CN104817556A - 9-O-ibuprofen berberine ester compound as well as preparation method and application of 9-O-ibuprofen berberine ester compound - Google Patents
9-O-ibuprofen berberine ester compound as well as preparation method and application of 9-O-ibuprofen berberine ester compound Download PDFInfo
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- CN104817556A CN104817556A CN201510241026.XA CN201510241026A CN104817556A CN 104817556 A CN104817556 A CN 104817556A CN 201510241026 A CN201510241026 A CN 201510241026A CN 104817556 A CN104817556 A CN 104817556A
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- 0 Cc(c(c(cc1)c2)c*3c2-c2cc(*CC4)c4cc2CC3)c1NC Chemical compound Cc(c(c(cc1)c2)c*3c2-c2cc(*CC4)c4cc2CC3)c1NC 0.000 description 5
- NNLMGRAAZPBLQQ-UHFFFAOYSA-N CC(C)Cc1ccc(C(C)C(N)=C2CC2)cc1 Chemical compound CC(C)Cc1ccc(C(C)C(N)=C2CC2)cc1 NNLMGRAAZPBLQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
Abstract
The invention discloses a 9-O-ibuprofen berberine ester compound which is prepared through the steps of carrying out high-temperature treatment on berberine serving as a raw material to obtain berberrabine; then, forming ester by using berberrabine and ibuprofen acyl chloride; and then, re-crystallizing and purifying through column chromatography. The compound has antibacterial and anti-inflammation effects and also has the effects of resisting to heart failure and platelet aggregation, treating hypertension, reducing blood fat and treating peptic ulcer and diabetes and the like, and can be prepared into capsules, suppositories, tablets, injections and the like.
Description
Technical field
The present invention relates to pharmaceutical chemistry, pharmaceutics, pharmacotherapeutics field, specifically 9-O-Ibuprofen BP/EP Berberine ester cpds and preparation method thereof and purposes.
Technical background
(molecular formula is C to Berberine (BBR)
20h
18clNO
4, relative molecular mass is 371.8) and be a kind of morphinane alkaloid, be pale yellow powder under normality, being khaki color after heating dehydration, is the main composition be present in the coptis.In recent years, BBR and derivative thereof receive extensive concern, especially in treatment diabetes, reducing blood-fat etc. in treatment obesity, diabetes, cancer, metabolism syndrome, senile dementia, dysthymia disorders, inflammation etc.As far back as 1988, Berberine, when patient's gastrointestinal tract infection of diabetes is carried in treatment, found that it has the effect for the treatment of diabetes.Relevant research proves that Berberine not only may be used for treating diabetes, also can be used for sacred disease and the concurrency inflammation thereof for the treatment of diabetes initiation.
Ibuprofen BP/EP is a kind of NSAID (non-steroidal anti-inflammatory drug) (NSAIDs) with antipyretic, anti-inflammatory, analgesic activity, has been widely used in the diseases such as treatment rheumatoid arthritis, neuritis, osteoarthritis, migraine, dysmenorrhoea.The mechanism of action of Ibuprofen BP/EP, mainly by suppressing the generation of cyclooxygenase (COX) thus reducing the prostaglandin E2 generation in human body, alleviates the symptom such as pain, swelling caused by prostaglandin E2 further.
Natural product and Ibuprofen BP/EP split is utilized to form new derivative, to develop new NSAIDs, document has been reported, as: bibliographical information has synthesized ibuprofen eugenol ester (Zhao Xiuli, Chen great Wei etc. the synthesis of ibuprofen eugenol ester prodrug and hydrolysis dynamics thereof. Shenyang Pharmaceutical University's journal, 23 (2): 70-73,118); Patent CN 1640870 A discloses Ibuprofen BP/EP 2-(3,5,6-trimethylammonium) pyrazine methyl esters and salt thereof.The present invention utilizes intermolecular principle of hybridization on 9 of Berberine, introduce Ibuprofen BP/EP synthesis 9-O-Ibuprofen BP/EP Berberine ester cpds.It does not destroy the active group position of Berberine and Ibuprofen BP/EP, has no bibliographical information yet.
Summary of the invention
The object of the present invention is to provide a kind of new medicine---9-O-Ibuprofen BP/EP Berberine ester cpds.
The present invention also aims to the preparation method that described 9-O-Ibuprofen BP/EP Berberine ester cpds is provided.
The object of the invention is also to provide described 9-O-Ibuprofen BP/EP Berberine ester cpds at antisepsis and anti-inflammation, heart failure resistance, platelet aggregation-against, the purposes of the aspects such as treatment hypertension, reducing blood-fat, treatment peptide ulceration, treatment diabetes.
9-O-Ibuprofen BP/EP Berberine ester of the present invention can be made into 9-O-Ibuprofen BP/EP Berberine ester crystalline hydrate.Therefore 9-O-Ibuprofen BP/EP Berberine ester also comprises its crystalline hydrate.
9-O-Ibuprofen BP/EP Berberine ester cpds provided by the invention, molecular formula is C
32h
32clNO
5, molecular weight is 545.5.There is following structural formula:
The preparation method of 9-O-Ibuprofen BP/EP Berberine ester cpds of the present invention, is characterized in that syntheti c route is as follows:
(1) take Berberine and be placed in 250mL round-bottomed flask, be heated to 180 ~ 190 DEG C (vacuum tightness 20 ~ 40mmHg), reaction 0.5 ~ 1.0h.Be cooled to room temperature, with recrystallizing methanol, suction filtration, it is berberrubine that filtration cakes torrefaction obtains dark red solid.
(2) in 250mL there-necked flask, add Ibuprofen BP/EP and sulfur oxychloride successively, drip 3 ~ 5 DMFs, in 70 ~ 80 DEG C of stirring reaction 3 ~ 5h, thin-layer chromatography detection reaction process.The unreacted sulfur oxychloride of pressure reducing and steaming, obtains Off-white solid and is Ibuprofen BP/EP acyl chlorides, adds appropriate acetonitrile and dissolves.
(3) berberrubine is taken, be dissolved in acetonitrile, add a little pyridine, Ibuprofen BP/EP solution of acid chloride is dripped with dropping funnel in 0 ~ 5 DEG C, after dropwising, at room temperature react 3 ~ 5h, filter, filter cake through 60 ~ 70 DEG C of oven dry, crude product with methanol recrystallization, silicagel column (elutriant: V (methylene dichloride): V (methyl alcohol)=10 ~ 15:1) separating-purifying again, remove solvent under reduced pressure, solid drying, obtain yellow crystals, be 9-O-Ibuprofen BP/EP Berberine ester, fusing point is 209 ~ 212 DEG C.
The confirmation analysis of 9-O-Ibuprofen BP/EP Berberine ester structure, as shown in Figure 1, Figure 2, Figure 3 shows.
Mass spectrum MS (ESI): m/z 510 (M
+);
Infrared spectra IR (KBr) ν/cm
-13426 (ν
c=C-H), 2953 (ν
c-H), 1763 (ν
c=O), 1614 (ν
c=C), 1506 (ν
c=C), 1396 (ν
c (CH3) 2), 1368 (ν
c (CH3) 2), 1278 (ν
c-O-C), 1226 (ν
c-O-C), 1039 (ν
c-O-C);
Proton nmr spectra (MeOD, TMS, 400Hz)
1HNMRδ9.26(s,1H),8.80(s,1H),8.21(d,J＝9.2Hz,1H),8.14(d,J＝9.2Hz,1H),7.68(s,1H),7.45(s,2H),7.29(s,2H),6.98(s,1H),6.13(s,2H),4.80(t,J＝6.0Hz,2H),4.33(q,J＝7.1Hz,1H),3.94(s,3H),3.25(m,2H),2.56(d,J＝7.2Hz,2H),1.93(m,J＝13.6,6.8Hz,1H),1.69(d,J＝7.1Hz,3H),0.97(d,J＝6.6Hz,6H).
