CN101475556B - 1',2',3',7'-tetrahydrotheaflavine, and preparation and use thereof - Google Patents
1',2',3',7'-tetrahydrotheaflavine, and preparation and use thereof Download PDFInfo
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- CN101475556B CN101475556B CN2009100368154A CN200910036815A CN101475556B CN 101475556 B CN101475556 B CN 101475556B CN 2009100368154 A CN2009100368154 A CN 2009100368154A CN 200910036815 A CN200910036815 A CN 200910036815A CN 101475556 B CN101475556 B CN 101475556B
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- IPMYMEWFZKHGAX-RIRCILFKSA-N O[C@H]1[C@@H](c(c(C=C(C([C@@H](C2)O)Oc3c2c(O)cc(O)c3)C=C2O)c3C2=O)cc(O)c3O)Oc2cc(O)cc(O)c2C1 Chemical compound O[C@H]1[C@@H](c(c(C=C(C([C@@H](C2)O)Oc3c2c(O)cc(O)c3)C=C2O)c3C2=O)cc(O)c3O)Oc2cc(O)cc(O)c2C1 IPMYMEWFZKHGAX-RIRCILFKSA-N 0.000 description 1
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Abstract
The invention provides a novel compound, which is 1',2',3'7'- tetrahydro theaflavin and the chemical structural formula thereof is shown as (1). The compound of the invention can be obtained by hydrogenating and reducing theaflavin-TF1, has the functions of inhibiting the activity of reverse transcriptase and the activity of HIV gp41 forming a six-strand helical core structure, can prevent HIV virus from entering a host cell, and has stronger inhibiting functions on the activity of the reverse transcriptase and the activity of HIV gp41 forming the six-strand helical core structure than the theaflavin- TF1.
Description
Technical field
The present invention relates to organic chemistry filed, be specifically related to a kind of new theoflavin analog derivative.
Background technology
Theoflavin is the main component in the black tea, is the material that a class has benzo phenolic ketone structure, forms by catechin benzo cyclic action.Studies confirm that in a large number both at home and abroad that at present theoflavin has effects such as antitumor, anti-inflammatory, anti-oxidant, antiviral, antibiotic and anti-cardiovascular disease, is the natural product of a class great exploitation potential for its.
The theoflavin kind of having found at present and having identified has 28 kinds, wherein TF1 (Theaflavin 1) is one of topmost theoflavin (Sang SM, L ambert J D, T ian S Y, et al., Enzymatic synthesis of tea theaflavin derivativesand their anti-inflammatory and cytotoxic activities.Bioorg Med Chem.2004; 12:459-467), its chemical structure as the formula (1).The inventor found once that TF1 had the effect that suppresses HIV-1 invasion target cell, and it is to the active IC of the cell-cytogamy of HIV coating mediation
50Be 31.25 ± 5.48 μ M (about 17 μ g/ml), to the IC of the virus-cytogamy of HIV coating mediation
50Be 13.5 ± 2.09 μ M (about 7 μ g/ml); The inventor further (comprises that gp120 combines with CD4 by HIV being entered each drug target of stage, gp120 combines with accessory receptor, gp120 conformational change etc.) detection, find that TF1 can act on gp41 specifically, suppress the formation of six bursts of helical core structures of gp41, its IC
50Be 28.10 ± 3.03 μ M (about 15 μ g/ml) (Liu, S., Lu, H, Zhao, Q., et al.Theaflavin derivatives in black tea and catechinderivatives in green tea inhibit HIV-1 entry by targeting gp41.Biochim Biophy Acta.2005; 1723 (1-3): 270-281).
Summary of the invention
The technical problem to be solved in the present invention provides a kind of theoflavin derivative.
The technical scheme that the present invention addresses the above problem is:
1 ", 2 ", 3 ", 7 " the tetrahydrochysene theoflavin, its chemical structural formula is shown in (2).
