CN106146394B - Hydroxytyrosol nicotinate and its preparation method and application - Google Patents
Hydroxytyrosol nicotinate and its preparation method and application Download PDFInfo
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- CN106146394B CN106146394B CN201610497401.1A CN201610497401A CN106146394B CN 106146394 B CN106146394 B CN 106146394B CN 201610497401 A CN201610497401 A CN 201610497401A CN 106146394 B CN106146394 B CN 106146394B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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Abstract
The invention discloses 3,4- dihydroxyphenyl ethanol nicotinate and its preparation method and application, belong to field of medicine preparing technology, derivation is carried out to the chemical structure of niacin (Niacin), hydroxytyrosol is introduced in its structure, its structure and niacin have larger difference, but have the effects that reduce blood glucose, reduction blood lipid and anti-oxidant.The present invention also provides the preparation methods of compound HT-N, i.e., niacin are reacted to obtain nicotinoyl chlorine with oxalyl chloride, then react into ester with the hydroxytyrosol of benzyl protection, be then deprotected and obtain, and the preparation method is easy to operate, low for equipment requirements, environmental-friendly.New compound 3 disclosed by the invention, 4- dihydroxyphenyl ethanol nicotinate is used to treat the compound of diabetes and hyperlipidemia, it can reduce blood glucose and blood lipid, and it can reduce malonaldehyde, improve the oxidative stress effect under diabetes and hyperlipidemia state, and improves the hepatic injury under diabetic disease states.
Description
Technical field
The invention belongs to field of medicine preparing technology, and in particular to Hydroxytyrosol nicotinate and preparation method thereof
And application.
Background technique
Diabetes are a kind of using hyperglycemia and insulin resistance as the chronic metabolic syndrome of main feature.The study found that
Height of the insulin in addition to adjusting blood glucose, also adjusts the metabolism of body fat mass in human body and protein in human body.Therefore, in patient of diabetes
In person, once there is obstacle in the biological regulation of insulin, and disorders of lipid metabolism will occur, abnormalities of sugar/lipid metabolism then occur,
Also it just will form dyslipidemia.When insulin resistance occurs in diabetic's body, the intracorporal insulin level of people will be risen
Height generates hyperinsulinemia.The latter, which will lead to very low density lipoprotein (VLDL)-triglycerides and generate, to be increased, and glycerol three is made
Ester concentration increases, and generates hypertriglyceridemia.When insulin deficit occurs in diabetic, lipoproteinesterase activity is significantly
It reduces, the function of making lipoproteinesterase remove triglycerides is impaired.Therefore, lipoproteinesterase shortage can cause plasma triglyceride
Increase, generates hypertriglyceridemia.And hypertriglyceridemia can be further exacerbated by insulin resistance.It can be seen that pancreas islet
Element resistance or insulin deficit and hypertriglyceridemia reciprocal causation relationship.
Research report, dyslipidemia can cause hyperglycemia, and the main feature of diabetes is exactly blood glucose rise.Intracorporal height
Blood glucose can induced oxidation stress, the generation of excessive active oxygen can further induce relevant damaging biochemical reactions, such as rouge
The complication such as matter peroxidating, blood vessel endothelium injury.
Existing hypoglycemic drug mainly controls blood glucose level by different mechanism of action, acts on more single.
Diabetes for pathologic process complexity and reduced with hyperlipidemia, while hypoglycemic blood lipid, blocking oxide stress, protection
The drug therapy of the multiple actions such as blood vessel endothelium injury, the more single hypoglycemic generation for delaying complications of diabetes have more
Specific meaning.
Summary of the invention
The purpose of the present invention is to provide a kind of new compound Hydroxytyrosol nicotinate, the present invention also provides
The preparation method of above compound and its application in diabetes and hyperlipidemia and its complication.
The present invention is to be achieved through the following technical solutions:
The invention discloses a kind of new compound Hydroxytyrosol nicotinate, the entitled acidum nicotinicums-of chemistry
3,4- dihydroxy benzenes ethyl esters, referred to as hydroxytyrosol nicotinate (hydroxyl-tyrosol niacin esters, HT-N).Its
Structural formula is as follows:
The invention also discloses the preparation methods of above-mentioned Hydroxytyrosol nicotinate, comprising the following steps:
1) using Hydroxytyrosol, bromobenzyl and potassium carbonate as reaction raw materials, with acetone solution, next time at 50~60 DEG C
Stream is stirred to react, end of reaction, is filtered, and concentration obtains concentrate, concentrate is used column chromatography, and 3,4- benzyloxy is made
Benzyl carbinol；
2) niacin is dissolved in methylene chloride, adds n,N dimethylformamide, oxalyl chloride, ice bath is added under condition of ice bath
Under the conditions of be stirred to react, end of reaction, vacuum rotary steam, be made nicotinoyl chlorine；
3) 3,4- benzyloxy benzyl carbinol is dissolved in methylene chloride, nicotinoyl chlorine methylene chloride is added dropwise under condition of ice bath
Reaction is stirred at room temperature in solution after dripping off, end of reaction washs reactant, and dry, concentration obtains concentrate；
4) concentrate is dissolved in dehydrated alcohol, palladium carbon, hydrogenolysis under hydrogen atmosphere is added, end of reaction filters, dense
Contracting, then by column chromatography for separation, hydroxytyrosol niacin ester compounds are made.
