CA2669827C - Compositions comprising a mixture of bioflavonols - Google Patents
Compositions comprising a mixture of bioflavonols Download PDFInfo
- Publication number
- CA2669827C CA2669827C CA2669827A CA2669827A CA2669827C CA 2669827 C CA2669827 C CA 2669827C CA 2669827 A CA2669827 A CA 2669827A CA 2669827 A CA2669827 A CA 2669827A CA 2669827 C CA2669827 C CA 2669827C
- Authority
- CA
- Canada
- Prior art keywords
- rutin
- isoquercetin
- composition according
- quercetin
- composition
- 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 - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to novel compositions containing a mixture of two or three bioflavonols like isoquercetin, quercetin-4'-glycoside, rutin and quercetin, which show differences in their pharmacokinetics. These compositions are useful as food supplements possessing preventive properties against damage to human tissues due to their antioxidant properties. Furthermore, these compositions secure a continuum of the presence of bioflavonols having the same aglycone in human plasma over an extended period of time.
Description
Compositions comprising a mixture of bioflavonols This is a divisional application of Canadian Patent Application No. 2,348,395 filed on October 16, 1999. It should be understood that the expression "present invention" or the like encompasses the subject matters of both this and the parent applications.
The present invention relates to novel compositions containing a mixture of two or three bioflavonols like isoquercetin, quercetin-4'-glycoside, ru-tin and quercetin, which show differences in their pharmacokinetics.
These compositions are useful as food supplements possessing preven-tive properties against damage to human tissues due to their antioxidant properties. Furthermore, these compositions secure a continuum of the presence of bioflavonols in human plasma.
Structures of body tissues are susceptible to damage caused by the oxi-dative stress, e.g., by the accumulation of reactive oxygen species dur-ing ageing, chronic environmental stress, inflammations or general metabolic dysfunctions. The role of reactive oxygen species in aetiology of human diseases (e.g. cancer, atherosclerosis, rheumatoid arthritis, inflammatory bowel diseases, immune system dysfunctions, brain func-tion decline, connective tissue dysfunctions) is well established. Chronic exposure to reactive oxygen species leads to chronic intracellular dam-age, to oxidative stress and premature ageing. Cells of the human body possess metabolic antioxidant defences which are supported by dietary antioxidants. The early observations of the antioxidant defence meta-bolic processes involved flavonoids.
Quercetin, an aglycone, isoquercetin, a quercetin glycoside, and rutin, a quercetin rutinoside, are flavonois that are being recently extensively studied due to their antioxidant properties. Gycosylation of an aglycone makes the molecule less reactive towards free radicals and more water-soluble. Kind and the position of the glycosylation are the sources of the pharmacokinetic differences among flavonols that have the same agly-cone.
Common glycosylation positions are: the 7-hydroxyl in flavones, isofla-vones and dihydroflavones; the 3- and 7-hydroxyl in flavonols and dihy-droflavonols, and the 3- and 5-hydroxyl in anthocyanidins. The sugar most usually involved in the glycoside formation is glucose, although galactose, rhamnose, xylose and arabinose also occur, as well as sev-eral disaccharides. For example, onions contain mostly isoquercetin, -~-apples contain various quercetin glycosides, galactosides, arabinosides, rhamnosides, xylosides and glucosides. Many plants contain the quer-cetin disaccharide, rutin.
Flavonols are metabolized by animal cells, especially those of the liver.
No residuals of flavonols are accumulated in the body (see Havsteen B.
(1983), Flavonoids, a class of natural products of high pharrnacofogical potency, Biochemical Pharmacology 32(7), 1141-1148).
