous salt in a ratio of 25 parts by weight of glucoheptonate salt to 3 parts by weight of stannous salt, calculated as calcium glucoheptonate and stannous chloride dihydrate.
  • the solution is adjusted to a neutral pH 6-8, subdivided, and lyophilized to produce individual vials containing a dry, sterile mixture comprising 25 mg. calcium glucoheptonate and 3 mg. stannous chloride dihydrate.
  • a vial containing the dry, sterile mixture of calcium glucoheptonate and stannous chloride dihydrate is reconstituted by mixing with 2-8 ml. of a USP saline solution.
  • the reconstituted solution is then used for injection of the patient to be examined. After a period of 30 minutes, a second injection of 2-8 ml. of a sterile saline solution of sodium pertechnetate is made. Following the injection of sodium pertechnetate, it is possible, after waiting from 30 seconds to 2 minutes, to image the blood pools in the patient being examined.
  • a solution is prepared under sterile conditions with 25 g. of calcium glucoheptonate in sterile pyrogen-free water which has been purged with nitrogen.
  • the solution of calcium glucoheptonate is stored and purged under nitrogen.
  • 3 g. of stannous chloride dihydrate is dissolved in 1 ml. of hydrochloric acid, and the resulting solution diluted with nitrogen-purged, sterile water to a volume of 10 ml.
  • the stannous chloride dihydrate solution is then added to the calcium glucoheptonate with stirring and flushing with nitrogen.
  • the solution is mixed thoroughly, and the pH is adjusted to neutrality with a solution of sterile 1N sodium hydroxide solution.
  • the volume is then adjusted to 2000 ml.
  • each vial contains 25 mg. of calcium glucoheptonate and 3 mg. of stannous chloride dihydrate.
  • a solution of sodium chloride for injection USP (2 ml.) is added to a vial containing a lyophilized mixture of 3 mg. of stannous chloride dihydrate and 25.0 mg. calcium glucoheptonate.
  • the resulting solution is used for the intravenous injection of patients for the purpose of imaging the blood pools for diagnostic purposes.
  • the amount of solution used is based on the weight of the patient and sufficient volume is used so that 30 mcg./kg. of stannous ion, measured as stannous chloride dihydrate, is injected. It is recommended that no more than the contents of one vial be administered to any patient.
  • a sterile saline solution of sodium pertechnetate-Tc99m (2-20 mCi) is injected. This tags the red blood cells and permits imaging of the blood pools of the patient being examined almost immediately (from 30 seconds to 2 minutes).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Dispersion Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Claims (3)

1. Dispositif diagnostique utilisé pour la visualisation d'hématomes, comprenant un flacon scellé stérile contenant un mélange lyophilisé d'un sel non toxique pharmaceutique- ment acceptable de l'acide glucoheptonique et d'un sel stanneux non toxique pharmaceutique- ment acceptable dans un rapport de 22,9 parties en poids d'ion glucoheptonate à 1,32 partie en poids d'ion stanneux, à condition que la dose individuelle d'ion stanneux soit de 2,5 à 4 mg, calculée sous forme de chlorure stanneux.
2. Dispositif selon la revendication 1, caractérisé en ce que le sel de l'acide glucoheptonique est le glucoheptonate de calcium et le sel stanneux est le chlorure stanneux dihydraté.
3. Dispositif selon la revendication 1, caractérisé en ce qu'il comprend un mélange lyophilisé de 3 mg de chlorure stanneux dihydraté et de 25 mg de glucoheptonate de calcium.
EP78300048A 1977-06-17 1978-06-15 Dispositif diagnostique pour la visualisation d'hématomes Expired EP0000253B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CA280764 1977-06-17
CA280,764A CA1105815A (fr) 1977-06-17 1977-06-17 Traduction non-disponible

Publications (2)

Publication Number Publication Date
EP0000253A1 EP0000253A1 (fr) 1979-01-10
EP0000253B1 true EP0000253B1 (fr) 1981-10-28