The molecular weight of 9-O-Ibuprofen BP/EP Berberine ester is 545.5, at the formation [M that ESI mass spectrum is formed
+] molecular ion peak be 510.Connexus spectrogram, hydrogen nuclear magnetic resonance spectrogram and infrared spectrogram comprehensively analyze provable compound structure as shown in (I).
9-O-Ibuprofen BP/EP Berberine ester provided by the present invention, has obvious hypoglycemic effect, and hypoglycemic ability is stronger than Berberine, Regular Insulin to a certain extent; Anti-inflammatory action is better than Berberine.
9-O-Ibuprofen BP/EP Berberine ester cpds provided by the present invention, selects appropriate auxiliary material and preparation method, can make pharmaceutically acceptable various pharmaceutical dosage form, as: tablet, capsule, suppository, injection, ointment, granule etc.
Its positively effect of preparation method of 9-O-Ibuprofen BP/EP Berberine ester provided by the present invention is embodied in: the raw material synthesizing this compound is easy to get, and reaction conditions is gentle, and by product is less, and post-reaction treatment is comparatively simple.
Accompanying drawing explanation
Fig. 1 is 9-O-Ibuprofen BP/EP Berberine ester mass spectrum of the present invention;
Fig. 2 is 9-O-Ibuprofen BP/EP Berberine ester infrared spectrogram of the present invention;
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of 9-O-Ibuprofen BP/EP Berberine ester of the present invention.
Specific implementation method
Below by embodiment, the present invention is further described, but be not limitation of the invention further.
Embodiment 1
The synthesis technique of 9-O-Ibuprofen BP/EP Berberine ester
Take 15.0g Berberine and be placed in 250mL round-bottomed flask, vacuum tightness is 20 ~ 40mmHg, is heated to 180 ~ 190 DEG C of reaction 0.5 ~ 1.0h, be cooled to room temperature, gained solids with methanol recrystallization, suction filtration, dry cake, obtains dark red solid berberrubine 8.7g, and yield is 60.4%.
In 250mL there-necked flask, add 7.2g Ibuprofen BP/EP and 20mL sulfur oxychloride successively, drip 3 ~ 5 DMFs, in 70 ~ 80 DEG C of stirring reaction 3 ~ 5h, thin-layer chromatography detection reaction process.The unreacted sulfur oxychloride of pressure reducing and steaming, obtains Off-white solid and is Ibuprofen BP/EP acyl chlorides, adds 20mL acetonitrile and dissolves.
Take 5.0g berberrubine, be dissolved in 80mL acetonitrile, add 3 ~ 5mL pyridine, drip the acetonitrile solution of Ibuprofen BP/EP acyl chlorides, after dropwising, at room temperature react 3 ~ 5h, filter, filter cake is through 60 ~ 70 DEG C of oven dry, and crude product first uses recrystallizing methanol, recycle silicon glue post (elutriant: V (methylene dichloride): V (methyl alcohol)=10 ~ 15:1) separating-purifying, remove solvent under reduced pressure, drying solid, obtain 9-O-Ibuprofen BP/EP Berberine ester 3.1g, yield is 40.6%, and fusing point is 209 ~ 212 DEG C.
Embodiment 2
The synthesis technique of 9-O-Ibuprofen BP/EP Berberine ester
Take 15.0g Berberine and be placed in 250mL round-bottomed flask, dissolve with 100mL perhydronaphthalene, N
2protection, be heated to 180 ~ 190 DEG C of reaction 0.5 ~ 1.0h, be cooled to room temperature, underpressure distillation, gained solid is dried.Crude product is through ethyl alcohol recrystallization, and suction filtration, filtration cakes torrefaction, obtains dark red solid 10.1g, be berberrubine, and yield is 70.1%.