Also absorption kinetics of flavonols is highly dependent on their chemi-cal structure. The bioavailabilities of isoquercetin, rutin and quercetin differ. The bioavaifability of rutin is only 30 % of the bioavaiiability of iso-quercetin. Hollman (see Holiman, P.C.H., et al. (1997) Bioavailability of the dietary antioxidant flavonol quercetin in man, Cancer Lett. 114: 139-140) explains the superior absorption of isoquercetin by the fact that isoquercetin is actively absorbed using sodium-glucose absorption mechanism. Quercetin is absorbed as an aglycone and is present in the human plasma in its free form (see Noteborn, H.P.J.M. et al. (1997) Oral absorption and metabolism of quercetin and sugar-conjugated deriva-tives in specific transport systems, Cancer Lett. 114:175-177; Conquer, J.A., et al. (1998) Supplementation with Quercetin Markedly increases Plasma Quercetin Concentration without Effect on Selected Risk Factors for Heart Disease in Healthy Subjects, J. Nutr. Mar 1; 128(3): 593-597) and in the giycosylated forms when absorbed as a glycoside. It has been shown that quercetin is preferentially absorbed as its monoglucosides (see Papanga, G. Rice-Evans, C.A. (1997) The identification of flavo-noids as giycosides in human plasma, FEBS Lett. 401(1): 78-82; and Hollman, P.C.H. et al. (1997) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man, FEBS Lett., Nov. 24;
418(1-2): 152-156).
As expected all of these compounds, quercetin, isoquercetin, quercetin-4'-glycoside and rutin differ in their pharmacokinetics.
For orally administered isoquercetin the time to reach peak is about 0.70 h (see Holiman, P.C.H., (1997) Determinants of the absorption of the dietary flavonoid quercetin in man; Proefschrift). For the free quercetin the time to peak could be evaluated at about 3 h(seL Da Silva, E.L., et al. (1998) Inhibition of mammafian 15-iipoxygenase-dependent lipid per-oxidation in low-density lipoprotein by quercetin and quercetim mnoglu-cosides, Archives of Biochemistry and Biophysics 349, (2) Jan. 15, ~ 313-320). For rutin the time was about 7 to 9 h (see Holiman, P.C.H., (1997) Determinants of the absorption of the dietary flavonoid quercetin in man;
Proefschrift).
After having reached the peak (after different periods of time), the con-centration of the flavonols quickly decreases by metabolization.
Therefore, it is not possible so far to obtain a continuum presence of bioflavonols in the human plasma for an extended time span.
However, it would be desirable to have orally applicable formulation of these specific antioxidants leading to an increased and continued pres-ent concentration of bioflavonols having the same aglycone in the hu-man plasma over a prolonged period of time.
Accordingly, there was a need for a composition useful for the en-hancement of antioxidant activity in human plasma during an extended time span in order to prevent damage to human tissues.
Now it has been found that the mixture of two or three flavonols, when administered jointly to humans, will secure the very similar concentra-?5 tions of flavonols in plasma assuring similar pharmacological and nu-traceutical activity for an extended time period.
One aspect of the present invention is therefore an orally applicable compo-sition comprising a niixture of the biotlavonois isoquercetin (quercetin-3-0 glucoside) or quercetin-4'-glucoside and rutin, optionally together with quercetin.
-3a-According to another aspect of the present invention, there is provided a composition suitable for oral administration comprising isoquercetin and rutin, wherein the isoquercetin to rutin molar ratio is about 1:4.
According to still another aspect of the present invention, there is provided a commercial package comprising a composition of the invention, together with a written matter describing instructions for the use thereof in the treatment of a disease or condition described herein.
It has been found that a mixture of isoquercetin or quercetin-4'-glucoside, quercetin and rutin in the molar ratio of 1:1.5:3 or similar ratios will secure pharmacological and nutraceutical activity for an extended period of time up to 48 hours.
The composition of these antioxidants according to the present invention is highly suitable for treatments like cardiovascular disease or the prevention of neoplastic growth.
Besides, the antiviral properties of quercetin are also effective in these compositions.
In a preferred embodiment of the present invention the composition comprises isoquercetin and rutin in a molar ration of about 1 : 4. When administered to humans, this composition will secure up to 24 hours a continued high concentration of flavonols in plasma assuring similar pharmacological activity during the 24-hour time period.
