Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Reexamination Certificate
2001-11-26
2002-08-27
Weddington, Kevin E. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
C514S866000
Reexamination Certificate
active
06440951
ABSTRACT:
TECHNICAL FIELD
This invention relates to a novel composition for therapeutically treating diabetes, which comprises as an active ingredient fosfomycin, a known antibiotic, or a pharmaceutically acceptable salt thereof. This invention also relates to a novel composition for therapeutically treating diabetes, which comprises fosfomycin or a pharmaceutically acceptable salt thereof and also a vanadyl compound (or a vanadyl salt) containing vanadyl group (VO
2+
) as active ingredients. This invention further relates to a novel method for treating diabetes by administration of fosfomycin or a salt thereof.
Furthermore, this invention includes the use of fosfomycin or a salt thereof or the use of a mixture of fosfomycin or a salt thereof with a vanadyl compound, in the preparation of a remedy of diabetes.
BACKGROUND ART
Diabetes are one of typical diseases incident to old adults, similarly to cancers, brain infarction, cardiac infarction, Alzheimer's disease and the like. There are numerous latent diabetes, too. Diabetes are diseases caused by occurrence of abnormal metabolisms of glucose, protein and lipid due to a deficiency or insufficiency of the actions of insulin. Typical signs of diabetes include an abnormal increase in the serum glucose level over the normal range of the glucose level and an excretion of glucose in the urine.
Insulin is one of hormones in pancreas and has such functions to promote the permeability of glucose through the cell membranes in liver, muscles and adipose tissues and thereby to increase the uptake of glucose by the cells, and further to promote the combustion of glucose in the glycolysis step and oxidation step of glucose in the muscles and also to elevate the activity of the enzyme system for synthesizing glycogen from glucose. It is known that by exhibiting the above biological functions, insulin has such action “in vivo” as to keep the serum glucose level at the normal levels.
In 1985, the classification of diabetes was proposed by The World Health organization (WHO). Diabetes are classified into two large groups, namely, the insulin-dependent diabetes mellitus (Type I, IDDM) where the patients do not-produce insulin; and the non-insulin-dependent diabetes mellitus (Type II, NIDDM) where the patients cause an insulin resistance. For the treatment of the type II diabetes, some orally administrable remedies are used. Under the present situation, however, the treatment of the type I diabetes has to resort on the injection of insulin. It has therefore been required worldwide to develope such novel oral remedies which are effective for treating the diabetes by oral administration.
It has been known from about 1960's that “ouabain” which has a digitalis-like cardiac action is effective as a strong inhibitor to Na,K-ATPase. Further, ouabain is known to have an insulin-like action in view of the fact that the action of inhibiting Na, K-ATPase can participate in the transportation and metabolism of glucose “in vivo”. In 1977, Cantley et al, found that sodium orthovanadate which is a penta-valent vanadium compound and which was accidentally mixed in ATP can strongly inhibit Na,K-ATPase (L. C. Cantley et al., “J.Biol.Chem.” Vol. 252, No.21, 7421-7423 (1977)). Judging from the fact that ouabain inhibits Na,K-ATPase and possesses the insulin-like action, many researchers then anticipated that the penta-valent vanadium compound, which was already admitted as an inhibitor to Na,K-ATPase similarly to ouabain, would also exhibit the insulin-like action (refer to Hiroshi Sakurai, “Gendai Kagaku” Current Chemistry in English, Jul. 14-20, 1996). As a result of many subsequent researches relating to the action of penta-valent vanadium on the uptake of glucose into cells, there is reported that some vanadates which are penta-valent vanadium compounds possess the insulin-like actions (see, for example, Degani et al, “Biochemistry” Vol.20, p.5795 (1981)).
Further, streptozotocin is known to be an antibiotic which is produced by actinimycetes. It is known that streptozotocin, if administered to animals, can specifically destroy &bgr;-cells of the islets of Langerhans in pancreas to stop the secretion of insulin and thus involve occurrence of experimental diabetes in the animals. In 1985, Heyliger et al, reported that when the diabatic rats which were made diabatic by administration of streptozotocin (abbreviated as STZ), namely the rats called as STZ diabatic rats, are given sodium metha-vanadate (NaVO
3
) in the form of an aqueous saline solution as drinking water, the so treated rats showed such a decrease in the glucose level in blood serum that the glucose level was returned to the normal level at 6th week after the administration of the vanadate. Heylinger et al also reported that a vanadate showed the insulin-like action with respect to the glucose metabolism (see C. B. Heyliger et al., “Science” Vol.27, p.1474-1477 (1985)).
Further, Japanese Patent Application Laid Open Publication, KOKAI-Hei 2-292217 specification (issued on Dec. 3, 1990) discloses that several vanadium complexes of the following formulae(A)~(G) possess a function of lowering the serum glucose level and that vanadyl sulfate (VOSO
4
) also possesses the function of lowering the serum glucose level.
Vanadium (VI) complex having the following formula (A)
Salicylaldehyde-vanadium (VI) complex having the following formula (B)
Gluconic acid- or L-lactic acid-vanadium (VI) complex having the following formula (C)
wherein R
1
stands for a group —CH(OH)CH(OH)CH(OH)CH
2
OH, or a methyl group.
L-Cystein methyl ester- or L-cysteamine-vanadium (VI) complex having the following formula (D)
wherein R
2
stands for a hydrogen atom or a methoxycarbonyl group.
L-(+)-Tartaric acid-vanadium (VI) complex having the following formula (E)
Oxalic acid-vanadium (VI) complex having the following formula (F)
Malonic acid-vanadium (VI) complex having the following formula (G)
While, Hiroshi Sakurai et al, report that vanadyl sulfate possesses the action of lowering the serum glucose level, and they report that comparisons are made between various vanadium compounds, including vanadium oxide, meta-vanadic acid, orthovanadic acid, vanadyl sulfate, potassium vanadate, sodium vanadate and the like, with remarking that the toxicity of sodium metavanadate (NaVO
3
) which is a penta-valent vanadium compound, when orally administered, was about 10 times higher than the toxicity of vanadyl sulfate(VOSO
4
) which is a tetra-valent vanadium compound (see Hiroshi Sakurai et al, “Trace Elements in vivo” published by Hirokawa Book Company, 1994).
Up to date, there have been synthesized a variety of vanadium compounds which are of a low toxicity and are orally administrable. Peroxo-vanadium compounds thus synthesized were studied on their function of lowering the serum glucose level, and further investigations were made to estimate whether a combined use of the penta-valent vanadium compounds synthesized and hydrogen peroxide can give rise to a synergistic effect on the action of lowering the serum glucose level. However, there is found no report to show that said combined use would have any synergistic effect in the action of lowering the serum glucose level (see B. I. Poner et al., “J.Biol.Chem.” , vol.269, No.6, 4596-4604 (1994)).
Specifically, fosfomycin is a known antibiotic having an antibiotic activity. Fosfomycin or a pharmaceutically acceptable salt thereof has the structure represented by the following general formula (I)
wherein R and R′ are each a hydrogen atom or a pharmaceutically acceptable monovalent metal atom, for example, an alkali metal atom, preferably sodium, potassium or ammonium radical, or R and R′ are combined together to show a divalent metal atom pharmaceutically acceptable, for example, an alkaline earth metal atom, preferably calcium or magnesium.
Fosfomycin and a salt thereof are useful as an antibiological agent and are also useful as a relieving or preventing agent for nephro-toxicity of aminoglycoside antibiotics (see Japanese Patent Publication Sho-64-5574) and
Niizato Tetsutaro
Shiotani Masaharu
Shoji Yoko
Larson & Taylor PLC
Meiji Seika Kaisha Ltd.
Weddington Kevin E.
LandOfFree
Method for treatment of diabetes does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for treatment of diabetes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for treatment of diabetes will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2929127