CN1704401A - Pharmaceutical use of 1-N-methoxy-2-oxo-indole-3-acetamide - Google Patents
Pharmaceutical use of 1-N-methoxy-2-oxo-indole-3-acetamide Download PDFInfo
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- CN1704401A CN1704401A CN 200510075358 CN200510075358A CN1704401A CN 1704401 A CN1704401 A CN 1704401A CN 200510075358 CN200510075358 CN 200510075358 CN 200510075358 A CN200510075358 A CN 200510075358A CN 1704401 A CN1704401 A CN 1704401A
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- compound
- endotoxemia
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- acetamide
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- DEGDLKBPHNRHGN-UHFFFAOYSA-N 2-(1-methoxy-2-oxo-3h-indol-3-yl)acetamide Chemical compound C1=CC=C2N(OC)C(=O)C(CC(N)=O)C2=C1 DEGDLKBPHNRHGN-UHFFFAOYSA-N 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- 239000007788 liquid Substances 0.000 claims abstract description 16
- 239000006187 pill Substances 0.000 claims abstract description 7
- 239000002775 capsule Substances 0.000 claims abstract description 5
- 239000008187 granular material Substances 0.000 claims abstract description 3
- 239000000829 suppository Substances 0.000 claims abstract description 3
- 239000003826 tablet Substances 0.000 claims abstract description 3
- 238000002347 injection Methods 0.000 claims abstract 2
- 239000007924 injection Substances 0.000 claims abstract 2
- 208000037487 Endotoxemia Diseases 0.000 claims description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 206010040047 Sepsis Diseases 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 210000000056 organ Anatomy 0.000 claims description 7
- 208000006454 hepatitis Diseases 0.000 claims description 6
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 5
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- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 description 15
- RJGBSYZFOCAGQY-UHFFFAOYSA-N hydroxymethylfurfural Natural products COC1=CC=C(C=O)O1 RJGBSYZFOCAGQY-UHFFFAOYSA-N 0.000 description 15
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
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- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
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- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical class O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 4
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- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
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- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 2
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- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention provides a pharmaceutical compound of 1-N-methoxy-2-oxo-indole-3-acetamide, which can be made into the dosage forms of tablet, capsule, pill, pelletized granule, drop pill, oral liquid, suppository, bowel lavage liquid or injection, the active dosage of the medicinal preparation is 0.8mg-8.0mg/kg, the pH range of the preparation is between 2.0-5.0.
Description
Technical field
The present invention relates to a kind of pharmaceutical use of compound, particularly the pharmaceutical use of 1-N-methoxyl group-2-oxygen-indole-3-acetamide.Patent application of the present invention is for dividing an application, and the original bill application number is 031020658, and the applying date is on January 30th, 2003, and denomination of invention is a kind of plant milk extract, compound and extracting method thereof and purposes for the treatment of endotoxemia.
Background technology
Intracellular toxin (Endotoxin ET) is lipopolysaccharides (Lopipolysacharide LPS) composition of leather Lan Shi negative bacillus cell walls, is immunity of mediation human body and the unusual crucial virulence factor of inflammatory reaction.Endotoxemia is to enter circulation of blood by endogenous and exogenous intracellular toxin are excessive, excite the human body immunocyte to discharge the various kinds of cell factor in a large number, destroy human body inflammatory reaction balance, cause microcirculation disturbance and organize major injury, cause extensively and the intensive pathologic reaction, and then high-risk property diseases such as the septic shock that causes, MOFE.In recent years, many studies show that, Sepsis, organ function injury and intestinal endotoxemia that the trauma stress state takes place are closely related.The intestinal mucosa mechanical masking function that occurs under the stress situation is impaired, make than the little intracellular toxin of bacteria particles at first transposition enter blood, cause endotoxemia, activate inflammatory cell, discharge a large amount of inflammatory mediators and cytokine and form Sepsis.Therefore, the generation of endotoxemia not merely is present in the various infectious diseases of inside and outside section, serious wound, burn, shock, major operation and cancer are put, chemotherapy etc. all be the main diseases that produces endotoxemia because of.And endotoxemia be clinical many refractory diseases such as severe complication such as acute lung declines, acute hepatic failure, acute renal failure, acute dic, septic shock and multiple organs dysfunction main diseases because of.Clinical observation confirms that burn patients endotoxemia incidence is 58%, presents significant Sepsis state more, finally can concurrent MODS and death.Occur tangible endotoxemia after the hemorrhagic shock, even Q volume of blood is supplied, pressor agent has been used maximum dose, and shock still can not corrected, and finally is developed to death.The incidence of hepatitis gravis, hepatitis liver cirrhosis, chronic hepatitis, acute hepatitis patient's intestinal endotoxemia (IETM) is respectively 93.3%, 84.3%, 79.0% and 75.0%.In bile duct obstruction and other abdomen operating endotoxemia progress of internal organs illness for renal insufficiency account for 51.4%, develop at last multiple organs failure death up to 28.3%.The multiple organ dysfunction syndrome that endotoxemia is brought out (MODS) is one of modal dead cause of disease of intensive care unit(ICU).Antiendotoxin treatment at the endotoxemia and the MOFE of bringing out is the key subjects and the most active fields of current Chinese scholars research, but does not also have a kind of medicine official listing so far.
Summary of the invention
The object of the invention is to provide the efficient part of Root of Indigowoad and wherein main chemical ingredients; The object of the invention also is to provide the efficient part of Root of Indigowoad and the preparation method of wherein main chemical ingredients; The 3rd purpose of the present invention is to provide the new purposes of the treating endotoxemia of the efficient part of Root of Indigowoad and wherein main chemical ingredients.
From Root of Indigowoad, extract efficient part, can take following any method with treating endotoxemia effect:
Raw medicinal material: the dry root of cruciferae isatis Isatis indigotica Fort..
1, ethanol is made the solvent extraction process of (containing immersion, diacolation, backflow): repeatedly soak or refluxing extraction with 80% ethanol, or use 80% ethanol percolate extraction, united extraction liquid leaves standstill, and gets supernatant liquid filtering, and filtrate recycling ethanol gets the efficient part fluid extract.
2, ion exchange resin extraction process: after a certain amount of Root of Indigowoad soaked, boiling 2 times, each 1.5h-2h, merge water decoction, leave standstill, get the supernatant liquor centrifugation, centrifugate exchanges by storng-acid cation exchange resin, collect effluent liquid, be concentrated into every milliliter of soup and contain about 2 grams of crude drug, add 95% ethanol and make and contain the alcohol amount and reach 80%, staticly settle, get supernatant liquid filtering, filtrate recycling ethanol gets the efficient part fluid extract.
3, macroporous adsorbent resin extraction process: after a certain amount of Root of Indigowoad soaked, boiling 2 times, each 1.5h-2h, merge water decoction, leave standstill, get the supernatant liquor centrifugation, parting liquid passes through macroporous adsorbent resin, respectively with the resin after 10%, 20%, 40%, 50% the ethanol elution absorption, and the collection elutriant, leave standstill, get supernatant liquid filtering, filtrate is reclaimed ethanol respectively, gets the efficient part fluid extract.
4, other organic solvent extraction technology: the medicinal extract thin up of extraction using alcohol is become every milliliter of aqueous solution that contains crude drug 1 gram, use sherwood oil, chloroform extraction respectively successively, sherwood oil, ethyl acetate extraction, sherwood oil, n-butanol extraction.Reclaim the organic solvent in chloroform, ethyl acetate, the butanol extraction liquid respectively, get the efficient part fluid extract.
