US20190175628A1 - Phospholipid complexes of curcumin having improved bioavailability - Google Patents
Phospholipid complexes of curcumin having improved bioavailability Download PDFInfo
- Publication number
- US20190175628A1 US20190175628A1 US16/274,623 US201916274623A US2019175628A1 US 20190175628 A1 US20190175628 A1 US 20190175628A1 US 201916274623 A US201916274623 A US 201916274623A US 2019175628 A1 US2019175628 A1 US 2019175628A1
- Authority
- US
- United States
- Prior art keywords
- curcumin
- phospholipids
- complexes
- phospholipid
- complex
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9066—Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
- A61K47/544—Phospholipids
Definitions
- the present invention relates to novel phospholipids complexes of curcumin or extracts containing it having improved bioavailability.
- Curcumin [1,7-bis(4-hydroxyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], is the major constituent of the spice turmeric extracted from the root of Curcuma longa Linn.
- Curcumin is a polyphenol that has powerful antioxidant and inhibits the expression of the enzyme cyclooxygenase 2 (Cox 2) at least in part via interference with activation of the transcription factor NFkB [2, 14].
- Cox 2 cyclooxygenase 2
- curcumin inhibits the growth of cancer cells with an IC 50 value of 20-75 ⁇ M [6, 16].
- curcumin has been shown to prevent cancer in the colon, skin, stomach, duodenum, soft palate, tongue, sebaceous glands and breast [9, 10, 15].
- curcumin could be considered a promising efficacious and safe cancer chemopreventive agents [18].
- clinical pilot studies have associated curcumin consumption with regression of pre-malignant lesions of bladder, soft palate stomach, cervix and skin [1, 11].
- Complex compounds of vegetable extracts or of purified components thereof with natural, synthetic or semi-synthetic phospholipids have been disclosed, e.g., in EP 209 038, EP 275 005, EP 283 713, EP 1 035 859 and EP 1 140 115. Said complexes improve the plasma bioavailability of the extract or purified component, thanks to their lipophilicity.
- EP 1 140 115 generically mentions ethanol among the various solvents that can be used of the preparation of said complexes, but does not provide preparation examples which make use of ethanol as the solvent.
- the complexes disclosed are phospholipid complexes of proanthocyanidin A2, which are quite different in the chemical structure with respect to the phospholipids complexes of curcumin of the present invention.
- the present invention relates to novel phospholipids complexes of curcumin having improved bioavailability.
- phospholipids of either vegetable or synthetic origin can be used, particularly preferred are soy phospholipids, such as phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine.
- the complexes are prepared by adding the phospholipid to curcumin dissolved in a protic solvent, more particularly adding the phospholipid to the ethanol solution of the hydroalcoholic extract of turmeric rhizomes, under reflux and with stirring.
- the resulting suspension is concentrated under reduced pressure to a residue which is dried in oven.
- the ratio of phospholipids to curcumin is in the range from 10 to 1 w/w, a more preferable mole ratio being 5:1 w/w.
- the present invention further relates to the use of the phospholipids complexes of curcumin of the invention for the preparation of medicaments having chemopreventive action.
- Ground dry turmeric rhizomes 1000 g were extracted with ethanol-water 9:1 mixture (6680 ml). The resulting hydroalcoholic solution was concentrated under reduced pressure and drying was completed in oven at 60° C. under vacuum to yield 69.3 g of an orange paste having a curcumin content of 17.4% w/w and a total curcuminoid content of 29.2% w/w.
- Ground dry turmeric rhizomes 1000 g were defatted with hexane (2500 ml) before being extracted with ethanol-water 95:5 mixture (7500 ml). Curcuminoids were then crystallized by slowly adding hexane (500 ml) to the hydroalcoholic solution and allowing the resulting mixture to stand for 24 hours. A microcrystalline orange solid was filtered and dried at 60° C. under vacuum to yield 36.7 g of extract having a curcumin content of 71.74% and a total curcuminoid content of 93.8% w/w.
- the 1 H-NMR spectrum of the complex in CDCl 3 shows the main signals of the phospholipids, typical of complexed phospholipids.
- the 1 H-NMR spectrum of the complex in DMSO-d 6 which is a solvent preventing the aggregation of the complex, shows the signals of the free starting extract as well as those of the phospholipids.
