Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Reexamination Certificate
2000-02-29
2001-11-06
Jones, Dwayne C. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
C514S502000
Reexamination Certificate
active
06313170
ABSTRACT:
TECHNICAL FIELDS OF INVENTION
This invention relates to a new derivative of L-threonic acid as a pharmaceutical active compound. More specifically, the invention concerns ferrous L-threonate, a method of making the same, a pharmaceutical composition thereof. In a further aspect, this invention relates to use of ferrous L-threonate for the preparation of a pharmaceutical composition for improving and treating the anemia diseases, particularly, nutritional iron-deficiency anemia (IDA) (hypoferric anemia), blood-loss anemia (hemorrhagic anemia) and hemolytic anemia.
TECHNICAL BACKGROUNDS OF INVENTION
L-threonic acid is one of metabolites of vitamin C. It is reported that some physiological functions of vitamin C were exerted very possibly by some of its metabolites, for example, L-threonic acid and the like. In the other hand, the existing of these compounds could profoundly influence the uptake and utilization of vitamin C.
Calcium L-threonate is a derivative of L-threonic acid. Calcium L-threonate can improve uptake of vitamin C by the lymphoma cells and can be used as the high efficient calcium nutrient for preventing and treating varied diseases caused by calcium deficiency (Chinese Patent, ZL 96 06507.9). Also, calcium L-threonate is useful for allaying inflammation and reducing blood pressure. But there was no report for other salts of L-threonic acid and their use as drugs on treating diseases.
Anemia is a common disease, which is caused by a various reasons. Their reasons mainly include: (1) a decrease of red blood corpuscle (RBC) in volume or in quantity; (2) a decrease of hemoprotein in amount due to chronic or acute blood loss and the injury of RBC due to its exposing to some chemical compounds; and (3) a reduction of the number of produced RBC due to deficiency of marrow or such nutrients as ferrous and vitamin B
12
used to produce RBC.
Nutritional iron-deficiency anemia (IDA) is a very common case among anemia diseases. The reason is that the body iron balance between excretion and storage has not been sustained. Consequently, there was more and more excretion but less and less storage of body iron with time. These phenomena often happened during the periods of growth, pregnancy and chronic blood loss due to various reasons. For example the less intake of iron from food is an important factor to lead to iron deficiency for body.
In fact, the nutritional IDA is a worldwide nutritional problem. For treating this kind of disease, simply taking iron-rich foods is hard to have good effects compared with using drugs. Among IDA drugs of iron preparations, ferrous sulfate is a relative popular drug with good effectiveness, low price and abundant resource. Even so, the extensive application of ferrous sulfate for treating IDA is limited because of its side effects (Chinese Child Blood, Vol. 1, p24-26, 1996). Therefore, it is desirable to provide new active compounds and compositions thereof for improving and treating IDA very efficiently.
Blood-loss anemia is a usual case of anemia. Most patients are women in the periods of pregnancy and menses.
Another anemia is hemolytic anemia. It is mainly caused by the following reasons: exposing to hemolytic chemical materials such as naphthalene and sulfanilamide; production of antibody in cells due to administration of drugs; and presence of cells with hereditary defection in body. A method for treating hemolytic anemia is to remove those harmful chemical reagents from body. Therefore, it is desirable to provide an active compounds and compositions thereof so as to improve and treat hemolytic anemia. It is in particularly desirable to provide an active compound and composition thereof so as to improve and cure these three kinds of anemia diseases.
OBJECT OF INVENTION
It is one object of this invention to provide a new derivative of L-threonic acid, in particularly, ferrous L-threonate.
It is another object of the invention is to provide compositions containing ferrous L-threonate for improving and treating such anemia as nutritional IDA, blood-loss anemia and hemolytic anemia.
It is a further object of the invention is to provide a method for improving and treating these anemia diseases.
ADVANTAGE OF INVENTION
Ferrous L-threonate of this invention has higher absorption rate compared with known iron preparations, for example, ferrous sulfate. Under the same dosages (element Fe/kg body weight) and the same body situation, animal test results showed that ferrous L-threonate was absorbed with higher absorptivity than ferrous sulfate. It is used safely and without toxicity. As iron preparation, ferrous L-threonate can significantly improve and cure hemolytic anemia, blood-loss anemia and nutritional IDA with the characters of high bioavailability and controlled release, compared with ferrous gluconate and ferrous fumarate. Ferrous L-threonate can be taken as both good iron supplement and drug for improving and treating anemia disease.
DETAIL DESCRIPTION OF INVENTION
This invention concerns the compound so-called ferrous L-threonate with chemical structure given as below.
Ferrous L-threonate has L-form optical structure. It is stable, soluble in water and exists mainly as the complex form in its solution.
Preparation methods for ferrous L-threonate:
1. Prepared by neutralization reaction of L-threonic acid with ferrous oxides or ferrous hydroxides, for example, with ferrous oxide (FeO) and ferrous hydroxide (Fe(OH)
2
);
2. Prepared by replacement reaction of L-threonic acid or calcium L-threonate with inorganic ferrous salts, such as ferrous sulfate (FeSO
4
), ferrous chloride (FeCl
2
) and ferrous nitrate (Fe(NO
3
)
2
), wherein L-threonic acid can be obtained by oxidizing vitamin C or by removing calcium from calcium L-threonate.
Ferrous oxides, ferrous hydroxides and inorganic ferrous salts can be prepared from the corresponding ferric compounds, such as, ferric nitrate, ferric sulfate and Fe3O4. If L-threonic acid is available in the market, it also can be used to prepare ferrous L-threonate according to the methods described above.
The reaction conditions for preparing ferrous L-threonate are,
(1) Under pH 6-10, preferably at pH 7-9, vitamin C was oxidized by oxidant, for example, by hydrogen peroxide solution to get a solution of L-threonic acid,
(2) Under the protection of inert gas such as nitrogen gas, the solution of L-threonic acid reacts with ferrous compounds, such as ferrous oxides, ferrous hydroxides and ferrous salts to produce ferrous L-threonate.
This invention also relates to compositions containing ferrous L-threonate as therapeutically active component. The composition also can include other therapeutically active compounds, pharmaceutically acceptable carrier and such medical supplementary materials as flavours, excipients and vitamins. Preferably, the composition of the invention contains ferrous L-threonate, vitamin C or vitamin B12, of which the weight ratio of ferrous L-threonate is 10-90%, preferred range is 30-80% and more preferred range is 40-60%.
The definition of the term “pharmaceutically acceptable” is that from the view of the point of pharmacy, those materials or components and their properties are acceptable by patients and pharmacists with stability and bioavailability.
The ferrous L-threonate of the invention can be prepared as any forms of drug. These forms include tablet, capsule, suppository, liquid, suspending agent, syrup, emulsion, gel, ointment, freeze-dried powder, pill, film, lipoplast, dispersible micro-powder and injection solution. Solid forms of tablet and powder are preferred.
According to the invention, the tablet can be prepared by mixing the active compound, ferrous L-threonate with excipients like calcium carbonate, calcium phosphate and lactose, with disintegrating agent like corn starch, with cohesive materials like starch and gelatin, with lubricants like magnesium stearate and talc powder, and with some controlled release materials like carboxypolymethylene and carboxymethyl cellulose.
Inner tablets used for preparing sugarcoating tablets can be made in the similar methods desc
Kou Fuping
Wang Zhiwen
Yu Kai
Alston & Bird LLP
Jones Dwayne C.
LandOfFree
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