Family

ID=4108910

Family Applications (1)

Application Number Title Priority Date Filing Date
EP78300048A Expired EP0000253B1 (fr) 1977-06-17 1978-06-15 Dispositif diagnostique pour la visualisation d'hématomes

Country Status (8)

Country Link
US (1) US4300569A (fr)
EP (1) EP0000253B1 (fr)
JP (1) JPS5417129A (fr)
CA (1) CA1105815A (fr)
DE (1) DE2861257D1 (fr)
DK (1) DK269578A (fr)
IE (1) IE47091B1 (fr)
IT (1) IT1105145B (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4372294A (en) * 1980-09-25 1983-02-08 The Massachusetts General Hospital Method and apparatus for radiolabeling red blood cells
US4443426A (en) * 1982-06-14 1984-04-17 Yale University Blood agent
US4581221A (en) * 1983-08-29 1986-04-08 Medi Nuclear Corporation, Inc. Ulcer detection
US4755375A (en) * 1984-01-27 1988-07-05 Associated Universities, Inc. Method and kit for the selective labeling of red blood cells in whole blood with TC-99M
JPS61103841A (ja) * 1984-10-26 1986-05-22 Nippon Mejifuijitsukusu Kk 放射性テクネチウム標識に供する安定な塩化第一スズ組成物
US4789541A (en) * 1985-10-04 1988-12-06 Davis Michael H Method and composition for in vivo radiolabeling of red blood cells with 99m Tc
US4692324A (en) * 1985-10-04 1987-09-08 Davis Michael H Method and composition for in vivo radiolabeling of red blood cells with 99m Tc
NZ283658A (en) * 1994-04-04 1999-09-29 William R Freeman Compositions and treatment of increased intraocular pressure with phosphonyl-alkyloxy-pyrimidines/purines (nucleosides)
US5529189A (en) * 1995-08-02 1996-06-25 Daxor Corporation Syringe assembly for quantitative measurement of radioactive injectate and kit having same
US7803970B2 (en) 2002-02-28 2010-09-28 University Of Tennessee Research Foundation Multi-substitued selective androgen receptor modulators and methods of use thereof
DE102007053722B4 (de) 2007-11-10 2011-08-25 Amphenol-Tuchel Electronics GmbH, 74080 Hermaphroditischer Steckverbinder

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3743714A (en) * 1970-12-04 1973-07-03 Cis Radiopharmaceuticals Inc Novel carrier preparations for injectable radioactive compositions
CA1027135A (fr) * 1973-06-11 1978-02-28 Research Corporation Complexe de technetium-99m se fixant dans le tissu osseux
US4027005A (en) * 1974-06-07 1977-05-31 New England Nuclear Corporation Diagnostic agents
US4042677A (en) * 1974-08-29 1977-08-16 Union Carbide Corporation Technetium-99m labeled radiodiagnostic agents and method of preparation
GB1535847A (en) * 1976-03-19 1978-12-13 Radiochemical Centre Ltd Technetium-99m labelled tin colloid for body scanning
US4054645A (en) * 1976-08-24 1977-10-18 Minnesota Mining And Manufacturing Company Radiodiagnostic complexes employing fluorine-containing tin reducing agents
US4070493A (en) * 1977-03-16 1978-01-24 Merck & Co., Inc. Diagnostic kit

Also Published As

Publication number Publication date
IE781195L (en) 1978-12-17
DK269578A (da) 1978-12-18
EP0000253A1 (fr) 1979-01-10
IE47091B1 (en) 1983-12-14
JPS6315248B2 (fr) 1988-04-04
DE2861257D1 (en) 1982-01-07
IT7849830A0 (it) 1978-06-12
IT1105145B (it) 1985-10-28
JPS5417129A (en) 1979-02-08
CA1105815A (fr) 1981-07-28
US4300569A (en) 1981-11-17

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