Compound of the present invention can obtain through hydro-reduction by theoflavin TF1, reaction process as the formula (3), concrete grammar is made up of following steps: theoflavin TF1 is dissolved in the tetrahydrofuran (THF), the palladium-carbon catalyst that adds theoflavin TF1 quality 30%, under room temperature and intense stirring condition, feed hydrogen reaction 4～7 days, remove by filter catalyzer, be dissolved in 95% ethanol behind the pressure reducing and steaming tetrahydrofuran (THF), through reversed phase column chromatography, remove ethanol and get final product.
The compounds of this invention is a faint yellow solid, and it is on the basis of phenyl ring in keeping theoflavin TF1 original structure and phenolic hydroxyl group group, and seven yuan of phenolic ketone rings in its benzo phenolic ketone structure are carried out the carbocyclic ring hydro-reduction.Because the benzene ring structure of theoflavin TF1 can combine with conservative hydrophobic residue in the HIV gp41 target cave, its phenolic hydroxyl group is weakly alkaline, can combine with conservative positive charge residue K574 in the target cave, therefore The compounds of this invention has the activity that suppresses six bursts of helical core structures of HIV gp41 formation, can stop HIV virus to enter host cell; Simultaneously, The compounds of this invention also can suppress the activity of reversed transcriptive enzyme.After seven yuan of phenolic ketone rings in the theoflavin TF1 benzo phenolic ketone structure are carried out the carbocyclic ring hydro-reduction, the restraining effect that its HIV gp41 forms six bursts of helical core structures is enhanced, this is because on the one hand ethylene linkage reduction back is strengthened to some extent than original structure stability, and phenyl ring and phenolic hydroxyl group still keep six bursts of activity that helical core structure target position combines with HIV gp41, the sterie configuration of seven-membered ring changes and makes that this compound is easier to combine with HIVgp41 target cave behind the hydro-reduction on the other hand, therefore The compounds of this invention stability is better, and HIV (human immunodeficiency virus)-resistant activity is stronger.
The compounds of this invention can be used for preparing the medicine of anti-AIDS.Described medicine can be a tablet, also can be hydrogel adhesive, and wherein the mass percentage content of The compounds of this invention in described medicine is 1～20%.
In order to understand the present invention better, will prove the technique effect that The compounds of this invention has by experiment below.
One, the activity of the inhibition reversed transcriptive enzyme of The compounds of this invention detects.
1, reagent:
Reverse Transcriptase Assay Kit.
2, experimental technique:
1) with poly A and oligod (T) 16 mixings, room temperature was placed 60 minutes.
2) with the reactant of polymerization buffer 200 times of dilutions polyA and oligod (T) 16, promptly get reaction mixture, change them over to 96 orifice plates, every hole adds 20 μ l.
3) with 1X HIV RT damping fluid the HIV RT of 10 units is diluted to 0.8 unit, the HIV RT of each concentration The compounds of this invention 10 μ l and 2.5 μ l, 0.8 unit is mixed.
4) mixture of adding 5 μ l The compounds of this invention compounds and HIV RT in every hole, 43 ℃ were reacted one hour.
5) every hole adds 2 μ L of 200mM EDTA stopped reactions, places 15 minutes for 4 ℃.
6) every hole adds 173 μ L PicoGreen Working Solution, and black out was hatched 3 minutes.
7) survey the OD value with microplate reader, exciting light 485nm, emission light 535nm.
Inhibiting rate calculates as follows: inhibiting rate=(control wells OD value-experimental port OD value)/control wells OD value) * 100%, compound partly imitate inhibition concentration (IC
50) employing CalcuSyn computed in software.Establish the TF1 contrast simultaneously.
2, experimental result:
Table 1
The result is as shown in table 1, and The compounds of this invention can effectively suppress the activity of hiv reverse transcriptase, medium effective concentration (IC
50) be 0.5705 ± 0.15 μ g/ml, its inhibiting rate increases progressively along with the increasing of dosage, and effect is better than TF1, and visible The compounds of this invention has HIV (human immunodeficiency virus)-resistant activity preferably.
Two, six bursts of helical bundle structures of The compounds of this invention inhibition HIVgp41 form active detection.