It has been found that these combinations are most effective in preven-tion of and in defence against stress dysfunctions, especially against oxidative damage of living tissues. Furthermore, the combinations ac-cording to this invention will secure pharmacological and nutraceutical effectiveness for an extended period time for specially designed treat-ments with these specific antioxidants, e.g. treatment of cardiovascular disease, or the prevention of neoplastic growth. The effect of the conti-nuity of their concentrations is obtained by the summation of their spe-cific concentration kinetics in the human body.
The daily dose of the mixture of the flavonols that have the same agly-cone is about 100 mg of quercetin glycoside and 400 mg of rutin. It is possible that the dose may be increased to an expected maximum of about 400 mg of quercetin glycoside and 1600 mg of rutin, maintaining the proportion of flavonols of 1:4 as discussed above. For the mixture of isoquercetin or quercetin-4'-glucoside, quercetin and rutin in the molar ratio of 1: 1,5 : 3 a similar daily dose is suggested like about 100 mg quercetin glycoside, 150 mg of quercetin and 300 mg of rutin up to a maximum dose of about 400 mg of quercetin glycoside, 600 mg of quer-cetin and 1200 mg of rutin, always maintaining the proportion.
)0 The compositions according to the present invention may be used in form of tablets, capsules or syrups with usable excipients.
The compositions of the present invention preferably are useful as food >> supplements, but they may also be administered in a pharmaceutical treatment.
- ~ -The present invention makes available:
- a method of maintaining a continued presence of high con-centrations of bioflavonols in human plasma for an extended period of time, - a method of protection against oxidative damage to human organs, tissues and ceils, - a method of supporting a pharmacological treatment of a dis-ease or dysfunction caused by oxidative damage, - a method of prevention of cardiovascular diseases, and other damage to vascular tissues, of bacterial and viral infections, of metabolic dysfunctions involving oxidative damages or of neopiastic growth, by oral administration of a composition described above.
The decision which further ingredients should be components of a com-position useful in one of the above-mentioned methods depends on the special indication. Usually, if the composition is administered as a way of protection or prevention, useful further ingredients may be vitamins, salts of Mg, Ca, K, Fe and trace elements in known amounts as used in food supplements. Compositions useful in a method of supporting phar-macological treatments may differ from them.
Therefore, a highly efficient dietary antioxidant composition is prepared using among other ingredients the mixtures of isoquercetin or quercetin-4'-glycoside and rutin, optionally together with quercetin. The advanta-geous properties of these compositions are induced by the effect of building a kind of bioflavanoid complex with delayed release of the bio-flavonols.
A subject of this invention is that in humans the oral administration of a mixture of isoquercetin or quercetin-4'-glycoside and rutin, optionally to-gether with quercetin, with a suitable molar ratio described above, con-veys veys sufficient protection against oxidative damages, due to a continued presence of bioflavonols assuring similar pharmacological and nutraceu-tical activity during a prolonged period of time.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifica-tions of the invention to adapt it to various applications and conditions.
Example 1 A composition according to this invention is prepared by mixing 400 mg rutin with 100 mg isoquercetin. The results of this formula are shown in diagram 1 .
The present invention relates to novel compositions containing a mixture of two or three bioflavonols like isoquercetin, quercetin-4'-glycoside, ru-tin and quercetin, which show differences in their pharmacokinetics.
These compositions are useful as food supplements possessing preven-tive properties against damage to human tissues due to their antioxidant properties. Furthermore, these compositions secure a continuum of the presence of bioflavonols in human plasma.
Structures of body tissues are susceptible to damage caused by the oxi-dative stress, e.g., by the accumulation of reactive oxygen species dur-ing ageing, chronic environmental stress, inflammations or general metabolic dysfunctions. The role of reactive oxygen species in aetiology of human diseases (e.g. cancer, atherosclerosis, rheumatoid arthritis, inflammatory bowel diseases, immune system dysfunctions, brain func-tion decline, connective tissue dysfunctions) is well established. Chronic exposure to reactive oxygen species leads to chronic intracellular dam-age, to oxidative stress and premature ageing. Cells of the human body possess metabolic antioxidant defences which are supported by dietary antioxidants. The early observations of the antioxidant defence meta-bolic processes involved flavonoids.