- the signal of 31 P in CDCl 3 is at 1.06 ppm and is 35.3 Hz wide, which is typical of complexed phospholipids.
- the complex is destroyed in DMSO-d 6 as confirmed by the signal of 31 P at 0.12 ppm with 3.80 Hz width typical of the free phospholipid.
- Tests were carried out to compare curcumin bioavailability afforded by the phospholipid complexes of the invention and by the extract containing uncomplexed curcumin.
- Rats were killed at 15, 30, 60 and 120 min. Whole blood was collected into heparinized tubes, centrifuged immediately at 7000 ⁇ g for 15 min, plasma was then decanted and stored at ⁇ 80° C. until analysis.
- curcumin and metabolites were verified by negative ion electrospray liquid chromatography/tandem mass spectrometry as previously described (4,5,7).
- the improved bioavailability of phospholipid complex of curcumin increases the potential scope of medical applications for curcumin as a chemopreventive agent.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medical Informatics (AREA)
- Botany (AREA)
- Alternative & Traditional Medicine (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Oncology (AREA)
- Toxicology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to novel phospholipids complexes of curcumin or extracts containing it having improved bioavailability.
Description
- This is a Continuation of Ser. No. 12/281,994 filed Dec. 1, 2008 which is a National Stage of International Application PCT/EP2007/001487, filed 21 Feb. 2007, which claims the benefit of application Ser. No. 06/004,820.4, filed in Europe on 9 Mar. 2006, the disclosures of which Applications are incorporated by reference herein.
- The present invention relates to novel phospholipids complexes of curcumin or extracts containing it having improved bioavailability.
- Curcumin, [1,7-bis(4-hydroxyl-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], is the major constituent of the spice turmeric extracted from the root of Curcuma longa Linn. Curcumin is a polyphenol that has powerful antioxidant and inhibits the expression of the enzyme cyclooxygenase 2 (Cox 2) at least in part via interference with activation of the transcription factor NFkB [2, 14]. In vitro, curcumin inhibits the growth of cancer cells with an IC50 value of 20-75 μM [6, 16]. In rodent models, curcumin has been shown to prevent cancer in the colon, skin, stomach, duodenum, soft palate, tongue, sebaceous glands and breast [9, 10, 15]. Therefore, curcumin could be considered a promising efficacious and safe cancer chemopreventive agents [18]. In fact, clinical pilot studies have associated curcumin consumption with regression of pre-malignant lesions of bladder, soft palate stomach, cervix and skin [1, 11].
- However, concentrations of curcumin achieved in plasma and target tissues are low, probably due, at least in part, to its extensive metabolism by conjugation (glucuronidation and sulfation) and reduction pathways [4, 5, 7, 8].
- Preclinical and clinical pilot studies suggest that In a phase I trial plasma and urine concentrations of curcumin in patients, who had ingested 3600 mg curcumin orally, were 11.1 nmol/L and 1.3 μmol/L, respectively [17]. In another study, peak plasma concentrations 1-2 h after oral dosing, reached 0.41-1.75 μM in patients receiving 4 to 8 g curcumin [1]. It is neither practical nor desirable to increase the oral dose of curcumin above that already investigated.
- Therefore, it is highly desirable to find novel curcumin derivatives having improved bioavailability.
- Complex compounds of vegetable extracts or of purified components thereof with natural, synthetic or semi-synthetic phospholipids, have been disclosed, e.g., in EP 209 038, EP 275 005, EP 283 713, EP 1 035 859 and EP 1 140 115. Said complexes improve the plasma bioavailability of the extract or purified component, thanks to their lipophilicity. EP 1 140 115 generically mentions ethanol among the various solvents that can be used of the preparation of said complexes, but does not provide preparation examples which make use of ethanol as the solvent. Furthermore, the complexes disclosed are phospholipid complexes of proanthocyanidin A2, which are quite different in the chemical structure with respect to the phospholipids complexes of curcumin of the present invention.
- It has now been found that the phospholipids complexes of curcumin, providing higher systemic levels of parent agent than unformulated curcumin, can be prepared in protic solvents.
- Therefore, the present invention relates to novel phospholipids complexes of curcumin having improved bioavailability.
- According to the invention, phospholipids of either vegetable or synthetic origin can be used, particularly preferred are soy phospholipids, such as phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine.
