CN111514151A - Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof - Google Patents
Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof Download PDFInfo
- Publication number
- CN111514151A CN111514151A CN202010386001.XA CN202010386001A CN111514151A CN 111514151 A CN111514151 A CN 111514151A CN 202010386001 A CN202010386001 A CN 202010386001A CN 111514151 A CN111514151 A CN 111514151A
- Authority
- CN
- China
- Prior art keywords
- galloyl
- compound
- erythro
- beta
- glucopyranose
- 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
Links
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7024—Esters of saccharides
-
- 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
- A61K31/11—Aldehydes
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- 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
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
- C07H13/08—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals directly attached to carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides application of a compound with anti-inflammatory activity in terminalia chebula miq in preparing an anti-inflammatory drug and a preparation method thereof. The invention obtains 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose from fresh fruits of Terminalia microcarpa; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; the Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether is prepared into solid, liquid or paste dosage forms by adopting a conventional anti-inflammatory activity evaluation model and adopting a thin-layer chromatography method for guidance and combining other phytochemical research means. The preparation method of the three chemical components is simple and convenient, the yield is high, the purity is excellent, and the obtained compound is a natural secondary metabolite and has obvious anti-inflammatory activity.
Description
The technical field is as follows:
the invention belongs to the field of medicines, and particularly relates to a compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; preparation of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether, application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in anti-inflammatory pharmaceutical compositions and application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in medicines.
Background art:
the inflammatory reaction can occur in tissues and organs of various parts of the body, is an important immune and epidemic prevention mechanism generated after the body acts on an inflammatory factor, and is helpful for alleviating the infection of pathogenic microorganisms. However, when the inflammatory reaction is disordered, the tissue cells are damaged, so that the tissue cells are degenerated and necrotized, tissue and organ damage is caused, and the disease is promoted. Invasion of pathogenic factors such as avian influenza, SARS and 2019-novel coronavirus can induce over-excitation of inflammatory reaction of organisms, induce cytokine storm, and seriously threaten life safety of human beings. At present, hormone medicines are mostly adopted for clinically inhibiting excessive immune cell activation and cytokine generation, and long-term large-scale hormone treatment easily causes adverse reactions such as body fatness, blood sugar rise, digestive tract ulcer, electrolyte disorder and osteoporosis to further cause femoral head necrosis. The wide exploration and directed excavation of the micromolecular compound with high-efficiency anti-inflammatory activity and low toxic and side effect is a new idea for regulating inflammatory reaction.
Terminalia chebula is a tree of Terminalia of Combretaceae, the fruit of the plant is a traditional common medicine for minority nationalities such as Tibetan, Mongolia, Dai and Uygur in China, has the effects of astringing intestines to stop diarrhea, astringing lung to stop cough, reducing pathogenic fire to relieve sore throat, clearing heat and removing toxicity and the like, and is one of the essential medicines of Tibetan medicine 'three-fruit decoction'. To explore the pharmacological action mechanism of the national essential drug, at present, the related research results have reported that 110 compounds are separated from the fruits of myrobalan plants, including
1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; erythro-guaiac-glycerol-beta-coniferaldehyde ether, but no research and report on the application of the compound in anti-inflammatory activity and medicaments thereof, and no related preparation method report.
The invention content is as follows:
the invention aims to provide 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; preparation of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether, application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in anti-inflammatory drug composition and application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in preparation of anti-inflammatory drugs.
In order to achieve the above purpose of the present invention, the present invention provides the following technical solutions:
a compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose represented by the following structural formula; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; the application of Erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether in preparing anti-inflammatory drugs,
1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose
4-O-(3”,4”-di-O-galloyl-α-L-rhamnopyranosyl)ellagic acid
Erythro-guaiacyl-glycerol-β-coniferyl aldehyde ether
the compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; the Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether is derived from Terminalia and other plant fruits and other parts of plants containing the compound, and has remarkable anti-inflammatory activity.
The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; application of Erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether in preparing medicines for preventing or treating inflammatory diseases.
The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in preparing medicines for preventing or treating superficial and deep inflammations.
The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; a pharmaceutical composition consisting of Erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether and a pharmaceutically acceptable carrier.
The application of the pharmaceutical composition in preparing a medicament for treating inflammatory diseases and the application thereof in preparing a medicament for preventing or treating superficial and deep inflammations.