(1) adopts the sandwich ELISA method to carry out six bursts of helical bundle structures of The compounds of this invention inhibition HIVgp41 and form active detection
1, experimental technique
(1) the 0.1M Tris-HCl damping fluid with pH8.8 is coated on monoclonal antibody 2 μ g/ml NC-1 on the 96 hole enzyme plates, every hole 100 μ l, and 4 ℃ are spent the night.The skimmed milk of every hole adding 1% (with the PBS dissolving of pH7.2) 200 μ l seal, and hatch 60 minutes for 37 ℃, wash plate three times.
(2) each 30 μ l of 2 μ M N36,30 μ l and compound are mixed, hatched 30 minutes for 37 ℃, add the 1 μ M C34 of 60 μ l again, hatched 30 minutes for 37 ℃.
(3) they are joined in the enzyme plate that has sealed, hatched 60 minutes for 37 ℃, wash plate three times.
(4) every hole adds the monoclonal antibody NC-1 of 100 μ l, 1 μ g/ml, hatches 60 minutes for 37 ℃, washes plate three times.
(5) every hole adds the polyclonal antibody IgG of the anti-N36/C34 mixture of 1: 5000 rabbit of 100 μ l, hatches 60 minutes for 37 ℃, washes plate three times.
(6) every hole adds the goat anti-rabbit igg (SA-HRP) of 1: 5000 horseradish peroxidase-labeled of 100 μ l, hatches 60 minutes for 37 ℃, washes plate three times.
(7) every hole add the chromogenic substrate 3,3 of 100 μ l ', 5,5 '-tetramethyl benzidine (TMB) stops, and is determined at the absorbance that wavelength is the 450nm place (OD value) with microplate reader, 570nm is as the reference wavelength.
Inhibiting rate is by formula: inhibiting rate=(control wells OD value-experimental port OD value)/control wells OD value) * 100% calculate, compound partly imitate inhibition concentration (IC
50) employing CalcuSyn computed in software.
2, experiment grouping
Experimental group of the present invention: it is The compounds of this invention that institute adds compound, and makes its final concentration in reaction system be respectively 1.5625 μ g/ml, 3.125 μ g/ml, 6.25 μ g/ml, 12.5 μ g/ml and 25 μ g/ml.
The TF1 control group: it is TF1 that institute adds compound, and makes its final concentration in reaction system be respectively 1.5625 μ g/ml, 3.125 μ g/ml, 6.25 μ g/ml, 12.5 μ g/ml and 25 μ g/ml.
3, experimental result
Shown in the table 2, The compounds of this invention can effectively suppress the formation of six strands of spirane structure bundles of HIVgp41, has HIV (human immunodeficiency virus)-resistant activity preferably as a result, and its inhibiting rate increases progressively along with the increasing of dosage, medium effective concentration (IC
50) be about 6.4 μ g/ml; When The compounds of this invention dosage was 25 μ g/ml, the inhibiting rate that gp41 six helical bundle structures are formed was greater than 85%, and its effect is better than TF1.
Table 2
(2) (Native PAGE, N-PAGE) method is carried out six bursts of helical bundle structures of The compounds of this invention inhibition HIVgp41 and is formed active detection to adopt natural gel electrophoresis
1, experimental technique
1) the discontinuous natural polypropylene acrylamide gel of preparation, wherein separation gel is 18%, spacer gel is 5%.
2) the N36 6 μ l of compound 3 μ l and 100 μ M were hatched 30 minutes jointly at 37 ℃, the C34 6 μ l that add 100 μ M were again hatched 30 minutes jointly at 37 ℃.
3) mixed solution that will hatch and the natural gel sample-loading buffer of 15 μ l, 2 * Tris-glycine mixing, (every hole 25 μ l) left standstill 5 minutes in the natural polypropylene acrylamide gel hole of application of sample to 10 * 0.1cm.Room temperature 120V voltage electrophoresis 2 hours, Coomassie blue R250 dyeing, decolouring back FluorChem 8800 gel imaging instrument Taking Pictures recordings.
2, experiment grouping
Experimental group of the present invention: it is The compounds of this invention that institute adds compound, is made into the solution that concentration is 1000 μ g/ml, 500 μ g/ml and 250 μ g/ml with PBS.
The TF1 control group: it is TF1 that institute adds compound, is made into the solution that concentration is 1000 μ g/ml, 500 μ g/ml and 250 μ g/ml with PBS.
3, experimental result
The inhibition effect that The compounds of this invention forms HIV gp41 six helical bundle structures is shown in the N-PAGE electrophorogram of Fig. 1 and Fig. 2, from Fig. 1 and Fig. 2 as can be seen, do not add in the pharmaceutically-active sample, equimolar N36 and C34 mixture can form two bands, top band (arrow A indication) is corresponding with six bursts of helical bundle structures, the band (arrow B indication) of below is excessive C34, and its reason is that the N36 generating unit divides gathering to cause fully combining with C34 six strands of helical bundles of formation; Add in the sample of The compounds of this invention or theoflavin TF1, almost do not have six bursts of helical bundle structures to form or only form on a small quantity, the formation of visible six bursts of helical bundle structures obviously is suppressed.The compounds of this invention suppresses the formation of most of HIVgp41 six helical bundle structures when final concentration 200 μ g/ml and 100 μ g/ml, when 50 μ g/ml, can suppress the formation of part HIV gp41 six helical bundle structures, the positive correlation that increases progressively into of its inhibition degree and dosage, and act on stronger than TF1, the proof The compounds of this invention can target in HIV gp41, suppress its six bursts of helical bundle structures and form.As seen, The compounds of this invention has HIV (human immunodeficiency virus)-resistant activity preferably.
Three. adopt the cytogamy experiment to carry out the activity detection that The compounds of this invention suppresses the cell-cytogamy of HIV coating mediation
(1) adopt the experiment of CHO-WT and MT2 cytogamy to carry out the activity detection that The compounds of this invention suppresses the cell-cytogamy of HIV coating mediation
The envelope glycoprotein gp120 of the last expression of CHO-WT HIV expresses acceptor and the accessory receptor of gp160 on the MT2 cell, two kinds of co-culture of cells can simulated infection HIV cell and the mechanism of normal target cell.
1, experimental technique
1) CHO-WT uses the digestion of 0.5mM EDTA-EGTA Digestive system to collect, and spares with abundant the beating of GMEM-S substratum washing, is diluted to 1 * 10 behind the counting
6/ ml, every hole 75 μ l add The compounds of this invention 50 μ l, hatch jointly 30 minutes for 37 ℃; Establish blank well, negative control hole (not adding any medicine) and positive simultaneously facing to hole (it is TF1 that institute adds medicine).
2) the MT2 cell is collected with the digestion of 0.25% trysinization liquid, and spares with abundant the beating of 1640 substratum washing, is diluted to 1 * 10 behind the counting
6/ ml, every hole adds 75 μ l MT2 cells (1 * 10
6In/ the mixture that ml) the supreme step hatches, 37 ℃, 5%CO
2Incubator is cultivated;
3) cultivate after 48 hours, under inverted microscope, observe plasmodial number and Taking Pictures recording (20 *);
4) by formula calculate inhibiting rate:
Inhibiting rate=1-(experimental port OD value-blank OD value)/(control wells OD value-blank OD value) * 100% calculates, compound partly imitate inhibition concentration (IC
50) employing CalcuSyn computed in software.
2, experimental result
Observe the control wells that does not add The compounds of this invention, CHO-WT and MT2 cytomixis are cultivated the back and are merged a large amount of synplasms of formation.The synplasm number obviously reduces in the culture hole of adding The compounds of this invention, illustrate that The compounds of this invention can act on the link that HIV enters target cell, suppress the fusion of CHO-WT and MT2 cell, its inhibiting rate is as shown in table 3, when The compounds of this invention dosage is 6.25 μ g/ml, to two kinds of cell inhibiting rates all greater than 50%, its inhibiting rate increases along with the increasing of dosage, as seen The compounds of this invention can effectively suppress the CHO-WT and the MT-cytogamy of HIV coating mediation, has HIV (human immunodeficiency virus)-resistant activity preferably.