Quercetin, an aglycone, isoquercetin, a quercetin glycoside, and rutin, a quercetin rutinoside, are flavonois that are being recently extensively studied due to their antioxidant properties. Gycosylation of an aglycone makes the molecule less reactive towards free radicals and more water-soluble. Kind and the position of the glycosylation are the sources of the pharmacokinetic differences among flavonols that have the same agly-cone.
Common glycosylation positions are: the 7-hydroxyl in flavones, isofla-vones and dihydroflavones; the 3- and 7-hydroxyl in flavonols and dihy-droflavonols, and the 3- and 5-hydroxyl in anthocyanidins. The sugar most usually involved in the glycoside formation is glucose, although galactose, rhamnose, xylose and arabinose also occur, as well as sev-eral disaccharides. For example, onions contain mostly isoquercetin, -~-apples contain various quercetin glycosides, galactosides, arabinosides, rhamnosides, xylosides and glucosides. Many plants contain the quer-cetin disaccharide, rutin.
Flavonols are metabolized by animal cells, especially those of the liver.
No residuals of flavonols are accumulated in the body (see Havsteen B.
(1983), Flavonoids, a class of natural products of high pharrnacofogical potency, Biochemical Pharmacology 32(7), 1141-1148).
Also absorption kinetics of flavonols is highly dependent on their chemi-cal structure. The bioavailabilities of isoquercetin, rutin and quercetin differ. The bioavaifability of rutin is only 30 % of the bioavaiiability of iso-quercetin. Hollman (see Holiman, P.C.H., et al. (1997) Bioavailability of the dietary antioxidant flavonol quercetin in man, Cancer Lett. 114: 139-140) explains the superior absorption of isoquercetin by the fact that isoquercetin is actively absorbed using sodium-glucose absorption mechanism. Quercetin is absorbed as an aglycone and is present in the human plasma in its free form (see Noteborn, H.P.J.M. et al. (1997) Oral absorption and metabolism of quercetin and sugar-conjugated deriva-tives in specific transport systems, Cancer Lett. 114:175-177; Conquer, J.A., et al. (1998) Supplementation with Quercetin Markedly increases Plasma Quercetin Concentration without Effect on Selected Risk Factors for Heart Disease in Healthy Subjects, J. Nutr. Mar 1; 128(3): 593-597) and in the giycosylated forms when absorbed as a glycoside. It has been shown that quercetin is preferentially absorbed as its monoglucosides (see Papanga, G. Rice-Evans, C.A. (1997) The identification of flavo-noids as giycosides in human plasma, FEBS Lett. 401(1): 78-82; and Hollman, P.C.H. et al. (1997) Relative bioavailability of the antioxidant flavonoid quercetin from various foods in man, FEBS Lett., Nov. 24;
418(1-2): 152-156).
As expected all of these compounds, quercetin, isoquercetin, quercetin-4'-glycoside and rutin differ in their pharmacokinetics.
For orally administered isoquercetin the time to reach peak is about 0.70 h (see Holiman, P.C.H., (1997) Determinants of the absorption of the dietary flavonoid quercetin in man; Proefschrift). For the free quercetin the time to peak could be evaluated at about 3 h(seL Da Silva, E.L., et al. (1998) Inhibition of mammafian 15-iipoxygenase-dependent lipid per-oxidation in low-density lipoprotein by quercetin and quercetim mnoglu-cosides, Archives of Biochemistry and Biophysics 349, (2) Jan. 15, ~ 313-320). For rutin the time was about 7 to 9 h (see Holiman, P.C.H., (1997) Determinants of the absorption of the dietary flavonoid quercetin in man;
Proefschrift).
After having reached the peak (after different periods of time), the con-centration of the flavonols quickly decreases by metabolization.
Therefore, it is not possible so far to obtain a continuum presence of bioflavonols in the human plasma for an extended time span.