The 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose, 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid, and Erythro-guaiacyl-glycerol- β -coniferyl alcohol ether are prepared by separating and purifying the plant fruits and other parts of Terminalia, such as Terminalia microcarpa, Terminalia chebula and Terminalia chebula by natural product separation method, and specifically, the fresh fruits and other plant materials of any one of the three compounds, such as Terminalia microcarpa, Terminalia chebula and Terminalia chebula are pulverized, extracted by cold immersion with 3 times of volume of 70% acetone aqueous solution at room temperature for 3 times, 5 days each time, filtered, the filtrate is concentrated under reduced pressure at 50 ℃ to remove organic solvent, and the residual aqueous solution is purified by thin layer chromatography, and eluted by 35% HP gradient chromatography and 35% methanol gradient.35，Fr.60。Fr.35Loading on Sephadex LH-20 chromatographic column with MeOH/H2And (2) eluting by using 80% and 90% of volume ratio of O, wherein an elution part with 90% of volume ratio of methanol/water is subjected to preparative liquid phase chromatography, eluting by using a mobile phase with 20% of volume ratio of acetonitrile + 0.15% of trifluoroacetic acid/water to obtain a compound 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid, and performing HPLC (high performance liquid chromatography) content detection to obtain the compound 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid with the purity of more than or equal to 90% and the yield of 0.03% of dry weight, and performing MCI-gel CHP20P (chemical vapor chromatography) on an elution part with 90% of volume ratio of methanol/water, and then performing preparative liquid phase chromatography on the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose with the purity of more than or equal to 90% and the compound 1,2,3, 4.60Eluting with MCI-gel CHP20P chromatographic column with 20-100% methanol/water volume ratio solution, concentrating, subjecting to silica gel column chromatography, eluting with chloroform/methanol volume ratio solution of 15: 1 to obtain Erythro-guaiacyl-glycerol- β -chloroferyl alcohol ether, and detecting by HPLC content to obtain product with purity of 90% or more and yield of 0.03% of dry weight.
The anti-inflammatory activity evaluation of the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose and 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid and Erythro-guaiacyl-glycerol- β -coniferyl aldehyde ether is carried out by inoculating mouse mononuclear macrophage strain RAW264.7 into a 96-well plate, wherein the inoculation density is 1.5 × 105Dissolving compounds 1-3 in DMSO solvent respectively, adding into cell culture medium to give final concentration of 50uM and continuous gradient concentration, treating cells with 3 times of each treatment, stimulating with botulinum toxin LPS with final concentration of 1 μ g/mL, evaluating generation of nitrogen monoxide in supernatant after 18 hr with Griess reagent, detecting absorbance at 570nm, and calculating half inhibitory concentration IC of each compound by Reed-Muench method50A value; at the same time, the half-inhibitory concentration IC of the nitric oxide synthase inhibitor L-NMMA is adopted5047.34 ± 0.66 μ M as a positive control.
The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose of the invention; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; erythro-guaiacyl-glycerol- β -coniferyl alcohol ether or a salt thereof may be administered orally or parenterally, and the amount administered varies depending on the drug, and is preferably 1 to 20mg per day for adults.
For oral administration, the compound is first mixed with conventional pharmaceutical adjuvants such as excipient, disintegrant, binder, lubricant, antioxidant, coating agent, colorant, aromatic agent, surfactant, etc., and made into granule, capsule, tablet, etc.; the non-oral administration can be in the form of injection, infusion solution, suppository or liniment. In preparing the above formulation, conventional formulation techniques may be used.
The specific implementation mode is as follows:
the invention will be further illustrated by the following examples which are intended to be purely exemplary of the preferred embodiments of the invention and are not intended to limit the scope of protection of the invention in any way.
Example 1:
1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose, its anti-inflammatory medicinal composition and its application in medicine.
