Organic compounds -- part of the class 532-570 series – Organic compounds – Heavy metal containing
Reexamination Certificate
2001-02-20
2003-04-15
Nazario-Gonzalez, Porfirio (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heavy metal containing
C514S492000
Reexamination Certificate
active
06548687
ABSTRACT:
TECHNICAL FIELD
This invention involves a new kind of compound—the chromate L-threonate, as well as its synthesis and application to medicine and health care.
TECHNICAL BACKGROUND
Diabetes mellitus is one of the common diseases over the world, the morbidity is 1-2 percent among the general population. Chromium(III) is an essential trace element in human body. Scientists have confirmed there is significant relationship between the long term deficiency of chromium(III) and adult diabetes as well as arteriosclerosis. Many individuals who take much refined food are often in the above problems because of the deficiency of chromium(III) in their diet. Chromium(III) also takes on one of important components of Glucose Tolerance Factor(GTF). Organic chromium(III) is much more easily absorbable in vivo condition than the inorganic form. (F. Dubois, Pathol. Biol. 1991, 39(8), 801-808). Chromium(III) will bind with some protein (e.g. transferrin) after being absorbed, but its reaction form and structure with insulin are still indefinite.
TECHNICAL CONTENT
The purpose of this invention is to search a new kind of chromate(III) organic acid which can active and cooperate with insulin more effectively; be in definite and controllable structure; be absorbed easily in human body; supply chromium(III) effectively for humans needs; be applied to prevention and treatment of diabetes mellitus. This invention also includes the synthesis methods and application of the chromate(III).
This new kind of chromate(III) is the chromate L-threonate which molecular formula shows below:
Cr
n
(C
4
H
8-n
O
5
)
3
n=1, 2, 3
L-threonic acid is one of main degradation products of Vitamin C (Clin Chem, 33, 572, 1987) and takes on positive physiological function in human body (J. Univ. PoonaSci. 2275, 1991; Technol. 54, 1-4, 1982; Bioorg. Med. Chem, 3(5), 487-494, 1995). Shourong Zhu and his colleagues reported there exists powerful affinity between metal coordination compound of L-threonate and amino acid (protein, polypeptide), that's to say, there is good compatibility between L-threonate acid and amino acid. Verlangeiri once pointed out in his research that L-threonic acid can cooperate with insulin (Life Sciences, 48, 2275, 1991). We combine L-threonic acid and Chromium(III) to produce the chromate L-threonate in this invention.
The synthesis methods of the chromate L-threonate include:
1. Take L-threonic acid as material to produce the chromate L-threonate.
2. Take calcium L-threonate as material to produce the chromate L-threonate.
According to the methods above, we can take vitamin C as raw material to synthesize calcium L-threonate, then derive the chromate L-threonate from calcium L-threonate with replacement of mild acid or cation exchange resin; also, we can take calcium L-threonate as material and derive the chromate L-threonate directly.
Chromate L-threonate, the product of this invention, can be applied to follows:
1. food additive in the form of solid or liquid for supplying the essential trace element
2. effective component in the prevention and health care of diabetes mellitus
3. combination of medicine preparation, such as tablet, capsule and other acceptable forms in pharmaceutics
4. effective ingredient of hypoglycemic medicine
As a kind of combination used in the prevention and health care of diabetes mellitus, even in hypoglycemic medicine, this invention includes chromate L-threonate, calcium L-threonate, carriers and accessories of medicine.
In the combination of this invention, the chromate L-threonate takes on the primary effective component and calcium L-threonate is the secondary. According to the requirements of pharmaceutics and medicine preparation, the carriers and accessories of the combination can be any material, which is accepted by the particular medicine.
The content of chromate L-threonate and calcium L-threonate of the combination can be changed to fit different requirement of particular preparation.
The chromate L-threonate and its combination of this invention can be taken by oral administration in almost conditions, and the dosage is changeable according to the different time and method of administration as well as the disease itself.
