CN1283237C - Curcumin and phosphatide composite and its preparation method - Google Patents
Curcumin and phosphatide composite and its preparation method Download PDFInfo
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- CN1283237C CN1283237C CN 200410036402 CN200410036402A CN1283237C CN 1283237 C CN1283237 C CN 1283237C CN 200410036402 CN200410036402 CN 200410036402 CN 200410036402 A CN200410036402 A CN 200410036402A CN 1283237 C CN1283237 C CN 1283237C
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Abstract
The present invention discloses a curcumin and phosphatide composition which is composed of curcumin or derivates thereof and phosphatide, wherein the molar ratio of the curcumin or the derivates thereof and the phosphatide is 1: 1 to 3. The present invention also discloses a preparing method for the curcumin and phosphatide composition. The curcumin and phosphatide composition prepared by the method of the present invention can effectively improve the biological availability of curcumin type components.
Description
Technical field
The present invention relates to medical technical field, exactly relate to phosphatide complexes of a kind of curcumin and derivant thereof and preparation method thereof.
Background technology
Zingiberaceae curcuma Rhizoma Curcumae Longae (CurcumalongaL.) is a kind of Chinese medicine commonly used, contained curcumin is made up of curcumin (Cur), demethoxycurcumin (Cur-2), two deoxidation base curcumins (Cur-3), wherein curcumin is main pharmacological component, have pharmacological actions widely such as antitumor, antioxidation, antiinflammatory, blood fat reducing, and toxicity is very low, LD50＞2gkg of curcumin mice
-1(Chen Minjuan, curcumin progress and application prospect, Strait Pharmaceutical Journal, 2003,15 (1): 4-6).Curcumin medicine source abundance, it is a kind of native compound that DEVELOPMENT PROSPECT is arranged very much, but Cur itself is water insoluble, do not dissolve to highly acid (stomach) aqueous medium at weak acid (duodenum and small intestinal), cause the regular dosage form tablet, capsules etc. are bad dispersibility under one's belt, absorb existing problems, add that it is in vivo easily by metabolism, blood drug level is lower, thereby influence it and enter clinical practice (Pan MH, Huang TM, Lin JK.Biotransformation of curcuminthrough reduction and glucuronidation in mice.Drug Metab Dispos 1999Apr; 27 (4): 486-94).
The research to its structure activity relationship is devoted in the further research of relevant curcumin composition, derivant synthetic, and the exploitations of dosage form etc. obtain bigger water solublity with expectation, high stability more, pharmacologically active is stronger, makes it to become more practical efficient, low cytotoxic drug.Research and inquirement such as Li Jianming the solubilization of HP-to Cur-3, Cur-3 dissolubility after forming the cyclodextrin saturate can improve nearly 150 times of (Li Jianming, poplar peace, HP-is to the solubilization of curcumin-3, China's new medicine, 2004,3 (7): 11-14).
Many in recent years foreign literature reports, carry out active skull cap components and phospholipid compound under certain condition, obtain active skull cap components phosphatide complexes (phytosomes), the more former chemical compound of its physicochemical property and biological nature all has change in various degree, has stronger lipotropy, by with the compound carrier system that forms of phospholipid, can improve some medicines in gastrointestinal tract or percutaneous absorb, can improve interior absorption of body of active skull cap components effectively, it is slower to obtain the interior elimination of higher blood drug level and body, and bioavailability is significantly improved.Research about active skull cap components phosphatide complexes bioavailability, (Wu Jianmei etc. such as water solublity and fat-soluble all not good silymarin, dolichol, asiaticoside, baicalin phosphatide complexes are arranged, active skull cap components phosphatide complexes study of pharmacy general introduction, Chinese Pharmaceutical Journal, 1998,33 (1): 9-11).
By literature search, have not yet to see the relevant preparation phospholipid complexes of curcumin that utilizes to improve the report of curcumin composition bioavailability.
Summary of the invention
At the deficiencies in the prior art, the problem to be solved in the present invention provides phosphatide complexes of a kind of curcumin and preparation method thereof.To improve the defective of curcumin composition bioavailability aspect.
Phospholipid complexes of curcumin of the present invention is composited by curcumin or derivatives thereof and phospholipid, and wherein the mol ratio of curcumin or derivatives thereof and phospholipid is 1: 1～3.