In step 1), the molar ratio of Hydroxytyrosol, bromobenzyl and potassium carbonate is 1:2:4.
In step 2), the molar ratio of niacin and oxalyl chloride is 1:(1~3)；The N of addition, the amount of N-dimethylformamide are as follows:
1~3 drop N, N-dimethylformamide is added in every mole of niacin.
In step 3), the molar ratio of 3,4- benzyloxy benzyl carbinols and nicotinoyl chlorine is 1:(1~1.5).
In step 1), being stirred to react the time is 20~30h；In step 2) and step 3), being stirred to react the time is 4~12h；
The reaction time is 20~30h in step 4).
Solvent used in column chromatography for separation is that petroleum ether and ethyl acetate are formulated by 4:1 volume ratio in step 1)；
Solvent used in column chromatography for separation is that chloroform and methanol press (20~40) in step 4): 1 volume ratio is formulated.
The invention also discloses above-mentioned Hydroxytyrosol nicotinate answering in the drug of preparation treatment diabetes
With.
The invention also discloses above-mentioned Hydroxytyrosol nicotinates in the drug of preparation treatment hyperlipemia
Using.
The invention also discloses above-mentioned Hydroxytyrosol nicotinates to prepare anti-diabetic merging hyperlipidemia
Application in drug.
Compared with prior art, the invention has the following beneficial technical effects:
The invention discloses a kind of new compound Hydroxytyrosol nicotinates, to the chemistry of niacin (Niacin)
Structure carries out derivation, introduces hydroxytyrosol in its structure, and structure and niacin have larger difference, but have reduce blood glucose,
Reduce blood lipid and it is anti-oxidant the effects of.The present invention also provides the preparation methods of compound HT-N, i.e., niacin is anti-with oxalyl chloride
Deserved nicotinoyl chlorine, then ester is reacted into the hydroxytyrosol of benzyl protection, it being then deprotected and obtains, the preparation method is easy to operate,
It is low for equipment requirements, it is environmental-friendly.
New compound Hydroxytyrosol nicotinate disclosed by the invention is for treating diabetes and hyperlipidemia
Compound, can reduce blood glucose and blood lipid, and can reduce malonaldehyde, improve the oxygen under diabetes and hyperlipidemia state
Change stress, and improves the hepatic injury under diabetic disease states.It is demonstrated experimentally that the compound is to chain urea institute rhzomorph (STZ) institute
The diabetes mice model of cause has significant hypoglycemic effect, has to induced Hyperlipidemia in Mice model caused by Triton WR-1339
There is significant lipid-lowering effect, is expected to become a kind of novel treatment diabetes and hyperlipidemia.
Detailed description of the invention
Fig. 1 is each group mouse blood sugar concentration histogram, (mmol/L) (n=8)；
Fig. 2 is each group mice plasma concentration of malondialdehyde histogram, (nmmol/L) (n=8)；
Fig. 3 is the glutamic-pyruvic transaminase of each group mouse and the concentration histogram of glutamic-oxalacetic transaminease, (U/L) (n=8)；
Fig. 4 is the influence histogram of the liver coefficient of each group mouse, (g/100g) (n=8)；
Fig. 5 is the concentration histogram of each group mice plasma total cholesterol and triglycerides, (mmol/L) (n=8)；
Fig. 6 is each group mice plasma concentration of malondialdehyde histogram, (nmmol/L) (n=8).
Specific embodiment
Below with reference to specific embodiment, the present invention is described in further detail, it is described be explanation of the invention and
It is not to limit.
The present invention provides a kind of new compound Hydroxytyrosol nicotinate and preparation method thereof, and the present invention also mentions
The purposes for treating diabetes and hyperlipidemia and its complication is being prepared for the compound.
A kind of new compound hydroxytyrosol ester nicotinate (I), entitled acidum nicotinicum -3, the 4- dihydroxy benzenes second of chemistry
Ester, referred to as hydroxytyrosol nicotinate (hydroxyl-tyrosol niacin esters, HT-N).
The new compound HT-N of one kind disclosed by the invention has diabetes mice model caused by chain urea institute's rhzomorph (STZ)
There is significant hypoglycemic effect, there is significant lipid-lowering effect to induced Hyperlipidemia in Mice model caused by Triton WR-1339.
It is expected to become a kind of novel treatment diabetes and hyperlipidemia.
Embodiment 1
Hydroxytyrosol (2.00g, 13.00mmol), potassium carbonate (7.20g, 52.18mmol) are dissolved in acetone
It in (50mL), is added bromobenzyl (2.80ml, 29.90mmol), for 24 hours, end of reaction filters heating reflux reaction, concentration.Column chromatography
It separates (solvent: petroleum ether and ethyl acetate) and obtains 3,4- benzyloxy benzyl carbinol faint yellow solid 2.92g, yield is
55~57 DEG C of 67.12%, mp.
Niacin (1.00g, 8.12mmol) is dissolved in methylene chloride, 1d DMF is added, grass is added dropwise under condition of ice bath
Acyl chlorides (1.05mL, 10.58mmol) reacts 12h under condition of ice bath, and end of reaction is concentrated under reduced pressure to obtain nicotinoyl chlorine, is then dissolved in two
In chloromethane alkane solvents, direct plunges into and react in next step.
The hydroxytyrosol (2.17g, 6.49mmol) of benzyl protection is dissolved in methylene chloride, is added dropwise under condition of ice bath
The nicotinoyl chlorine dichloromethane solution of previous step synthesis, drips off in half an hour.12h, end of reaction, reactant are reacted under condition of ice bath
With 5% NaHCO3Solution washs 2 times, and saturated sodium chloride solution is washed 2 times, anhydrous Na2SO4It is dry, it is concentrated to give 2.78g yellow
Grease.Enriched product is direct plungeed into and is reacted in next step.
The resulting yellow oil of previous step is dissolved in dehydrated alcohol, is added palladium carbon (0.28g), under the conditions of hydrogen shield
Reaction is for 24 hours.End of reaction filters, and saturated sodium chloride solution is washed 2 times, anhydrous Na2SO4It is dry, concentration.Pass through column chromatography (exhibition
Open agent: chloroform and methanol ester) separate to obtain 1.26g white solid, yield 74.91%, 145.1~146.2 DEG C of mp.
Nuclear magnetic resonance data:1H NMR (400MHz, DMSO) δ 9.06 (d, J=1.7Hz, 1H), 8.86-8.79 (m, 2H),
8.73 (s, 1H), 8.26 (m, 1H), 7.58 (dd, J=7.9,4.9Hz, 1H), 6.65-6.69 (m, 2H), 6.55 (dd, J=
8.0,2.0Hz, 1H), 4.42 (t, J=6.8Hz, 2H), 2.86 (t, J=6.8Hz, 2H)13C NMR(400MHz,DMSO)δ
165.10,154.12,150.39,145.61,144.27,137.24,129.01,126.17,124.40,120.05,116.72,
116.01,66.45,34.19。
Embodiment 2
The pharmacodynamic action of HT-N of the invention is by HT-N to diabetes mice model caused by streptozotocin (STZ)
Hypoglycemic effect and the effect for reducing blood fat of induced Hyperlipidemia in Mice model caused by Triton WR-1339 is realized.
1. experimental material and instrument
Material: streptozotocin (Streptozocin, STZ, Sigma Co., USA), (U.S. Triton WR-1339
Sigma company), Xi Gelieting (Wuhan Hong Ruikang reagent Co., Ltd), niacin (Wuhan Hong Ruikang reagent Co., Ltd), HT-N
(laboratory self-control), monohydrate potassium, two citric acid monohydrate trisodiums are that analysis is pure.
Instrument: the stable blood glucose meter of three promises and mating blood sugar test paper (Sinocare Biosensing Co., Ltd), ultraviolet-visible
Spectrophotometer etc..
Animal: kunming mice (20.0 ± 2.0g).
2, experimental method and result
2.1.1 the foundation of diabetic mouse model
Mouse adaptable fed 3d, fasting 12h, intraperitoneal injection STZ (use 0.1mol/L, pH4.5 citrate buffer solution,
200mg/kg) fasting 6h surveys blood glucose after 72h, and blood glucose is greater than 16.0mmol/L, and more drinks, more foods, weight loss occur is modeling
Success.