- According to the invention, the complexes are prepared by adding the phospholipid to curcumin dissolved in a protic solvent, more particularly adding the phospholipid to the ethanol solution of the hydroalcoholic extract of turmeric rhizomes, under reflux and with stirring. The resulting suspension is concentrated under reduced pressure to a residue which is dried in oven. The ratio of phospholipids to curcumin is in the range from 10 to 1 w/w, a more preferable mole ratio being 5:1 w/w.
- The present invention also relates to pharmaceutical compositions containing as the active principle one of the phospholipids complexes of curcumin according to the invention, in admixture with a suitable pharmaceutical carrier.
- The present invention further relates to the use of the phospholipids complexes of curcumin of the invention for the preparation of medicaments having chemopreventive action.
- The following examples further illustrate the invention.
- Ground dry turmeric rhizomes (1000 g) were extracted with ethanol-water 9:1 mixture (6680 ml). The resulting hydroalcoholic solution was concentrated under reduced pressure and drying was completed in oven at 60° C. under vacuum to yield 69.3 g of an orange paste having a curcumin content of 17.4% w/w and a total curcuminoid content of 29.2% w/w.
- Ground dry turmeric rhizomes (1000 g) were defatted with hexane (2500 ml) before being extracted with ethanol-water 95:5 mixture (7500 ml). Curcuminoids were then crystallized by slowly adding hexane (500 ml) to the hydroalcoholic solution and allowing the resulting mixture to stand for 24 hours. A microcrystalline orange solid was filtered and dried at 60° C. under vacuum to yield 36.7 g of extract having a curcumin content of 71.74% and a total curcuminoid content of 93.8% w/w.
- 20 g of the product from Example 1 were dissolved in ethanol (400 ml) and the solution was refluxed. 30 g of soy phospholipids were slowly added in portions, under reflux and with stirring. The resulting suspension was refluxed with stirring for 1 hr, then hot concentrated under reduced pressure and finally dried in oven. 46.7 g of an orange waxy product were obtained, having a curcumin content of 7.54% and a total curcuminoid content of 12.1% w/w.
- While the starting extract is insoluble in chlorinated solvent, the resulting product is soluble in CHCl3 in a 4% w/v concentration thus confirming the complexation of the extract by the phospholipid and the formation of a molecular complex.
- The 1H-NMR spectrum of the complex in CDCl3 shows the main signals of the phospholipids, typical of complexed phospholipids. On the other hand, the 1H-NMR spectrum of the complex in DMSO-d6, which is a solvent preventing the aggregation of the complex, shows the signals of the free starting extract as well as those of the phospholipids.
- In the 31P-NMR spectra, the signal of 31P in CDCl3 is at 1.06 ppm and is 35.3 Hz wide, which is typical of complexed phospholipids. The complex is destroyed in DMSO-d6 as confirmed by the signal of 31P at 0.12 ppm with 3.80 Hz width typical of the free phospholipid.
- 20 g of turmeric rhizomes extract having a total curcuminoid content of 93.8% w/w were dissolved in ethanol (800 ml) and the solution was refluxed. 80 g of soy phospholipids were slowly added in portions, under reflux and with stirring. The resulting suspension was refluxed with stirring for 1 hr, then hot concentrated under reduced pressure and finally dried in oven. 97.6 g of an orange waxy product were obtained, having a curcumin content of 13.2% and a total curcuminoid content of 16.9% w/w.
- The solubility of the product in CHCl3 at a concentration of 4% w/v and the NMR spectra are the same as those of Example 3, confirming the formation of the complex.
- Tests were carried out to compare curcumin bioavailability afforded by the phospholipid complexes of the invention and by the extract containing uncomplexed curcumin.
- Materials and Methods
- Male Wistar rats (250 g) were fasted overnight and received by oral gavage either extract obtained by Example 2 or complex obtained by the Example 4 at dose of 340 mg/Kg in terms of curcumin.
- Rats were killed at 15, 30, 60 and 120 min. Whole blood was collected into heparinized tubes, centrifuged immediately at 7000×g for 15 min, plasma was then decanted and stored at −80° C. until analysis.
- The presence of curcumin and metabolites was verified by negative ion electrospray liquid chromatography/tandem mass spectrometry as previously described (4,5,7).
- Pharmacokinetic Analysis
- Peak plasma levels and area under the plasma concentration time curve (AUC) values for parent curcumin after administration of curcumin complexed with phospholipids as described in Example 4 were five-fold higher than the equivalent values seen after treatment with extract of Example 2 (uncomplexed curcumin) (Table 1).
-
TABLE 1 Estimated plasma Cmax, Tmax and AUC values for unformulated and formulated curcumin. AUC Cmax (nM) Tmax (min) (μg · min/mL)* Extract of Example 2 Curcumin 6.5 ± 4.5 30 4.8 Curcumin glucuronide 225 ± 0.6 30 200.7 Curcumin sulfate 7.0 ± 11.5 60 15.5 Complex of Example 4 Curcumin 33.4 ± 7.1 15 26.7 Curcumin glucuronide 4420 ± 292 30 4764.7 Curcumin sulfate 21.2 ± 3.9 60 24.8 *AUC was calculated using WinNonLin and employing a non-compartmental model. - Results
- The results show that the phospholipids complexes of curcumin of the invention provides higher systemic levels of parent agent than uncomplexed curcumin.
- The improved bioavailability of phospholipid complex of curcumin increases the potential scope of medical applications for curcumin as a chemopreventive agent.
-
- 1. Cheng A L, et al., Anticancer Res 21: 2895-2900.
- 2. Duvoix A, et al., Cancer Lett 223: 181-190.
- 3. Fagerholm U, et al., J Pharm Pharmacol 50: 467-443.
- 4. Garcea G, et al., Br J Cancer 90: 1011-1015.
- 5. Garcea G, et al., Cancer Epidemiol Biomarkers Prev 14: 120-125.
- 6. Goel A, et al., Cancer Letters 172: 111-118.
- 7. Ireson C, et al., Cancer Res 61: 1058-1064.
- 8. Ireson C, et al., Cancer Epidemiol. Biomarkers & Prev 11: 97-104.
- 9. Kawamori T, et al., Cancer Res 59: 597-601.
- 10. Kelloff G J, et al., J Cell Biochem 63: 54-71.
- 11. Kuttan R, et al., Tumors 3: 29-31.
- 12. Li, L., et al., Cancer 104: 1322-1331.
- 13. Mourao S C, et al., Int J Pharmaceut 295: 157-162.
- 14. Plummer S M., et al., Oncogene 18: 6013-6020.
- 15. Rao C V, et al., Cancer Res 55: 259-266.
- 16. Shao Z-M, et al., Int J Cancer 98: 234-240.
- 17. Sharma R A, et al., Clin Cancer Res 10: 6847-6854.
- 18. Surh Y J Nature Rev Cancer 3: 768-780.
- 19. Workman P, et al., Brit J Cancer 77: 1-10.
Claims (10)
1. Phospholipids complexes of curcumin or extracts containing it.
2. The complexes of claim 1 , wherein the phospholipids are soy phospholipids.
3. The complexes of claim 2 , wherein the phospholipids are selected from phosphatidyl choline, phosphatidyl serine, phosphatidyl ethanolamine.
4. The complexes of claim 1 , wherein the phospholipid to curcumin ratio is in the range from 10 and 1 w/w.
5. The complex compounds of claim 2 , wherein the phospholipid to curcumin ratio is from 5:1 w/w.
6. A process for the preparation of the complex compounds of claim 1 , wherein a hydroalcoholic extract of turmeric rhizomes is reacted with phospholipids in an alcoholic solvent, and the complex compound is then isolated by concentration and drying.
7. The process of claim 6 , wherein the alcoholic solvent is ethanol.
8. Pharmaceutical compositions containing as the active principle a complex as claimed in claim 1 , in admixture with a suitable pharmaceutical carrier.