Wherein, the mol ratio of described curcumin or derivatives thereof and phospholipid is preferably 1: 1.
Wherein, described phospholipid complexes of curcumin preferably is composited by curcumin and phospholipid, and the mol ratio of curcumin and phospholipid is preferably 1: 1.
Wherein, the derivant of described curcumin is demethoxycurcumin or Bisdemethoxycurcumin.
Wherein, described phospholipid is the phospholipid of mean molecule quantity 700～800, and phospholipid mainly refers to soybean phospholipid, egg yolk lecithin.
The preparation method of phospholipid complexes of curcumin of the present invention comprises the step of following order:
(1) get in the fat-soluble solvent that the curcumin or derivatives thereof is dissolved in 40 ℃～60 ℃, red clear liquid;
(2) under 40 ℃～70 ℃ conditions, be incubated, add the phospholipid that is equivalent to 1～3 times of mole of curcumin or derivatives thereof, stir, clear and bright until solution;
After (3) 5～15 minutes, take back the stream device, continuous oscillating reactions is 1～2 hour in the time of with above-mentioned condition heat tracing;
(4) remove reflux, when 60 ℃ of conventional distilling under reduced pressure were concentrated into reaction volume and are 200～300ml, in impouring 1500～2500ml normal hexane, the solution upper strata was yellow troubled liquor immediately, lower floor's grease that takes on a red color;
(5) get red oil, vacuum drying gets brick-red dry thing, is phospholipid complexes of curcumin.
Wherein, the described fat-soluble solvent of step (1) is meant acetone, ethanol, chloroform, methanol.
Wherein, the described fat-soluble solvent of step (1) preferably is meant dehydrated alcohol.
Wherein, the described phospholipid of step (2) is meant that mean molecule quantity is 700～800 phospholipid, and phospholipid mainly refers to soybean phospholipid, egg yolk lecithin.Preferred mean molecule quantity is 750 soybean lecithin, and mean molecule quantity is 780 Ovum Gallus domesticus Flavus lecithin, and mean molecule quantity is 700 lecithin; Most preferably mean molecule quantity is 750 soybean lecithin.
Wherein, the described holding temperature of step (2) is preferred 55 ℃.
Gained complex of the present invention shows the speckle with the identical Rf value of curcumin on thin layer chromatography, what formation was described is complex, rather than newly-generated chemical compound, the physical mixture of this complex and curcumin and phospholipid differential thermal analysis (DSC), infrared spectrum (IR) and hydrogen nuclear magnetic resonance collection of illustrative plates (
1HNMR) have tangible difference in: mixture has a more weak heat absorption recess among the DSC near 125 ℃, tangible heat absorption phenomenon is arranged near 160 ℃, and complex thermal change temperature is near 151 ℃; The OH absworption peak of curcumin own is at 3416cm among the IR
-1About, with the phospholipid physical mixture after move to 3505cm
-1About, form behind the complex at 3223cm
-1About, the P=O of phospholipid own absorbs the position at 1234cm
-1About, and move to 1283cm behind the curcumin physical mixture
-1About, form behind the complex at 1292cm
-1About, show that association to a certain degree may take place with the P=O key of phospholipid the OH of curcumin; Complex
1In the HNMR collection of illustrative plates, the peak that is occurred is the adduction of curcumin and phospholipid, phospholipid hydrogen proton part is compared with independent phospholipid signal and is presented strong peak, the peak that curcumin hydrogen proton part is compared with independent curcumin signal a little less than, but each peaking displacement study value and to split branch also high-visible.The prepared curcumin phosphatide complexes of this explanation is not newly-generated chemical compound, but is different from its two simple mixing really yet, but exist with a kind of form of complex.
Test has improved bioavailability after showing the formation complex.Get male white rat Mus random group, respectively with the phosphatide complexes filling stomach of curcumin and curcumin, dosage all is equivalent to curcumin 500mg/kg behind the fasting 12h.Before each medicine is irritated stomach and the back 0.5,1,2,4,8 of taking medicine, 16h get blood 0.5ml by carotid artery, put in the test tube that heparin is handled, centrifugal separation plasma, after plasma sample is handled, with husky this amine alcohol is interior mark, adopts the methods analyst phospholipid complexes of curcumin of LC-MS and the blood drug level-time data of curcumin, uses the 3P87 medicine for dynamical program machine match as calculated respectively, check preference pattern with AIC value and F behind average blood drug level-time match, calculate pharmacokinetic parameter.The result shows and forms glucuronic acid combination rate and the metabolism ratio that does not change curcumin behind the complex, but blood drug level-time graph show curcumin phosphatide complexes group blood drug level apparently higher than the curcumin group, the Cmax of complex has improved 3 times approximately, illustrates that the phosphatide complexes of curcumin can promote curcumin in the intravital absorption of rat really.
