CN119055624B - Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines - Google Patents
Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines Download PDFInfo
- Publication number
- CN119055624B CN119055624B CN202411562982.3A CN202411562982A CN119055624B CN 119055624 B CN119055624 B CN 119055624B CN 202411562982 A CN202411562982 A CN 202411562982A CN 119055624 B CN119055624 B CN 119055624B
- Authority
- CN
- China
- Prior art keywords
- compound
- pinnatifolone
- preparation
- parkinson
- parkinsonism
- 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.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 47
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 229940079593 drug Drugs 0.000 title abstract description 13
- 208000027089 Parkinsonian disease Diseases 0.000 title description 10
- 206010034010 Parkinsonism Diseases 0.000 title description 10
- 239000000939 antiparkinson agent Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 229940035678 anti-parkinson drug Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 abstract description 10
- 241001104043 Syringa Species 0.000 abstract description 8
- 208000018737 Parkinson disease Diseases 0.000 abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 6
- 235000004338 Syringa vulgaris Nutrition 0.000 abstract description 6
- 238000001953 recrystallisation Methods 0.000 abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 5
- 238000000605 extraction Methods 0.000 abstract description 5
- 239000003208 petroleum Substances 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 5
- 230000000648 anti-parkinson Effects 0.000 abstract description 4
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 239000012046 mixed solvent Substances 0.000 abstract description 3
- 238000010898 silica gel chromatography Methods 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 238000001727 in vivo Methods 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000009194 climbing Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 3
- QIMGSZURBOTPMW-UHFFFAOYSA-N 2-methoxy-5-(2,3,4-trimethoxyphenyl)cyclohepta-2,4,6-trien-1-one Chemical compound COC1=C(OC)C(OC)=CC=C1C1=CC=C(OC)C(=O)C=C1 QIMGSZURBOTPMW-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 241000207834 Oleaceae Species 0.000 description 3
- 241000775848 Syringa oblata Species 0.000 description 3
- 206010044565 Tremor Diseases 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- LKBQARGGDFBGFF-UHFFFAOYSA-N eremophilane Natural products CC1C(O)CCC2C(=O)CC(CC12C)C(=C)C LKBQARGGDFBGFF-UHFFFAOYSA-N 0.000 description 2
- AJWBFJHTFGRNDG-GBJTYRQASA-N eremophilane Chemical compound C1CC[C@H](C)[C@@]2(C)C[C@H](C(C)C)CC[C@H]21 AJWBFJHTFGRNDG-GBJTYRQASA-N 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 2
- 229960004502 levodopa Drugs 0.000 description 2
- 230000027939 micturition Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229930004725 sesquiterpene Natural products 0.000 description 2
- -1 sesquiterpene compound Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- 206010002653 Anosmia Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 208000012639 Balance disease Diseases 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 238000011746 C57BL/6J (JAX™ mouse strain) Methods 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 206010018713 Gravitational oedema Diseases 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 206010050515 Hyposmia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102000010909 Monoamine Oxidase Human genes 0.000 description 1
- 108010062431 Monoamine oxidase Proteins 0.000 description 1
- 208000001089 Multiple system atrophy Diseases 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 206010061533 Myotonia Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 206010031127 Orthostatic hypotension Diseases 0.000 description 1
- 206010071390 Resting tremor Diseases 0.000 description 1
- 206010039424 Salivary hypersecretion Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000045 anti-neurotoxic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000002027 dichloromethane extract Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 231100000880 dysequilibrium Toxicity 0.000 description 1
- 231100000317 environmental toxin Toxicity 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000019559 hyposmia Nutrition 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000000968 medical method and process Methods 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000026451 salivation Diseases 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/79—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
- C07C2602/28—Hydrogenated naphthalenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Crystallography & Structural Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明属于医药技术领域，公开了化合物Pinnatifolone A在制备抗帕金森药物中的应用，所述化合物Pinnatifolone A是中药紫丁香茎的主要活性成分，本发明还公开了化合物Pinnatifolone A的制备方法，取紫丁香茎进行醇提，依次用二氯甲烷、乙酸乙酯进行萃取，取二氯甲烷萃取部位进行硅胶柱层析分离，然后采用石油醚与丙酮的混合溶剂进行重结晶纯化，即可得到目标化合物。通过体内试验表明，本发明的化合物Pinnatifolone A在抗帕金森疾病方面具有较强的活性，疗效明确，毒副作用小，可作为潜在的抗帕金森疾病药物。
The invention belongs to the field of medical technology, and discloses the use of a compound Pinnatifolone A in the preparation of an anti-Parkinson's disease drug. The compound Pinnatifolone A is the main active ingredient of a traditional Chinese medicine lilac stem. The invention also discloses a preparation method of the compound Pinnatifolone A, wherein the lilac stem is extracted with alcohol, and then extracted with dichloromethane and ethyl acetate in sequence, and the dichloromethane extraction portion is separated by silica gel column chromatography, and then a mixed solvent of petroleum ether and acetone is used for recrystallization and purification, so as to obtain a target compound. In vivo tests show that the compound Pinnatifolone A of the invention has strong activity in anti-Parkinson's disease, clear efficacy, and small toxic and side effects, and can be used as a potential anti-Parkinson's disease drug.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of a compound Pinnatifolone A in preparation of an anti-parkinsonism medicament.
Background
Parkinson's Disease (PD) is a chronic, progressive neurodegenerative Disease whose main pathological feature is the loss of dopaminergic neurons in the brain, leading to the appearance of motor and non-motor symptoms. The cause of this disease may involve genetic factors, environmental toxin exposure, and aging of the nervous system. Motor symptoms of parkinson's disease include resting tremor, myotonia, bradykinesia and dysequilibrium, whereas non-motor symptoms include depression, anxiety, dementia, hyposmia or disappearance of smell, salivation, dysphagia, constipation, frequent urination, urgent urination, insomnia, excessive daytime sleepiness, fatigue, etc.
Modern medical methods for treating parkinson's disease mainly comprise medication, surgical treatment, exercise therapy, psychological intervention, care and the like. Among them, drug therapy is the first choice and the main therapeutic means. The therapeutic drugs include compound levodopa, dopamine receptor agonists (DAs), monoamine oxidase B-type inhibitors (MAO-BI), catechol-O-methyltransferase inhibitors (COMTI), anticholinergic agents, etc. However, the existing treatment methods have limitations such as side effects of medicines, complications caused by long-term use, and the like. For example, prolonged use of levodopa may lead to motor complications, such as catabolism, while neuropsychiatric side effects, such as hallucinations and consciousness disturbance, may also occur. In addition, some drugs may cause other side effects such as orthostatic hypotension, edema, and the like. Therefore, the medicine for treating the parkinsonism has no toxic or side effect, is convenient to take, is economical and practical, and has become a hot spot for the development of modern medicines.
Compound Pinnatifolone A (C 15H20O3, molecular weight 248.141) is an eremophilane type sesquiterpene compound with wide pharmacological activity extracted from plants of Syringa of Oleaceae, and belongs to natural sesquiterpene compounds. As the sesquiterpenoids have novel structures, modern researches have found that the sesquiterpenoids have wide biological activities, including anti-tumor, antibacterial, anti-inflammatory, anti-neurotoxic, antiviral, immunosuppressive, liver protecting and heart strengthening effects. Recent studies have shown that Pinnatifolone A has potential as a sedative hypnotic. At present, the traditional Chinese medicine is a precious resource for identifying and developing new medicines, pinnatifolone A is taken as an active ingredient of the traditional Chinese medicine, and has the potential of further development. In addition, the preparation method of the compound Pinnatifolone A in the prior art is complex, and brings inconvenience to practical application.
Disclosure of Invention
The invention aims to explore the activity of the traditional Chinese medicine of a compound Pinnatifolone A and provide the application of the compound Pinnatifolone A in preparing anti-parkinsonism medicines. The inventor finds that the compound has stronger activity in the aspect of anti-parkinsonism, definite curative effect and small toxic and side effect, and can be used as a potential anti-parkinsonism medicament.
The technical scheme of the invention is as follows:
the application of the compound Pinnatifolone A in preparing anti-parkinsonism medicines.
Preferably, the chemical structural formula of the compound Pinnatifolone A is:
。
Preferably, the stereo configuration of the compound Pinnatifolone A is any one of the following:
。
more preferably, the compound Pinnatifolone A has the steric configuration of 。
Preferably, the content of compound Pinnatifolone A in the medicament is 1-99.5%, more preferably 2-50%.
Preferably, the medicament further comprises a pharmaceutically acceptable carrier or adjuvant.
The compound can be directly or indirectly added into various pharmaceutically acceptable common carriers or auxiliary materials (such as filling agents, disintegrating agents, lubricants, adhesives and the like) required by preparing different dosage forms by a person skilled in the art, and is prepared into common oral preparations or injection preparations by a conventional pharmaceutical preparation method in the pharmaceutical field.
Preferably, the oral preparation is one of a tablet, a capsule, a granule, a fat emulsion, a microcapsule and a pill.
Preferably, the injection preparation is injection or powder injection.
Preferably, the oral formulation is administered at a dose of from 5 to 200mg/kg, more preferably from 10 to 40mg/kg, of compound Pinnatifolone A.
The invention also provides a preparation method of the compound Pinnatifolone A, which comprises the following steps:
(1) Extracting dry stem of Syringa oblata with 10 times of 70% (volume percent) ethanol water solution twice for 2 hr each time, mixing extractive solutions, concentrating until no ethanol smell exists, and extracting with dichloromethane and ethyl acetate to obtain dichloromethane extract and ethyl acetate part;
(2) Mixing dichloromethane extraction part with 100-200 mesh silica gel 1:1, drying, separating by silica gel (200-300 mesh) column chromatography, eluting with petroleum ether-acetone (volume ratio of 100:0, 50:1, 25:1, 10:1, 5:1, 1:1, 0:100) as mobile phase, collecting with 2000ml unit, combining and concentrating by thin layer chromatography detection to obtain 12 fractions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12;
(3) And (3) taking fraction 3, carrying out recrystallization purification in a mixed solvent of petroleum ether and acetone in a volume ratio of 5:1, and repeatedly carrying out recrystallization purification to obtain the compound Pinnatifolone A.
The beneficial effects of the invention are as follows:
1. According to the invention, through an influence experiment of the compound Pinnatifolone A on the length of the pole climbing time and the length of the rotating rod fatigue movement of the MTPT induced mice, the compound Pinnatifolone A has strong activity on the aspect of anti-parkinsonism, has definite curative effect and small toxic and side effects, and can be used as a potential anti-parkinsonism drug.
2. The preparation method of the compound Pinnatifolone A is simple, the target compound can be obtained through silica gel column chromatography separation and recrystallization purification, and compared with the complicated preparation process in the prior art, the preparation method has the advantages of time and cost saving.
Drawings
FIG. 1 is an X-ray single crystal diffraction pattern of compound Pinnatifolone A.
Detailed Description
The following description of the embodiments of the present invention will be made in detail and with reference to the accompanying drawings, wherein it is apparent that the embodiments described are only some, but not all embodiments of the present invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Unless otherwise specified, all experimental procedures involved in embodiments of the present invention are conventional, all reagents involved are commercially available, and all reagents are commercially available.
The eremophilane sesquiterpenoids Pinnatifolone A can be extracted and separated from plants of the genus Syringa of the family Oleaceae, or can be prepared by other existing technologies.
Compared with the prior art that the target compound Pinnatifolone A is obtained from the lilac roots by adopting a plurality of separation steps, the method provided by the invention has the advantages that the target compound Pinnatifolone A can be obtained by only one silica gel column chromatography separation and combined recrystallization after the effective components are extracted from the lilac stems, and the method is simpler, and the time and the cost are saved.
1. Preparation of Compound Pinnatifolone A
The compound Pinnatifolone A is prepared by the laboratory, is extracted and separated from plants of lilac Syringa oblata Lindl of lilac of the genus lilac of the family oleaceae, and is prepared by the following specific preparation method:
Dried stem of Syringa oblata (10 kg) is crushed, soaked for 24 hours at room temperature, extracted twice by adding 70% (volume percent) ethanol water solution with the amount of 10 times, each time for 2 hours, the extracting solutions are combined and concentrated until no ethanol smell exists, and extraction is carried out by using dichloromethane (10L) and ethyl acetate (10L) respectively, so as to obtain a dichloromethane extraction part 385 g and an ethyl acetate extraction part 296 g. Mixing dichloromethane extraction part with 100 mesh silica gel 1:1, drying, separating by silica gel (200-300 mesh) column chromatography, taking petroleum ether-acetone (volume ratio of 100:0, 50:1, 25:1, 10:1, 5:1, 1:1, 0:100) as mobile phase, collecting in 2000ml unit, combining and concentrating by thin layer chromatography detection to obtain 12 fractions (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). The fraction 3 is taken to be recrystallized and purified in a mixed solvent of petroleum ether and acetone with the volume ratio of 5:1, the compound Pinnatifolone A (10.2 g) is obtained after repeated recrystallization and purification, the purity is more than 95 percent by adopting a high-performance liquid phase area normalization method for detection, meanwhile, the structure of the compound is identified by adopting mass spectrum, nuclear magnetic resonance (1H-NMR, 13C-NMR and 2D-NMR), and the compound is Pinnatifolone A, the molecular formula is C 15H20O3, the molecular weight is 248.14 and the planar chemical structural formula is as follows through structural analysis and comparison with the literature:
。
the stereochemistry of compound Pinnatifolone A was also determined by X-single crystal diffraction pattern analysis of fig. 1 to be:
。
2. Compound pharmacodynamic experimental study
1. Experimental animal
C57BL/6J mice, 8-10 week old, male, weight 22+ -2 g, purchased from Hunan Stokes Leyda laboratory animals Co., ltd., license number SCXK (Hunan) 2024-000.
2. Experimental method
Mice were randomly grouped into normal, model, pinnatifolone A low-dose (10 mg/kg), pinnatifolone A medium-dose (20 mg/kg), pinnatifolone A high-dose (40 mg/kg), positive drug (shafenamide gavage, 40 mg/kg) groups, 9 animals each after one week of adaptive feeding. The normal group was given an equal volume of 0.5% CMC-Na (sodium carboxymethylcellulose) solution by intragastric administration in a volume of 0.1ml/10g, continuously or after 0.5% CMC-Na for 9 days, and the remaining groups except the normal group were intraperitoneally injected with MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, 25 mg/kg) simultaneously with molding, and again after 1 hour, continuously for 5 days for 14 days, and subjected to rod-turning and pole-climbing behavioural assay experiments on day 14.
3. Experimental results
1. Effect of Compound Pinnatifolone A on MTPT-induced mice climbing time
The results are shown in Table 1, and normal mice can smoothly climb from the top of the pole to the bottom of the pole in pole climbing experiments. Compared with the normal group, the movement time of the mice in the model group from the top of the rod to the bottom of the rod is obviously prolonged to 80.97+/-52.17 s, and the progress of rod climbing of the mice in the model group is slowed down due to the fact that the mice are static on the rod caused by the reduction of the movement capacity and the tremor of muscles. The length of movement of mice on the rod was significantly reduced after Pinnatifolone A different dose groups compared to the model group.
TABLE 1
2. Effect of Compound Pinnatifolone A on length of time that MTPT induces rod fatigue movement in mice
The experiment of the length of time of fatigue exercise of the rotating rod shows that after MPTP injection, mice show the manifestations of shortness of breath, tremors, tail stiffness, gait instability and limited behavior ability. The results of the rotating rod experiments are shown in Table 2, compared with a control group, the movement time of the mice in the model group on the rotating rod fatigue tester is obviously shortened to 11.18+/-8.37 s, and compared with the model group, the movement time of the mice in the model group on the rotating rod fatigue tester after being dosed in Pinnatifolone A different dose groups is obviously prolonged.
TABLE 2
Taken together, compound Pinnatifolone A has been shown to have significant antiparkinsonian effects. Thus, compound Pinnatifolone A can be used for preparing an anti-parkinsonism medicament.
Finally, it should be noted that the foregoing description is only a preferred embodiment of the present invention, and the present invention is not limited to the above-mentioned embodiment, but may be modified or some of the technical features thereof may be replaced by other technical solutions described in the foregoing embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (7)
1. Use of compound Pinnatifolone A in the preparation of an anti-parkinson drug, wherein the chemical structural formula of compound Pinnatifolone A is:
。
2. The method according to claim 1, wherein the content of compound Pinnatifolone A in the medicament is 1-99.5%.
3. The method of claim 1, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or adjuvant.
4. The method according to claim 1, wherein the pharmaceutical composition is in the form of an oral or injectable preparation.
5. The method according to claim 2, wherein the content of compound Pinnatifolone A in the medicament is 2-50%.
6. The method according to claim 4, wherein the oral preparation is administered in an amount of about 5-200mg/kg of the compound Pinnatifolone A.
7. The method according to claim 6, wherein the oral preparation is administered in an amount of 10-40mg/kg of the compound Pinnatifolone A.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411562982.3A CN119055624B (en) | 2024-11-05 | 2024-11-05 | Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202411562982.3A CN119055624B (en) | 2024-11-05 | 2024-11-05 | Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN119055624A CN119055624A (en) | 2024-12-03 |
| CN119055624B true CN119055624B (en) | 2025-02-14 |
Family
ID=93646802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202411562982.3A Active CN119055624B (en) | 2024-11-05 | 2024-11-05 | Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN119055624B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007269800A (en) * | 2007-05-11 | 2007-10-18 | Nitto Denko Corp | Food composition containing novel sesquiterpene compound |
| KR20210055172A (en) * | 2019-11-07 | 2021-05-17 | 엠에프씨 주식회사 | Novel sesquiterpene derivatives and use thereof |
| CN112245416A (en) * | 2020-11-17 | 2021-01-22 | 广西馨海药业科技有限公司 | Application of pinnatifone A in preparation of drugs with sedative and hypnotic effects and drug composition |
| CN116077476A (en) * | 2022-12-05 | 2023-05-09 | 云南中医药大学 | Application of a sesquiterpene compound in the preparation of neuroprotective agent and its preparation method |
-
2024
- 2024-11-05 CN CN202411562982.3A patent/CN119055624B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 紫丁香中1个新的倍半萜类化合物;邰巴达拉胡 等;《中国中药杂志》;20240531;第49卷(第9期);第2-3节 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN119055624A (en) | 2024-12-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101209274B (en) | Saussurea involucrata extract and and producing method thereof | |
| US9278948B2 (en) | Line leaf inula flower lactone A and methods for preparing and using the same for treating multiple sclerosis | |
| WO2006097043A1 (en) | Bacopa monnieri extract and process for preparation and use thereof | |
| CN102091111B (en) | Saussurea cataplasm and production method thereof | |
| CN104840527A (en) | Composition containing tenuifoliside and ginsenoside | |
| CN119055624B (en) | Application of compound Pinnatifolone A in preparation of anti-parkinsonism medicines | |
| CN101385736A (en) | Application of Paeoniflorin in Drugs for Preventing and Treating Depression and Its Pharmaceutical Composition | |
| CN103191198A (en) | Rhizoma corydalis extract as well as preparation method and use thereof | |
| CN103721148B (en) | Yizhi kernel composition for treating acute and chronic gastroenteritis and preparation method thereof | |
| CN113149945A (en) | Serial lignan compounds, pharmaceutical compositions, preparation methods and applications thereof | |
| CN101904894B (en) | Application of lamiophlomis rotate total glycosides in preparing medicines | |
| CN113956229B (en) | Lignan compound in lilac and preparation method and application thereof | |
| CN101347562A (en) | Anti-depression medicament as well as preparation method and application thereof | |
| CN100479837C (en) | Weinakang for treating ischemic cerebrovascular disease and senile dementia and preparation method thereof | |
| CN101164571A (en) | Application of active component of cape jasmine for treating senile dementia | |
| CN112691136A (en) | Swertia extract and application thereof in preparation of antidepressant drugs | |
| CN108030794A (en) | Purposes of the Rhizoma Chuanxiong total alkaloid in the medicine for preparing treatment headache | |
| CN104130232B (en) | The method of purification of a kind of EGCG and the EGCG of acquisition and pharmaceutical composition | |
| CA3009533A1 (en) | Novel molecule with anti-cancer activity | |
| CN1799564A (en) | Application of valeriana wallichii and its extract in preparation of medicine for treating anxiety neurosis | |
| CN114736106B (en) | Lignan dimer compound, and preparation method and application thereof | |
| JP2729340B2 (en) | Dementia treatment | |
| CN115448826B (en) | Separation and identification of natural borneol metabolites | |
| CN116270632B (en) | A herba Achillea Wilsonianae alkaloid composition with detoxified effect and its preparation method | |
| CN110934884B (en) | Application of isobiflorin or its pharmaceutically acceptable salt in the preparation of antidepressant pharmaceutical composition |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |