US3743712A - Macroaggregates of copper-64 and gelatin,application and method of preparation of same - Google Patents
Macroaggregates of copper-64 and gelatin,application and method of preparation of same Download PDFInfo
- Publication number
- US3743712A US3743712A US00038489A US3743712DA US3743712A US 3743712 A US3743712 A US 3743712A US 00038489 A US00038489 A US 00038489A US 3743712D A US3743712D A US 3743712DA US 3743712 A US3743712 A US 3743712A
- Authority
- US
- United States
- Prior art keywords
- copper
- gelatin
- solution
- macroaggregates
- preparation
- 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 - Lifetime
Links
- 239000008273 gelatin Substances 0.000 title abstract description 30
- 229920000159 gelatin Polymers 0.000 title abstract description 29
- 108010010803 Gelatin Proteins 0.000 title abstract description 27
- 235000019322 gelatine Nutrition 0.000 title abstract description 27
- 235000011852 gelatine desserts Nutrition 0.000 title abstract description 27
- RYGMFSIKBFXOCR-IGMARMGPSA-N copper-64 Chemical compound [64Cu] RYGMFSIKBFXOCR-IGMARMGPSA-N 0.000 title abstract description 24
- 238000000034 method Methods 0.000 title abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 239000000243 solution Substances 0.000 abstract description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 10
- 239000012153 distilled water Substances 0.000 abstract description 8
- 239000000725 suspension Substances 0.000 abstract description 7
- 239000012670 alkaline solution Substances 0.000 abstract description 6
- 230000007935 neutral effect Effects 0.000 abstract description 4
- 238000002405 diagnostic procedure Methods 0.000 abstract description 2
- 239000000700 radioactive tracer Substances 0.000 abstract description 2
- 229940014259 gelatin Drugs 0.000 description 25
- 239000002245 particle Substances 0.000 description 8
- 230000002685 pulmonary effect Effects 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910052802 copper Inorganic materials 0.000 description 6
- 239000010949 copper Substances 0.000 description 6
- 235000018553 tannin Nutrition 0.000 description 5
- 229920001864 tannin Polymers 0.000 description 5
- 239000001648 tannin Substances 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 210000003456 pulmonary alveoli Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
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
- A61K51/12—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
- A61K51/1217—Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
-
- 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
- A61K51/1241—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 particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins
- A61K51/1244—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 particles, powders, lyophilizates, adsorbates, e.g. polymers or resins for adsorption or ion-exchange resins microparticles or nanoparticles, e.g. polymeric nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- 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
- the present invention relates to macroaggregates of copper-64 and gelatin as well as to a method of preparation of macroaggregates of thin type and to their uses in human medicine, one application for which these macroaggregates are of particular interest being in the field of pulmonary scintiscanning by intravenous injection.
- a radioactive preparation which is intended to be employed in pulmonary scintiscanning must exhibit properties which permit retention of said preparation at the level of the pulmonary alveoli without causing any permanent obstruction of the capillary system. This entails the need to ensure that the particles of a preparation of this type must be of sufficiently large size in order to be efiFective while remaining sufficiently small and friable to ensure that the aggregate which is formed by said particles can readily be broken down by the blood stream.
- a particle diameter of the order of 50 microns makes it possible to satisfy these two conditions.
- this invention relates to the novel industrial product which is constituted by the macroaggregates of copper-64 and gelatin.
- the invention is also concerned with a method of preparation of macroaggregates of copper-64 and gelatin which essentially consists in forming a copper-gelatin compleX by addition in the cold state of an alkaline solution of copper-64 to a solution of gelatin, in precipitating said complex in the hot state with a solution of tannin 'ice and in completing the suspension obtained by addition of distilled water, the proportions being calculated so as to maintain a pH in the vicinity of 7 or in other words a neutral value and in such a manner as to ensure that said suspension does not contain any copper in the ionic form or any gelatin which has remained in solution.
- the present invention is further concerned with the applications of the macroaggregates of copper-64 and gelatin in the field of human medicine.
- the copper chloride obtained is washed a number of times, then crystallized and retreated with a small quantity of water. There are then added 3.8 cm. of an 8% solution of double tartrate of sodium and potassium, then 1 cm. of a 2 N sodium hydroxide solution and finally the quantity of distilled water which is necessary to produce a volume of 7.8 cm, which corresponds to a concentration of 6.4 mg. of copper-64 per liter.
- stage (d) Formation of the macroaggregates
- the complex obtained in stage (c) is precipitated and heated to a temperature of 50 C. by addition of 0.25 cm. of a 12% solution of tannin and the suspension is completed to 10 cm. by addition of distilled water.