The present invention breaks through the pattern that increases the bioavailability of curcumin by the water solublity that increases curcumin, but to have selected be that the method for carrier changes its bioavailability with phospholipid, prepared the curcumin phosphatide complexes, thin layer chromatography, DSC, IR, NMR analyzes all show it is to have formed complex, rather than simple physical mixed or generate new chemical compound, method by LC-MS is analyzed in intravital metabolism of rat and pharmacokinetic characteristics curcumin and phosphatide complexes thereof, finds that it improved greatly in organic intravital absorption after curcumin was made phosphatide complexes.This will solve curcumin not high problem of bioavailability in human body and animal body effectively, be very beneficial for this and have multiple bioactive natural product curcumin and further move towards clinical as medicine.
Description of drawings
The thin layer chromatography result of Fig. 1 phospholipid complexes of curcumin and mixture is (a, curcumin contrast relatively; B, complex c, physical mixture; D, the phospholipid contrast; Unfolding condition from left to right is followed successively by 1. ethyl acetate: methanol=20: 1; 2. ethyl acetate: acetone=2: 1; 3. ethyl acetate: cyclohexane extraction=1: 2)
The differential thermal analysis result of Fig. 2 phospholipid complexes of curcumin and mixture is (a, curcumin relatively; B, phospholipid; C, complex; D, physical mixture)
The infrared spectrum of Fig. 3 phospholipid complexes of curcumin and mixture is (a, curcumin relatively; B, phospholipid; C, complex; D, physical mixture)
Fig. 4 phospholipid complexes of curcumin and mixture
1The HNMR spectrogram is (a, curcumin relatively; B, phospholipid; C, complex; D, physical mixture)
The specific embodiment
Get curcumin 37g (being equivalent to 0.1mol approximately), be dissolved among 45 ℃～55 ℃ the dehydrated alcohol 1000ml, get red clear liquid, 55 ℃ of insulations down add 75g soybean lecithin (mean molecule quantity 750), stir, clear and bright until solution, behind about 10min, take back the stream device, limit heat tracing limit oscillating reactions 1 hour, remove reflux, 60 ℃ of routines are evaporated to reaction volume when being 250ml, immediately among the impouring normal hexane 2000ml, the solution upper strata is yellow troubled liquor, lower floor is a red oil, gets red oil, the conventional method vacuum drying, get brick-red dry thing 102g, be phospholipid complexes of curcumin.
Adopt following development system respectively: 1. ethyl acetate: methanol=20: 1; 2. ethyl acetate: acetone=2: 1; 3. ethyl acetate: cyclohexane extraction=1: 2, with curcumin, phospholipid complexes of curcumin, the curcumin mixture of phospholipids, lecithin launches respectively, shown in its thin-layer chromatogram accompanying drawing 1.The result shows that the Rf value in three kinds of development systems of curcumin and phospholipid complexes of curcumin is all consistent, is respectively 0.4,0.35,0.2, and what this explanation phospholipid and curcumin formed is a kind of complex, rather than chemical compound.