Four compounds that contain in the efficient part of the present invention are respectively: furfural compounds, lignin compound, Benzazole compounds, organic acid compound.Main effective constituent in the classes of compounds is: the furfural compounds: 5 hydroxymethyl furfural, English name: 5-hydroxymethylfurfural (5-HMF), molecular formula: C
6H
6O
3, molecular weight: 126; Lignin compound: Cyclolariciresinol.English name: Isolariciresinol molecular formula: C
20H
24O
6Molecular weight: 360; Benzazole compounds: 1-N-methoxyl group-2-oxygen-indole-3-acetamide; Organic acid compound: the longer chain fatty acid of anthranilic acid, Whitfield's ointment, phenylformic acid, syringic acid, hydroxyl and two keys etc.Furfural compounds, lignin compound, the Benzazole compounds content 5-60% in efficient part comprises that the content of organic acid compound in efficient part of the longer chain fatty acid of anthranilic acid, Whitfield's ointment, syringic acid, quinazolone acid and hydroxyl and two keys is 5-30%.
The part by weight of the best of breed of effective constituent is in the efficient part: 5 hydroxymethyl furfural 20-50: different tamarack resin alcohol 1-3: 1-N-methoxyl group-2-oxygen-indole-3-acetamide 10-40.
The compounds of this invention clinical application dosage range is respectively: 5 hydroxymethyl furfural is 1.0mg～10.0mg/kg, and different tamarack resin alcohol is 0.1mg～1.0mg/kg, and 1-N-methoxyl group-2-oxygen-indole-3-acetamide is 0.8mg～8.0mg/kg.The pH scope of preparation of the present invention is at 2.0-5.0.
The present invention's compound 1-N-methoxyl group-2-oxygen-indole-3-acetamide that separation obtains from this plant first is the main effective constituent in the efficient part.English name: the 1-N-methoxy-2-oxo-indolyl-3-acetamide structural formula is:
Molecular formula: C
11H
12O
3N
2, molecular weight: 220;
The extracting method of above-mentioned new compound is: the ethyl acetate extract of Root of Indigowoad separates with silica gel column chromatography, uses chloroform successively: methyl alcohol=80: 1 (500ml*18), 40: 1 (500ml*20), 30: 1 (500ml*5), 20: 1 (500ml*32) wash-outs.At chloroform: among stream part 7B of methyl alcohol=40: 1 wash-out two fluorescence spots are arranged, will flow part 7B and continue a column chromatography, further use sherwood oil: chloroform: methyl alcohol=15: 15: 1 wash-outs obtains a white, needle-shaped crystals.
Efficient part of the present invention or its chemical ingredients can be made into pharmaceutically acceptable preparation, for example be prepared into oral Preparation: tablet, capsule, pill, granule, pill, oral liquid, be prepared into the rectal administration preparation: suppository, enema liquid, be prepared into the percutaneous drug delivery preparation: paste, emulsion, liniment, patch, transdermal absorption formulation are prepared into injecting and administering preparations: intramuscular dose, intravenous injection.When the treatment viral infection, active ingredient can or be made compound preparation with suitable virucide administration.This active ingredient can be used as freeze-dried preparation.
Following experimental example is used to further specify the present invention:
Experimental example 1: the present invention confirms that by animal vivo test Root of Indigowoad has the efficient part for the treatment of endotoxemia effect
The test soup: the extract thin up that above each extraction process obtains is made into every milliliter of soup that contains 2 gram crude drugs.
Test intracellular toxin: the O that is provided is provided with Chinese pharmaceutical biological product
111B
4Intestinal bacteria through this prepared in laboratory, purifying intracellular toxin, and are identified the O that is provided with Chinese pharmaceutical biological product
111B
4The escherichia coli endotoxin demarcation of tiring.The mouse dosage range of preparation endotoxemia model is a per kilogram of body weight 15-18 milligram.
Test animal: available from Chinese Academy of Medical Sciences animal reproduction field, Kunming kind, secondary mouse.Weight range: 18-22 gram, male and female half and half.By the body weight random packet, every treated animal is no less than 30.And carry out the t check of each treated animal body weight, and there is not significant difference between each group, take out one group at random and make negative control.