Table 3
(2) adopt the experiment of HeLa-CD4-LTR-β-gal and HL2/3 cytogamy to carry out active detection of cell-cell bonded that The compounds of this invention suppresses the mediation of HIV coating
HeLa-CD4-LTR-β-gal cell is loaded with the beta-galactosidase gene of expressing CD4 and LTR startup, the HeLa cell can be expressed HIV albumen such as envelope protein gp120/gp41 and Tat, two kinds of cells start β-gal expression of enzymes in conjunction with the back, β-gal enzyme is dyeed, blue spot occurs and show two kinds of cytogamy, thus the mechanism of simulated infection HIV cell and normal target cell.
1, experimental technique
1) the HL2/3 cell is collected with the digestion of 0.25% trysinization liquid, and spares with abundant the beating of DMEM substratum washing, is diluted to 1 * 10 behind the counting
6/ ml, every hole 75 μ l add The compounds of this invention 50 μ l, hatch jointly 30 minutes for 37 ℃; Establish blank well, negative control hole (not adding any medicine) and positive simultaneously facing to hole (it is TF1 that institute adds medicine);
2) HeLa-CD4-LTR-β-gal cell uses the digestion of 0.5mM EDTA-EGTA Digestive system to collect, and spares with abundant the beating of DMEM substratum washing, is diluted to 1 * 10 behind the counting
6/ ml, every hole adds 75 μ l HeLa-CD4-LTR-β-gal cells (1 * 10
6In/ the mixture that ml) the supreme step hatches, 37 ℃, 5%CO
2Incubator is cultivated;
3) cultivate after 48 hours, discard substratum, wash cell with pH7.2PBS;
4) add 4% Paraformaldehyde 96 as stationary liquid, every hole 100 μ l;
5) room temperature was placed 5 minutes, inhaled and abandoned stationary liquid, and PBS washes cell;
6) add staining fluid, every hole 100 μ l placed 50 minutes for 37 ℃;
7) under inverted microscope observation of cell in conjunction with situation (blue spot) and Taking Pictures recording (20 *);
8) calculate inhibiting rate as follows:
Inhibiting rate=(experimental port OD value-blank OD value)/(control wells OD value-blank OD value) * 100% calculated, compound partly imitate inhibition concentration (IC
50) employing CalcuSyn computed in software.
2, experimental result
Observe the control wells that does not add The compounds of this invention, can produce a large amount of blue spot after HeLa-CD4-LTR-β-gal and the HL2/3 mixed culture, illustrate that fusion has taken place two kinds of cells.Observation has added the culture hole of The compounds of this invention, and the blue spot number obviously reduces, and illustrates that The compounds of this invention can act on the link that HIV enters target cell, suppresses to adopt the combination of HeLa-CD4-LTR-β-gal and HL2/3 cell, and it suppresses effect and sees Table 4.When The compounds of this invention dosage is 12.5 μ g/ml, the bonded inhibiting rate of gp41HeLa-CD4-LTR-β-gal and HL2/3 cell greater than 50%, and is had dose-dependently, prove that The compounds of this invention has HIV (human immunodeficiency virus)-resistant activity preferably.
Table 4
Description of drawings
Fig. 1 is that theoflavin TF1 suppresses the N-PAGE electrophorogram that HIV gp41 six helical bundle structures form, wherein, the 1st, C34, the 2nd, the electrophoresis result after N36 and C34 are hatched altogether, 3～5th, be respectively electrophoresis result after N36 that the theoflavin TF1 of 200 μ g/ml, 100 μ g/ml and 50 μ g/ml handles and C34 are hatched altogether with final concentration.
