CN109369747A - Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application - Google Patents
Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application Download PDFInfo
- Publication number
- CN109369747A CN109369747A CN201811271185.4A CN201811271185A CN109369747A CN 109369747 A CN109369747 A CN 109369747A CN 201811271185 A CN201811271185 A CN 201811271185A CN 109369747 A CN109369747 A CN 109369747A
- Authority
- CN
- China
- Prior art keywords
- icariside
- compound
- icariine
- oligopeptides
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/06—Benzopyran radicals
- C07H17/065—Benzo[b]pyrans
- C07H17/07—Benzo[b]pyran-4-ones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Present disclose provides icariside I compounds and its derivative, pharmaceutical composition and its preparation method and application.The structural formula of the compound and its derivative is shown in formula I:
Description
Technical field
The present invention relates to icariside I compound and its derivative, pharmaceutical composition and its preparation method and application,
Such compound is related in disease treatment in the effect for preventing or treating patients with osteoporosis, and based on this principle
With the application of health care product etc..
Background technique
The single compound of the principle active component of natural products is as chemicals itself or the guideization of medicament research and development
Closing object is one of the important research method that medicament research and development personnel is engaged in chemicals research and development for many years, and flavonoid glycoside compound is excessive
Sheep leaves of pulse plants glycosides also has become a hot topic of research.Show that icariin has antitumor efficacy, bone strengthening, adjusts immune function, improves painstaking effort
Pipe function, anti-aging and anti-oxidation function, the antitoxin sick physiological activity such as ability and enhancing sexual function of enhancing.
Herba Epimedii is traditional Chinese medicine simply, is used for being under instruction of Chinese Medicine theory in the prior art using excessive
The decoction of sheep leaves of pulse plants plant, infusing drugs in wine, cook paste, pill dissipate etc..
Summary of the invention
Inventor is by the research to natural constituent, while the research of inventor's long campaigns biosynthesis, hair
Existing icariin/element obtains that synthesising biological effect is more preferable, the higher Herba Epimedii of economic benefit is secondary by the method for bio-enzyme engineering
I analog derivative of glycosides.It can be used for preparing prevention or treat the drug of osteoporosis.
Icariin has the effect of bone strengthening, but there is a problem of that solubility is low, bioavailability is low, icariin
Utilization rate substantially reduces, and strong dose product is needed to can be only achieved medical effect, this has aggravated suction of the body to drug
The burden of receipts, especially hepatic and kidney function obstacle person take strong dose object and do not have effect not only, increase kidney instead.
Icariine is the aglycon of icariin, therefore the present invention is excessive by being synthesized using icariine by bio-enzyme engineering method
The sheep leaves of pulse plants time I derivative of glycosides, chains glucose in icariine, increases the water-soluble and fat-soluble of icariine；Inventor
It is found by literature survey, methyl or other aliphatic chain groups are chained on citrus flavonoids hydroxyl can increase Huang
Bioactivity (the D. Wang etal.Journal of Pharmaceutical and Biomedical Analysis of ketone
44(2007) 63–69).Herba Epimedii is barberry class plant, and primary bioactive components are icariine and icariin, but
It is that the best icariside I content of activity is few, the present invention is by passing through the excessive to methylating of biological enzyme in icariine
Then sheep leaves of pulse plants element is chaining glucose at the position 7- by biological enzyme, is obtaining the compound of the present invention --- Herba Epimedii
I compound of glycosides.The aliphatic chains groups such as methyl are linked on the hydroxyl of icariside I compound of the invention, increase Herba Epimedii
The bioactivity of secondary glycosides I, effectively improves its medical value and economic value.
Although Herba Epimedii effect in terms of bone strengthening has had a large amount of research report, there is no excessive sheep both at home and abroad at present
Research report of the leaves of pulse plants time glycosides I in terms of bone strengthening, inventor have carried out a series of Bioexperiment to the compound of the present invention, demonstrate,prove
The purposes that the compound of the present invention-icariside I has bone strengthening is illustrated.
