US3689516A - Bis-carboxyethyl germanium sesquioxide and process for preparing same - Google Patents

Bis-carboxyethyl germanium sesquioxide and process for preparing same Download PDF

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Publication number
US3689516A
US3689516A US805370A US3689516DA US3689516A US 3689516 A US3689516 A US 3689516A US 805370 A US805370 A US 805370A US 3689516D A US3689516D A US 3689516DA US 3689516 A US3689516 A US 3689516A
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US
United States
Prior art keywords
bis
germanium sesquioxide
trichlorogermanium
compound
carboxyethyl germanium
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
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US805370A
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English (en)
Inventor
Kazuhiko Asai
Kazuo Makabe
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DAIICHI YAKUHIN SANGYO KK
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DAIICHI YAKUHIN SANGYO KK
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/30—Germanium compounds

Definitions

  • the compound of the invention inhibits the proliferation of Ehrlich ascites tumor cells.
  • Germanium which has the atomic number of 32, is an atom having 32 electrons. Four of these electrons are located in an outer orbit and are unstable, being capable of separation from the rest under certain conditions. This property of germanium is utilized for transistors or diode rectifiers, as is popularly known. And there is a phenomenon that, when one of these four electrons has escaped, there results what is referred to as a positive hole of electric potential, to which other nearby electrons are drawn in. The composition of germanium being so, its organic compound is apt to cause electric charge transfer and to generate organic free radicals.
  • Applicants have for a long time studied the components of plant substances used for the so-called Chinese medical herbs, which have been known to be effective to check abnormal cells in the living body, and discovered that they contained a very large content of germanium, for example, 320 ppm in ginseng, 257 ppm in water-caltrop nut, 124 ppm in box-thorn nut, 108 ppm in wisteriaknot, 50 ppm in pearlbarley seed, 58 ppm in erythrorhizon, 76 ppm in comfry, and 756 ppm in garlic. This fact appears to indicate that germanium exists within these plants in the form of organic compounds.
  • B-cyanoethyltrichlorogermanium trichlorogermanium ethylene cyanide is obtained by the action of acrylonitrile on the known compound trichlorogermanium (germaniumchloroform).
  • B-Cyanoethyltrichlorogermanium is converted into B- trichlorogermanium propionic acid (trichlorogermanium propionic acid) by hydrolysis in the presence of a mineral acid and by the action of thionylchloride, this latter compound is converted to trichlorogermanium propionyl chloride. Hydrolysis of this compound with water produces bis-carboxylethyl germanium sesquioxide.
  • Test mice DD Shizuoka, 4 weeks old.
  • the administered group were very vigorous and had good appetite compared with the control group, showing no external appearance of reaction, the control group showed stagnant ascites whereas the administered group showed neither ascites stagnation nor bleeding, the proportion of the number of tumor cells in the bodies of the administered group was approximately 26 percent against percent in the bodies of the control group, and that there was a good indication of the effective checking of fissiparism.
  • the compound, bis-carboxyethyl germanium sesquioxide is a, are white, crystalline powder, and capable of polymerization on heating. Its melting point is impossible to measure, since heating to a higher temperature causes decomposition. In water solution, the oxygen in germanium sesquioxide is hydrated and the hydrogen stimulates charge transfer, thus causing activation. 7
  • the novel compound according to the present invention is of a very low order of toxicity.
  • the LD in mice as determined by hypodermic injection is 3,5g/kg of body weight.
  • the compound of the invention is soluble in water, and therefore it is most convenient to formulate it as solutions in sterile, pyrogen-free water, although any pharmaceutically acceptable carrier may be used.
  • a preferred therapeutic composition of the invention will comprise an aqueous solution containing from 0.01 to 0.4 by weight of the active ingredient.
  • compositions containing the compound according to the invention can be administered orally or Number of E.A.'I. Ascites amount, Aver- '1.I.,
  • Example l To 18 gr. of germaniumchloroform are added 6 gr. of acrylonitrile, and by heating under an atmosphere of 55 nitrogengas, Byanoethyltrichlorogermanium is obtained. This is converted to B-trichlorogermanium propionic acid by adding hydrochloric acid solution and heating. This is converted through reaction upon the dropwise addition of 12 gr. of thionylchloride, to trichlorogermanium propionyl chloride, which is recovered by distillation in vacuo. After complete hydrolysis takes place with water, bis-carboxyethyl germanium sesquioxide is obtained. This is washed with water until chlorine reaction disappears and a white powder is obtained. The yield is about 6 gr. Anal. calcd. for C,l-l ,O,(I1E Calculated value: 1 H2294, Ge:42.64 Found 113.00, Ge:42.41
  • the carrier can be a solid and in the form of a powder or tablet.
  • the solid carrier can be any of those commonly used in making medicinal formulations.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US805370A 1968-03-29 1969-03-07 Bis-carboxyethyl germanium sesquioxide and process for preparing same Expired - Lifetime US3689516A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2008568 1968-03-29

Publications (1)