9. A chemopreventive medicament comprising the complexes of claim 1 .
10. The phospholipids complexes as claimed in claim 1 , wherein the phospholipids complexes are from a hydroalcoholic extract of turmeric rhizomes containing curcumin wherein the phospholipid to curcumin ratio is in a range from 10:1 to 1:1 w/w.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16/274,623 US20190175628A1 (en) | 2006-03-09 | 2019-02-13 | Phospholipid complexes of curcumin having improved bioavailability |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06004820.4 | 2006-03-09 | ||
EP06004820A EP1837030A1 (en) | 2006-03-09 | 2006-03-09 | Phospholipid complexes of curcumin having improved bioavailability |
PCT/EP2007/001487 WO2007101551A2 (en) | 2006-03-09 | 2007-02-21 | Phospholipid complexes of curcumin having improved bioavailability |
US28199408A | 2008-12-01 | 2008-12-01 | |
US16/274,623 US20190175628A1 (en) | 2006-03-09 | 2019-02-13 | Phospholipid complexes of curcumin having improved bioavailability |
Related Parent Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/281,994 Continuation US10603329B2 (en) | 2006-03-09 | 2007-02-21 | Phospholipid complexes of curcumin having improved bioavailability |
PCT/EP2007/001487 Continuation WO2007101551A2 (en) | 2006-03-09 | 2007-02-21 | Phospholipid complexes of curcumin having improved bioavailability |
Publications (1)
Publication Number | Publication Date |
---|---|
US20190175628A1 true US20190175628A1 (en) | 2019-06-13 |
Family
ID=36677274
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/281,994 Active 2032-08-24 US10603329B2 (en) | 2006-03-09 | 2007-02-21 | Phospholipid complexes of curcumin having improved bioavailability |
US16/274,623 Abandoned US20190175628A1 (en) | 2006-03-09 | 2019-02-13 | Phospholipid complexes of curcumin having improved bioavailability |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/281,994 Active 2032-08-24 US10603329B2 (en) | 2006-03-09 | 2007-02-21 | Phospholipid complexes of curcumin having improved bioavailability |
Country Status (17)
Country | Link |
---|---|
US (2) | US10603329B2 (en) |
EP (2) | EP1837030A1 (en) |
JP (1) | JP5448462B2 (en) |
KR (1) | KR101423269B1 (en) |
CN (1) | CN101400360A (en) |
AU (1) | AU2007222667B2 (en) |
CA (1) | CA2644017C (en) |
DK (1) | DK1991244T3 (en) |
ES (1) | ES2757580T3 (en) |
HU (1) | HUE046597T2 (en) |
IL (1) | IL193966A (en) |
NO (1) | NO344242B1 (en) |
PL (1) | PL1991244T3 (en) |
PT (1) | PT1991244T (en) |
RU (1) | RU2450818C2 (en) |
SI (1) | SI1991244T1 (en) |
WO (1) | WO2007101551A2 (en) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1993365B1 (en) * | 2006-03-06 | 2013-05-08 | The Regents of the University of California | Bioavailable curcuminoid formulations for treating alzheimer's disease and other age-related disorders |
CN101903034B (en) | 2007-12-21 | 2013-07-31 | Asac生物技术研究股份公司 | Method for increasing the therapeutic efficacy of curcuminoids and analogues |
US9700525B2 (en) | 2008-08-20 | 2017-07-11 | Board Of Supervisors Of Louisiana State University And Agricultural & Mechanical College | Continuous local slow-release of therapeutics for head and neck problems and upper aerodigestive disorders |
WO2010023128A1 (en) * | 2008-08-29 | 2010-03-04 | Chr. Hansen A/S | Turmeric curcumin compositions with low residual solvent |
IT1395086B1 (en) * | 2009-03-11 | 2012-09-05 | Velleja Res Srl | COMPOSITIONS INCLUDING CURCUMINA IN A COMPLEX FORM WITH PHOSPHOLIPIDES AND PIPERINA WITH A CHEMIO-SENSITIZING ACTION |