Test method: each treated animal fasting be can't help water 12 hours before the test, the administration group irritates stomach for 0.5 milliliter for different process gained extracting solution by per 20 gram body weight, negative control group is irritated stomach with volume distilled water, after the administration 45 minutes, inject the endotoxin solution of 80% lethal quantity from mouse tail vein, preparation endotoxemia and MOFE model.
Observation index and data processing method: with survival rate and survival time be index, be leading indicator with the survival rate.Observe also and write down in 72 hours, the dead number of elements of every mouse diing time and every group calculates the survival time and the survival rate of every treated animal, and whether there were significant differences between the survival time with t inspection administration group and negative control group, uses X
2Whether there were significant differences between inspection administration group and the negative control group survival rate.Test-results: see Table 1.
The anti-endotoxin effect of the extractive part that table 1 different methods extraction Root of Indigowoad obtains
| Ethyl acetate fraction extracting n-butyl alcohol position, chloroform extraction position, different process extraction components 80% alcohol extract position cationic ion-exchange resin efflux alcohol extracting position macroporous absorbent resin 10%-50% alcohol wash-out position | Survival time (h) | Survival rate (%) | ??X 2Check (X 2≥3.84) ??22.92 ??6.86 ? ??5.23 ??9.92 ??11.32 ??13.44 | T checks (P≤0.05) 4.04*10 -9??3.33*10 -3? ??9.60*10 -3??3.80*10 -4??4.04*10 -5??3.17*10 -5 | ||
| Control group 31.15 38.90 31.15 24.57 33.86 25.62 | Administration group 67.45 59.33 47.20 45.58 61.56 55.40 | Control group 8,/32 12,/30 8,/32 4,/34 9,/30 5/30 | Administration group 28,/32 23,/30 18,/32 17,/34 23,/30 20/30 | |||
Conclusion: 6 kinds of extract parts that (1) obtains with above 4 kinds of extraction and separation method all have remarkable treating endotoxemia and reduce the effect of mortality ratio due to its MOFE of bringing out.
(2) in 6 kinds of extract parts, 80% extraction using alcohol part treating endotoxemia and to reduce due to its MOFE of bringing out the effect of mortality ratio the strongest, propyl carbinol, ethyl acetate and chloroform extraction part also have extremely significant treating endotoxemia and reduce the effect of mortality ratio due to its MOFE of bringing out, the 50% following ethanol elution that obtains from macroporous adsorbent resin technology partly has remarkable treating endotoxemia and reduces the effect of mortality ratio due to its MOFE of bringing out, and composition is the middle polarity material in the prompting efficient part.
(3) storng-acid cation exchange resin effluent liquid 80% extraction using alcohol partly has remarkable treating endotoxemia and reduces the effect of mortality ratio due to its MOFE of bringing out, and the part main active ingredient in the prompting efficient part is not by cationic exchange resin adsorption.
(4) after deliberation, mainly contain following four compounds in the efficient part of discovery Root of Indigowoad treating endotoxemia: furfural compounds, lignin compound, Benzazole compounds and organic acid compound.
Experimental example 2: the separation of effective constituent monomeric compound in the efficient part of the present invention: the effective extract part that proves through animal experiment in the above-mentioned table 1, its high performance liquid chromatography has 3 main absorption peaks, and the thin-layer chromatography chromatogram has 3 main spots and curative effect closely related.Because 3 main component content are higher at the ethyl acetate extraction position, are about to the ethyl acetate extraction position and carry out column chromatography for separation.
Material: Haiyang Chemical Plant, Qingdao produces column chromatography silica gel, thin-layer chromatography G plate and GF254 plate.The analytical reagent chloroform of the sharp chemical company of Beijing benefit, methyl alcohol, sherwood oil, ethyl acetate etc.Development system: sherwood oil-chloroform-methanol=4: 4: 1,2: 4: 1, chloroform-methanol=80: 1,40: 1,20: 1.