The preparation of 0.1mmol/L pH4.5 citrate buffer solution: the preparation (0.1mol/L aqueous citric acid solution) of A liquid: lemon
Distilled water is added to 100mL in lemon acid 2.10g.The preparation (0.1mol/L trisodium citrate aqueous solution) of B liquid: trisodium citrate
2.94g adds distilled water to 100mL.0.1mol/L aqueous citric acid solution and 0.1mol/L trisodium citrate aqueous solution are by volume
1:1.44 is mixed, and can prepare to form 0.1mmol/L pH4.5 citrate buffer solution.
STZ solution is prepared: with the dissolution of 4.5 citrate buffer solution of 0.1mmol/LpH, being configured to the solution of 20mg/mL, ice
Bath, is protected from light, and has injected in half an hour.
2.1.2 the hypoglycemic drug effect research of diabetic mice
It takes diabetes at mould mouse, weigh respectively and measures fasting blood sugar, according to principle similar in weight, blood glucose value point
For 3 groups (model group, HT-N group, Xi Gelieting groups), separately taking Normal male mice is blank group, and every group 8: 1. blank group fills
Stomach gives distilled water；2. model group, distilled water is given in stomach-filling；3. HT-N group, HT-N 164.3mg/kg is given in stomach-filling；4. western lattice
Spit of fland group is arranged, Xi Gelieting 13.0mg/kg is given in stomach-filling.Remaining point in addition to equal dosage distilled water is given in blank group and model group stomach-filling
Other gastric infusion is deprived of food but not water the blood glucose of measurement each group mouse after 6h one time a day after continuous 8d, 7d administration；8d administration
Eyeball is plucked after 6h and takes blood, and the whole blood being collected into stands 1h on ice bath, and then 5 000r/min are centrifuged 15min and obtain blood plasma, so
Plasma malonaldehyde content is measured according to kit method afterwards, biochemical instruments measure glutamic-pyruvic transaminase and glutamic-oxalacetic transaminease activity.
2.1.3 experimental result:
Each group mouse blood sugar concentration is shown in Table 1 and Fig. 1:
1 each group mouse blood sugar concentration (mmol/L) (n=8) of table
Note: ## indicates to indicate the P < 0.05 compared with model group compared with P < 0.01, * compared to the blank group.
From the analysis of table 1 and Fig. 1, it can be concluded that, compound HT-N can significantly reduce the blood glucose of diabetic mice, have drop
Blood glucose activity.
Each group mice plasma mda content is shown in Table 2 and Fig. 2:
2 each group mice plasma mda content (nmmol/L) (n=8) of table
Note: ## indicates to indicate the P < 0.01 compared with model group compared with P < 0.01, * * compared to the blank group.
From the analysis of table 2 and Fig. 2, it can be concluded that, compound HT-N can reduce containing for malonaldehyde in diabetic mice body
Amount, shows that the compound can play the effect of anti-oxidation stress.
The glutamic-pyruvic transaminase of each group mouse and the activity of glutamic-oxalacetic transaminease are shown in Table 3 and Fig. 3:
The activity (U/L) (n=8) of glutamic-oxalacetic transaminease and glutamic-pyruvic transaminase in 3 each group mice serum of table
Note: ## indicates to indicate the P < 0.05 compared with model group, * * expression and mould compared with P < 0.01, * compared to the blank group
Type group compares P < 0.01.
The liver index of each group mouse is shown in Table 4 and Fig. 4:
The liver index (g/100g) (n=8) of 4. each group mouse of table
Note: ## indicates to indicate the P < 0.01 compared with model group compared with P < 0.01, * * compared to the blank group.
From table 3, table 4, Fig. 3 and Fig. 4 analysis, it can be concluded that, millet straw is can be significantly reduced in diabetic mice in compound HT-N
The activity of transaminase and glutamic-pyruvic transaminase, and the liver index of diabetic mice is reduced, show the compound in glycosuria symptom
There is hepatoprotective effect under state.
The foundation of 2.2 hyperlipemia in mice models
Mouse adaptable fed 3d is randomly divided into 4 groups (blank group, model group, HT-N group, niacin group) every group 8: 1. empty
White group, distilled water is given in stomach-filling；2. model group, distilled water is given in stomach-filling；3. HT-N group, HT-N 164.3mg/kg is given in stomach-filling；
4. niacin group, niacin 78.0mg/kg is given in stomach-filling.In addition to equal dosage distilled water is given in Normal group and model group stomach-filling remaining
Gastric infusion respectively, one time a day, continuous 7d, the 18h before last dose, in addition to Normal group, remaining each group tail vein injection
Triton WR-1339 400mg/kg。
Dosage determines dosage according to conversion formula:
Dosage=people dosage/70 × 9.1
In 6h after the last administration, each group mouse plucks eyeball and takes blood, and the whole blood being collected into stands 1h on ice bath, and then 5
000r/min centrifugation 15min obtains blood plasma, then measures the content of total plasma cholesterol, triglycerides respectively according to kit method
And plasma malonaldehyde content.