SI2229940T1 (en) | 2009-03-20 | 2016-01-29 | Bioxtract S.A. | Pharmaceutical composition presenting anti-inflammatory and anti-histaminic properties |
MA33220B1 (en) | 2009-03-20 | 2012-04-02 | Bioxtract S A | Pharmaceutical composition of anti-inflammatory |
IT1395351B1 (en) | 2009-07-09 | 2012-09-14 | Axioma Srl | ORAL FORMULATIONS WITH HIGH BIOAVAILABILITY ORAL AVAILABLE MIXED BY LIPOFILE AND HYDROPHILE FRACTIONS OBTAINED FROM THE PROPOLIS |
CA2786255A1 (en) | 2009-12-31 | 2011-07-07 | Organomed Corporation | Formulations from natural products, turmeric, and aspirin |
CN102068419A (en) * | 2010-12-28 | 2011-05-25 | 神威药业有限公司 | Curcumin composition |
US8785380B2 (en) | 2011-02-01 | 2014-07-22 | M/S Akay Flavours & Aromatics Pvt Ltd. | Formulation containing curcuminoids exhibiting enhanced bioavailability |
AU2011368608B2 (en) | 2011-05-16 | 2015-04-23 | Omniactive Health Technologies Ltd. | A water soluble composition comprising curcumin having enhanced bioavailability and process thereof |
ITTO20110901A1 (en) * | 2011-10-10 | 2013-04-11 | Medestea Biotech S P A | SYNERGIC COMPOSITION FOR THE PREVENTION AND TREATMENT OF DISTURBANCES RELATED TO AGING |
ITPD20120021A1 (en) | 2012-01-26 | 2013-07-27 | Fidia Farmaceutici | "NEW PHARMACEUTICAL COMPOSITIONS CONTAINING PHOSPHATIDHYSERINE AND CURCUMINE". |
KR20190090075A (en) * | 2012-05-22 | 2019-07-31 | 해럴드 고든 케이브 | Improved complexes and compositions containing curcumin |
US20150110866A1 (en) * | 2012-05-22 | 2015-04-23 | Harold Gordon Cave | Complexes and compositions containing curcumin |
CN103120798A (en) * | 2013-01-10 | 2013-05-29 | 施冬云 | Preparation method and application of phospholipid complex with anti-oxidative stress |
WO2014135967A1 (en) | 2013-03-06 | 2014-09-12 | Capsugel Belgium Nv | Curcumin solid lipid particles and methods for their preparation and use |
US10835566B2 (en) * | 2013-05-14 | 2020-11-17 | Mars, Incorporated | Joint care composition |
US10286028B2 (en) * | 2014-02-20 | 2019-05-14 | Indena S.P.A. | Compositions containing extracts of Curcuma longa and Echinacea angustifolia which are useful to reduce peripheral inflammation and pain |
RU2571270C1 (en) * | 2014-07-17 | 2015-12-20 | Открытое Акционерное Общество "Фаберлик" | Liposomal nano-means based on products derived from turmeric rhizomes |
US11185507B2 (en) | 2014-10-08 | 2021-11-30 | Boston Biopharm Inc. | Compositions and methods for increasing the bioavailability of one or more compounds |
EP3218006A4 (en) * | 2014-11-11 | 2018-08-15 | Verdure Sciences | Stable solid lipid particle composition for improved bioavailability of lipophilic compounds for age-related diseases |
EP3226845A1 (en) | 2014-12-04 | 2017-10-11 | Capsugel Belgium NV | Lipid multiparticulate formulations |
EP3150214A1 (en) | 2015-10-01 | 2017-04-05 | INDENA S.p.A. | Compositions containing extracts of curcuma spp and zingiber officinale which are useful to reduce peripheral inflammation and pain |
WO2017095138A1 (en) * | 2015-11-30 | 2017-06-08 | Gil Medical Center | Curcumin-containing lipid nanoparticle complex comprising ginsenosides |
CN108366974A (en) * | 2015-12-16 | 2018-08-03 | 维韦克·阿南德·帕拉库尔 | Three molecular complexes of native compound |
CN105999290B (en) * | 2016-04-21 | 2019-04-09 | 中国人民解放军第四军医大学 | A kind of curcumin nanoparticles of phosphatidylserine modification |
CN109562118A (en) | 2016-06-29 | 2019-04-02 | 株式会社生物制药治疗 | Non-oral administration medical composition |
US20170172921A1 (en) * | 2016-12-14 | 2017-06-22 | Mahmoud Reza Jaafari | Polyphenolic compounds encapsualated in long circulating liposomes and use thereof |