The Spectrum Analysis of monomeric compound and structural identification: from above component, isolate monomeric compound, determine 25 compounds that have of structure through analytic centre of Military Medical Science Institute mass spectrum, hydrogen spectrum, carbon spectrum analysis and spectrum unscrambling, wherein 22 is known compound, and 3 for separating the compound that obtains first from this plant.
The present invention's compound 1-N-methoxyl group-2-oxygen-indole-3-acetamide that separation obtains from this plant first is the main effective constituent in the efficient part.Its spectral data is as follows: FAB-MS m/z[M+H]
+Be 221.
1HNMR(CDCL3)，δ：2.71(1H，dd，J＝15.9，7.0Hz?H-10a)，2.97(1H，dd，J＝15.9，5.7Hz?H-10b)，3.85(1H，t，J＝6.4Hz?H-3)，4.03(3H，S，OCH
3)，6.09(1H，br.s，-NH)，6.28(1H，br.s，-NH)，6.99(1H，dd，J＝7.8，1.0Hz?H-7)，7.09(1H，td，J＝7.8，1.0Hz?H-5)，7.32(1H，dd，J＝7.8，1.0Hz?H-4)，7.33(1H，td，J＝7.8，1.0Hz?H-6)。By
13The CNMR spectrum can infer further that there are two hydroxyls in compound.This compound bismuth potassium iodide test is positive, and is illustrated as alkaloid compound.By mass-spectrometric data and combination
1HNMR,
13The CNMR spectrum infers that the molecular formula of compound 6 is C
11H
12N
2O
3According to the source of students relation, this compound may be Benzazole compounds, and has 2-indolone skeleton.By
1Observed two reactive hydrogens reach among the HNMR
13Existence-C=O-NH2 (acid amides) group is inferred in carbonylation displacement in the CNMR spectrum.
13In the CNMR spectrum δ value be 63.42-OCH3 conforms to this compounds numerical value in the document with 1 N atom is continuous.The molecular formula of inferring this compound in view of the above is: C
11H
12O
3N
2, structural formula is: called after: 1-N-methoxyl group-2-oxygen-indole-3-acetamide.
Experimental example 3: the action intensity of each main component and ratio in the efficient part of the present invention
The preparation of test liquid: acetic acid ethyl ester extract is carried out silica gel column chromatography separate, with chloroform wash-out position and chloroform: methyl alcohol=solvent was reclaimed at the wash-out position in 10: 1, adding water, to be made into concentration be the background solution that contains crude drug amount 2g/ml, 5 hydroxymethyl furfural, different fallen leaves pine tree alcohol ester, 1-N-methoxyl group-2-oxygen-indole-3-acetamide that chloroform-methanol different ratios wash-out is obtained than adding in the background liquid, screen best proportioning by Different Weight.For guaranteeing the stability of effective constituent, the background solution of No. 3 efficient parts is transferred pH=2.5 with 5% hydrochloric acid, and the background solution of No. 6 efficient parts is transferred pH=4.5 with 5% sodium hydroxide, and it is the same that experimental animal, medication and result add up.Test-results sees Table 2.
Each main component ratio of table 2 and corresponding results of pharmacodynamic test
| Medicine-feeding part numbering medicine-feeding part 1 medicine-feeding part 2 medicine-feeding parts 3 medicine-feeding parts 4 medicine-feeding parts 5 medicine-feeding parts 6 background solution 7 | Each position proportion (weight ratio) animal experiment data | |||||
| ??5-HMF ? ??17.00 ??17.00 ??51.00 ??0.00 ??0.00 ??0.00 ??0.00 | Different fallen leaves pine tree alcohol ester 1.00 1.00 0.00 1.00 1.50 0.00 0.00 | 1-N-methoxyl group-2-oxygen-indole-3-acetamide 15.0 0.00 0.00 7.5 0.00 30.0 0.00 | Soup pH value 4.00 2.80 2.50 3.80 3.50 4.50 3.50 | ??X 2Check (X 2≥3.84) ??20.43 ??13.08 ??4.19 ??4.22 ??3.95 ??4.19 ??0.00 | T checks (P≤0.05) 5.16*10 -9??7.04*10 -5??0.05 ??0.01 ??0.00 ??0.05 ??0.00 | |
Conclusion:
(1) in the 5 hydroxymethyl furfural in the efficient part, different tamarack resin alcohol, 1-N-methoxyl group-3 main component Individual existences of the 2-oxygen-indole-3-acetamide background solution, all can reduce the mouse death rate due to the MOFE that endotoxemia brings out significantly.
(2) with under the dosage condition, the action intensity of various combinations is: 5 hydroxymethyl furfural+different tamarack resin alcohol+1-N-methoxyl group-2-oxygen-indole-3-acetamide＞5 hydroxymethyl furfural+different tamarack resin alcohol＞different tamarack resin alcohol+1-N-methoxyl group-2-oxygen-indole-3-acetamide.
(3) part by weight of the best of breed of effective constituent is in the efficient part: 5 hydroxymethyl furfural 20-50: different tamarack resin alcohol 1-3: 1-N-methoxyl group-2-oxygen-indole-3-acetamide 10-40.
(4) action intensity of each effective constituent, the combination of effective constituent different ratios is relevant with concentration separately in the efficient part, strengthens with concentration increase effect.
(5) the main effective constituent in the efficient part is that 5 hydroxymethyl furfural, different tamarack resin alcohol, 1-N-methoxyl group-2-oxygen-indole-3-acetamide, organic acid can be used as the quality control index that the present invention treats the efficient part of endotoxemia.
(6) 5 hydroxymethyl furfural to the treatment concentration range of the mouse endotoxemia and the MOFE of bringing out at per kilogram of body weight 10mg～100mg/kg, at per kilogram of body weight 1mg～10.0mg/kg, the treatment concentration range of 1-N-methoxyl group-2-oxygen-indole-3-acetamide is at per kilogram of body weight 8mg～80.0mg/kg to the treatment concentration range of mouse for different tamarack resin alcohol.
The principal indication of efficient part of the present invention: efficient part of the present invention can reduce the mortality ratio of the Sepsis of being brought out by endotoxemia, septic shock, MOFE effectively.Be applicable to serious wound (burn, fight) wound, infection, major operation, severe hemorrhagic shock, put the endotoxemia that produces under the stress situations such as (change) treatment, organ transplantation, concurrent endotoxemias such as hepatitis gravis, liver cirrhosis, gastrointestinal tract disease, malnutrition, biliary tract/intestinal obstruction, Sepsis, septic shock, multiple organs dysfunction even the depletion brought out by endotoxemia.This efficient part has the clearing heat and detoxicating of theory of traditional Chinese medical science, activate blood circulation and disperse blood clots, the recuperating deplered YANG and rescuing the patient from collapse effect, be applicable to the warm disease witness of the evil straight middle defensive-qi-nutrient-blood of heat poison: as the excessive noxious heat of septicemia, the heat poison of acute pneumonia becomes silted up to wet to stop up and stagnates in lung the scorchingly hot string of attacking of acute hepatic failure, damp-heat gluing each other, the heresy of the heat poison of acute dic is gone into ying blood, the syncope of severe hemorrhagic shock etc.
This efficient part can treat or prevent any and the LPS diseases associated effectively, and described disease includes, but are not limited to endotoxemia (or Sepsis syndromes), also suppresses the generation of the virus of LPS stimulation.The effect of duplicating of these viruses is the control that directly or indirectly is subjected to the NF-KB regulatory region.These viruses comprise cytomegalovirus, simplexvirus, but be not limited to this, in addition, because the activation of influenza virus is subjected to that the effect of LPS strengthens and the increase of TNF-α burst size is relevant with the comprehensive condition of influenza virus A and bacterial infection, the present invention also may play restraining effect to the activation of influenza virus.
Embodiment 1:
5 hydroxymethyl furfural 120 gram adds vehicle system particle 300 grams routinely, fills and makes 1000 of 0.3 gram/capsules, and modulator ph value is 2-5, day 3 times, each 1 oral.