With AL
2O
3Be reference substance, heating rate: 10 ℃/min, sweep limits: 30～400 ℃, N
2Flow velocity is 0.2ml/min, takes by weighing curcumin respectively, soybean phospholipid, and complex and physical mixture 10～20mg carry out differential thermal analysis, the results are shown in accompanying drawing 2.Can find out that from the DSC collection of illustrative plates fusing point of curcumin is 185.3 ℃.Soybean phospholipid is a mixture, does not have tangible fusing point endothermic peak, just 2 concaves occurred at 119.5 and 168.6 ℃, may represent the corresponding thermal change that its different component presents with the rising of ambient temperature.Compare with phospholipid with curcumin, significant change has all taken place the DSC collection of illustrative plates of the two mixture and complex: the fusing point peak of curcumin disappears, and the heat absorption peak position (recess) of phospholipid changes.Complex and the mixture DSC collection of illustrative plates of comparing presents more different: mixture has a more weak heat absorption recess near 125 ℃, shows tangible heat absorption phenomenon at 159.8 ℃, and the unit caloric receptivity is 137.77J/g; And the temperature of thermal change is at 151.3 ℃ in the DSC collection of illustrative plates of complex, and the unit caloric receptivity is 242.89J/g.From above result of the test as can be known, 1. in complex or mixture because the existence of phospholipid, the macroscopic property of curcumin is covered fully; 2. compare with mixture, complex is lower than mixture with the temperature value of the rising heat absorption peak position of ambient temperature, unit caloric receptivity is that the destruction of active force between curcumin and the soybean phospholipid needs bigger energy greater than mixture obviously, illustrates in the complex that curcumin and soybean phospholipid molecule disperse more equably and exist certain active force between the two.
To curcumin, soybean phospholipid, the two complex and physical mixture carry out infrared scan, the results are shown in accompanying drawing 3.Vibration peak position to corresponding group among the figure is concluded, and the results are shown in Table 1.
Table 1 curcumin, soybean phospholipid and the two complex thereof, the main group vibration peak position of mixture
| Curcumin | Soybean phospholipid | Mixture | Complex | |
| υ OH | 3373 3238 | 3288 3010 | 3498 3319 3010 | 3395 3224 3010 |
| υ CH | 2920 | 2925 2854 | 2925 2854 | 2926 2854 |
| υ C＝O | 1632 | 1738 | 1740 1627 | 1739 1632 |
| υ C＝C | 1610 1590 1567 1514 1446 | 1547 1466 1416 | 1601 1509 1458 1428 | 1590 1516 1463 1445 1416 |
| δ OH | 1395 | 1378 | 1377 1317 | 1366 |
| δ C-O | 1254 | 1275 1258 | 1293 1264 | |
| υ P＝O | 1234 | 1233 1206 | 1242 | |
| υ C-O | 1057 | 1086 1042 | 1088 1027 | 1087 1031 |
By data in the chart to curcumin, lecithin, curcumin lecithin physical mixture, it is as follows that phospholipid complexes of curcumin carries out infrared spectrum analysis: the characteristic absorption peak of curcumin: (1) OH, 3416.28cm
-1, its INFRARED ABSORPTION position is than free hydroxyl group (3610-3640cm
-1) shift to than lower wave number, and peak shape broad and blunt, this explanation curcumin exists intermolecular association, and has formed the polymer that links to each other with hydrogen bond.(2)C＝C，1627.56cm
-1，1510.45cm
-1。The characteristic absorption peak of lecithin: (1) CH
2, 2923.57cm
-1(2) C=O, 1738.18cm
-1(3) CH
3, 1463.34cm
-1(4) P=O, 1234.45cm
-1(5) P-O-C, 1059.02cm
-1(6) OH, 2923.57cm
-1, 2853.50cm
-1In the physical mixture, OH is arranged, 3505.51cm
-1, and in complex OH, 3223.83cm
-1, the hydroxyl of curcumin is obviously shifted to than lower wave number, and this shows that when forming phospholipid complexes of curcumin, the intermolecular association that the hydroxyl of curcumin takes place obviously weakens.P=O 1283.44cm in the physical mixture
-1, in the complex at 1292.83cm
-1, move to high wave number than phospholipid itself the absorption position of P=O, and association to a certain degree may take place with the P=O key of soybean lecithin in this OH that shows curcumin.The absorption position 1739.27cm of mixture C=O
-1And the 1739.21cm of complex
-11738.18cm with phospholipid itself
-1Be more or less the same, this shows that the carbonyl in the soybean lecithin does not participate in the formation of phospholipid complexes of curcumin.The infrared spectrum of phospholipid complexes of curcumin is different from the spectrum of the physical mixture of curcumin lecithin, and the prepared phospholipid complexes of curcumin of this explanation is different from its two simple mixing really, but exist with a kind of form of complex.