However, it would be desirable to have orally applicable formulation of these specific antioxidants leading to an increased and continued pres-ent concentration of bioflavonols having the same aglycone in the hu-man plasma over a prolonged period of time.
Accordingly, there was a need for a composition useful for the en-hancement of antioxidant activity in human plasma during an extended time span in order to prevent damage to human tissues.
Now it has been found that the mixture of two or three flavonols, when administered jointly to humans, will secure the very similar concentra-?5 tions of flavonols in plasma assuring similar pharmacological and nu-traceutical activity for an extended time period.
One aspect of the present invention is therefore an orally applicable compo-sition comprising a niixture of the biotlavonois isoquercetin (quercetin-3-0 glucoside) or quercetin-4'-glucoside and rutin, optionally together with quercetin.
-3a-According to another aspect of the present invention, there is provided a composition suitable for oral administration comprising isoquercetin and rutin, wherein the isoquercetin to rutin molar ratio is about 1:4.
According to still another aspect of the present invention, there is provided a commercial package comprising a composition of the invention, together with a written matter describing instructions for the use thereof in the treatment of a disease or condition described herein.
It has been found that a mixture of isoquercetin or quercetin-4'-glucoside, quercetin and rutin in the molar ratio of 1:1.5:3 or similar ratios will secure pharmacological and nutraceutical activity for an extended period of time up to 48 hours.
The composition of these antioxidants according to the present invention is highly suitable for treatments like cardiovascular disease or the prevention of neoplastic growth.
Besides, the antiviral properties of quercetin are also effective in these compositions.
In a preferred embodiment of the present invention the composition comprises isoquercetin and rutin in a molar ration of about 1 : 4. When administered to humans, this composition will secure up to 24 hours a continued high concentration of flavonols in plasma assuring similar pharmacological activity during the 24-hour time period.
It has been found that these combinations are most effective in preven-tion of and in defence against stress dysfunctions, especially against oxidative damage of living tissues. Furthermore, the combinations ac-cording to this invention will secure pharmacological and nutraceutical effectiveness for an extended period time for specially designed treat-ments with these specific antioxidants, e.g. treatment of cardiovascular disease, or the prevention of neoplastic growth. The effect of the conti-nuity of their concentrations is obtained by the summation of their spe-cific concentration kinetics in the human body.
The daily dose of the mixture of the flavonols that have the same agly-cone is about 100 mg of quercetin glycoside and 400 mg of rutin. It is possible that the dose may be increased to an expected maximum of about 400 mg of quercetin glycoside and 1600 mg of rutin, maintaining the proportion of flavonols of 1:4 as discussed above. For the mixture of isoquercetin or quercetin-4'-glucoside, quercetin and rutin in the molar ratio of 1: 1,5 : 3 a similar daily dose is suggested like about 100 mg quercetin glycoside, 150 mg of quercetin and 300 mg of rutin up to a maximum dose of about 400 mg of quercetin glycoside, 600 mg of quer-cetin and 1200 mg of rutin, always maintaining the proportion.
)0 The compositions according to the present invention may be used in form of tablets, capsules or syrups with usable excipients.
The compositions of the present invention preferably are useful as food >> supplements, but they may also be administered in a pharmaceutical treatment.
- ~ -The present invention makes available:
- a method of maintaining a continued presence of high con-centrations of bioflavonols in human plasma for an extended period of time, - a method of protection against oxidative damage to human organs, tissues and ceils, - a method of supporting a pharmacological treatment of a dis-ease or dysfunction caused by oxidative damage, - a method of prevention of cardiovascular diseases, and other damage to vascular tissues, of bacterial and viral infections, of metabolic dysfunctions involving oxidative damages or of neopiastic growth, by oral administration of a composition described above.
The decision which further ingredients should be components of a com-position useful in one of the above-mentioned methods depends on the special indication. Usually, if the composition is administered as a way of protection or prevention, useful further ingredients may be vitamins, salts of Mg, Ca, K, Fe and trace elements in known amounts as used in food supplements. Compositions useful in a method of supporting phar-macological treatments may differ from them.
Therefore, a highly efficient dietary antioxidant composition is prepared using among other ingredients the mixtures of isoquercetin or quercetin-4'-glycoside and rutin, optionally together with quercetin. The advanta-geous properties of these compositions are induced by the effect of building a kind of bioflavanoid complex with delayed release of the bio-flavonols.
A subject of this invention is that in humans the oral administration of a mixture of isoquercetin or quercetin-4'-glycoside and rutin, optionally to-gether with quercetin, with a suitable molar ratio described above, con-veys veys sufficient protection against oxidative damages, due to a continued presence of bioflavonols assuring similar pharmacological and nutraceu-tical activity during a prolonged period of time.
From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifica-tions of the invention to adapt it to various applications and conditions.
Example 1 A composition according to this invention is prepared by mixing 400 mg rutin with 100 mg isoquercetin. The results of this formula are shown in diagram 1 .
Claims (22)
1. A composition for oral administration comprising isoquercetin or quercetin-4'-glycoside; quercetin; and rutin.
2. A composition according to claim 1, comprising isoquercetin or quercetin-4'-glycoside, quercetin and rutin in a molar ratio of about 1:1.5:3.
3. A composition according to claim 1 or 2, comprising a sufficient amount of isoquercetin and rutin, wherein when administered to a human, the composition maintains a concentration of isoquercetin and rutin in plasma for about 7 to 48 hours sufficient to achieve substantially constant pharmacological and nutraceutical activity of the isoquercetin and rutin.
4. A composition according to any one of claims 1 to 3, in a unit dosage form comprising about 100 to 400 mg of isoquercetin, about 150 to 600 mg of quercetin and about 300 to 1200 mg of rutin.
5. A composition according to any one of claims 1 to 3, in a unit dosage form comprising about 100 mg of isoquercetin, about 150 mg of quercetin and about 300 mg of rutin.
6. A composition according to any one of claims 1 to 5, which is in the form of a food supplement.
7. A composition according to any one of claims 1 to 6, which is for maintaining a concentration of isoquercetin and rutin in plasma for about 7 to hours sufficient to achieve substantially constant pharmacological and nutraceutical activity of the isoquercetin and rutin.
8. A composition according to any one of claims 1 to 6, which is for protecting against oxidative damage to human organs, tissues or cells, in a patient in need thereof.
9. A composition according to any one of claims 1 to 6, which is for treating a disease or dysfunction caused by oxidative damage.
10. A composition according to any one of claims 1 to 6, which is for treating a cardiovascular disease in a patient in need thereof.
11. Use of a composition according to any one of claims 1 to 6 for maintaining a concentration of isoquercetin and rutin in plasma for about 7 to hours sufficient to achieve substantially constant pharmacological and nutraceutical activity of the isoquercetin and rutin.
12. Use of a composition according to any one of claims 1 to 6 for protecting against oxidative damage to human organs, tissues or cells, in a patient in need thereof.
13. Use of a composition according to any one of claims 1 to 6 for treating a disease or dysfunction caused by oxidative damage.
14. Use of a composition according to any one of claims 1 to 6 for treating a cardiovascular disease in a patient in need thereof.
15. Use of a composition according to any one of claims 1 to 6 in the preparation of a medicament for maintaining a concentration of isoquercetin and rutin in plasma for about 7 to 24 hours sufficient to achieve substantially constant pharmacological and nutraceutical activity of the isoquercetin and rutin.
16. Use of a composition according to any one of claims 1 to 6 in the preparation of a medicament for protecting against oxidative damage to human organs, tissues or cells, in a patient in need thereof.
17. Use of a composition according to any one of claims 1 to 6 in the preparation of a medicament for treating a disease or dysfunction caused by oxidative damage.
18. Use of a composition according to any one of claims 1 to 6 in the preparation of a medicament for treating a cardiovascular disease in a patient in need thereof.