Embodiment 2:
Different tamarack resin alcohol 2 grams add PEG-6000 48 grams, and modulator ph value is 2-5, and heating and melting drips and makes 1000 of 50 milligrams of/dripping pills, day 3 times, each 5, sublingual administration.
Embodiment 3:
1-N-methoxyl group-2-oxygen-indole-3-acetamide 120g adds vehicle routinely, modulator, system particle 300 gram is pressed into 1000 in the tablet of 0.3 gram/sheet, day 3 times, each 1 oral.
Embodiment 4:
5 hydroxymethyl furfural: different tamarack resin alcohol: 1-N-methoxyl group-2-oxygen-indole-3-acetamide=15.0: 1.0: 15.0, totally 100.0 grams add vehicle routinely, modulator, system particle 300 grams are filled and are made 1000 of 0.3 gram/capsules.Days 3 times, each 1 oral.
Claims (7)
1, a kind of compound is characterized in that this compound is 1-N-methoxyl group-2-oxygen-indole-3-acetamide.
2, compound as claimed in claim 1 is characterized in that this compound medicine preparation is tablet, capsule, pill, granule, pill, oral liquid, suppository, enema liquid or injection.
3, compound as claimed in claim 2 is characterized in that this compound medicine preparation effective dose is definite by clinical dosage 0.8mg～8.0mg/kg.
4, as claim 1, the application of 2 or 3 described compounds in medicine dead due to the MOFE for preparing treatment endotoxemia and reduction so bring out.
5, the endotoxemia that under the serious wound of preparation treatment burning, war wound, infection, major operation, severe hemorrhagic shock, radiotherapy, chemotherapy, organ transplantation stress situation, produces as claim 1,2 or 3 described compounds; Application in endotoxemia that hepatitis gravis, liver cirrhosis, gastrointestinal tract disease, malnutrition, biliary tract intestinal obstruction are concurrent or the Sepsis of bringing out, septic shock, multiple organs dysfunction or the depleted medicine by endotoxemia.
6, as the application in the medicine of the disease that the syncope of preparation treatment septicemia, acute pneumonia, acute hepatic failure, acute dic, severe hemorrhagic shock and cytomegalovirus, simplexvirus, influenza virus cause of claim 1,2 or 3 described compounds.
7, the preparation method of compound as claimed in claim 1 is characterized in that this method is:
The ethyl acetate extract of Root of Indigowoad separates with silica gel column chromatography, uses chloroform successively: methyl alcohol=80: 1,40: 1,30: 1,20: 1 wash-outs; At chloroform: among stream part 7B of methyl alcohol=40: 1 wash-out two fluorescence spots are arranged, will flow a part 7B column chromatography, use sherwood oil: chloroform: methyl alcohol=15: 15: 1 wash-outs, acquisition white, needle-shaped crystals.
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| CN101234134B (en) * | 2008-02-27 | 2011-01-05 | 广州白云山和记黄埔中药有限公司 | Application of compound isatis root preparation in preparing medicaments for preventing and controlling endotoxaemia |
| CN101933966B (en) * | 2010-08-31 | 2011-12-21 | 南京中医药大学 | Active site composition of isatis roots, as well as preparation method and application thereof |
| CN102614206A (en) * | 2011-01-31 | 2012-08-01 | 澳门科技大学 | Application of 7S,8R,8'R-(+)-lariciresinol-4,4'-bi-O-beta-D-glucopyranoside in preparing medicines |
| CN106565468A (en) * | 2016-11-15 | 2017-04-19 | 河南中医药大学 | Syringic acid extracted from mulberry barks, preparation method for syringic acid and application of syringic acid |
| CN109438221B (en) * | 2018-11-21 | 2021-09-03 | 集美大学 | Method for preparing syringic acid from spirulina |
| CN111450135A (en) * | 2020-05-18 | 2020-07-28 | 山西省芮城县红宝兽药有限责任公司 | High-purity radix isatidis and preparation method of injection thereof |
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