With CDCl
3(deuterochloroform) is solvent, to curcumin, lecithin, curcumin lecithin physical mixture, phospholipid complexes of curcumin, carry out respectively nuclear magnetic resonance spectroscopy (
1HNMR 600MHz), sees accompanying drawing 4.The peak that phospholipid complexes of curcumin occurred is the adduction of curcumin and phospholipid, shows that it is complex (1: 1), and does not form chemical compound.Phospholipid complexes of curcumin
1Phospholipid moiety hydrogen proton presents strong peak in the HNMR collection of illustrative plates, the peak of curcumin part hydrogen proton a little less than, but each peaking displacement study value and to split branch also high-visible, this further specifies curcumin and phospholipid has formed phosphatide complexes.
Remove methoxyl group curcumin (Cur-2) 37g (being equivalent to 0.1mol approximately), be dissolved among 60 ℃ the acetone 1000ml, get red clear liquid, 70 ℃ of insulations down add the Ovum Gallus domesticus Flavus lecithin (mean molecule quantity 780) that is equivalent to 2 times of moles of curcumin or derivatives thereof approximately, stir, clear and bright until solution, behind about 5min, take back the stream device, limit heat tracing limit oscillating reactions 2 hours, remove reflux, when vacuum concentration is 300ml to reaction volume, immediately among the impouring normal hexane 2500ml, the solution upper strata is yellow troubled liquor, lower floor is a red oil, gets red oil, vacuum drying, get brick-red dry thing 160g, be phospholipid complexes of curcumin.
Get two deoxidation base curcumin (Cur-3) 37g (being equivalent to 0.1mol approximately), be dissolved among 40 ℃ the methanol 1000ml, get red clear liquid, 40 ℃ of insulations down add the lecithin (mean molecule quantity 700) that is equivalent to 3 times of moles of curcumin or derivatives thereof approximately, stir, clear and bright until solution, about 15min takes back the stream device, limit heat tracing limit oscillating reactions 1.5 hours, remove reflux, 60 ℃ of routines are evaporated to reaction volume when being 200ml, immediately among the impouring normal hexane 1500ml, the solution upper strata is yellow troubled liquor, lower floor is a red oil, gets red oil, vacuum drying, get brick-red dry thing 230g, be phospholipid complexes of curcumin.
Phospholipid complexes of curcumin human body pharmacokinetics and preparation bioavailability study
Laboratory animal: 8 of male white rats, age in 6-7 week is about body weight 350g.Dosage regimen: 8 rat are divided into first and second liang of groups at random, irritate stomach with the phosphatide complexes of curcumin and curcumin respectively for two groups behind the fasting 12h, and dosage all is equivalent to curcumin 500mg/kg.Sample collecting: before each medicine is irritated stomach and the back 0.5,1,2,4,8 of taking medicine, 16h get blood 0.5ml by carotid artery, put in the test tube that heparin is handled, centrifugal separation plasma is preserved until analysis in-20 ℃ of refrigerators.Plasma sample is handled: get rat plasma sample 100 μ l, add methanol 50 μ l, eddy oscillating 1min, add inner mark solution (this amine of sand alcohol mobile phase solution of 1 μ g/ml) 50 μ l then, eddy current 1min, add the 1ml ethyl acetate, eddy oscillating 3min, supersound extraction 15min, centrifugal (5000r/min) 7min, get upper organic phase as in the 5ml point end tool plug test tube, dry up under air flow under the room temperature, residue adds 100 μ l mobile phase solution, ultrasonic dissolution, centrifugal (5000r/min) 7min moves supernatant as standby in the point end bottle.
Plasma sample is analyzed:
Chromatographic condition: chromatographic column: Phenomenex Luna 5u C
18Stainless steel column (U.S. Phonex Corp. produces for 5 μ m particle diameters, 250mm * 46mmID); Mobile phase: acetonitrile-water-acetic acid (30: 70: 1); Flow velocity: 0.2mlmin
-1Column temperature: 25 ℃; Sample size: 10 μ l.The mass spectrum condition: cation detects; Ion source injection electric 4.25kv; 350 ℃ of capillary temperatures; Capillary voltage 30V; Sheath gas (N
2) flow: 1.05Lmin
-1Auxiliary gas (N
2) flow: 0.15Lmin
-1Collision gas (He) flow: 0.2Lmin
-1With selecting ion full scan one-level mass spectrum (Fullscan MS
n) mode detects.
