Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heavy metal containing doai
Reexamination Certificate
1986-03-05
2003-09-02
Sneed, Helen M. S. (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heavy metal containing doai
C556S136000, C556S137000, C554S071000, C424S450000
Reexamination Certificate
active
06613799
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a platinum (II) complex. More particularly, the present invention pertains to a platinum (II) complex having excellent antibacterial activity and anticancer activity, in particular, effective to use as a anticancer agent and a process for preparing the same.
2. Description of the Prior Art
Recently, a remarkable development has been achieved in medical and pharmaceutical fields, and as a result, diseases conventionally considered to be incurable and showing a high mortality have been protected, restrained or cured (or recovered) to a substantial degree. Under such circumstances, cancer has drawn a great attention because of its high mortality. However, up to now, there has not yet been proposed an effective solution to reduce the mortality of patients suffering from cancer.
There have been proposed conventional therapeutics for cancer, such as surgical operation inclusive of the operation utilizing laser such as YAG laser in which the affected part of patients is cut off, irradiation (radiotherapy), chemical therapy (chemotherapy) by administrating medicines as well as immunological therapy (immunotherapy) and interferon therapy.
However, the surgical operation and the radiotherapy among others are a kind of locally applied techniques of therapy and are effective means for treating patients only if the disease is in its primitive state or there is no metastasis, while these therapeutics are not effective against the progressive cancer i.e., those accompanying metastasis in the whole body of patients as well as the systematic diseases such as leukemia and malignant lymphoma in which a specific system in the whole body is gradually affected. On the other hand, the chemotherapy is the only effective therapeutics against the latter systematic diseases and some of the cancer may be cured by the chemical therapy. It is also recognized that the chemotherapy is an effective tool for treating patients suffering from cancer, in particular, when it is applied as an additional or auxiliary treatment after the surgical operation or it is applied in combination with the radiotherapy and thus, this is one of the therapeutic technique in which a great future development is expected.
Up to now, various kind of anticancer agents have been developed and proposed and each of them differs in its property and the effectiveness thereof varies depending on the kind of cancer. There may be mentioned such as mitomycin C, adriamycin as the medicine against adenocarcinoma (carcinoma in digestive organs, oophoroma); vincristine, bleomycin against the malignant lymphoma; cytocine arabinoside, L-asparaginase for acute leukemia. On the other hand, a metal complex such as cis-diamminedichloro platinum (II) has recently been proposed and already sold.
The chemotherapy for the cancer is based on the fact that the cancer may be caused by the parasite such as cancer cells in a human body as encountered in the case of bacteria in the general infectious diseases. In other words, the cancer cells are considered to be normal cells which are converted to a variant by some causes and the variant once formed in a body is considered to be the parasite exhibiting autonomous proliferation.
Although, cancer cells as well as normal cells are different in their biological and biochemical properties from each other, the difference is simply a quantitative one, while the qualitative difference between them has not yet been made clear. Therefore, the normal cells may possibly be impaired by the action of chemical agents (medicine) in the chemotherapy and this is revealed as so-called side-effects due to the medicine (such as anticancer agents). Thus, it is quite difficult to restrain only the proliferation of cancer cells or destroy only these cells utilizing such medicines.
BRIEF EXPLANATION OF THE INVENTION
As seen from the above, the development of a new technique for treating cancer is a principal subject to be solved in the medical and pharmaceutic fields and an absolute therapy therefor should be developed. However, it can not be expected to achieve a new drastic development in the therapy such as surgical therapy and the radiotherapy. Thus, it is more preferable or practical to improve chemotherapy or to develop a new medicine since a significant future development may be expected. It is expected, in particular, as the additional or auxiliary treatment means after the surgical operation of the affected part and it may be used in combination with the radiotherapy. Furthermore, the chemotherapy may be an effective tool for treating the progressive cancer as well as the systematic diseases such as malignant lymphoma, leukemia. Thus, there is a great need to develop a new therapeutic technique in medical or pharmaceutical science to remedy the patients suffering from these diseases. It must be said, however, that such agents should fulfill the requirement such that they affect on the cancer cells specifically and preferentially.
The principal object of this invention is to provide a novel platinum (II) complex.
Another object of this invention is to provide a an anticancer composition which affects on cancer cells specifically and preferentially.
A further object of this invention is to provide an anticancer composition having no side-effect.
An other object of this invention is to provide a method for preparing the platinum (II) complex effective as the anticancer active component.
These and other objects of this invention may be accomplished by providing a liposoluble platinum (II) complex represented by the following general formula (I):
wherein R
1
and R
2
, which may be identical or different, stand for a ligand ammine which may have an organic substituent and may be bonded together through a bivalent organic group and R
3
represents a saturated or unsaturated higher fatty acid residue(acyloxy group) and the platinum (II) complex can be prepared according to the following method comprising nitrifying a cis-dichloro-di (substituted or unsubstitutes) ammine platinum (II) complex of the formula (A):
with a nitrifying agent to form a nitrate of the diaqua form thereof and then reacting the same with a compound of the formula: R
3
—M (wherein R
3
has the same meaning as defined above and M is an alkali metal).
DETAILED EXPLANATION OF THE INVENTION
Conventionally, various kinds of watersoluble platinum (II) complexes have been known and some of them have already been put in practical use. Among the well known examples of such complexes, cisplatin (cis-diamminedichloroplatinum (II)) has been approved and manufactured and sold by BRISTOL-BANYU Pharmaceutical Co., Ltd. and NIPPON KAYAKU Co., Ltd. under the trade name of “Briplatin” and “Randa”, respectively.
It is known that the complex is effective to orchidoncus, bladder carcinoma, oophoroma, lung cancer, osteosarcoma, cancer of the esophagus or the like. However, the complex causes a lot of severe side-effects such as diarrhea, celialgia (side-effects in digestive system) and, in particular, this exhibits nephrotoxicity which is known to cause the increase in concentration of blood urea nitrogen (BUN), serum creatinine.
While, carboplatin (cis-diammine-1,1-cyclobutane-dicarboxylate platinum (II); Johnson-Matthey, Inc.), 4′-carboxyphthalato-(1,2-di-aminocyclohexane) platinum (II) (DACCP; Johnson-Matthey, Inc.), spiroplatin (cis-1,1-di-(aminomethyl) cyclohexane platinum (II) sulfate; Organic Chemistry TNO (Utrecht)) or the like have been developed in order to reduce the toxicity, in particular, nephrotoxicity of the cisplatin and to improve the antitumor activity of cis-platinum (II) complex.
These platinum (II) complexes are all water soluble compounds and have water solubility of 17.8 mg/ml (carboplatin), 0.1 mg/ml (DACCP: the solubility in 1.5% NaHCO
3
aq. solution being 25 mg/ml) and 1 mg/ml (spiroplatin) respectively. According to these compounds, the nephrotoxicity can somewhat be reduced compared with cisplatin, however, they still exhibit various kinds of side-effects. As
Maeda Mitsuaki
Sasaki Takuma
Clarke Dennis P.
Miles & Stockbridge
Sneed Helen M. S.
Sumitomo Pharmaceuticals Company Ltd.
LandOfFree
Liposoluble platinum (II) complex and preparation thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Liposoluble platinum (II) complex and preparation thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Liposoluble platinum (II) complex and preparation thereof will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3057718