19. A commercial package comprising the composition as defined in any one of claims 1 to 6, together with a written matter describing instructions for the use thereof for maintaining a concentration of isoquercetin and rutin in plasma for about 7 to 24 hours sufficient to achieve substantially constant pharmacological and nutraceutical activity of the isoquercetin and rutin.
20. A commercial package comprising the composition as defined in any one of claims 1 to 6, together with a written matter describing instructions for the use thereof for protecting against oxidative damage to human organs, tissues or cells, in a patient in need thereof.
21. A commercial package comprising the composition as defined in any one of claims 1 to 6, together with a written matter describing instructions for the use thereof for treating a disease or dysfunction caused by oxidative damage.
22. A commercial package comprising the composition as defined in any one of claims 1 to 6, together with a written matter describing instructions for the use thereof for treating a cardiovascular disease in a patient in need thereof.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10608098P | 1998-10-29 | 1998-10-29 | |
| US60/106,080 | 1998-10-29 | ||
| EP99105035.2 | 1999-03-22 | ||
| EP99105035 | 1999-03-22 | ||
| US66982799A | 1999-10-16 | 1999-10-16 | |
| CA002348395A CA2348395C (en) | 1998-10-29 | 1999-10-16 | Compositions comprising a mixture of bioflavonols |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002348395A Division CA2348395C (en) | 1998-10-29 | 1999-10-16 | Compositions comprising a mixture of bioflavonols |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2669827A1 CA2669827A1 (en) | 2000-05-11 |
| CA2669827C true CA2669827C (en) | 2011-03-22 |
Family
ID=40983731
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2669827A Expired - Fee Related CA2669827C (en) | 1998-10-29 | 1999-10-16 | Compositions comprising a mixture of bioflavonols |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2669827C (en) |
-
1999
- 1999-10-16 CA CA2669827A patent/CA2669827C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2669827A1 (en) | 2000-05-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1014968B1 (en) | NARINGIN AND NARINGENIN AS 3-HYDROXY-3-METHYLGLUTARYL CoA(HMG-CoA) REDUCTASE INHIBITOR | |
| EP3116520B1 (en) | Phytocomplexes from citrus bergamia | |
| JP2010512384A (en) | Polyphenol-containing composition | |
| EP1072265A1 (en) | Use of plant polyphenols for treating iron overload | |
| JP2002523456A (en) | Ascorbate-isoquercetin composition | |
| US6514527B1 (en) | Compositions comprising a mixture of bioflavonols | |
| WO2003092666A1 (en) | Calcium-containing tissue strengthening agents and use thereof | |
| JP4390428B2 (en) | Calcium-containing tissue strengthening agent | |
| Carresi et al. | Studies on the protective role of Bergamot polyphenols in doxorubicin-induced cardiotoxicity | |
| CA2348395C (en) | Compositions comprising a mixture of bioflavonols | |
| CA2669827C (en) | Compositions comprising a mixture of bioflavonols | |
| CZ20021564A3 (en) | Preparation containing propionyl L-carnitine a chitosan for prophylaxis and/or treatment of disorders caused by abnormal metabolism of fats | |
| US20070184132A1 (en) | Methods of treating canine osteosarcoma | |
| Abdulhameed et al. | Enhancing the bioavailability of quercetin by concomitant administration with enzyme inhibitor | |
| Arshad et al. | Bioflavonoids: sources, types, and nutraceutical maneuvers | |
| Sroka et al. | Phenolic extracts from meadowsweet and hawthorn flowers have antioxidative properties | |
| KR19990034092A (en) | 3-hydroxy-3-methylglutaryl koei reductase activity inhibitor composition comprising vitamin C and tangerine extract concentrate as active ingredients | |
| Gangopadhyay | Natural flavans and flavanones with antioxidant activities: An overview | |
| EP4051381A1 (en) | Compositions for the cardiovascular risk reduction | |
| EP1474998B1 (en) | Composition useful for weight control | |
| Wong | The Pharmacological Actions of Grapefruit Extracts: Naringin and Naringinin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20141016 |