Fig. 2 is that The compounds of this invention suppresses the N-PAGE electrophorogram that HIV gp41 six helical bundle structures form, wherein 1 is C34, the 2nd, the electrophoresis result after N36 and C34 are hatched altogether, 3～5th, be respectively electrophoresis result after N36 that the The compounds of this invention of 200 μ g/ml, 100 μ g/ml and 50 μ g/ml handles and C34 are hatched altogether with final concentration.
Fig. 3 is HR-MS (ESI) collection of illustrative plates of The compounds of this invention, and wherein the peak at m/z:567.1505 place is [M-H] of The compounds of this invention
-Quasi-molecular ion peak.
Embodiment
Preparation example
Example 1
56.4mg theoflavin TF1 is dissolved in the 30ml tetrahydrofuran (THF), add 16.9mg palladium carbon and make catalyzer, under room temperature and intense stirring condition, fed hydrogen reaction 4 days, remove by filter catalyzer, be dissolved in 95% ethanol behind the pressure reducing and steaming tetrahydrofuran (THF),, remove ethanol through reversed phase column chromatography, get the 21mg faint yellow solid, productive rate is 37%.
Products therefrom is identified by high resolution ESI mass spectrum: by Q-TOF mass spectrometer (Bruker Daltonics, MA USA) measure, and the result is: HR-MS (ESI) m/z:[M-H]
-: 567.1505 (calcd.for C
29H
27O
12: 567.1503), as shown in Figure 3.The gained solid is the simplification compound as can be known, and molecular formula is C
29H
28O
12, molecular weight is 568.1581.This presentation of results reaction products therefrom Duo 4 hydrogen than reaction raw materials theoflavin TF1, considers that the phenyl ring among the theoflavin TF1 can not be hydrogenated reduction under palladium carbon is done the condition of catalyzer, occurs on seven yuan of phenolic ketone rings so infer that hydro-reduction reacts.
Example 2
56.4mg theoflavin TF1 is dissolved in the 30ml tetrahydrofuran (THF), add 16.9mg palladium carbon and make catalyzer, under room temperature and intense stirring condition, fed hydrogen reaction 5 days, remove by filter catalyzer, be dissolved in 95% ethanol behind the pressure reducing and steaming tetrahydrofuran (THF),, remove ethanol through reversed phase column chromatography, get the 21.46mg faint yellow solid, productive rate is 38.05%.Adopt with example 1 same procedure and carry out Analysis and Identification, the result shows that resultant faint yellow solid is 1 ", 2 ", 3 " and, 7 " tetrahydrochysene theoflavin.
Example 3
56.4mg theoflavin TF1 is dissolved in the 30ml tetrahydrofuran (THF), add 16.9mg palladium carbon and make catalyzer, under room temperature and intense stirring condition, fed hydrogen reaction 7 days, remove by filter catalyzer, be dissolved in 95% ethanol behind the pressure reducing and steaming tetrahydrofuran (THF),, remove ethanol through reversed phase column chromatography, get the 22.31mg faint yellow solid, productive rate is 39.57%.Adopt with example 1 same procedure and carry out Analysis and Identification, the result shows that resultant faint yellow solid is 1 ", 2 ", 3 " and, 7 " tetrahydrochysene theoflavin.
Application examples
Example 4
1, prescription:
1 ", 2 ", 3 ", 7 " tetrahydrochysene theoflavin 20g, starch 50g, dextrin 28g, tartrate 1g, 50% ethanol is an amount of and Magnesium Stearate 1g, makes 1000 altogether, every contains this compound 20mg.
2, method for making:
Take by weighing compound 1 ", 2 ", 3 ", 7 " tetrahydrochysene theoflavin 20g, starch 50g, dextrin 28g mix.In addition 1g tartrate is dissolved in 50% ethanol, once adds in the mixed powder, make softwood, make wet grain by 18-20 order nylon mesh by sufficient quantity, dry below 60 ℃, whole grain, with the 1g Magnesium Stearate mixing that sieves, compressing tablet (every 0.1g).
3, usage and dosage: each 3, every day 3 times.