Method is estimated: investigate linear relationship, the curcumin range of linearity: 0.5～500ng/ml (r=0.9962) with curcumin and its main metabolite tetrahydrocurcumin; The tetrahydrocurcumin range of linearity: 5～5000ng/ml (r=0.9968).Specificity is investigated and to be shown in the blood plasma not interference measurement result of endogenous material, and interior mark and standard substance separating degree are good.The response rate of this method curcumin and tetrahydrocurcumin is respectively 73.11 ± 3.97 and 69.3 ± 5.02, curcumin in a few days, in the daytime RSD be respectively 2.76%～6.17%, 3.92%～9.76%, tetrahydrocurcumin in a few days, RSD is respectively 2.36%～7.01%, 3.67%～10.16% in the daytime.
Determination of plasma concentration the results are shown in Table 2, table 3:
Table 2 curcumin rat through the stomach administration the blood drug level of different time (mean ± s, n=4)
| Time (h) | C (curcumin) | C (tetrahydrocurcumin) |
| 0.5 1 2 6 8 16 | 0.75±0.39 1.36±0.81 2.54±1.48 1.27±0.85 1.04±0.82 0.73±0.57 | 2.59±1.00 5.18±2.06 14.01±13.92 6.28±5.68 3.87±2.76 2.81±1.26 |
Table 3 phospholipid complexes of curcumin rat through the stomach administration the blood drug level of different time (mean ± s, n=4)
| Time (h) | C (curcumin) | C (tetrahydrocurcumin) |
| 0.5 1 2 6 8 16 | 1.79±0.56 4.31±1.91 7.86±3.44 2.99±1.04 2.04±0.44 1.83±0.73 | 4.15±2.40 9.85±5.30 21.73±8.02 12.37±6.78 8.48±5.21 7.18±3.01 |
Pharmacokinetic parameters is calculated:
Blood drug level-the time data of phospholipid complexes of curcumin and curcumin uses the 3P87 medicine for dynamical program machine match as calculated respectively, checks preference pattern with AIC value and F behind average blood drug level-time match, calculates pharmacokinetic parameter.Rat all meets one compartment model through the pharmacokinetics process of stomach administration phospholipid complexes of curcumin and curcumin, sees Table 4 and table 5 through the main pharmacokinetic parameter of 3p97 pharmacokinetics computed in software.
The pharmacokinetic parameter of table 4 curcumin rat oral gavage administration (mean ± s, n=4)
| Parameter | Curcumin | Tetrahydrocurcumin |
| T 1/2Ka(h) T 1/2Ke(h) T peak(h) C max(ng/ml) AUC(ng/ml)*h | 1.26±0.55 0.13±0.11 2.28±0.17 2.22±1.33 21.75±4.15 | 0.76±0.56 0.27±0.12 2.52±0.42 12.22±13.16 80.93±29.62 |
The pharmacokinetic parameter of table 5 phospholipid complexes of curcumin rat oral gavage administration (mean ± s, n=4)
| Parameter | Curcumin | Tetrahydrocurcumin |
| T 1/2Ka(h) T 1/2Ke(h) T peak(h) C max(ng/ml) AUC(ng/ml)*h | 1.02±0.48 0.24±0.15 2.19±0.21 6.96±1.62 44.69±5.06 | 1.26±0.68 0.12±0.15 2.45±0.55 18.97±8.65 199.95±33.86 |
Two groups of main pharmacokinetic parameters are carried out the two t of survey checks, and the result shows T
1/2Ka (h), T
1/2Ke (h), T
Peak(h) there are no significant difference, C
Max(ng/ml), there is significant difference (P＜0.05) in AUC (ng/ml) * h, can think that phospholipid complexes of curcumin can obviously improve curcumin in the intravital bioavailability of rat, its relative bioavailability is 205.47%.
The glucuronic acid combination rate:
In rat plasma, curcumin and tetrahydrocurcumin mainly are that the form with glucuronide conjugate exists, its the two and the combination rate of glucuronic acid be respectively 99.54% and 95.52%, during with the form administration of phosphatide complexes, the glucuronic acid combination rate of the two is respectively 99.07% and 93.49%.By the F-check, there is significant difference in P＜0.05 between curcumin and the tetrahydrocurcumin, infers curcumin than the easier glucuronidation of tetrahydrocurcumin, and its combination rate situation is as shown in table 6.
Table 6 curcumin and glucuronic acid combination rate
| The curcumin group | The phospholipid complexes of curcumin group | |
| The curcumin tetrahydrocurcumin | 99.54％ 95.52％ | 99.07％ 93.49％ |
Curcumin metabolism ratio:
By experiment, curcumin is studied at rat internal metabolism ratio, by the F-check, P＞0.05, curcumin group and phospholipid complexes of curcumin group rat intravital curcumin metabolism ratio and form of administration are irrelevant, and its metabolism ratio is as shown in table 7.
The metabolism ratio of table 7 curcumin in rat plasma
| Enzyme *Before separating | Enzyme *After separating | |
| Curcumin group phospholipid complexes of curcumin group | 78.02％ 70.14％ | 32.71％ 26.27％ |
*This place's enzyme is the beta-glucuronic acid hydrolytic enzyme
Claims (8)
1. a phospholipid complexes of curcumin is composited by curcumin and lecithin, and wherein the mol ratio of curcumin and lecithin is 1: 1～3.
2. phospholipid complexes of curcumin as claimed in claim 1 is characterized in that, the mol ratio of described curcumin and lecithin is 1: 1.
3. phospholipid complexes of curcumin as claimed in claim 1 or 2 is characterized in that described lecithin is the lecithin of mean molecule quantity 700～800.
4. the preparation method of claim 1 or 2 described phospholipid complexes of curcumin comprises the step of following order:
(1) get in the fat-soluble solvent that curcumin is dissolved in 40 ℃～60 ℃, red clear liquid;
(2) under 40 ℃～70 ℃ conditions, be incubated, add the lecithin that is equivalent to 1～3 times of mole of curcumin, stir, clear and bright until solution;
After (3) 5～15 minutes, take back the stream device, continuous oscillating reactions is 1～2 hour in the time of with above-mentioned condition heat tracing;
(4) remove reflux, when 60 ℃ of conventional distilling under reduced pressure were concentrated into reaction volume and are 200～300ml, in impouring 1500～2500ml normal hexane, the solution upper strata was yellow troubled liquor immediately, lower floor's grease that takes on a red color;
(5) get red oil, vacuum drying gets brick-red dry thing, is phospholipid complexes of curcumin.
5. as the preparation method of phospholipid complexes of curcumin as described in the claim 4, it is characterized in that the described fat-soluble solvent of step (1) is meant acetone, ethanol, chloroform, methanol.
6. as the preparation method of phospholipid complexes of curcumin as described in the claim 5, it is characterized in that the described fat-soluble solvent of step (1) is meant dehydrated alcohol.
7. as the preparation method of phospholipid complexes of curcumin as described in the claim 4, it is characterized in that the described lecithin of step (2) is meant that mean molecule quantity is 750 soybean lecithin.
8. as the preparation method of phospholipid complexes of curcumin as described in the claim 4, it is characterized in that the described holding temperature of step (2) is 55 ℃.
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| CN1895239B (en) * | 2006-06-20 | 2010-05-12 | 中国人民解放军第二军医大学 | Curcumin preparation and its making method |
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| DE102013220974A1 (en) * | 2013-10-16 | 2015-04-16 | Briu Gmbh | Composition for oral administration of curcumin |
| CA3005700A1 (en) | 2015-12-16 | 2017-06-22 | Vivek Anand PARACHUR | Tri-molecular complex of natural compounds |
| CN106692979A (en) * | 2016-12-29 | 2017-05-24 | 广东药科大学 | Atorvastatin calcium and phospholipid compound and preparation method thereof |
| CN107213467A (en) * | 2017-05-22 | 2017-09-29 | 江苏大学 | A kind of preparation method of phospholipid complexes of curcumin |
| CN109481689B (en) * | 2018-12-25 | 2021-12-03 | 广州白云山汉方现代药业有限公司 | Composition for enhancing water solubility of curcumin 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 |
| 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 |
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2004
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10781158B2 (en) | 2014-09-02 | 2020-09-22 | Bhupinder Singh | Methods of protecting an organ using tetrahydrocurcumin and phosphatidylcholine |
| US11642316B2 (en) | 2021-04-30 | 2023-05-09 | Henan Zhongda Hengyuan Biotechnology Stock Co., Ltd. | Water-soluble curcumin mixture with high bioavailability and preparation method and application thereof |
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