In 250mL there-necked flask, add 10.0g Ibuprofen BP/EP, 75mL trichloromethane and 5mL sulfur oxychloride successively, drip 3 ~ 5 pyridines, in 70 ~ 80 DEG C of stirring reaction 3 ~ 5h, thin-layer chromatography detection reaction process.Pressure reducing and steaming trichloromethane and unreacted sulfur oxychloride, obtain Off-white solid and be Ibuprofen BP/EP acyl chlorides, adds 15mL trichloromethane and dissolve.
Take 7.0g berberrubine, be dissolved in 90mL trichloromethane, add 3 ~ 5mL pyridine, drip Ibuprofen BP/EP solution of acid chloride, after dropwising, at room temperature react 3 ~ 5h, filter, dry filter cake, crude product first uses recrystallizing methanol, recycle silicon glue post (elutriant: V (methylene dichloride): V (methyl alcohol)=10 ~ 15:1) separating-purifying, remove solvent under reduced pressure, drying solid, obtain 9-O-Ibuprofen BP/EP Berberine ester 5.9g, yield is 55.2%, and fusing point is 211 ~ 213 DEG C.
Embodiment 3
The synthesis technique of 9-O-Ibuprofen BP/EP Berberine ester
Take 15.0g Berberine and be placed in 250mL round-bottomed flask, pass into N
2protection, is heated to 180 ~ 190 DEG C, and reaction 0.5 ~ 1.0h, be cooled to room temperature, gained solids with methanol recrystallization, suction filtration, filtration cakes torrefaction, obtains dark red solid 7.2g, be berberrubine, and yield is 50.0%.
Take 10.0g Ibuprofen BP/EP to add and be equipped with in the 250mL there-necked flask of thermometer, dissolve with 100mL methylene dichloride, be cooled to less than 0 DEG C, drip 3 ~ 5 DMF, stir, add 7mL sulfur oxychloride, after dropwising, be heated to 70 ~ 80 DEG C, stirring reaction 3 ~ 5h, pressure reducing and steaming methylene dichloride and unreacted sulfur oxychloride, obtain Off-white solid and be Ibuprofen BP/EP acyl chlorides.
Take 7.0g berberrubine and put into there-necked flask, fully mix with Ibuprofen BP/EP acyl chlorides, add 90mL acetonitrile again to dissolve, be cooled to less than 0 DEG C, drip 3 ~ 5mL pyridine, after dropwising, at room temperature react 3 ~ 5h, filter, dry filter cake, crude product first uses recrystallizing methanol, and recycle silicon glue post (elutriant: V (methylene dichloride): V (methyl alcohol)=10 ~ 15:1) separating-purifying, removes solvent under reduced pressure, dry, obtain 9-O-Ibuprofen BP/EP Berberine ester 3.9g, yield is 36.5%, and fusing point is 209 ~ 212 DEG C.
Embodiment 4
9-O-Ibuprofen BP/EP Berberine ester gum capsule
Take the solid materials of above-mentioned prescription according to quantity, pulverize and fully mix and sieve, whole grain afterwards, point to be filled in 1000 Capsuleses.
Embodiment 5
9-O-Ibuprofen BP/EP Berberine ester suppository
Prescription: 9-O-Ibuprofen BP/EP Berberine ester 5g
Cocoa butter 195g
Preparation method: sieve after 9-O-Ibuprofen BP/EP Berberine ester is ground to form fine powder, slow heating makes cocoa butter melt, and adds in the cocoa butter of fusing, fully mix the 9-O-Ibuprofen BP/EP Berberine ester after sieving, pour in mould, until temperature cooling after 9-O-Ibuprofen BP/EP Berberine ester suppository.