1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose
The method comprises the following steps: preparation of 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose:
50kg of fresh fruits of Terminalia chebula Retz, which is produced by Yongde, is crushed, is extracted by cold soaking for 3 times at room temperature by using acetone aqueous solution with the volume of 3 times and 70 percent, each time is 5 days, the filtration is carried out, the filtrate is decompressed and concentrated at 50 ℃ to remove the organic solvent, the residual aqueous solution is processed by Diaion HP-20 column chromatography, and gradient elution is carried out by using solution with the volume ratio of methanol to water of 35 percent and 60 percent to obtain Fr.35，Fr.60。Fr.35Loading on Sephadex LH-20 chromatographic column with MeOH/H2Eluting with 80% and 90% by volume of O, wherein the 90% by volume of methanol/water is subjected to MCI-gel CHP20P column chromatographyThen, using preparative liquid column chromatography, eluting with acetonitrile and mobile phase with 0.15% trifluoroacetic acid/water volume ratio of 22% to obtain compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose, and detecting by HPLC content, the purity is not less than 90%, and the yield is 0.02% of dry weight
Step two: evaluation of anti-inflammatory Activity of 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose
Inoculating mouse mononuclear macrophage strain RAW264.7 into 96-well plate at an inoculation density of 1.5 × 105Dissolving compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose in DMSO solvent, adding into cell culture medium to make compound final concentration 50uM and continuous gradient concentration, performing cell treatment with 3 times of each treatment, stimulating with botulinum toxin LPS with final concentration of 1 μ g/mL, evaluating generation of nitrogen monoxide in supernatant with Griess reagent after 18 hr, detecting absorbance at 570nm, and calculating half inhibitory concentration IC of each compound by Reed-Muench method5036.43 ± 0.21 μ M; at the same time, the half-inhibitory concentration IC of the nitric oxide synthase inhibitor L-NMMA is adopted50Compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose has a significantly better nitric oxide production inhibitory activity than L-NMMA.
Example 2
4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid, its anti-inflammatory pharmaceutical composition, and its application in medicine are provided.
4-O-(3”,4”-di-O-galloyl-α-L-rhamnopyranosyl)ellagic acid
The method comprises the following steps: preparation of 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid
Pulverizing fresh fruit of Terminalia chebula Retz 50kg, cold soaking in 70% acetone water solution 3 times the volume of the fruit for 5 days at room temperature for 3 times, filtering, concentrating the filtrate at 50 deg.C under reduced pressure to remove organic solvent, and adding Diaion HP-2 to the rest water solutionPerforming 0 column chromatography, and performing gradient elution with 35% methanol/water and 60% solution to obtain Fr.35，Fr.60。Fr.35Loading on Sephadex LH-20 chromatographic column with MeOH/H2And (3) eluting with 80% and 90% of O by volume, wherein the elution part with 90% of methanol/water by volume is subjected to preparative liquid phase chromatography, is eluted by a mobile phase with 20% of acetonitrile + 0.15% of trifluoroacetic acid/water by volume, and the eluent is concentrated and dried to obtain the compound 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid, wherein the purity is more than or equal to 90% by HPLC content detection, and the yield is 0.03% of the dry weight.
Step two: evaluation of anti-inflammatory Activity of 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid
Inoculating mouse mononuclear macrophage strain RAW264.7 into 96-well plate at an inoculation density of 1.5 × 105Dissolving compound 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid in DMSO solvent, adding to cell culture medium to give compound final concentration of 50uM and its continuous gradient, treating cells at 3 times, stimulating with botulinum toxin LPS at 1 μ g/mL final concentration, evaluating nitric oxide production in supernatant with Griess reagent 18 hours later, detecting absorbance at 570nm, and calculating half inhibitory concentration IC of each compound by Reed-Muench method5042.28 ± 0.09 μ M; at the same time, the half-inhibitory concentration IC of the nitric oxide synthase inhibitor L-NMMA is adopted50Compound 4-O- (3 ", 4" -di-O-galloyl- α -L-rhamnopyrno-syl) ellagic acid has a superior nitric oxide production inhibitory activity to L-NMMA as a positive control.
Example 3
Preparation of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether, anti-inflammatory pharmaceutical composition thereof, and application thereof in medicine.
Erythro-guaiacyl-glycerol-β-coniferyl aldehyde ether
The method comprises the following steps: preparation of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether
50kg of fresh fruits of Terminalia chebula Retz, which is produced by Yongde, is crushed, is extracted by cold soaking for 3 times at room temperature by using acetone aqueous solution with the volume of 3 times and 70 percent, each time is 5 days, the filtration is carried out, the filtrate is decompressed and concentrated at 50 ℃ to remove the organic solvent, the residual aqueous solution is processed by Diaion HP-20 column chromatography under the detection guidance of thin layer chromatography, and gradient elution is carried out by using solution with the volume ratio of methanol to water of 35 percent and 60 percent to obtain Fr.35，Fr.60。Fr.60Eluting with MCI-gel CHP20P chromatographic column with 20-100% methanol/water volume ratio solution, concentrating, subjecting to silica gel column chromatography, eluting with chloroform/methanol volume ratio solution of 15: 1 to obtain Erythro-guaiacyl-glycerol- β -chloroferyl alcohol ether, and detecting by HPLC content to obtain product with purity of 90% or more and yield of 0.03% of dry weight.