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US3689516A true US3689516A (en) 1972-09-05

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Family Applications (1)

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US805370A Expired - Lifetime US3689516A (en) 1968-03-29 1969-03-07 Bis-carboxyethyl germanium sesquioxide and process for preparing same

Country Status (7)

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US (1) US3689516A (fr)
BE (1) BE730615A (fr)
CH (1) CH521376A (fr)
DE (1) DE1793288B1 (fr)
FR (1) FR2005110A1 (fr)
GB (1) GB1257225A (fr)
NL (1) NL6904836A (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4066678A (en) * 1975-10-23 1978-01-03 Ryuichi Sato 3-trihydroxygermyl propionic acid and its salts and a process for the production thereof
US4271084A (en) * 1978-03-01 1981-06-02 Ryuichi Sato Germanium-containing organic polymer and the process for the production of the same
US4361579A (en) * 1979-09-19 1982-11-30 Yoshitomi Pharmaceutical Industries, Ltd. Organogermanium compounds
EP0085513A1 (fr) * 1982-02-01 1983-08-10 Industrial Technology Research Institute Procédé de préparation de dérivés d'acides organogermanium propioniques
US4508654A (en) * 1982-02-01 1985-04-02 Industrial Technology Research Institute Preparation of bis-carboxy ethyl germanium sesquioxide and its propionic acid derivatives
DE3514659A1 (de) * 1984-04-25 1985-10-31 Asai Germanium Research Institute, Tokio/Tokyo Antioxidans
US4579961A (en) * 1982-08-23 1986-04-01 Norihiro Kakimoto Organogermanium compounds having both hydrophilicity and lipophilicity and process for producing the same
US4956272A (en) * 1987-10-29 1990-09-11 Asai Germanium Research Institute Co., Ltd. Organogermanium containing solution for washing and storing separated organs
US5006553A (en) * 1987-10-29 1991-04-09 Asai Germanium Research Institute Co., Ltd. Agent for improving reduced functions of organs caused by inhibited blood circulation

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3812167A (en) * 1971-08-27 1974-05-21 Pahk Heart Foundation Germanium derivative
JPS5473129A (en) * 1977-11-22 1979-06-12 Asai Germanium Res Inst External skin remedy
JPS55122717A (en) * 1979-03-15 1980-09-20 Asai Gerumaniumu Kenkyusho:Kk Interferon inducer
JPS6016924A (ja) * 1983-07-11 1985-01-28 Asai Gerumaniumu Kenkyusho:Kk 抗腫瘍剤
JP2698870B2 (ja) * 1987-10-29 1998-01-19 株式会社浅井ゲルマニウム研究所 シクロスポリンの投与による腎毒性の軽減剤
US5008416A (en) * 1989-06-20 1991-04-16 Sanwa Kagaku Kenkyusho Co., Ltd. Organogermanium compound, process for the preparation of same as well as use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Lesbre et al. Compt. Rend. Vol. 247 (1958) p. 471 474 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4066678A (en) * 1975-10-23 1978-01-03 Ryuichi Sato 3-trihydroxygermyl propionic acid and its salts and a process for the production thereof
US4271084A (en) * 1978-03-01 1981-06-02 Ryuichi Sato Germanium-containing organic polymer and the process for the production of the same
US4361579A (en) * 1979-09-19 1982-11-30 Yoshitomi Pharmaceutical Industries, Ltd. Organogermanium compounds
EP0085513A1 (fr) * 1982-02-01 1983-08-10 Industrial Technology Research Institute Procédé de préparation de dérivés d'acides organogermanium propioniques
US4420430A (en) * 1982-02-01 1983-12-13 Industrial Technology Research Institute Method for preparing organo germanium propionic acid derivatives
US4508654A (en) * 1982-02-01 1985-04-02 Industrial Technology Research Institute Preparation of bis-carboxy ethyl germanium sesquioxide and its propionic acid derivatives
US4579961A (en) * 1982-08-23 1986-04-01 Norihiro Kakimoto Organogermanium compounds having both hydrophilicity and lipophilicity and process for producing the same
DE3514659A1 (de) * 1984-04-25 1985-10-31 Asai Germanium Research Institute, Tokio/Tokyo Antioxidans
US4720564A (en) * 1984-04-25 1988-01-19 Asai Germanium Research Institute Antioxidant organogermanium compound
US4956272A (en) * 1987-10-29 1990-09-11 Asai Germanium Research Institute Co., Ltd. Organogermanium containing solution for washing and storing separated organs
US5006553A (en) * 1987-10-29 1991-04-09 Asai Germanium Research Institute Co., Ltd. Agent for improving reduced functions of organs caused by inhibited blood circulation

Also Published As

Publication number Publication date
NL6904836A (fr) 1969-10-01
CH521376A (de) 1972-04-15
BE730615A (fr) 1969-09-01
FR2005110A1 (fr) 1969-12-05
GB1257225A (fr) 1971-12-15
DE1793288B1 (de) 1971-05-27

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