Technical solution is as follows:
Icariside I class compound and its derivative, structural formula compound shown in formula I
Or its stereoisomer of compound shown in Formulas I, geometric isomer, tautomer, nitrogen oxides, hydration
Object, solvate, metabolite, pharmaceutically acceptable salt or prodrug；Wherein,
1)R1Selected from H, OH, OCH3、CH3COO、NH2、CH3NH、(CH3)2N、 CH3CONH or CN；
2)R2Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、CH3、CF3、 C1-C6-NH2、NH2、CH3NH、(CH3)2N、
(CH3CH2)2N、CH3CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino-, oligopeptides acyl group or oligopeptides acylamino-；
Wherein, the C1-C6-NH2C1-C6For with 1-6 C alkyl, naphthenic base, alkylene, cycloalkenyl group, clopentylamino,
Cyclohexylamino, morpholine base, methyl piperazine base；
3)R3Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、CH3、CF3、 C1-C6-NH2、NH2、CH3NH、(CH3)2N、
(CH3CH2)2N、CH3CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino-, oligopeptides acyl group or oligopeptides acylamino-；
Wherein, the C1-C6-NH2C1-C6For with 1-6 C alkyl, naphthenic base, alkylene, cycloalkenyl group, clopentylamino,
Cyclohexylamino, morpholine base, methyl piperazine base.
Further, 1) R1Selected from H, OCH3；2)R2Selected from selected from OC2H5、OC3H7、CH3、C1-C6-NH2, Br, Cl, F, amino
Sour acyl group, amino acid acylamino-, oligopeptides acyl group, oligopeptides acylamino-；3)R3Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、
CH3Or CF3。
Meanwhile a kind of pharmaceutical composition is also disclosed, it include above-mentioned icariside I class compound or derivatives thereof, with
And pharmaceutically acceptable carrier, excipient, diluent, medium or their combination.
Any one of the above compound or composition can be used as preparation prevention, mitigate or treat patients with osteoporosis
Drug purposes.
A kind of method that icariine prepares icariside I is also related to, comprising steps of
1) using icariine as substrate, it is added in icariine solution with buffer at icariine solution
Enter S-adenosylmethionine and O- transmethylase, react 6~12 hours, after boiling water inactivator, obtains the excessive of product methylation
Sheep leaves of pulse plants element；
2) during the phosphate-buffered for product being dissolved in pH6.8 is molten, fixation glucose based transferase, UDP grape is added
Sugar stirs 8~12h of lower reaction at 60 DEG C, and solid is collected by filtration in crystallization, and recrystallizing methanol processing obtains product Herba Epimedii
Glycosides I.
Further, the step 1) buffer is that 0.1mM contains Mg2+: Ca2+: Fe2+: Cu2+=50:23.6:15.8:
10.6 buffer salt solution, the buffer salt are sulfate, chlorate, nitrate or borate etc.；The O- transmethylase
Concentration is 100 μ g/mL, and S-adenosylmethionine concentration is 600 μ g/mL, and S-adenosylmethionine concentration maintains in the process
In 100 μ g/mL.
Show icariside I 3.5- very higher than the bioavilability of icariine and solubility by comparative experiments
9.6 again.Therefore, the present invention has a good application prospect.Icariside I is also disclosed simultaneously to pass through using icariine
Bio-enzyme engineering method synthesizes, and glucose is connected on chain, and it is water-soluble and fat-soluble to increase it.
Detailed description of the invention
Fig. 1 be 17b-oestradiol in embodiment 6, icariine, methylation icariside I it is thin to MG63 skeletonization
The cell activity of born of the same parents compares figure.
Specific embodiment
The invention will be further described by the following examples, and the present invention illustrates this hair as example using icariine
Bright design, but example of the invention is not limited to specific example, only a kind of synthesis thinking.
Embodiment 1: icariine enzyme process methylation
1) using icariine as substrate, by it with buffer at icariine solution, the concentration of Herba Epimedii is 5~
20mg/mL (purity 98%), buffer are to contain (Mg containing 0.1mM2+(50%), Ca2+(23.6%), Fe2+
(15.8%), Cu2+(10.6%)) buffer salt solution, the buffer salt are sulfate, chlorate, nitrate or borate etc., are used
Salt acid for adjusting pH 5；
2) S-adenosylmethionine and O- transmethylase are added in buffer solution, with salt acid for adjusting pH 4.0, O- first
The concentration of based transferase is 100 μ g/mL, and S-adenosylmethionine concentration is 600 μ g/mL, and S-adenosylmethionine concentration maintains
It in 100 μ g/mL, reacts 6~12 hours, after boiling water inactivator, obtains product ICA-J.1H-NMR(400MHz,DMSO-d6): δ
12.05 (s, 1H), 8.69 (t, 1H), 8.03 (d, J=11.2Hz, 2H), 7.15 (d, J=10.8Hz, 2H), 6.33 (d, J=
7.2Hz, 1H), 3.87 (s, 6H), 3.05 (d, J=4.15 (t, 2H), 2.56 (t, 2H), 1.74 (d, 3H), 1.63 (d, 3H).