Example 5
1, prescription:
1 ", 2 ", 3 ", 7 " tetrahydrochysene theoflavin 10g, starch 58g, dextrin 30g, tartrate 1g, 50% ethanol is an amount of and Magnesium Stearate 1g, makes 1000 altogether, every contains this compound 10mg.
2, method for making:
Take by weighing compound 1 ", 2 ", 3 ", 7 " tetrahydrochysene theoflavin 10g, starch 58g, dextrin 30g mix.In addition 1g tartrate is dissolved in 50% ethanol, once adds in the mixed powder, make softwood, make wet grain by 18-20 order nylon mesh by sufficient quantity, dry below 60 ℃, whole grain, with the 1g Magnesium Stearate mixing that sieves, compressing tablet (every 0.1g).
3, usage and dosage: each 3, every day 3 times.
Example 6
1, prescription:
1 ", 2 ", 3 ", 7 " an amount of, propylene glycol 40g, glycerine 35g of tetrahydrochysene theoflavin 20g, carbomer 1g, 50% ethanol and trolamine are an amount of, make 1000 grams altogether, and every gram contains this compound 20mg.
2, method for making:
Get carbomer 1g, add the less water swelling; Other gets 1 ", 2 ", 3 " and, 7 " tetrahydrochysene theoflavin 20g, behind 50% dissolve with ethanol, add propylene glycol 40g and glycerine 35g successively, slowly add then in the carbomer after the swelling, the limit edged stirs, drip trolamine again to pH4-5, add purified water at last, stir evenly to 1000g.
3, usage and dosage: each 3 grams, every day 3 times, external application.
Example 7
1, prescription:
1 ", 2 ", 3 ", 7 " an amount of, propylene glycol 40g, glycerine 35g of tetrahydrochysene theoflavin 10g, carbomer 1g, 50% ethanol and trolamine are an amount of, make 1000 grams altogether, and every gram contains this compound 10mg.
2, method for making:
Get carbomer 1g, add the less water swelling; Other gets 1 ", 2 ", 3 " and, 7 " tetrahydrochysene theoflavin 10g, behind 50% dissolve with ethanol, add propylene glycol 40g and glycerine 35g successively, slowly add then in the carbomer after the swelling, the limit edged stirs, drip trolamine again to pH4-5, add purified water at last, stir evenly to 1000g.
3, usage and dosage: each 3 grams, every day 3 times, external application.
Claims (6)
- " 1.1,2 ", 3 ", 7 " tetrahydrochysene theoflavin, its chemical structural formula be shown in (2),
- 2. the preparation method of the described compound of claim 1, this method is made up of following steps: theoflavin TF1 is dissolved in the tetrahydrofuran (THF), the palladium-carbon catalyst that adds theoflavin TF1 quality 30%, under room temperature and intense stirring condition, fed hydrogen reaction 4～7 days, remove by filter palladium-carbon catalyst, be dissolved in 95% ethanol behind the pressure reducing and steaming tetrahydrofuran (THF),, remove ethanol and get final product through reversed phase column chromatography.
- 3. the application of the described compound of claim 1 in the preparation anti-AIDS drug.
- 4. the medicine of an anti-AIDS, this medicine are that 1～20% the described compound of claim 1 is formed by acceptable accessories and mass percent.
- 5. medicine as claimed in claim 4 is characterized in that described medicine is a tablet.
- 6. medicine as claimed in claim 4 is characterized in that described medicine is a hydrogel adhesive.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081844A (en) * | 2006-06-01 | 2007-12-05 | 北京工商大学 | Method for large-batch separating preparation of high-purity theaflavine monomer |
| CN101190909A (en) * | 2006-11-24 | 2008-06-04 | 中国农业科学院茶叶研究所 | Method for preparing four kinds of theaflavin monomer |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101081844A (en) * | 2006-06-01 | 2007-12-05 | 北京工商大学 | Method for large-batch separating preparation of high-purity theaflavine monomer |
| CN101190909A (en) * | 2006-11-24 | 2008-06-04 | 中国农业科学院茶叶研究所 | Method for preparing four kinds of theaflavin monomer |
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