CN112142806A - Compound and salt, pharmaceutical composition and application thereof - Google Patents

Compound and salt, pharmaceutical composition and application thereof Download PDF

Info

Publication number
CN112142806A
CN112142806A CN202010998882.0A CN202010998882A CN112142806A CN 112142806 A CN112142806 A CN 112142806A CN 202010998882 A CN202010998882 A CN 202010998882A CN 112142806 A CN112142806 A CN 112142806A
Authority
CN
China
Prior art keywords
compound
disease
pharmaceutical composition
pharmaceutically acceptable
parkinson
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.)
Granted
Application number
CN202010998882.0A
Other languages
Chinese (zh)
Other versions
CN112142806B (en
Inventor
张培成
杨广森
段陈平
罗霞
李文梼
宋志英
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanxi Deyuantang Pharmaceutical Co ltd
Original Assignee
Shanxi Deyuantang Pharmaceutical Co ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Shanxi Deyuantang Pharmaceutical Co ltd filed Critical Shanxi Deyuantang Pharmaceutical Co ltd
Priority to CN202010998882.0A priority Critical patent/CN112142806B/en
Publication of CN112142806A publication Critical patent/CN112142806A/en
Application granted granted Critical
Publication of CN112142806B publication Critical patent/CN112142806B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
    • 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
    • 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
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C07H1/06—Separation; Purification
    • C07H1/08—Separation; Purification from natural products
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention relates to a compound, a salt, a pharmaceutical composition and application thereof, wherein the compound has the following structure:

Description

Compound and salt, pharmaceutical composition and application thereof
Technical Field
The invention belongs to the field of medicines, and particularly relates to a compound, a salt, a pharmaceutical composition and application thereof.
Background
Stroke is a serious disease that seriously threatens human health and social development. Studies have shown that 150 million people die of stroke each year in china, and three out of four survivors suffer from different degrees of disability. With the rapid development of medical science and technology, the diagnosis and treatment level of cerebrovascular diseases is continuously improved, but the diseases still have the characteristics of high morbidity, high recurrence rate, high disability rate and high fatality rate. Therefore, there is an increasing need to further study the pathogenesis of cerebrovascular diseases and to develop effective therapeutic agents. There is no clinically effective treatment for this type of disease. The research on the high-efficiency low-toxicity multi-target multi-link anti-cerebral ischemic injury medicament is a hot problem of domestic and foreign research in recent years.
Parkinson 'S disease (PD) and Alzheimer' S disease (AD) are chronic neurodegenerative diseases that occur worldwide. Most of the patients with AD and PD are the elderly and have no hereditary character. Although the mechanism of pathogenesis of neurodegenerative diseases is not clear, the degeneration and damage of neurons are the direct causes of the disease. Modern pharmacological research shows that oxidative stress reaction, inflammatory reaction, mitochondrial function damage and the like in organisms are all important factors causing neuron degenerative change, and the current medicaments and medical means are only limited to prevention and alleviation of PD and AD, and no effective medicament capable of curing the diseases exists, so that the search and development of a novel nerve protective agent which has high efficiency, low toxicity and multiple target points, can protect neurons, prevent injuries, even repair and reconstruct nerve synapses and restore the normal functions of neurotransmitters for treating the neurodegenerative diseases is always a difficult point and a hot point of research of pharmacologists at home and abroad.
Carthami flos is dried flower of Carthamus tinctorius L of Carthamus of Compositae, has effects of promoting blood circulation, dredging channels, removing blood stasis, relieving pain, lowering blood pressure, and reducing blood lipid, and can be used for treating amenorrhea, dysmenorrhea, traumatic injury, coronary heart disease, angina pectoris and hypertension. Safflower is an important Chinese medicament for preventing and treating diseases such as coronary heart disease, myocardial infarction, cerebral thrombosis and the like in modern clinic.
Disclosure of Invention
The invention aims to provide a new compound in safflower, a preparation method and a pharmaceutical composition thereof and application in preparing or treating neurodegenerative diseases.
The research of applicants discovers that a compound with a novel structure, namely hydroxy safflower yellow-4 '-O-beta-D-glucoside, is separated from safflower, the chemical structure is as follows, pharmacological experiments prove that the compound can effectively improve the survival rate of primary neuron cells of rats with glutamic acid damage, has good effects of preventing and treating Parkinson, Alzheimer's disease and cerebral apoplexy, the effective dose is 10 mu M, and the activity of the compound is higher than that of a positive control medicament, namely butylphthalide under the same dose.
Figure BDA0002693526610000021
In order to solve the technical problem, the invention provides the following technical scheme:
the first aspect of the technical scheme of the invention provides a compound or a pharmaceutically acceptable salt thereof, which is characterized in that the structure of the compound is as follows:
Figure BDA0002693526610000022
the pharmaceutically acceptable salt is selected from salts of compounds, inorganic bases and organic bases. The organic base comprises methylamine, ethylamine, ethylenediamine, dimethylamine, trimethylamine, triethylamine, propylamine, isopropylamine, tripropylamine, butylamine, isobutylamine, tert-butylamine, hexylamine, octylamine, aniline, benzylamine, cyclohexylamine, pyridine, n-butyllithium, potassium tert-butoxide, sodium methoxide, sodium ethoxide, potassium ethoxide, butyllithium and phenyllithium, and the inorganic base comprises lithium hydroxide, sodium hydroxide, magnesium hydroxide, calcium hydroxide and potassium hydroxide.
In a second aspect of the present invention, there is provided a process for preparing a compound of the first aspect, which comprises: purified water extraction, concentration, alcohol precipitation, supernatant fluid concentration, filtration, macroporous adsorption resin chromatography, polyamide chromatography, gel column chromatography, reversed phase silica gel column chromatography and preparative HPLC separation purification are carried out on the safflower medicinal material to obtain the compound hydroxy safflor yellow-4 '-O-beta-D-glucoside, and the structure of the compound hydroxy safflor yellow-4' -O-beta-D-glucoside is analyzed and identified by means of spectroscopy such as UV, IR, NMR, MS, CD and the like, and the substance is not reported at present.
In a third aspect of the present invention, there is provided a pharmaceutical composition comprising a compound of the first aspect of the present invention or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or excipient. The dosage forms of the pharmaceutical composition comprise tablets, capsules, pills, granules, oral liquid, suspensions, injections and the like.
The fourth aspect of the technical scheme of the invention provides an application of the compound of the first aspect of the invention in preparing a medicament for preventing or/and treating neurodegenerative diseases. The neurodegenerative disease comprises cerebral apoplexy, Parkinson's disease and Alzheimer's disease. The cerebral apoplexy, Parkinson's disease or Alzheimer's disease is selected from cerebral apoplexy, Parkinson's disease or Alzheimer's disease related to neuron damage.
The beneficial technical effects are as follows:
1. the new compound in the safflower has obvious effect of preventing and treating neurodegenerative diseases, and pharmacological experiments prove that the compound can effectively improve the survival rate of primary neuron cells of rats damaged by glutamic acid, has good effect of preventing and treating cerebral apoplexy, Parkinson's disease and Alzheimer's disease, has the effective dose of 10 mu M, and has higher activity than a positive control medicament of butylphthalide under the same dose.
2. The novel compound in the safflower has a novel structure, is not reported in documents, and has the potential of being further developed into a medicament for preventing and treating neurodegenerative diseases.
Detailed Description
The following examples and pharmacological activity experiments are intended to further illustrate the invention, but are not intended to limit the invention in any way.
Example 1 preparation and characterization of the monomer Compound hydroxysafflor yellow-4' -O-beta-D-glucoside in safflower
Extracting 10 kg of safflower medicinal material with pure water for 3 times, each time for 2 hours, concentrating the extracting solution, carrying out alcohol precipitation by using 80% ethanol final concentration, concentrating the supernatant until no alcohol smell exists, carrying out macroporous adsorption resin chromatography, polyamide chromatography, gel column chromatography, reversed phase silica gel column chromatography and preparative HPLC separation and purification to obtain a compound, namely hydroxysafflor yellow-4 '-O-beta-D-glucoside, and analyzing and identifying the structure of the compound by using spectral means such as UV, IR, NMR, MS, CD and the like to obtain the hydroxysafflor yellow-4' -O-beta-D-glucoside.
The spectrum information and nuclear magnetic signal attribution of the new compound are as follows:
hydroxy safflower yellow-4' -O-beta-D-glucoside, yellow powder; [ alpha ] to]25D-95.0(c 0.1,MeOH)；UV(MeOH)λmax(log):227(4.09),328(4.12),399(4.39)nm；ECD(c 1.3×10-3,MeOH)λmax(Δ)216(-8.64),268(-16.90),328(3.32),402(1.42)nm；IR(KBr)νmax3394,2890,1625,1603,1511,1447,1364,1237,1178,1078,1015,927,894,833,657,624cm-1；1H NMR(DMSO-d6,500MHz):7.44(1H,d,J＝16.0Hz,H-8),7.31(1H,d,J＝16.0Hz,H-9),7.51(2H,d,J＝8.5Hz,H-2',H-6'),7.02(2H,d,J＝8.5Hz,H-3',H-5'),3.64(1H,d,J＝9.5Hz,H-1”),3.27-3.35(3H,m,H-2”,Hα-6”,Hα-6”'),3.07-3.09(2H,m,H-3”,H-3”'),2.87(1H,m,H-4”),2.94(1H,m,H-5”),3.55-3.61(2H,m,Hβ-6”,Hβ-6”'),4.18(1H,d,J＝9.5Hz,H-1”'),4.11(1H,m,H-2”'),3.02-3.04(2H,m,H-4”',H-5”'),4.89(1H,d,J＝7.5Hz,H-1””),3.21-3.27(1H,m,H-2””),3.24-3.31(1H,m,H-3””),3.16(1H,m,H-4””),3.31-3.35(1H,m,H-5””),3.46(1H,m,Hα-6””),3.69(1H,m,Hβ-6””).13C NMR(DMSO-d6,125MHz):182.5(C-1),106.5(C-2),195.4(C-3),85.5(C-4),189.5(C-5),99.4(C-6),178.6(C-7),124.9(C-8),134.8(C-9),130.1(C-1'),129.0(C-2',6'),116.3(C-3',5'),157.9(C-4'),85.7(C-1”),69.6(C-2”),78.4(C-3”),69.9(C-4”),80.3(C-5”),61.2(C-6”),73.8(C-1”'),68.6(C-2”'),79.2(C-3”'),71.0(C-4”'),80.8(C-5”'),61.6(C-6”'),100.2(C-1””),73.3(C-2””),76.6(C-3””),69.7(C-4””),77.2(C-5””),60.7(C-6””).HRESIMS m/z:773.2154[M-H]-(calcd.for773.2146.C33H41O21).
Pharmacological experiments
Experimental example 1 protective Effect of Hydroxysafflor yellow-4' -O-beta-D-glucoside on glutamic acid damage of Primary neuronal cells
Wistar rat mammary rat cortical neuronal cells within 12 hours of birth were cultured in DMEM containing 10% Fetal Bovine Serum (FBS), 100U/mL cyan, streptomycin in 5% CO2And culturing at 37 ℃ in an incubator. Rat primary neuronal cells were plated at 5X 105Density of individual/mL, 100 μ L per well was seeded in 96-well plates. 10 μ M of the positive drug PHPB, compound hydroxysafflor yellow A-4' -O- β -D-glucoside, respectively, were incubated with primary neuronal cells for 1 hour. 80mM glutamic acid stock solution was prepared and diluted to 8mM dilution with neuronal maintenance medium. mu.L of glutamic acid diluent and 10. mu.L of corresponding 10. mu.M PHPB, hydroxysafflor yellow A-4' -O-beta-D-glucoside were added to each well, respectively, and incubated for 20 hours. Thereafter, 10. mu.L of CCK-8(5mg/mL) was added to each well, incubation was continued for 4 hours, and OD was measured at 450nm in each well on a microplate reader, 3 wells per set, and each experiment was repeated 3 times.
The result shows that the glutamic acid can obviously reduce the survival rate of primary neuron cells, both the 10 mu M positive medicine PHPB and the compound hydroxysafflor yellow A-4 '-O-beta-D-glucoside have a protective effect on the damage of the primary neuron cells induced by the glutamic acid, the 10 mu M PHPB can improve the cell survival rate by 28.6 percent, and the 10 mu M hydroxysafflor yellow A-4' -O-beta-D-glucoside can improve the cell survival rate by 37.9 percent.
The results in example 1 show that, in the Wistar rat cortical neuron cell glutamic acid damage model, the hydroxysafflor yellow A-4' -O-beta-D-glucoside shows stronger protective effect, and the activity is obviously higher than that of the positive drug PHPB. The results indicate that the hydroxysafflor yellow A-4' -O-beta-D-glucoside has potential to be developed into the treatment of neurodegenerative diseases such as cerebral apoplexy, Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis and the like.

Claims (9)

1. A compound having the structure:
Figure FDA0002693526600000011
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1, wherein said pharmaceutically acceptable salt is selected from the group consisting of salts of the compound with inorganic and organic bases.
3. The compound of claim 2, wherein said organic base comprises methylamine, ethylamine, ethylenediamine, dimethylamine, trimethylamine, triethylamine, propylamine, isopropylamine, tripropylamine, butylamine, isobutylamine, tert-butylamine, hexylamine, octylamine, aniline, benzylamine, cyclohexylamine, pyridine, n-butyllithium, potassium tert-butoxide, sodium methoxide, sodium ethoxide, potassium ethoxide, butyllithium or phenyllithium, and said inorganic base comprises lithium hydroxide, sodium hydroxide, magnesium hydroxide, calcium hydroxide or potassium hydroxide.
4. The compound of claim 1, characterized in that said preparation is as follows: extracting purified water of safflower, concentrating, precipitating with ethanol, collecting supernatant, concentrating, filtering, performing macroporous adsorbent resin chromatography, polyamide chromatography, gel column chromatography, reversed phase silica gel column chromatography and preparative HPLC separation and purification to obtain hydroxysafflor yellow-4' -O-beta-D-glucoside.
5. A pharmaceutical composition comprising a compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.
6. The pharmaceutical composition of claim 5, wherein the pharmaceutical composition is in the form of tablet, capsule, pill, granule, oral liquid, suspension, injection, etc.
7. Use of a compound according to any one of claims 1 to 3 for the preparation of a medicament for the prophylaxis or/and treatment of neurodegenerative diseases.
8. The use according to claim 7, wherein said neurodegenerative disease is stroke, Parkinson's disease, Alzheimer's disease.
9. The use according to claim 8, wherein the stroke, parkinson or alzheimer's disease is selected from the group consisting of stroke, parkinson or alzheimer's disease associated with primary neuronal damage.
CN202010998882.0A 2020-09-22 2020-09-22 Compound and salt, pharmaceutical composition and application thereof Active CN112142806B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202010998882.0A CN112142806B (en) 2020-09-22 2020-09-22 Compound and salt, pharmaceutical composition and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010998882.0A CN112142806B (en) 2020-09-22 2020-09-22 Compound and salt, pharmaceutical composition and application thereof

Publications (2)

Publication Number Publication Date
CN112142806A true CN112142806A (en) 2020-12-29
CN112142806B CN112142806B (en) 2023-03-03

Family

ID=73893558

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010998882.0A Active CN112142806B (en) 2020-09-22 2020-09-22 Compound and salt, pharmaceutical composition and application thereof

Country Status (1)

Country Link
CN (1) CN112142806B (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1640392A (en) * 2004-01-08 2005-07-20 山东绿叶天然药物研究开发有限公司 High-dose hydroxy safflower yellow A or its medically-acceptable salt application for preparing medicine for cerebral apoplexy induced from being ischemic
CN102702150A (en) * 2012-06-19 2012-10-03 浙江永宁药业股份有限公司 Preparation method and application of hydroxysafflor yellow A
CN103006633A (en) * 2012-11-27 2013-04-03 广东省中医院 Application of hydroxysafflor yellow A in preparation of medicament for resisting Alzheimer disease
CN111662261A (en) * 2019-03-05 2020-09-15 中国医学科学院药物研究所 Quinoid dihydrochalcone dicarboside compound with glucose in ring A, preparation method and neuroprotective activity

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1640392A (en) * 2004-01-08 2005-07-20 山东绿叶天然药物研究开发有限公司 High-dose hydroxy safflower yellow A or its medically-acceptable salt application for preparing medicine for cerebral apoplexy induced from being ischemic
CN102702150A (en) * 2012-06-19 2012-10-03 浙江永宁药业股份有限公司 Preparation method and application of hydroxysafflor yellow A
CN103006633A (en) * 2012-11-27 2013-04-03 广东省中医院 Application of hydroxysafflor yellow A in preparation of medicament for resisting Alzheimer disease
CN111662261A (en) * 2019-03-05 2020-09-15 中国医学科学院药物研究所 Quinoid dihydrochalcone dicarboside compound with glucose in ring A, preparation method and neuroprotective activity

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HAIBO ZHU ET AL.: "Neuroprotective Effects of Hydroxysafflor Yellow A: In Vivo and in Vitro Studies", 《PLANTA MED》 *
ZI-MING FENG ET AL.: "NMR Solution Structure Study of the Representative Component Hydroxysafflor Yellow A and Other Quinochalcone C‑Glycosides from Carthamus tinctorius", 《J. NAT. PROD.》 *

Also Published As

Publication number Publication date
CN112142806B (en) 2023-03-03

Similar Documents

Publication Publication Date Title
CN100575358C (en) Flos Lonicerae extract, its preparation method and application
US20120041062A1 (en) Compound of salvianolic acid l, preparation method and use thereof
CN111087285B (en) Method for extracting bibenzyl compounds from dendrobium officinale and application of bibenzyl compounds
AU2003242135B2 (en) Preparation Method of Danshentotalphenolic Acid and the Use Thereof
CN101993429A (en) Method for extracting dihydroquercetin from larch sawdust
CN110305014B (en) Cycloneolignanoid enantiomers, preparation and application thereof
CN109134486B (en) Coumarin lignan, preparation method and application thereof
CN1210289C (en) Radde anemone rhizome extract and its prepn process and use
CN112142806B (en) Compound and salt, pharmaceutical composition and application thereof
CN104926825B (en) Neolignan alkane derivatives promoting neurotrophic activity, and preparation method and application thereof
WO2012061984A1 (en) Method for preparing albiflorin and paeoniflorin
CN113912482B (en) Guaiane sesquiterpene compound and preparation and application thereof
CN113773409A (en) Polysaccharide of radix scutellariae Siniperca and its application
CN110872240B (en) Method for extracting guanidine alkaloid of scorpion and scorpion alkaloid A and/or scorpion and scorpion alkaloid B in scorpion and medical application
CN103113196B (en) Glechoma longituba phenol, and preparation method and application thereof
KR20210109733A (en) A pharmaceutical composition comprising loganic acid for preventing or treating cognitive impairment related disease
CN101669637B (en) Application of cornflower-3-O-galactoside in preparing foods or medicaments for improving cognitive functions of old people
EP0606497A1 (en) Remedy for biotoxin type bacterial intestinal infectious diseases
CN116789721B (en) Application of farnesane sesquiterpenoids in preventing trichinosis
CN111004296B (en) Oligomeric agar oligosalts and application thereof in preparation of medicines for treating neurodegenerative diseases and cardiovascular and cerebrovascular diseases
CN114028366B (en) Application of monocyclic monoterpene compound in preparation of anti-senile dementia drugs
CN108272869B (en) Preparation method of traditional Chinese medicine composition oral liquid preparation for treating lower urinary tract infection
CN101235060B (en) Isograndidentatin, preparation method thereof and application of the same in preparing antineoplastic medicament
CN115703753A (en) Benzofuran type derivative and preparation method and application thereof
CN116178328A (en) Biflavone compound with preventing and protecting effect on myocardial injury

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