Step two: evaluation of anti-inflammatory Activity of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether
Inoculating mouse mononuclear macrophage strain RAW264.7 into 96-well plate at an inoculation density of 1.5 × 105Dissolving Erythro-guaiac-glycerol- β -coniferyl alcohol ether in DMSO solvent, adding into cell culture medium to give compound final concentration of 50uM and continuous gradient concentration, treating cells with 3 times of each treatment, stimulating with botulinum toxin LPS (1 μ g/mL) for 18 hr, evaluating the generation of nitrogen monoxide in the supernatant with Griess reagent, detecting absorbance at 570nm, and calculating half inhibitory concentration IC of each compound by Reed-Muench method5018.17 ± 0.57 μ M; at the same time, the half-inhibitory concentration IC of the nitric oxide synthase inhibitor L-NMMA is adopted50The compound Erythro-guaiacyl-glycerol- β -coniferyl alcohol ether has a very significantly better nitric oxide generation inhibitory activity than L-NMMA as a positive control.
Formulation example 1:
the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose was prepared according to the procedure of examples 1 to 3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether. Adding water for injection, fine filtering, bottling, and sterilizing to obtain injection.
Formulation example 2:
the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose was prepared according to the procedure of examples 1 to 3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid;
erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether is dissolved in sterile water for injection, stirred to be fully dissolved, filtered by a sterile suction filter funnel, then sterile and fine filtered, subpackaged in 2 ampoules, frozen and dried at low temperature, and then sterile melt-sealed to obtain the powder injection.
Formulation example 3:
the compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose was prepared according to the method of examples 1-3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid;
adding excipient into Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether and the excipient in the weight ratio of 9:1, and preparing into powder.
Formulation example 4:
the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose was prepared according to the procedure of examples 1 to 3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid;
adding excipient into Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether according to the weight ratio of the Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether to the excipient of 1:5-1:10, granulating and tabletting.
Formulation example 5:
the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose was prepared according to the procedure of examples 1 to 3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid;
erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether, or making into oral liquid by conventional oral liquid preparation method.
Formulation example 6:
the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose was prepared according to the procedure of examples 1 to 3; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid;
adding excipient, smearing agent or cleaning agent into Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether according to the weight ratio of the Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether to the excipient of 5: 1.
Formulation example 7:
the procedure of examples 1 to 3 was followed to prepare 1,2,3,4, 6-penta-O-galloyl-D-glucopyranose compound; 4-O- (3 ', 4' -di-O-galloyl-L-rhodopyranyl) ellagic acid; adding excipient into Erythro-guaiacyl-glycerol-coniferyl alcohol ether according to the weight ratio of the Erythro-guaiacyl-glycerol-coniferyl alcohol ether to the excipient of 3:1, and preparing into smearing preparation or cleaning agent.
Claims (10)
1. Compound 1 represented by the following structural formula: 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose; compound 2: 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; compound 3: the application of Erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether in preparing anti-inflammatory drugs,
2. use according to claim 1, characterized in that said compound is derived from secondary metabolites of the fresh fruits and other parts of the plants myrobalan, myrobalan and hevea brasiliensis.
3. The use according to claim 1, characterized in that said compound has a significant anti-inflammatory activity.
4. The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; application of Erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether in preparing medicines for preventing or treating inflammatory diseases.
5. The compound 1,2,3,4, 6-penta-O-galloyl-beta-D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; application of Erythro-guaiacyl-glycerol-beta-coniferyl alcohol ether in preparing medicines for preventing or treating superficial and deep inflammations.
6. The preparation method of the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose and 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid and Erythro-guaiac-glycol- β -Coniferyl aldehyde ether is characterized in that the method comprises the following steps of crushing fresh fruits and other plant materials of Terminalia microcarpa, Terminalia chebula and the like, cold-soaking and extracting for 3 times by using 3 times of 70% acetone aqueous solution at room temperature for 5 days, filtering, concentrating the filtrate at 50 ℃ under reduced pressure to remove organic solvent, subjecting the residual aqueous solution to DiailHP-20 column chromatography under the detection guidance of thin layer chromatography, and performing gradient elution by using 35% methanol/water volume ratio and 60% solution to obtain Freon.35，Fr.60；Fr.35Loading on Sephadex LH-20 chromatographic column with MeOH/H2Eluting with 80% and 90% of O by volume, eluting with 90% of methanol/water by volume using preparative liquid phase column chromatography, eluting with 20% of acetonitrile + 0.15% of trifluoroacetic acid/water by volume to obtain 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid, detecting with HPLC to obtain a compound with purity of not less than 90%, eluting with 90% of methanol/water by volume to obtain a compound with MCI-gel CHP20P, performing preparative liquid phase column chromatography, eluting with 22% of acetonitrile + 0.15% of trifluoroacetic acid/water by volume to obtain 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose with HPLC to obtain a compound with purity of not less than 90%, and Fr.60Loading onto MCI-gel CHP20P chromatographic column, eluting with 20-100% methanol/water solution at volume ratio of 60-70%, concentrating, loading onto silica gel column, eluting with 15: 1 chloroform/methanol solution to obtain Erythro-guaiacyl-glycerol- β -chloroferyl alcohol ether,the purity is more than or equal to 90 percent through HPLC content detection.
7. A pharmaceutical composition consisting of the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose; 4-O- (3 ', 4' -di-O-galloyl-alpha-L-rhamnopyranosyl) ellagic acid; erythro-guaiacyl-glycerol-beta-coniferyl aldehyde ether and a pharmaceutically acceptable carrier.
8. Use of the pharmaceutical composition of claim 7 for the manufacture of a medicament for the treatment of an inflammatory disorder.
9. Use of the pharmaceutical composition of claim 7 for the preparation of a medicament for the prevention or treatment of superficial and deep inflammation.
10. The method for evaluating the influence of the compound 1,2,3,4,6-penta-O-galloyl- β -D-glucopyranose, 4-O- (3 ', 4' -di-O-galloyl- α -L-rhamnopyranosyl) ellagic acid and Erythro-guaiacyl-glycerol- β -coniferyl aldehyde ether on the inhibition of the generation of nitric oxide of mouse mononuclear macrophage strain RAW264.7 is characterized in that the mouse mononuclear macrophage strain RAW264.7 is inoculated into a 96-well plate, and the inoculation density is 1.5 × 105Dissolving compounds 1-3 in DMSO solvent respectively, adding into cell culture medium to give final concentration of 50uM and continuous gradient concentration, treating cells with 3 times of each treatment, stimulating with botulinum toxin LPS with final concentration of 1 μ g/mL, evaluating generation of nitrogen monoxide in supernatant after 18 hr with Griess reagent, detecting absorbance at 570nm, and calculating half inhibitory concentration IC of each compound by Reed-Muench method50A value; at the same time, the half-inhibitory concentration IC of the nitric oxide synthase inhibitor L-NMMA is adopted5042.34 ± 0.66 μ M as a positive control.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010386001.XA CN111514151B (en) | 2020-05-09 | 2020-05-09 | Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010386001.XA CN111514151B (en) | 2020-05-09 | 2020-05-09 | Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111514151A true CN111514151A (en) | 2020-08-11 |
| CN111514151B CN111514151B (en) | 2022-08-09 |
Family
ID=71906887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010386001.XA Active CN111514151B (en) | 2020-05-09 | 2020-05-09 | Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111514151B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115737664A (en) * | 2023-01-05 | 2023-03-07 | 中央民族大学 | Acer truncatum leaf extract with anti-inflammatory activity and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106065023A (en) * | 2015-04-23 | 2016-11-02 | 中国医学科学院药物研究所 | Hydrolysable tannin compounds, its medical composition and its use |
| CN109966328A (en) * | 2019-04-29 | 2019-07-05 | 白吉日木吐 | Ellagic acid and the extracting method of chebulinic acid and combinations thereof in a kind of myrobalan |
-
2020