Embodiment 2: enzyme process preparation methylation icariside I
By 15g ICA-J, be dissolved in pH 6.8 phosphate-buffered it is molten in, fixation glucose based transferase 5- is added
10g, UDP 7.5~10g of glucose, at 60 DEG C, stir it is lower react 8~12h, crystallization is collected by filtration solid, at recrystallizing methanol
Reason.Obtain 13.5 grams of methylation icariside Is (ICA-T).1H-NMR(400MHz,DMSO-d6): δ 12.02 (s, 1H), 7.73
(d, J=7.8Hz, 2H), 7.54 (d, J=8.6Hz, 2H), 6.45 (m, 1H), 5.83 (d, J=7.2Hz, 2H), 4.66 (t,
3H),4.25(t,H),3,62-3.81(m,14H),3.38(m,2H),1.84(d, 3H),1.73(d,3H)。
The Bioavailability Determination of embodiment 3::ICA-T
1, sample preparation: ICA-T sample is taken；
2, test method: experimental animal is using healthy rabbits 40 of weight about 2kg (by Zhongshan University experimental animal
The heart provides), animal is randomly divided into four groups, and after preparatory fasting 12h, above-mentioned sample, dosage 320mg/kg are given in stomach-filling respectively
(being equivalent to 70kg Coming-of-Age Day taking dose 4g) gives the content that ICA-T in blood plasma is intensively measured after sample, until peak time
Half an hour after detects blood peak concentration of drug (Cmax)；
After test specimen stomach-filling, it is discontinued a period of time, until animal vivo sample is metabolized completely, is then injected intravenously
Equal dose samples solution is given, and measures sample size in blood plasma (μ g/mL), in this, as reference data；It the results are shown in Table 1:
Table 1: hypo-glycosylated Pu Luning bioavilability
| Test specimen | ICA-T |
| Dosage (g) | 0.60 |
| Sample size (%) | 2.66 |
| Sample dosage (mg) | 16.00 |
| Vein gives sample plasma sample concentration (μ g/mL) | 72.91 |
| It takes orally to sample peak concentration C max (μ g/mL) in sample blood plasma | 15.98 |
| Absorptivity (%) | 30.06 |
Test result shows: ICA-T of the present invention has good bioavilability, has very high application prospect.
The solubility and dissolution rate of embodiment 4:ICA-T measures
1, the measurement of solubility
ICA-T granule is dissolved in water, and the size of solvability directly influences drug in solution system and cell system
Using.Because ICA-T is stable in aqueous solution, we are using ultraviolet spectrophotometry to the water of the ICA-T of saturation state
The measurement of solution progress solubility values.In this experiment, we prepare the aqueous solution of 0.3g/L Pu Luning, dilute according to a certain percentage
Absorbance is surveyed after releasing and makes standard curve, and integral is carried out as ordinate to the characteristic peak in the section 270nm.Preparation is measured again
The light absorption value of saturated solution dilution obtains the concentration of dilution by internal standard method, finally calculates saturated solution concentration.
Calibration curve equation is y=1568.6840A-16.92, R2=0.9923.Saturated solution is inhaled after 50 times of dilutions
Luminosity integrated value is 435.16, and concentration 0.310g/L, then the solubility of ICA-T is 13.52g/L.
2, the measurement of dissolution rate
1) foundation of analysis method
The determination of Detection wavelength: claiming ICA-T, icariine (ICA) and right amount of auxiliary materials respectively, be configured to methanol be suitable for
The solution of concentration, and using methanol as blank control, in being scanned within the scope of 200~700nm.The result shows that having at 270nm
The maximum absorption band of ICA-T and ICA；And auxiliary material is noiseless to the measurement of ICA-T and ICA here.Therefore, 270nm is selected
As measurement wavelength.Standard curve: precision claims ICA-T and appropriate ICA, and the solution of series of concentrations is configured to methanol, in
Trap is measured at 270nm, and linear regression is carried out to trap (A) with concentration (C).
2) measuring method of ICA-T dissolution rate
Weighing is dissolved out containing the solid particle samples of ICA-T 83nmol (44mg) and ICA83nmol (29mg)
Degree test.Every group of sample is measured in parallel 3 parts, carries out by 2015 editions the second methods of Chinese Pharmacopoeia.Dissolution medium is the distillation of 900mL
Water, temperature are 37 ± 0.5 DEG C, and revolving speed is 100 ± 3rpm.5mL is sampled in 3,6,9,12,15min respectively and fills into same volume
Long-pending dissolution medium, sample is through 0.8 μm of filtering with microporous membrane.Trap is measured after taking subsequent filtrate to dilute at 270 nm, is calculated
Change the dissolution rate of ICA-T and ICA.
3) measurement result
Calibration curve equation C=13.5941A+0.2651, R2=0.9907, the range of linearity: 1.051~53.246 μ g/
mL.The present invention uses dissolution in vitro experiment with ICA-T and ICA bulk pharmaceutical chemicals for control, measurement ICA-T and ICA in vitro molten
Artificial situation, the results showed that, ICA-T dissolves out all right in vitro.It the results are shown in Table 2
The dissolution rate of table 2 ICA-T- PVP K30 and ICA- PVP K30 particle
ICA-T of the invention reaches the 82.53%-93.11% of scalar, the extracorporeal releasing speed of drug in 3-15min
Well, it can be utilized well by organism, the extracorporeal releasing speed of ICA will be far smaller than ICA-T, therefore the present invention has very
Good application prospect.
Purposes in the protection of embodiment 5:ICA-T, processing, treatment fracture and osteoporosis agents
The compounds of this invention is to the proliferation of osteoclast and the activity experiment of differentiation.
Principle: the osteoclastic precursor of monokaryon, can be gradually under the noble cells factor (such as RANKL, M-CSF) induction
Fusion is divided into the mature osteoclast of multicore.Osteoclastic precursor does not have the ability of bone resorption, and only differentiation and maturation is osteoclastic
The ability that cell just has dissolution stubborn, therefore, the level of differentiation of osteoclast can react its bone resorption ability.
Method: osteoclastic neural progenitor cell line or the primary osteoclastic precursor of mouse being separately cultured are inoculated into the culture of 12 holes
In plate, 10000 cells/wells.Control group, single dosing group 1 (ICA-T), single dosing group 2 (RANKL) and double dosing groups are set
(ICA-T+RANKL).After cell is adherent overnight, the compounds of this invention and/or 50ng/ml of various dose is added
RANKL is persistently cultivated 3~5 days.Deng single plus RANKL cell fusion it is complete after, with the 37 degree distillation preheated washing cells one
It is secondary, methanol is added and fixes 30 seconds, the distillation washing cell of 37 degree of preheatings three times, then carries out TRAP dyeing, counts under the microscope
The multi-nucleus cell number of the number TRAP positive.
As a result with evaluation: the results are shown in Table shown in 3.Compared with the control group, after the compounds of this invention is added, no matter broken
In bone neural progenitor cell line or the primary osteoclastic precursor of mouse being separately cultured, by the amount of osteoclast of RANKL induction differentiation
Significantly reduce, this result proves: the compounds of this invention can effectively inhibit the differentiation of the osteoclast of RANKL induction.
The influence that 3 ICA-T of table breaks up the marrow BMMs cell of originally culture to osteoclast
| Compound | Concentration | Appreciation rate (%) |
| Blank control | -/- | 0.00 |
| Single dosing group 1 | 0.5μM | 28.6% |
| Single dosing group 2 | 1.0μM | 22.5% |
| Double dosing groups | 1.0μM | 20.1% |
From table 3 it can be seen that compared with the control group, after ICA-T is added, no matter in osteoclastic neural progenitor cell line or primary
In the osteoclastic precursor of the mouse being separately cultured, significantly reduced by the amount of osteoclast of RANKL induction differentiation, this result
Prove: ICA-T can effectively inhibit the differentiation of the osteoclast of RANKL induction.
Influence of the embodiment 6:ICA-T to MG63 osteoblast differentiation
Osteoblasts cultivation
After the recovery of MG63 osteoblast.Then 1000r/min is centrifuged 10min, abandons supernatant, and PBS liquid is resuspended, 1000r/
Min is centrifuged 10min, abandons supernatant.It is resuspended with the DMEM culture solution containing 15% fetal calf serum, piping and druming uniformly, is seeded to six orifice plates.
37 DEG C, 5%CO2It is cultivated under saturated humidity, every 3d is changed liquid 1 time.After cell covers with, disappeared with 0.25% trypsase-EDTA liquid
Change passage.
4 osteoblast of table point culture grouping
| Blank control group |
| Expression vector 17b-oestradiol transfection group 10-8 |
| Expression vector icariine transfection group 10-10 |
| Expression vector icariine transfection group 10-8 |
| Expression vector icariine transfection group 10-6 |
| Expression vector methylation icariside I transfection group 10-10 |
| Expression vector methylation icariside I transfection group 10-9 |
| Expression vector methylation icariside I transfection group 10-8 |
| Expression vector methylation icariside I transfection group 10-7 |
| Expression vector methylation icariside I transfection group 10-6 |
First generation osteoblast covers with, and by 1:9 had digestive transfer culture, is added to six well culture plates.37 DEG C, 5%CO2Under the conditions of
Culture.Transfection when cell reaches 70%~80% fusion, transfection procedure are operated by transfection reagent specification.37 DEG C after transfection,
5%CO2Continue culture 48 hours in incubator.17b-oestradiol, icariine, methylation icariside I group turn
For 24 hours, it is as shown in table 4 that concentration is added in dye.Cell activity is as described in Figure 1.
The result shows that: methylation icariside I is 10-12M to 10-6Can be obviously increased in M concentration range MG63 at
The growth of osteocyte；And 10-11M to 10-9Within the scope of M low concentration with positive control estrogen (10-8M effect phase)
When, it is shown that the higher performance for the icariside I that methylates.Meanwhile methylate icariside I with icariin pair
As can be seen that 10 in the effect relatively of MG63 Oesteoblast growth-10M to 10-6In M concentration range, methylate icariside I
Increase Oesteoblast growth effect more stronger than icariin is all shown, especially 10-10M to 10-9M low concentration model
It encloses, more confirms that methylation icariside I is high-effect, prompt its potential high bioavilability.
Claims (6)
1. icariside I class compound and its derivative, it is characterised in that: its structural formula compound shown in formula I
Or the pharmaceutically acceptable salt of compound shown in Formulas I；Wherein,
1)R1Selected from H, OH, OCH3、CH3COO、NH2、CH3NH、(CH3)2N、CH3CONH or CN；
2)R2Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、CH3、CF3、C1-C6-NH2、NH2、CH3NH、(CH3)2N、
(CH3CH2)2N、CH3CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino-, oligopeptides acyl group or oligopeptides acylamino-；Its
In, the C1-C6-NH2C1-C6For alkyl, naphthenic base, alkylene, cycloalkenyl group, clopentylamino, ring with 1-6 C
Hexylamino, morpholine base, methyl piperazine base；
3)R3Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、CH3、CF3、C1-C6-NH2、NH2、CH3NH、(CH3)2N、
(CH3CH2)2N、CH3CONH, CN, Br, Cl, F, amino acid acyl, amino acid acylamino-, oligopeptides acyl group or oligopeptides acylamino-；Its
In, the C1-C6-NH2C1-C6For alkyl, naphthenic base, alkylene, cycloalkenyl group, clopentylamino, ring with 1-6 C
Hexylamino, morpholine base, methyl piperazine base.
2. icariside I class compound according to claim 1 and its derivative, it is characterised in that: 1) R1Selected from H,
OCH3；
2)R2Selected from OC2H5、OC3H7、CH3、C1-C6-NH2, Br, Cl, F, amino acid acyl, amino acid acylamino-, oligopeptides acyl group,
Oligopeptides acylamino-；
3)R3Selected from H, OH, OCH3、OC2H5、OC3H7、CH3COO、CH3Or CF3。
3. a kind of pharmaceutical composition, it is characterised in that: comprising icariside I class compound of any of claims 1 or 2 or its
Derivative and pharmaceutically acceptable carrier, excipient, diluent, medium or their combination.
4. any one compound or composition of claims 1 to 3 is used to prepare the purposes of drug, the drug is for preventing, subtracting
Purposes in light or treatment osteoporosis.
5. a kind of method that icariine prepares icariside I, which is characterized in that comprising steps of
1) using icariine as substrate, S- is added in icariine solution at icariine solution with buffer in it
Adenosylmethionine and O- transmethylase react 6~12 hours, after boiling water inactivator, obtain the Herba Epimedii of product methylation
Element；
2) during the phosphate-buffered for product being dissolved in pH6.8 is molten, fixation glucose based transferase, UDP glucose is added, 60
DEG C, 8~12h of lower reaction is stirred, solid is collected by filtration in crystallization, and recrystallizing methanol processing obtains product icariside I.
6. preparation method according to claim 5, which is characterized in that the step 1) buffer is that 0.1mM contains Mg2+:
Ca2+: Fe2+: Cu2+The buffer salt solution of=50:23.6:15.8:10.6, the buffer salt be sulfate, chlorate, nitrate or
Borate；The concentration of the O- transmethylase is 100 μ g/mL, and S-adenosylmethionine concentration is 600 μ g/mL, in the process
S-adenosylmethionine concentration maintains 100 μ g/mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811271185.4A CN109369747A (en) | 2018-10-29 | 2018-10-29 | Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811271185.4A CN109369747A (en) | 2018-10-29 | 2018-10-29 | Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109369747A true CN109369747A (en) | 2019-02-22 |
Family
ID=65390634
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811271185.4A Pending CN109369747A (en) | 2018-10-29 | 2018-10-29 | Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109369747A (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228287A (en) * | 2020-04-15 | 2020-06-05 | 广东金骏康生物技术有限公司 | Application of epimedium flavone glycoside compound in preparing medicine for treating melanoma |
| CN111870609A (en) * | 2020-07-01 | 2020-11-03 | 广东金骏康生物技术有限公司 | Intestinal flora regulator and application thereof |
| CN112375059A (en) * | 2021-01-05 | 2021-02-19 | 遵义医科大学 | Icaritin methylation structure modified compound and preparation method and application thereof |
| CN113249357A (en) * | 2021-06-22 | 2021-08-13 | 广东金骏康生物技术有限公司 | Rhamnosidase TpeRhha-H570A mutant and preparation method and application thereof |
| CN113512542A (en) * | 2021-06-22 | 2021-10-19 | 广东金骏康生物技术有限公司 | Rhamnosidase mutant and preparation method and application thereof |
| CN113940943A (en) * | 2021-10-18 | 2022-01-18 | 广东金骏康生物技术有限公司 | Application of icariside I |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101113157A (en) * | 2006-07-28 | 2008-01-30 | 上海特化医药科技有限公司 | Isoamylene radical chromocor derivative, preparation method and uses thereof |
| CN104825479A (en) * | 2015-05-20 | 2015-08-12 | 佛山市金骏康健康科技有限公司 | Icariside derivatives as well as preparation method and application thereof in promoting human cells to generate interferon-gamma and treating disease |
-
2018
- 2018-10-29 CN CN201811271185.4A patent/CN109369747A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101113157A (en) * | 2006-07-28 | 2008-01-30 | 上海特化医药科技有限公司 | Isoamylene radical chromocor derivative, preparation method and uses thereof |
| CN104825479A (en) * | 2015-05-20 | 2015-08-12 | 佛山市金骏康健康科技有限公司 | Icariside derivatives as well as preparation method and application thereof in promoting human cells to generate interferon-gamma and treating disease |
Non-Patent Citations (4)
| Title |
|---|
| LI TIAN，等: "Biosynthesis and genetic engineering of proanthocyanidins", 《PHYTOCHEM. REV.》 * |
| LUPING QIN，等，: "Antiosteoporotic chemical constituents from Er-Xian Decoction,a traditional Chinese herbal formula", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| YINA XIAO，等: "Microbial metabolism of prenylated apigenin derivatives by Mucor hiemalis", 《PHYTOCHEMISTRY LETTERS》 * |
| 张传丽，等: "植物类黄酮O-甲基转移酶研究进展", 《西北植物学报》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228287A (en) * | 2020-04-15 | 2020-06-05 | 广东金骏康生物技术有限公司 | Application of epimedium flavone glycoside compound in preparing medicine for treating melanoma |
| CN111870609A (en) * | 2020-07-01 | 2020-11-03 | 广东金骏康生物技术有限公司 | Intestinal flora regulator and application thereof |
| CN112375059A (en) * | 2021-01-05 | 2021-02-19 | 遵义医科大学 | Icaritin methylation structure modified compound and preparation method and application thereof |
| CN113249357A (en) * | 2021-06-22 | 2021-08-13 | 广东金骏康生物技术有限公司 | Rhamnosidase TpeRhha-H570A mutant and preparation method and application thereof |
| CN113249357B (en) * | 2021-06-22 | 2021-09-14 | 广东金骏康生物技术有限公司 | Rhamnosidase TpeRhha-H570A mutant and preparation method and application thereof |
| CN113512542A (en) * | 2021-06-22 | 2021-10-19 | 广东金骏康生物技术有限公司 | Rhamnosidase mutant and preparation method and application thereof |
| CN113512542B (en) * | 2021-06-22 | 2021-11-23 | 广东金骏康生物技术有限公司 | Rhamnosidase mutant and preparation method and application thereof |
| CN113940943A (en) * | 2021-10-18 | 2022-01-18 | 广东金骏康生物技术有限公司 | Application of icariside I |
| WO2023065478A1 (en) * | 2021-10-18 | 2023-04-27 | 广东金骏康生物技术有限公司 | Use of icariside i |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109369747A (en) | Icariside I compound and its derivative, pharmaceutical composition and its preparation method and application | |
| CN107213466B (en) | A kind of column aromatic hydrocarbons compound, preparation method, pharmaceutical composition and purposes | |
| CN102417544B (en) | Ziyang selenium-rich green tea selenium-containing polysaccharide, and preparation method and application thereof | |
| CN106928246B (en) | A kind of compound and preparation method thereof and purposes | |
| EP1421933A1 (en) | Use of stilbene compounds in preparing medicaments for treating or preventing diabetes and diseases associated with retrovirus | |
| CN109438536A (en) | The application and preparation method of a kind of isoquercitin and its derivative | |
| JP5671622B2 (en) | Fructosylated puerarin and its preparation and use | |
| US20110218161A1 (en) | Cycloastragenol monoglucoside, preparation, pharmaceutical composition and application thereof | |
| CN103768024B (en) | Ginsenoside Rh2's albumin compound nano-particle and preparation method thereof | |
| CN105566317A (en) | Compound and preparation method thereof | |
| CN106831375A (en) | A kind of Chalcone Compounds with antitumor activity and its production and use | |
| CN109320570A (en) | A kind of icariside I class compound, derivative, officinal salt and application | |
| JP6923861B2 (en) | Dicafe oil spermidine derivative glycoside and its use | |
| CN109369748A (en) | A kind of icariside I class compound, derivative, pharmaceutical composition and its application | |
| CN106977467A (en) | A kind of compound and preparation method thereof and purposes | |
| CN105566271B (en) | The purposes of biflavone compound and its drug of preparation treating cancer | |
| CN104161759A (en) | Antitumor use of Anagrelide and its derivatives | |
| CN101723997A (en) | Puerarin glycosylation derivative, medicine compound, preparation method and application thereof | |
| CN106966997A (en) | A kind of compound and preparation method thereof and purposes | |
| CN113577086B (en) | Application of isovaleryl spiramycin compound or composition thereof in preparation of medicines for treating immune disorder | |
| CN102038678A (en) | Application of dihydroartemisinin to preparation of tumor cell autophagy induction medicament | |
| CN101541717B (en) | A trans-cinnamic acid derivative, its preparation method and the use | |
| CN103494813A (en) | Application of hydrochloric acid demethyleneberberine in preparation of drug for preventing and/or treating acute or chronic alcoholic liver disease | |
| CN104926804B (en) | One kind has compound, the preparation method and use of antitumor action | |
| CN103159710B (en) | Antiviral decalin derivate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190222 |