KR101948407B1 (en) | 2017-01-20 | 2019-02-14 | 가천대학교 산학협력단 | Compositions for preventing or treating of infection by helicobacter pylori comprising curcumin-encapsulated ginsenoside and phospholipid-based lipid nanoparticle |
CN107213467A (en) * | 2017-05-22 | 2017-09-29 | 江苏大学 | A kind of preparation method of phospholipid complexes of curcumin |
RU2684111C1 (en) * | 2018-02-07 | 2019-04-04 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Южно-Уральский государственный медицинский университет" Министерства здравоохранения Российской Федерации (ФГБОУ ВО ЮУГМУ Минздрава России) | Method for preparing medicine with methionine and turmeric extract in granular type with intestinal sustainable coating of system action |
FR3082425B1 (en) * | 2018-06-18 | 2020-09-11 | Normaphar | COMPOSITION FOR USE IN THE TREATMENT OF OSTEOPENIA AND / OR OSTEOPOROSIS |
BE1026393B1 (en) * | 2018-06-18 | 2020-01-28 | Normaphar | Composition for use in the treatment of osteopenia and / or osteoporosis |
CN109846865B (en) * | 2018-12-26 | 2022-03-25 | 晨光生物科技集团股份有限公司 | Curcumin preparation and preparation method thereof |
CN109589410B (en) * | 2018-12-26 | 2022-02-01 | 晨光生物科技集团股份有限公司 | Curcumin preparation and preparation method thereof |
IT201900003907A1 (en) | 2019-03-18 | 2020-09-18 | Indena Spa | COMPOSITIONS INCLUDING CURCUMIN AND COENZYME Q10 |
CN111803632B (en) | 2019-04-09 | 2022-04-29 | 北京五和博澳药业股份有限公司 | Flavone polyphenol medicine self-emulsifying composition, preparation method thereof, medicine composition and application |
GB202011069D0 (en) | 2020-07-17 | 2020-09-02 | Univ Of Lincoln | New curcumin products and uses |
KR20220086467A (en) | 2020-12-16 | 2022-06-23 | 가톨릭대학교 산학협력단 | Nanocomposites for enhancing stability and bioavailability of curcumin using polysaccharide and preparation method thereof |
KR20220086018A (en) | 2020-12-16 | 2022-06-23 | 가톨릭대학교 산학협력단 | Nanocomposites for enhancing stability and bioavailability of curcumin using cellulose and preparation method thereof |
KR102488134B1 (en) | 2021-09-28 | 2023-01-13 | (주)바이노텍 | A Nano Particle Complex With A Modified Particle Surface And A Method For Preparing The Same |
JP7321229B2 (en) * | 2021-10-20 | 2023-08-04 | 義美食品股▲ふん▼有限公司 | Method for isolating curcuminoids from turmeric rhizome |
CN114557965B (en) * | 2022-02-09 | 2023-06-09 | 汕头大学 | Phospholipid complex nanoparticle for improving stability and bioavailability of curcumin and preparation method thereof |
CN117582417A (en) * | 2022-08-09 | 2024-02-23 | 湖南健瑞医药科技有限公司 | Medicine-lipid particle and preparation method and application thereof |
WO2024032507A1 (en) * | 2022-08-09 | 2024-02-15 | 湖南健瑞医药科技有限公司 | Metal-phospholipid complex, metal-phospholipid complex particle, drug-lipid particle, method for preparing same, and use thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1215291B (en) | 1985-07-17 | 1990-01-31 | Inverni Della Beffa Spa | FLAVANOLIGNANI COMPLEXES WITH PHOSPHOLIPIDS, THEIR PREPARATION AND RELATED PHARMACEUTICAL COMPOSITIONS. |
IT1201149B (en) | 1987-01-14 | 1989-01-27 | Indena Spa | BIOFLAVONOID COMPLEXES WITH PHOSPHOLIPIDS, THEIR PREPARATION, USE AND PHARMACEUTICAL AND COSMETIC COMPOSITIONS |
IT1203515B (en) | 1987-02-26 | 1989-02-15 | Indena Spa | SAPONINE COMPLEXES WITH PHOSPHOLIPIDS AND PHARMACEUTICAL AND COSMETIC COMPOSITIONS CONTAINING THEM |
IT1296920B1 (en) | 1997-12-04 | 1999-08-03 | Indena Spa | USE OF VITIS VINIFERA EXTRACT COMPLEXES WITH PHOSPHOLIPIDS AS ANTI-ATHEROSCLEROTIC AGENTS |
IT1304183B1 (en) | 1998-12-18 | 2001-03-08 | Indena Spa | PROANTOCYANIDINE A2 COMPLEXES WITH PHOSPHOLIPIDES AS AGENTIANTIATEROSCLEROTICI. |
EP1658061A2 (en) * | 2003-08-26 | 2006-05-24 | Research Development Foundation | Aerosol delivery of curcumin |
CN1283237C (en) | 2004-11-22 | 2006-11-08 | 山东大学 | Curcumin and phosphatide composite and its preparation method |
-
2006
- 2006-03-09 EP EP06004820A patent/EP1837030A1/en not_active Withdrawn
-
2007
- 2007-02-21 ES ES07703532T patent/ES2757580T3/en active Active
- 2007-02-21 PL PL07703532T patent/PL1991244T3/en unknown
- 2007-02-21 EP EP07703532.7A patent/EP1991244B1/en active Active
- 2007-02-21 PT PT77035327T patent/PT1991244T/en unknown
- 2007-02-21 DK DK07703532T patent/DK1991244T3/en active
- 2007-02-21 WO PCT/EP2007/001487 patent/WO2007101551A2/en active Application Filing
- 2007-02-21 CN CNA2007800082936A patent/CN101400360A/en active Pending
- 2007-02-21 KR KR1020087021905A patent/KR101423269B1/en active IP Right Grant
- 2007-02-21 AU AU2007222667A patent/AU2007222667B2/en active Active
- 2007-02-21 US US12/281,994 patent/US10603329B2/en active Active
- 2007-02-21 CA CA2644017A patent/CA2644017C/en active Active
- 2007-02-21 SI SI200732132T patent/SI1991244T1/en unknown
- 2007-02-21 HU HUE07703532A patent/HUE046597T2/en unknown
- 2007-02-21 JP JP2008557619A patent/JP5448462B2/en active Active
- 2007-02-21 RU RU2008136189/15A patent/RU2450818C2/en active
-
2008
- 2008-09-08 NO NO20083850A patent/NO344242B1/en unknown
- 2008-09-08 IL IL193966A patent/IL193966A/en active IP Right Grant
-
2019
- 2019-02-13 US US16/274,623 patent/US20190175628A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1837030A1 (en) | 2007-09-26 |
US10603329B2 (en) | 2020-03-31 |
CA2644017C (en) | 2019-07-30 |
CN101400360A (en) | 2009-04-01 |
KR101423269B1 (en) | 2014-07-25 |
EP1991244A2 (en) | 2008-11-19 |
NO344242B1 (en) | 2019-10-14 |
IL193966A0 (en) | 2011-08-01 |
PL1991244T3 (en) | 2020-03-31 |
CA2644017A1 (en) | 2007-09-13 |
US20090131373A1 (en) | 2009-05-21 |
WO2007101551A2 (en) | 2007-09-13 |
HUE046597T2 (en) | 2020-03-30 |
SI1991244T1 (en) | 2019-11-29 |
JP5448462B2 (en) | 2014-03-19 |
NO20083850L (en) | 2008-12-03 |
PT1991244T (en) | 2019-11-29 |
AU2007222667A1 (en) | 2007-09-13 |
JP2009529506A (en) | 2009-08-20 |
KR20080112224A (en) | 2008-12-24 |
IL193966A (en) | 2015-01-29 |
AU2007222667B2 (en) | 2012-11-08 |
WO2007101551A3 (en) | 2007-10-25 |
RU2008136189A (en) | 2010-03-20 |
EP1991244B1 (en) | 2019-10-02 |
RU2450818C2 (en) | 2012-05-20 |
DK1991244T3 (en) | 2019-11-18 |
ES2757580T3 (en) | 2020-04-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10603329B2 (en) | Phospholipid complexes of curcumin having improved bioavailability | |
US10485843B2 (en) | Composition to enhance the bioavailability of curcumin | |
US9878040B2 (en) | Composition to enhance the bioavailability of curcumin | |
JP2009529506A5 (en) | ||
KR20130001147A (en) | Composition comprising phosphatidylcholine as an active ingredient for attenuating toxicity of anticancer agent | |
JP5528799B2 (en) | Phospholipid complex of olive fruit or leaf extract with improved bioavailability | |
CN113573722A (en) | Composition comprising curcumin and coenzyme Q10 | |
AU2017239585B2 (en) | Curcuminoid compositions and preparation methods |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
AS | Assignment |
Owner name: INDENA S.P.A., ITALY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GIORI, ANDREA;FRANCESCHI, FEDERICO;REEL/FRAME:048594/0676 Effective date: 20080915 |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |