CN105859717A - Acetazolamide medicine composition and medical application thereof - Google Patents
Acetazolamide medicine composition and medical application thereof Download PDFInfo
- Publication number
- CN105859717A CN105859717A CN201610321672.1A CN201610321672A CN105859717A CN 105859717 A CN105859717 A CN 105859717A CN 201610321672 A CN201610321672 A CN 201610321672A CN 105859717 A CN105859717 A CN 105859717A
- Authority
- CN
- China
- Prior art keywords
- acetazolamide
- compound
- extract
- preparation
- ethanol elution
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an acetazolamide medicine composition and medical application thereof. The acetazolamide medicine composition provided by the invention contains acetazolamide and a natural product compound (I) which is separated from dry roots of polygonum cuspidatum and is of a novel structure; when the acetazolamide and the natural product compound (I) work alone, a treatment effect on Parkinson's disease is poorer; when the acetazolamide and the compound (I) work together, the treatment effect on the Parkinson's disease can be further enhanced. Therefore, the acetazolamide and the compound (I) can be prepared into a medicine for treating the Parkinson's disease. Compared with the prior art, the acetazolamide medicine composition disclosed by the invention has outstanding substantial characteristics and remarkable progresses.
Description
Technical field
The invention belongs to biomedicine field, relate to Parkinsonian preventing and treating, be specifically related to the pharmaceutical composition of a kind of acetazolamide and prevent and treat Parkinsonian medical usage.
Background technology
The chemical name of acetazolamide is N-(5-sulfamoyl-1,3,4-thiadiazoles-2-bases) acetamide, and current clinic is usually used in preventing and treating glaucoma, cardiac edema, cerebral edema, also for petit mal epilepsy.
Acetazolamide is carbonic anhydrase inhibitors.The distribution of carbonic anhydrase is all had in renal cells, gastric mucosa, pancreatic cell, eye corpus ciliare epithelial cell, erythrocyte and axoneure.The major function of this enzyme is to promote CO2And H2O is combined into carbonic acid, and makes carbonic acid be dissociated into H again+With HCO3-.When the function of carbonic anhydrase is suppressed, any ore deposit and a large amount of and without interruption functional activities is needed all to be affected, such as: 1. the carbonic anhydrase in renal tubules proximal convoluted tubule is suppressed, H+Generation reduce, H+With Na+Exchange slow down, Na+Heavily absorb minimizing, Na+、H2O discharges with heavy carbonate to be increased, thus produces diuresis, discharges alkaline urine.But diuresis is the most weak, and long-term taking can lead tolerogenic generation, therefore is seldom individually used for diuresis at present, but, it is for then having good diuretic antihypertensive effect with the eclamptic patients of edema；2. all there is the existence of carbonic anhydrase in ophthalmic each portion tissue (such as corpus ciliare, retina, crystal), and when suffering from glaucoma, in ciliary epithelium, the activity of carbonic anhydrase increases, and intraocular pressure rises.The activity of this product suppression intracellular carbonic anhydrase of ciliary epithelium, makes intraocular pressure decline.This product has similar sulfanilamide structure, and oral absorption is good.Take medicine the rear pH that can affect urine for 30 minutes, and 1 ~ 1.5 hour starts to reduce intraocular pressure, tmaxIt is 2 ~ 4 hours, effect lasts 8 ~ 12 hours.t1/2It is about 3 ~ 6 hours.Overwhelming majority medicine is with original shape by tubular secretion, and the 80% of dose was discharged in 8 ~ 12 hours, within 24 hours, can drain completely.
Parkinson disease (Parkinson ' s disease, PD) it is a kind of common nervous system degeneration disease, old people is common, and average age of onset is about 60 years old, and the young parkinson disease of less than 40 years old onset are more rare.The prevalence of China over-65s crowd PD is about 1.7%.Major part Parkinsonian is Sporadic cases, and only having the patient less than 10% has family history.The topmost pathological change of parkinson disease be substantia nigra of midbrain dopamine (dopamine,
DA) degeneration of serotonergic neuron is dead, causes striatum DA level significance to reduce and cause a disease therefrom.The definite cause of disease causing this pathological change is the most unclear, and inherited genetic factors, environmental factors, age ageing, oxidative stress etc. all may participate in the degeneration death process of PD dopaminergic neuron.
Up to now, there is not yet the pharmaceutical composition of acetazolamide and the dependency report of parkinson disease preventing and treating.
Summary of the invention
It is an object of the invention to provide the pharmaceutical composition of a kind of acetazolamide, this pharmaceutical composition can be worked in coordination with prevent and treat parkinson disease containing acetazolamide and a kind of natural product of the novel structure of isolated from draft, acetazolamide and this natural product.
The above-mentioned purpose of the present invention is achieved by techniques below scheme:
A kind of compound (I) with following structural formula,
。
The pharmaceutical composition of a kind of acetazolamide, including acetazolamide, compound as above (I) and pharmaceutically acceptable carrier.
The preparation method of compound (I) as above, comprise following operating procedure: the dry root of Rhizoma Polygoni Cuspidati is pulverized by (a), extract with 75 ~ 85% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 10% ethanol elution, then with 10 column volumes of 70% ethanol elution, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, obtain 4 components with the methylene chloride-methanol gradient elution that volume ratio is 60:1,30:1,15:1 and 5:1 successively；D in () step (c), component 4 separates further by purification on normal-phase silica gel, obtain 3 components with the methylene chloride-methanol gradient elution that volume ratio is 10:1,5:1 and 2:1 successively；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collects 10 ~ 15 column volume eluents, and eluent is concentrated under reduced pressure to give compound (I).
Further, in step (a), extract with 80% alcohol heat reflux, united extraction liquid.
Further, described macroporous resin is D101 type macroporous adsorbent resin.
The compound (I) as above application in preparation prevents and treats Parkinsonian medicine.
The application in preparation prevents and treats Parkinsonian medicine of the pharmaceutical composition of acetazolamide as above.
Advantages of the present invention:
Time in the pharmaceutical composition of the acetazolamide that the present invention provides containing acetazolamide and a kind of natural product of the novel structure of isolated from Rhizoma Polygoni Cuspidati, acetazolamide and this natural product independent role, more weak to Parkinsonian prevention effect；During the two synergy, Parkinsonian prevention effect is significantly improved, the Parkinsonian medicine of preventing and treating can be developed into.The present invention compared with prior art has prominent substantive distinguishing features and significantly progress.
Detailed description of the invention
Further illustrate the essentiality content of the present invention below in conjunction with embodiment, but do not limit scope with this.Although the present invention being explained in detail with reference to preferred embodiment, it will be understood by those within the art that, technical scheme can be modified or equivalent, without deviating from the spirit and scope of technical solution of the present invention.
Embodiment 1: compound (I) separates preparation and structural identification
Reagent source: ethanol, petroleum ether, ethyl acetate, n-butyl alcohol, dichloromethane are analytical pure, purchased from Shanghai Ling Feng chemical reagent company limited, methanol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Separation method: the dry root (2kg) of Rhizoma Polygoni Cuspidati is pulverized by (a), (15L × 3 time) are extracted with 80% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste (3L), successively with petroleum ether (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated n-butyl alcohol (3L × 3 time) extraction, respectively obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B acetic acid ethyl ester extract D101 type macroporous resin remove impurity in () step (a), first with 8 column volumes of 10% ethanol elution, then with 10 column volumes of 70% ethanol elution, collects 70% eluent, concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, be 60:1(10 column volume by volume ratio successively), 30:1(8 column volume), 15:1(10 column volume) and 5:1(8 column volume) methylene chloride-methanol gradient elution obtain 4 components；D in () step (c), component 4 separates further by purification on normal-phase silica gel, be 10:1(10 column volume by volume ratio successively), 5:1(8 column volume) and 2:1(6 column volume) methylene chloride-methanol gradient elution obtain 3 components；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collecting 10 ~ 15 column volume eluents, eluent is concentrated under reduced pressure to give compound (I) (435mg, HPLC normalization purity is more than 98%).
Structural identification: yellow amorphous solid；The quasi-molecular ion peak that HRESIMS is givenm/z 413.1698[M+H]+, show that compound molecule formula is C22H24N2O6, degree of unsaturation is 12.1H-NMR composes (pyridine-d5, 500MHz) in, H-1(11.86, s), H-3(3.66, d,J=10.6Hz), H-6(6.44, s), H-9(7.53, d,J=2.3Hz), H-11(7.24, dd,J=8.5,2.3Hz), H-12(7.46, d,J=8.5Hz), H-14a(2.72, d,J=12.2Hz), H-14b(2.04, ddd,J=12.2,12.7,10.6Hz), H-15(2.16, m), H-16(3.15, m), H-17(9.77, d,J=4.9Hz), H-18(0.93, t,J=7.5Hz), H-19a(1.59, m), H-19b(1.24, m), H-20(2.10, m), H-21a(3.83, dd,J=10.6,2.5Hz), H-21b(2.26, d,J=10.6Hz), 22-OMe(3.65, s)；13C-NMR composes (pyridine-d5, 125MHz) in, C-2(135.7, C), C-3(56.3, CH), C-5(147.5, C), C-6(108.6, CH), C-7(105.4, C), C-8(127.1, C), C-9(103.5, CH), C-10(152.3, C), C-11(112.4, CH), C-12(112.0, CH), C-13(131.4, C), C-14(32.6, CH2), C-15(38.1, CH), C-16(60.2, CH), C-17(201.8, CH) and, C-18(11.3, CH3), C-19(23.7, CH2), C-20(39.9, CH), C-21(55.2, CH2), C-22(173.8, C), C-23(175.3, C), 22-OMe(51.7, CH3).Infrared spectrum shows that this compound contains carbonyl (1725cm-1With 1625cm-1) group；Ultraviolet waves stave this compound bright contains indole (absorption maximum 205nm, 276nm and 311nm) group.1H-NMR spectrum display existence 1,2,4-trisubstituted benzene proton signal δ H7.53(1H, d,J=2.3Hz, H-9), 7.24(1H, dd,J=8.5,2.3Hz, H-11) and 7.46(1H, d,J=8.5Hz, H-12)；One olefinic proton signals δ H6.44(1H, s, H-6)；Three groups of methene protons signal δ H2.72(1H, d,J=12.2Hz, H-14a) and 2.04(1H, ddd,J=12.2,12.7,10.6Hz, H-14b), 1.59(1H, m, H-19a) and 1.24(1H, m, H-19b), 3.83(1H, dd,J=10.6,2.5Hz, H-21a) and 2.26(1H, d,J=10.6Hz, H-21b)；Four groups of methine proton signal δ H3.66(1H, d,J=10.6Hz, H-3), 2.16(1H, m, H-15), 3.15(1H, m, H-16) and 2.10(1H, m, H-20)；One aldehyde radical proton signal δ H9.77(3H, d,J=4.9Hz, H-17)；One company oxygen methyl proton signal δ H3.65(3H, s, 22-OMe)；One methyl proton signal δ H0.93(3H, t,J=7.5Hz, H-18)；One azine proton signal δ H11.86(1H, s, H-1).13C-NMR spectrum shows two groups of double bonds with DEPT spectrum；Two carbonyls；One aldehyde radical；Two methyl；Three methylene；Four methines.1H-1H
In COSY spectrum, it was demonstrated that there is obvious H-3/H2-14/H-15/H-16/H-17, H3-18/H2-19/H-20/H2-21, H-15/H-20 with
H-11/H-12 signal correction.Understanding according to HMBC analysis of spectrum, there is signal correction explanation OMe with C-22 position and is connected in methoxyl group H with C-22；Analyzing the directly related signal of carbon carbon in the range of δ C120-180 by 2D-INADEQUAR further, there is coherent signal in C-5 Yu C-23, it was demonstrated that carboxyl is connected with C-5 position.In this Alkaloid skeleton, H-15 is always at the α position of configuration；It addition, the coupling constant between H-3, H-14b and H-15 threeJ 3 , 14bWithJ 14b , 15It is 10.6 and 12.7, shows that H-3, H-14b and H-15 are coaxial cis-configuration.In ROESY spectrum, with the dependency of H-20 and H-15 and H-20, H-3 and H-15, H-3 show that H-3 Yu H-20 is α configuration.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and ROESY spectrum, and document is about correlation type nuclear magnetic data, can substantially determine that this compound is as follows, spatial configuration is determined by ECD test further, and theoretical value is basically identical with experiment value.
。
Embodiment 2: the preventive and therapeutic effect to Parkinson disease model
The present embodiment uses MPTP(1-methyl 4-phenyl-1,2,3,6-tetrahydropyridines) prepare parkinson disease (PD) mouse model, observe medicine and improve in the animal limb coordination ability, regulation brain that neurotransmitter is unbalance, recover the anti-PD effect of the aspects such as DA serotonergic neuron function.
1, materials and methods
1.1 animal
C57BL/6 mice 72, ♂, 7 ~ 8 week old, weight 18 ~ 22g, purchased from Institute of Experimental Animals, Chinese Academy of Medical Sciences, the quality certification number: SCXK (capital) 2014-0001.Animal feeding temperature (22 ± 1) DEG C, relative humidity 55% ~ 65%, 12h periodicity of illumination aeration-drying environment in, use big mice maintain material 1022 raising.
1.2 reagent and sample
Acetazolamide is purchased from Ji Wei bio tech ltd, Shanghai.Compound (I) is made by oneself, and preparation method is shown in embodiment 1.Madopar tablet (Shanghai company limited of Roche Group produces, lot number: SH0502).MPTP, DA, dihydroxyphenyl acetic acid (dioxyphenylacetic
Acid, DOPAC), 4-hydroxy-3-methoxy-.alpha.-toluic acid. (homovanilic
Acid, HVA), 5-hydroxy tryptamine (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-hydroxyindoleacetic
Acid, 5-HIAA) it is purchased from Sigma-aldrich company；Tyrosine hydroxylase (trysine hydroxylase, TH) antibody is purchased from Chemicon company；DAT (dopamine
Transporter, DAT), glial cell line-derived fibrin (glial
Fibrillary acidic protein, GFAP) antibody is purchased from Santa Cruz company；Avidin-biotin-peroxidase complex (avidin biotin-peroxidase complex, ABC) test kit, diaminobenzidine (diaminobenzidine, DAB) developer are purchased from Beijing Bioisystech Co., Ltd of Zhong Shan Golden Bridge.Acetazolamide, compound (I) and combinations thereof thing is first with a small amount of DMSO ultrasonic dissolution, then by purified water dissolved dilution gavage.
1.3 instrument
Mice Grasping clubglass test device (XPS-2, institute of Materia Medica,Chinese Academy of Medical Sciences), mice hangs experimental provision (making by oneself), freezing microtome (SM900, Leica company of the U.S.), high speed low temperature centrifugal machine (5810R, Eppendorf company of the U.S.), fluorescence microscope (X71, OLYPUS company of Japan), high performance liquid chromatography coulomb electrochemical analysis system (HPLC-ECD
Coulchem III, ESA, the U.S.).
Prepared by 1.4 mice group and model
C57BL/6 mice is randomly divided into 6 groups, often group 12, respectively Normal group, model control group, positive controls (madopar group, 50mg kg-1) and acetazolamide group (280mg kg-1), compound (I) group (280mg kg-1), acetazolamide and compound (I) compositions group [140mg kg-1Acetazolamide+140mg kg-1Compound (I)].Adaptation environment is after 1 week, and continuous gastric infusion 7d, Normal group and model control group mouse stomach give purified water；8th day starts, and after every day gastric infusion 45min in addition to Normal group gives equal-volume 0.9% sodium chloride solution, remaining respectively organizes equal lumbar injection MPTP(30mg kg-1), continuous 5d.After per injection MPTP, observe the various acute performance of mice immediately, carry out behavioristics's detection.
1.5 Grasping clubglass test
Use XPS-2 mice Grasping clubglass test device, guide mice climb at the bottom of bar from masthead, every train 4 times, record mice climb at the bottom of bar required for time, more than 60s in terms of 60s.1h after last lumbar injection MPTP, measures its pole-climbing time again, and every mice is surveyed and averages for 3 times.Measurement mice causes the limbs coordination ability to decline degree because of MPTP.
1.6 hang experiment
Test mice two fore paw is hung on (diameter 1mm, away from ground 30cm) on a horizontal metal wire and stops 10s, every day 2 times.After mice last lumbar injection MPTP, 1.5h tests.Mice hanging capacity standards of grading: in front 10s, mice catches metal wire to remember 3 points with 2 rear solid ends, catches metal wire to remember 2 points with 1 rear solid end, and 2 rear solid ends all fail to grip with metal wire and remember 1 point, finally calculate scoring event and record the time that mice falls down from metal wire, more than 60s in terms of 60s.
1.7 statistical method
Experimental data mean ± standard deviation (x ± s) represents, application 18.0 editions statistical softwares of SPSS carry out one factor analysis of variance and t inspection, statistically significant for difference with P ＜ 0.05.
2, experimental result
2.1 impacts on PD model mice sports coordination ability
After mice gives MPTP 3 ~ 5min, it can be observed that mice is trembled, hypokinesia, muscular hypotonus, rapid breathing, hind leg open, instability of gait, the back of a bow, sialorrhea, perpendicular tail, perpendicular hair etc..Indivedual there is the outbreak of insane sample, and these symptoms usually disappear in 30 ~ 60min, substantially recovers normal after 24h.Continuously after 5d lumbar injection MPTP, there is the dyskinesia in various degree in model control group mice, when showing as muscular rigidity, climbing, limb coordination ability reduces, can not control limbs balance etc., causes pole-climbing ability to decline, and pole-climbing required time significantly extends (P ＜ 0.01)；Comparing with model control group, acetazolamide significantly shortens (P ＜ 0.01 or P ＜ 0.05) with compound (I) compositions group and madopar group pole-climbing time, and the limbs coordination ability of mice significantly improves；Comparing with model control group, acetazolamide group, compound (I) the group pole-climbing time shortens (P ＜ 0.05), and the limbs coordination ability of mice is improved.The results are shown in Table 1.
PD model mice is hung the impact of behavior by 2.2
Comparing with Normal group, the hanging capacity of model control group mice substantially reduces, and shows as hanging scoring and is remarkably decreased (P ＜ 0.01), and the suspension time substantially shortens (P ＜ 0.05).Comparing with model control group, acetazolamide hangs scoring with compound (I) compositions group and madopar group and significantly improves (P ＜ 0.01), and the suspension time significantly extends (P ＜ 0.01)；Comparing with model control group, acetazolamide group, compound (I) group hangs scoring and improves (P ＜ 0.05), hangs time lengthening (P ＜ 0.05).Result see table.
The above results shows, during compound (I) independent role that acetazolamide and the present invention provide, more weak to Parkinsonian prevention effect；During compound (I) synergy that acetazolamide and the present invention provide, Parkinsonian prevention effect is significantly improved, the Parkinsonian medicine of preventing and treating can be developed into.
The effect of above-described embodiment indicates that the essentiality content of the present invention, but does not limit protection scope of the present invention with this.It will be understood by those within the art that, technical scheme can be modified or equivalent, without deviating from essence and the protection domain of technical solution of the present invention.
Claims (7)
1. a compound (I) with following structural formula,
。
2. the pharmaceutical composition of an acetazolamide, it is characterised in that: include acetazolamide, compound as claimed in claim 1 (I) and pharmaceutically acceptable carrier.
3. the preparation method of the compound (I) described in claim 1, it is characterized in that, comprise following operating procedure: the dry root of Rhizoma Polygoni Cuspidati is pulverized by (a), extract with 75 ~ 85% alcohol heat reflux, united extraction liquid, it is concentrated into without alcohol taste, successively with petroleum ether, ethyl acetate and water saturated n-butanol extraction, respectively obtains petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract；B in () step (a), n-butyl alcohol takes thing macroporous resin remove impurity, first with 8 column volumes of 10% ethanol elution, then with 10 column volumes of 70% ethanol elution, collect 70% eluent, and concentrating under reduced pressure obtains 70% ethanol elution concentrate；C in () step (b), 70% ethanol elution concentrate purification on normal-phase silica gel separates, obtain 4 components with the methylene chloride-methanol gradient elution that volume ratio is 60:1,30:1,15:1 and 5:1 successively；D in () step (c), component 4 separates further by purification on normal-phase silica gel, obtain 3 components with the methylene chloride-methanol gradient elution that volume ratio is 10:1,5:1 and 2:1 successively；E reverse phase silica gel that in () step (d), component 2 is bonded by octadecylsilane separates, and with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collects 10 ~ 15 column volume eluents, and eluent is concentrated under reduced pressure to give compound (I).
The preparation method of compound the most according to claim 3 (I), it is characterised in that: in step (a), extract with 80% alcohol heat reflux, united extraction liquid.
The preparation method of compound the most according to claim 3 (I), it is characterised in that: described macroporous resin is D101 type macroporous adsorbent resin.
6. the application in preparation prevents and treats Parkinsonian medicine of the compound (I) described in claim 1.
7. the pharmaceutical composition of the acetazolamide described in claim 2 application in preparation prevents and treats Parkinsonian medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610321672.1A CN105859717A (en) | 2016-05-16 | 2016-05-16 | Acetazolamide medicine composition and medical application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610321672.1A CN105859717A (en) | 2016-05-16 | 2016-05-16 | Acetazolamide medicine composition and medical application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105859717A true CN105859717A (en) | 2016-08-17 |
Family
ID=56634111
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610321672.1A Pending CN105859717A (en) | 2016-05-16 | 2016-05-16 | Acetazolamide medicine composition and medical application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105859717A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105663143A (en) * | 2016-03-23 | 2016-06-15 | 钱浩 | Propyl gallate pharmaceutical composition and pharmaceutical application thereof in preventing and treating Parkinson's disease |
| CN105753826A (en) * | 2016-05-09 | 2016-07-13 | 宋晓梅 | Medicinal composition of gemfibrozil and medicinal application of medicinal composition |
| CN105884858A (en) * | 2016-05-16 | 2016-08-24 | 苏州毕诺佳医药技术有限公司 | Pharmaceutical composition of aceclofenac and pharmaceutical application thereof |
| CN105906626A (en) * | 2016-05-16 | 2016-08-31 | 苏州毕诺佳医药技术有限公司 | Medicine composition of adenosine cyclophosphate and medical purpose thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524063A (en) * | 2016-02-28 | 2016-04-27 | 李月升 | Novel terpene indole alkaloid compound, and preparation method and medical application thereof |
| CN105663143A (en) * | 2016-03-23 | 2016-06-15 | 钱浩 | Propyl gallate pharmaceutical composition and pharmaceutical application thereof in preventing and treating Parkinson's disease |
| CN105732628A (en) * | 2016-03-18 | 2016-07-06 | 温州聚宜创科技有限公司 | Pharmaceutical composition of amikacin sulfate and medical application of pharmaceutical composition |
| CN105777478A (en) * | 2016-03-18 | 2016-07-20 | 葛斌 | Prostaglandin E1 pharmaceutical composition and medical application thereof |
| CN105777752A (en) * | 2016-03-31 | 2016-07-20 | 河南省洛正制药厂 | Quality control method for lamiophlomis rotata kudo particles |
| CN105906626A (en) * | 2016-05-16 | 2016-08-31 | 苏州毕诺佳医药技术有限公司 | Medicine composition of adenosine cyclophosphate and medical purpose thereof |
-
2016
- 2016-05-16 CN CN201610321672.1A patent/CN105859717A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524063A (en) * | 2016-02-28 | 2016-04-27 | 李月升 | Novel terpene indole alkaloid compound, and preparation method and medical application thereof |
| CN105732628A (en) * | 2016-03-18 | 2016-07-06 | 温州聚宜创科技有限公司 | Pharmaceutical composition of amikacin sulfate and medical application of pharmaceutical composition |
| CN105777478A (en) * | 2016-03-18 | 2016-07-20 | 葛斌 | Prostaglandin E1 pharmaceutical composition and medical application thereof |
| CN105663143A (en) * | 2016-03-23 | 2016-06-15 | 钱浩 | Propyl gallate pharmaceutical composition and pharmaceutical application thereof in preventing and treating Parkinson's disease |
| CN105777752A (en) * | 2016-03-31 | 2016-07-20 | 河南省洛正制药厂 | Quality control method for lamiophlomis rotata kudo particles |
| CN105906626A (en) * | 2016-05-16 | 2016-08-31 | 苏州毕诺佳医药技术有限公司 | Medicine composition of adenosine cyclophosphate and medical purpose thereof |
Non-Patent Citations (1)
| Title |
|---|
| CONG, HAIJIAN等: "Terpenoid indole alkaloids from Mappianthus iodoides Hand.-Mazz.", 《PHYTOCHEMISTRY》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105663143A (en) * | 2016-03-23 | 2016-06-15 | 钱浩 | Propyl gallate pharmaceutical composition and pharmaceutical application thereof in preventing and treating Parkinson's disease |
| CN105753826A (en) * | 2016-05-09 | 2016-07-13 | 宋晓梅 | Medicinal composition of gemfibrozil and medicinal application of medicinal composition |
| CN105884858A (en) * | 2016-05-16 | 2016-08-24 | 苏州毕诺佳医药技术有限公司 | Pharmaceutical composition of aceclofenac and pharmaceutical application thereof |
| CN105906626A (en) * | 2016-05-16 | 2016-08-31 | 苏州毕诺佳医药技术有限公司 | Medicine composition of adenosine cyclophosphate and medical purpose thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105859717A (en) | Acetazolamide medicine composition and medical application thereof | |
| CN103191174B (en) | Chemical component of eucommia bark used is as the new application of blood vessel protective agent | |
| CN104873531B (en) | A kind of adenosine receptor excitement reagent and application thereof | |
| JP2009539780A (en) | Use of 20 (S) -protopanaxadiol for the production of antidepressants | |
| CN108175770A (en) | It is a kind of to treat the reagent of kidney failure by acting on adenosine receptor | |
| CN1176101C (en) | Compound (I), method for extracting it and pharmaceutical composition containing it | |
| CN106496245A (en) | The pharmaceutical composition of lisinopril and its application in biological medicine | |
| BRPI0706865A2 (en) | Method for preparing shinyleaf yellowhorn extract and shinyleaf yellowhorn extract | |
| CN104530176B (en) | GAOH derivative and medicinal use thereof | |
| CN105777854A (en) | Pharmaceutical composition of etimicin sulfate and application of pharmaceutical composition in biomedicine | |
| CN106083876A (en) | The pharmaceutical composition of cytarabine hydrochloride and the application in biological medicine thereof | |
| CN105663143A (en) | Propyl gallate pharmaceutical composition and pharmaceutical application thereof in preventing and treating Parkinson's disease | |
| CN110156784B (en) | Indole alkaloid 11-MT and preparation method and application thereof | |
| CN1994277B (en) | Solid preparation of salvianolic acid A of red sage root and preparation process thereof | |
| CN105777683A (en) | Bicyclol medicine composition and medical application thereof | |
| CN110183414B (en) | One of two color jackfruits isopentene group talan and its purposes in preparation treatment diseases associated with inflammation drug | |
| CN111662349B (en) | Flos Buddlejae extract, and preparation method and application thereof | |
| EP2830641B1 (en) | New valerian extracts and uses thereof | |
| CN106554349A (en) | Wild anistree new isopentene group replaces C6‑C3Class compound and preparation method thereof, application and its pharmaceutical composition | |
| CN105801541A (en) | Pharmaceutical composition of amoxicillin and medical application of pharmaceutical composition | |
| CN110559307A (en) | albizzia julibrissin new lignan compound and new application thereof | |
| Schorderet | The effects of dopamine, piribedil (ET-495) and its metabolite S-584 on retinal adenylate cyclase | |
| CN113264975B (en) | An extract with antiinflammatory activity extracted from fructus Rosae Normalis rhizome and its application | |
| CN112755036A (en) | Agent for altering smooth muscle properties by modulating MYPT1 and uses thereof | |
| CN105777478A (en) | Prostaglandin E1 pharmaceutical composition and medical application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160817 |
|
| RJ01 | Rejection of invention patent application after publication |