The chromate L-threonate can be used as some clinical drugs to reinforce and cooperate with the physiological function of insulin. For this purpose, chromate L-threonate can be made any preparation, such as tablet, capsule, solution, suspension, emulsion, gelatum, ointment, lyophilized powder, pill, liposome and so on.
The chromate L-threonate can be used as food additive in the form of liquid or solid powder for drinks, cheese, bread, flour etc.
The element analogy of the chromate L-threonate shows in the following table:
Element Analogy
Theoretical
Experimental
n
Model
Molecular Formula
Value
Value
1
A
Cr(C
4
H
7
O
5
)
3
.H
2
O
C30.31, H4.88
C29.95, H4.93
2
B
Cr
2
(C
4
H
6
O
5
)
3
.3H
2
O
C25.71, H4.32
C25.56, H4.14
3
C
Cr(C
4
H
5
O
5
).2H
2
O
C21.71, H4.10
C21.31, H3.93
The characteristics of the chromate L-threonate include:
1. active structure of left-handed rotation
2. stability in high thermal condition (temperature of decomposition>300° C.)
3. dissolution in water (no dissolution in alcohol and ether)
Chromic(III) ion and L-threonic acid can form a stable coordination compound. Although the formation of the coordination is changeable in different pH value solution, there is no precipitate of chromic hydroxide even in basic condition (solution of chromic chloride or chromic sulphate forms precipitate just at pH~4).
The following two charts show the curves of titration and distribution of the reaction in which L-threonic acid and chromic ion form a dibasic coordination compound. According to these curves, we believe that the coordination compound derived from L-threonic acid and chromic ion has enough stability. With computer simulation, the models, stable constant and pH range of the coordination compound are deduced. See the following table:
Model
Stable Constant
pH
B
−0.74 ± 0.34
3.5-4.0
A
−4.42 ± 0.14
~4.5
C
−9.35 ± 0.26
~6.0
We select L-threonic acid as the ligand for chromic ion, because L-threonic acid can accelerate the absorption of the ion, also, there is no precipitate of chromic hydroxide even in small intestine (pH~7), thus will improve the absorptive ratio of chromium(III). Meanwhile, it is beneficial to bind with proteins that chromium is taken into the body as the form of chromic(III). Moreover, the chromate L-threonate reinforces the function of insulin by two hands: the activation of chromic ion and the cooperation of L-threonic acid.
According to these advantages, the chromate L-threonate can be applied to a high performance supplement of chromium(III) as well as an effective hypoglycemic treatment for those diabetes patients.
Appendix Figures
Appendix figures of this invention are:
FIG. 1: Titration Curve
FIG. 2: Distribution Curve
Detail of Synthesis Examples:
The synthesis examples below are explanation to this invention, not limitation.
REFERENCES:
patent: 4822816 (1989-04-01), Markham
patent: 1143464 (1997-02-01), None
patent: 1194865 (1998-10-01), None
patent: 1200366 (1998-12-01), None
Chemical Journal of Chinese Universities vol. 19, No. 6, p. 849-853, 1998.
Beverly A, et al. “Metabolic Profiles of Urinary Organic Acids Recovered from Absorbent Filter Paper” Clin Chem, 33/4, 572-576, 1987.
F.Dubois, et al. “Role Physiologique et Interet en Pathologie Humaine” Path Biol, 1991, 39(8), 801-808.
Anthony J.V, et al. “Comparison of the Anti-Scorbutic Activity of L-Ascorbic Acid and Ester C in the Non-Ascorbate Synthesizing Osteogenic Disorder Shionogi (ODS) Rat” Life Sciences, 48, 2275-2281, 1991.
Tatsuya Yamagishi, et al. “Total Synthesis of Trehalase Inhibitor Salbostatin” Bioor. Med. Chem Let. 3(5), 487-494. 1995.
Kou Fuping
Wang Zhiwen
Yu Kai
Nazario-Gonzalez Porfirio
Rabin & Berdo P.C.
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