Experimental result: each group mice plasma total cholesterol and content of triglyceride are shown in Table 5 and Fig. 5:
5 each group mice plasma total cholesterol of table and content of triglyceride (mmol/L) (n=8)
Note: ## indicates to indicate the P < 0.05 compared with model group, * * expression and mould compared with P < 0.01, * compared to the blank group
Type group compares P < 0.01.
From the analysis of table 5 and Fig. 5, it can be concluded that, compound TH-N can reduce the total cholesterol of hyperlipemia in mice and sweet
Oily three ester contents, have the activity for reducing total cholesterol and triglycerides.
Each group mice plasma mda content is shown in Table 6 and Fig. 6:
6 each group mice plasma mda content (nmmol/L) (n=8) of table
Note: ## indicates to indicate the P < 0.01 compared with model group compared with P < 0.01, * * compared to the blank group.
From the analysis of table 6 and Fig. 6, it can be concluded that, compound HT-N can reduce the intracorporal malonaldehyde of hyperlipemia in mice and contain
Amount plays the effect of anti-oxidation stress in hyperlipemia model.
To sum up, hydroxytyrosol nicotinate (HT-N) reactive compound provided by the invention has hypoglycemic, improvement sugar
Urinate the hepatic injury under diseased state, the multiple activities such as reducing blood lipid and anti-oxidation stress.
Claims (7)
1.3,4- dihydroxyphenyl ethanol nicotinates, which is characterized in that its structural formula is as follows:
2. the preparation method of Hydroxytyrosol nicotinate described in claim 1, which is characterized in that including following step
It is rapid:
1) it using Hydroxytyrosol, bromobenzyl and potassium carbonate as reaction raw materials, with acetone solution, flows back and stirs at 50~60 DEG C
Reaction is mixed, end of reaction filters, and concentration obtains concentrate, concentrate is used column chromatography, and 3,4- dibenzyloxy benzene second is made
Alcohol；Wherein, the molar ratio of Hydroxytyrosol, bromobenzyl and potassium carbonate is 1:2:4；
2) niacin is dissolved in methylene chloride, adds n,N dimethylformamide, oxalyl chloride, condition of ice bath is added under condition of ice bath
Under be stirred to react, end of reaction, vacuum rotary steam, be made nicotinoyl chlorine；The molar ratio of niacin and oxalyl chloride is 1:(1~3)；It is added
N, the amount of N-dimethylformamide are as follows: 1~3 drop N, N-dimethylformamide is added in every mole of niacin；
3) 3,4- benzyloxy benzyl carbinol is dissolved in methylene chloride, it is molten that nicotinoyl chlorine methylene chloride is added dropwise under condition of ice bath
Reaction is stirred at room temperature in liquid after dripping off, end of reaction washs reactant, and dry, concentration obtains concentrate；Bis- benzyloxy of 3,4-
The molar ratio of base benzyl carbinol and nicotinoyl chlorine is 1:(1~1.5)；
4) concentrate being dissolved in dehydrated alcohol, palladium carbon, hydrogenolysis under hydrogen atmosphere is added, end of reaction filters, concentration,
Again by column chromatography for separation, hydroxytyrosol niacin ester compounds are made.
3. the preparation method of Hydroxytyrosol nicotinate according to claim 2, which is characterized in that step 1)
In, being stirred to react the time is 20~30h；In step 2) and step 3), being stirred to react the time is 4~12h；In step 4) when reaction
Between be 20~30h.
4. the preparation method of Hydroxytyrosol nicotinate according to claim 2, which is characterized in that in step 1)
Solvent used in column chromatography for separation is that petroleum ether and ethyl acetate are formulated by 4:1 volume ratio；Step 4) center pillar chromatography point
Be that chloroform and methanol press (20~40) from solvent used: 1 volume ratio is formulated.
5. application of the Hydroxytyrosol nicotinate described in claim 1 in the drug of preparation treatment diabetes.
6. application of the Hydroxytyrosol nicotinate described in claim 1 in the drug of preparation treatment hyperlipemia.
7. Hydroxytyrosol nicotinate described in claim 1 is in the drug for preparing anti-diabetic merging hyperlipidemia
Application.
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