- the proportions given above satisfy these ditferent conditions and result in the production of macroaggregates which are suitable for use in pulmonary scintiscanning.
- the diameter of the particles thus obtained is suitably of the order of 50 microns and must in any case always be greater than 30 microns; this diameter varies slightly as a function of the proportion of gelatin and of tannin.
- the macroaggregates in accordance with the present invention can find applications other than pulmonary scintiscanning (e.g. scintiscanning of the liver) and that a given particle diameter corresponds to each particular application.
- pulmonary scintiscanning e.g. scintiscanning of the liver
- each particle having a diameter greater than 30 microns and on the order of 50 microns.
- a method of pulmonary scintiscanning in humans consisting of the step of injecting intravenously the complex of claim 1 into the patient. 7
- a method of preparing a copper-64/gelatin complex, each particle having a diameter greater than 30 microns and on the order of 50 microns consisting of the steps of mixing an alkaline solution of a copper-64 salt and a solution of gelatin in the cold state, heating the mixture, precipitating a copper-64/gelatin complex by the addition of a solution of tannin, and completing the precipitation by the addition of distilled water, the proportions of the ingredients used leaving substantially no copper-64 or gelatin in solution in uncomplexed form.
- the alkaline solu- 7 tion of the copper-64 salt being prepared by treating copper-64 chloride with aqueous sodium hydroxide in the presence of sodium potassium tartrate.
- gelatin solution being prepared by a dispersing gelatin in hot distilled water and sterilizing the resulting solution in an autoclave.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Public Health (AREA)
- Dispersion Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nanotechnology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR6917455A FR2043487A1 (enrdf_load_stackoverflow) | 1969-05-28 | 1969-05-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3743712A true US3743712A (en) | 1973-07-03 |
Family
ID=9034721
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00038489A Expired - Lifetime US3743712A (en) | 1969-05-28 | 1970-05-18 | Macroaggregates of copper-64 and gelatin,application and method of preparation of same |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US3743712A (enrdf_load_stackoverflow) |
| BE (1) | BE750785A (enrdf_load_stackoverflow) |
| DE (1) | DE2025095A1 (enrdf_load_stackoverflow) |
| FR (1) | FR2043487A1 (enrdf_load_stackoverflow) |
| GB (1) | GB1276205A (enrdf_load_stackoverflow) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4756904A (en) * | 1986-06-05 | 1988-07-12 | Oak Ridge Associated Universities, Inc. | Method of imaging the heart using copper-64 citrate |
| US20080233182A1 (en) * | 2007-03-23 | 2008-09-25 | Georg Ludwig Kis | Organic compounds |
| EP1974733A1 (en) * | 2007-03-23 | 2008-10-01 | Novartis AG | Use of a masked or coated copper salt for the treatment of macular degeneration |
-
1969
- 1969-05-28 FR FR6917455A patent/FR2043487A1/fr active Pending
-
1970
- 1970-05-18 US US00038489A patent/US3743712A/en not_active Expired - Lifetime
- 1970-05-21 GB GB24624/70A patent/GB1276205A/en not_active Expired
- 1970-05-22 BE BE750785D patent/BE750785A/xx unknown
- 1970-05-22 DE DE19702025095 patent/DE2025095A1/de active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4756904A (en) * | 1986-06-05 | 1988-07-12 | Oak Ridge Associated Universities, Inc. | Method of imaging the heart using copper-64 citrate |
| US20080233182A1 (en) * | 2007-03-23 | 2008-09-25 | Georg Ludwig Kis | Organic compounds |
| EP1974733A1 (en) * | 2007-03-23 | 2008-10-01 | Novartis AG | Use of a masked or coated copper salt for the treatment of macular degeneration |
| WO2008116806A1 (en) * | 2007-03-23 | 2008-10-02 | Novartis Ag | Use of a masked or coated copper salt for the treatment of macular degeneration |
| AU2008231847B2 (en) * | 2007-03-23 | 2012-12-06 | Alcon Inc. | Use of a masked or coated copper salt for the treatment of macular degeneration |
| CN101668533B (zh) * | 2007-03-23 | 2013-04-03 | 诺瓦提斯公司 | 被掩蔽或包涂的铜盐在治疗黄斑变性中的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1276205A (en) | 1972-06-01 |
| DE2025095A1 (de) | 1970-12-03 |
| FR2043487A1 (enrdf_load_stackoverflow) | 1971-02-19 |
| BE750785A (fr) | 1970-11-03 |
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