- 2020-05-09 CN CN202010386001.XA patent/CN111514151B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106065023A (en) * | 2015-04-23 | 2016-11-02 | 中国医学科学院药物研究所 | Hydrolysable tannin compounds, its medical composition and its use |
| CN109966328A (en) * | 2019-04-29 | 2019-07-05 | 白吉日木吐 | Ellagic acid and the extracting method of chebulinic acid and combinations thereof in a kind of myrobalan |
Non-Patent Citations (4)
| Title |
|---|
| HEE WON LEE，等: "Anti-inflammatory effects of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose in LPS-stimulated macrophages", 《KOREAN SOCIETY OF FOOD SCIENCE AND NUTRITION》 * |
| LEE SUNG-JIN，等: "Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 activity by 1,2,3,4,6-penta-O-galloyl-β-D-glucose in murine macrophage cells", 《ARCHIVES OF PHARMACAL RESEARCH 》 * |
| 张媛媛，等: "藏药诃子的化学成分与药理活性研究进展", 《中国药房》 * |
| 杨雁: "诃子化学成分、生物活性及分析方法研究进展", 《西藏科技》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115737664A (en) * | 2023-01-05 | 2023-03-07 | 中央民族大学 | Acer truncatum leaf extract with anti-inflammatory activity and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111514151B (en) | 2022-08-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102772500B (en) | Relingqing Polygonum capitatum Buch-Ham ex D.Don raw material extract with anti-inflammatory action | |
| CN111514151B (en) | Application of three compounds in myrobalan in preparing anti-inflammatory drugs and preparation method thereof | |
| KR20140126661A (en) | Composition containing complex extracts for preventing, improving or treating colitis | |
| CN110437247B (en) | Mixed source terpenoid with liver protection function and application thereof | |
| CN102805767B (en) | Heat stranguria removal granule raw material polygonum capitatum extract with anti-gonococcus effect | |
| JPS60243016A (en) | Anti-influenza virus agent | |
| WO2023193601A1 (en) | Method for simultaneously separating and purifying two galloylmyricitrins from myrica rubra leaves and use | |
| CN102875615B (en) | Extraction method and application of falcate dolichos root or leaf glucoside A and total saponins of falcate dolichos root or leaf | |
| EP2772264B1 (en) | Application of albizzia chinensis extract in preparation of medicine for treatment of gastric ulcer | |
| CN112592328B (en) | Diaryl heptane-chalcone polymer in alpinia katsumadai, and pharmaceutical composition and application thereof | |
| CN113429452B (en) | Acylated mogroside derivatives as anti-inflammatory agents and anti-inflammatory compositions | |
| CN112898357B (en) | Diterpene glycoside novel compound in trollius chinensis bunge and separation and purification method and application thereof | |
| CN110903270B (en) | 2, 6-epoxy diphenyl heptane compound, preparation method and application thereof, pharmaceutical composition and application thereof | |
| CN111150754B (en) | Application of chestnut flower extract in preparation of food or anti-inflammatory drugs | |
| CN109705183B (en) | Clerodendrum cyrtonema metabolite, pharmaceutical composition thereof, preparation method and application thereof | |
| CN109512847B (en) | Application of plumbagin in preparing medicine for treating pulmonary fibrosis diseases | |
| CN108148105B (en) | Dimeric iridoid compound and preparation method and application thereof | |
| CN114213476B (en) | Separation method and application of 4-pentanetriol-beta-methyl gentiobioside in badam | |
| KR101647506B1 (en) | Detoxifying methods for extracts of Coptidis Rhizoma, detoxified herbal extracts manufactured by the same, and composition comprising for preventing and treating a respiratory organ disease comprising the herbal extracts | |
| CN114601891B (en) | Composition with anti-ulcerative colitis effect and preparation method thereof | |
| KR101028865B1 (en) | A method of separation to sulforaphene from Raphanus sativus L and the use of sulforaphene | |
| CA3117196C (en) | Process for extracting compounds from dendrobium nobile lindl. and application thereof | |
| CN110776482B (en) | Compound with activity of inhibiting macrophage from releasing NO, and preparation method and application thereof | |
| WO2022236789A1 (en) | Extract of dendrobium sinense, dendrobium densiflorum, or dendrobium bensoniae, and application of main components thereof as anti-inflammatory formulation | |
| CN108514576B (en) | Folium Mori extract prepared by ultrasonic extraction technology and its application |
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 | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230508 Address after: No. 51, Hongxiang Road, Singapore Industrial Park, Luoyang Sub-district Office, Economic Development Zone, Kunming District, Kunming City, Yunnan Province, 650000 Patentee after: YUNNAN WEST GRASS RESOURCES DEVELOPMENT CO.,LTD. Address before: 650201 No. 132 Lanhei Road, Kunming City, Yunnan Province Patentee before: KUNMING INSTITUTE OF BOTANY, CHINESE ACADEMY OF SCIENCES |
|
| TR01 | Transfer of patent right |