Embodiment 6
9-O-Ibuprofen BP/EP Berberine ester particle
Prescription: 9-O-Ibuprofen BP/EP Berberine ester 10g
Wood sugar 500g
Xylo-Mucine 500g
Starch is a little
Preparation method: take 10g 9-O-Ibuprofen BP/EP Berberine ester, fully crosses 100 mesh sieves after grinding, adds Xylo-Mucine, wood sugar and a certain amount of tackiness agent and fully mix, granulation of sieving.
Embodiment 7
9-O-Ibuprofen BP/EP Berberine ester tablet
Preparation method: take 100g 9-O-Ibuprofen BP/EP Berberine ester, fully crosses 100 mesh sieves after grinding, adds Xylo-Mucine, medical starch and a certain amount of lubricant and fully mix, direct compression, 9-O-Ibuprofen BP/EP Berberine ester tablet.
Test example 1
9-O-Ibuprofen BP/EP Berberine ester blood sugar reducing function
1. medicine
9-O-Ibuprofen BP/EP Berberine ester is prepared, Berberine, Recombulin according to above-described embodiment.
2. divide into groups
Be divided into following several groups of culture hepatocytes according to the medicine difference of adding in nutrient solution: blank group, Berberine group, Regular Insulin group and 9-O-Ibuprofen BP/EP Berberine ester dosage group (concentration is respectively 5,10,25,50,100 μ g/mL)
3. experimental technique
Extraction and isolation normal SD rats liver cell, concentration is adjusted to 1 × 10
6individual/mL, adds in 96 orifice plates, 100 μ L/ holes, 37 DEG C, 5%CO
212h is cultivated in incubator.Institute's cultured cells in 96 orifice plates is changed liquid, add the DMEM substratum of 50mmol/L glucose, 100 μ L/ holes, be the 9-O-Ibuprofen BP/EP Berberine ester intervention of 5,10,25,50,100 μ g/mL respectively by concentration, and establish blank group, Berberine group and Regular Insulin group contrast, its empty group does not add any medicine, and Berberine group adds the Berberine intervention that concentration is 100 μ g/mL, and it is 10 that Regular Insulin group adds concentration
-7the Regular Insulin intervention of mol/L.Each group is respectively done 5 multiple holes above, 37 DEG C, cultivates 24h in 5%CO2 incubator.Cultivate the supernatant liquor terminated in rear collection substratum, 4 DEG C, the centrifugal 5min of 5000 turns/min, abandon cell debris, preserve in-20 DEG C of cryogenic refrigerators.The concentration detecting glucose in substratum supernatant completely with automatic biochemistry analyzer is all collected until each group.
4. data processing
Use all data of this experiment of SPSS 17.0 statistics software processes acquisition, data carry out after Normal distribution test with
represent.
5. experimental result
Table 1 9-O-Ibuprofen BP/EP Berberine ester is on the impact of liver cell consumption of glucose
Note: compare with blank group, * P<0.05, * * P<0.01; Compare with Regular Insulin group,
△p<0.05,
△ △p<0.01; Compare with Berberine group,
▲p<0.05,
▲ ▲p<0.01
Result shows: 9-O-Ibuprofen BP/EP Berberine ester each dosage group all has obvious hypoglycemic effect, and becomes dose-dependently.The hypoglycemic energy force rate Berberine group of Regular Insulin group and 9-O-Ibuprofen BP/EP Berberine ester 25 μ g/mL, 50 μ g/mL, 100 μ g/mL groups is strong.9-O-Ibuprofen BP/EP Berberine ester 100 μ g/mL group promotes that the ability of cell consumption glucose is better than Regular Insulin group.
Test example 2
9-O-Ibuprofen BP/EP Berberine ester anti-inflammatory action
1. animal
ICR mouse, 60, male and female half and half, body weight 18 ~ 22g.
2. medicine
9-O-Ibuprofen BP/EP Berberine ester is prepared, Berberine, Ibuprofen BP/EP according to above-described embodiment.
3. divide into groups
ICR mouse is divided into 6 groups at random by sex body weight, is respectively blank group, Berberine group, Ibuprofen BP/EP group, basic, normal, high group of 9-O-Ibuprofen BP/EP Berberine ester, often organizes 10, male and female half and half.
4. experimental technique
Its mouse oral gastric infusion, daily 1 time, continuous 7 days.Blank group is to 0.5% Xylo-Mucine.Each group all after last administration 1h, at right side of mice auricle pros and cons uniform application dimethylbenzene 20 μ L, left ear is as normal control.After 1h, mouse is plucked eyeball blood sampling, cut two ears along auricle baseline, prepare mouse auricle with 7mm diameter punch tool, precise electronic analytical balance is weighed, and represents inflammatory swelling degree with left and right auricle weight (mg) difference.Inhibitory rate of intumesce (%)=(the average swelling of control group-average swelling of administration group) average swelling × 100% of/control group.Inflammatory factor (IL-2, IL-6, TNF-α) relative content in blood is measured by ELISA kit.
5. data processing
Use all data of this experiment of SPSS 17.0 statistics software processes acquisition, data carry out after Normal distribution test with
represent.
6. experimental result
The impact of the mice ear that table 2 9-O-Ibuprofen BP/EP Berberine ester p-Xylol causes
Note: compare with blank group, * P<0.05, * * P<0.01, compares with Berberine group,
△p<0.05,
△ △p<0.01, compares with Ibuprofen BP/EP group,
▲p<0.05,
▲ ▲p<0.01
The ear thickness of 9-O-Ibuprofen BP/EP Berberine ester high, medium and low dosage group mouse is respectively (5.42 ± 0.61), (5.68 ± 0.37), (8.07 ± 0.49) mg, be starkly lower than blank group (11.60 ± 0.88) mg, illustrate that 9-O-Ibuprofen BP/EP Berberine ester obviously can slow down the mice ear degree caused by dimethylbenzene, and become dose-dependently.High, the middle dosage group of 9-O-Ibuprofen BP/EP Berberine ester to mice ear restraining effect apparently higher than Berberine group, with Ibuprofen BP/EP group without significant difference.9-O-Ibuprofen BP/EP Berberine ester low dose group antiphlogistic effects and Berberine group are without significant difference.
Table 3 9-O-Ibuprofen BP/EP Berberine ester is on the impact of TNF-α, IL-2, IL-6 in mice serum
Note: compare with blank group, * P<0.05, * * P<0.01, compares with Berberine group,
△p<0.05,
△ △p<0.01, compares with Ibuprofen BP/EP group,
▲p<0.05,
▲ ▲p<0.01
The high, medium and low dosage group of 9-O-Ibuprofen BP/EP Berberine ester significantly can reduce IL-2, IL-6, TNF-alpha levels in mice serum, in dose-dependently.The ability that the high, medium and low dosage group of 9-O-Ibuprofen BP/EP Berberine ester reduces IL-2 level in serum compares no significant difference with Berberine group and Ibuprofen BP/EP group; 9-O-Ibuprofen BP/EP Berberine ester high dose group reduces the ability of IL-6 level in serum higher than Berberine group, with Ibuprofen BP/EP group without significant difference; In 9-O-Ibuprofen BP/EP Berberine ester, IL-6 level and Berberine group and the more equal no significant difference of Ibuprofen BP/EP group of low dose group.The TNF-alpha levels of the high, medium and low dosage group of 9-O-Ibuprofen BP/EP Berberine ester is all starkly lower than Berberine group, with Ibuprofen BP/EP group without significant difference.Result shows that 9-O-Ibuprofen BP/EP Berberine ester significantly can reduce the content of inflammatory factor IL-2 in mice serum, IL-6, TNF-α, has anti-inflammatory action.
Claims (7)
1. a 9-O-Ibuprofen BP/EP Berberine ester cpds, is characterized in that having following structural formula:
Molecular formula is C
32h
32clNO
5, molecular weight is 545.5, and fusing point is 209 ~ 212 DEG C.
2. according to claim 1,9-O-Ibuprofen BP/EP Berberine ester also comprises its crystalline hydrate.
3. the preparation method of 9-O-Ibuprofen BP/EP Berberine ester cpds according to claim 1, is characterized in that syntheti c route is as follows:
(1) take Berberine and be placed in 250mL round-bottomed flask, be heated to 180 ~ 190 DEG C (vacuum tightness 20 ~ 40mmHg), reaction 0.5 ~ 1.0h.Be cooled to room temperature, use organic solvent recrystallization, suction filtration, filtration cakes torrefaction spends the night to obtain dark red solid berberrubine.
(2) in 250mL there-necked flask, add Ibuprofen BP/EP, sulfur oxychloride successively, drip several DMFs, in 70 ~ 80 DEG C of stirring reaction 3 ~ 5h, thin-layer chromatography detection reaction process.The unreacted sulfur oxychloride of pressure reducing and steaming, obtains Off-white solid and is Ibuprofen BP/EP acyl chlorides, add appropriate organic solvent dissolution.
(3) take berberrubine, be dissolved in organic solvent, add appropriate pyridine, Ibuprofen BP/EP solution of acid chloride is dripped in 0 ~ 5 DEG C, after dropwising, at room temperature react 3 ~ 5h, filter, crude product with methanol recrystallization, silicagel column (elutriant: V (methylene dichloride): V (methyl alcohol)=10 ~ 15:1) separating-purifying, removes solvent under reduced pressure, dry, obtain yellow solid, be 9-O-Ibuprofen BP/EP Berberine ester.
4. the preparation method of 9-O-Ibuprofen BP/EP Berberine ester of the present invention, is characterized in that: the organic solvent in (1) described in claim 3 can be in methyl alcohol, ethanol, methylene dichloride, acetone, ethyl acetate; Organic solvent in (2) described in claim 3 can be acetonitrile, chloroform, methylene dichloride, toluene; Organic solvent in (3) described in claim 3 can be acetonitrile, chloroform, methylene dichloride, toluene.
5. 9-O-Ibuprofen BP/EP Berberine ester cpds according to claim 1, it is characterized in that: 9-O-Ibuprofen BP/EP Berberine ester cpds can be used for treating following disease: antisepsis and anti-inflammation, heart failure resistance, platelet aggregation-against, reducing blood-fat, treatment hypertension, treatment peptide ulceration, treatment diabetes etc.
6. a medicine, is characterized in that: described medicine is made up of 9-O-Ibuprofen BP/EP Berberine ester according to claim 1 and pharmaceutically acceptable auxiliaries.
7. medicine according to claim 6, is characterized in that adopting appropriate pharmaceutical excipient and preparation method, can be made into acceptable pharmaceutical dosage form on any medicine.As tablet, capsule, suppository, injection, ointment, granule etc.
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Cited By (3)
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| CN110041325A (en) * | 2018-01-15 | 2019-07-23 | 中国医学科学院药物研究所 | Berberine hydrochloride and brufen eutectic object and preparation method and its composition and purposes |
| CN112062761A (en) * | 2020-09-25 | 2020-12-11 | 常州大学 | Method for synthesizing berberrubine ester substances |
| CN112480108A (en) * | 2020-12-25 | 2021-03-12 | 常州方圆制药有限公司 | Preparation method of berberberrubine hydrochloride |
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| CN112062761A (en) * | 2020-09-25 | 2020-12-11 | 常州大学 | Method for synthesizing berberrubine ester substances |
| CN112480108A (en) * | 2020-12-25 | 2021-03-12 | 常州方圆制药有限公司 | Preparation method of berberberrubine hydrochloride |
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