CN101555199A - Branched chain fatty acid compound and derivative thereof for preventing and curing ischemical reperfusion injury - Google Patents
Branched chain fatty acid compound and derivative thereof for preventing and curing ischemical reperfusion injury Download PDFInfo
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- CN101555199A CN101555199A CNA2008100910143A CN200810091014A CN101555199A CN 101555199 A CN101555199 A CN 101555199A CN A2008100910143 A CNA2008100910143 A CN A2008100910143A CN 200810091014 A CN200810091014 A CN 200810091014A CN 101555199 A CN101555199 A CN 101555199A
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Abstract
The invention relates to an application of a compound with the tail end being branched chain fatty acid and a compound of a derivative for preparing medicine curing ischemia and reperfusion injury of tissues or organs of people. The ischemia and reperfusion injury comprises cerebral ischemia and reperfusion injury caused by operations of cerebrovascular disorder, cardiac arrest and cardio-pulmonary resuscitation, and ischemia and reperfusion injury of therapy of miocardial infarction, ischemia of intestine, hepatic ischemia and thrombolysis, operations on vessels of heart, and histoorgan transplantation.
Description
Technical field
The present invention relates to a kind of is the anti-histoorgan ischemic of effective ingredient and the medicine of reperfusion injury with terminal branched chain fatty acid compound and derivative thereof, and in the purposes in cardiovascular and cerebrovascular diseases field.
Background technology
The tissue of human body or organ are at long ischemic and subsequent pour into the damage even the necrosis that all can cause the ischemic region tissue again.Ischemic normally causes histanoxia and lacks the immediate cause of energy matter supply.For brain, oxygen-consumption such as heart are big, and concerning the organ of energy matter sensitivity, the length of Ischemia Time determines that normally whether it damage the reversible determinative.With the acute cerebral infarction is example, and nervous tissue is mainly ischemia injury at first, along with the prolongation of Ischemia Time, and the damage that can further show more serious nervous tissue and function usually after pouring into again, i.e. reperfusion injury.Prolong irreversible damage of appearance and necrosis in time in the central section of ischemic.Only in the neighboring area of ischemic (half blanking bar), because side Zhi Xunhuan and the infiltration of the blood oxygen of blood supply healthy tissues on every side, its damage is lighter, it is reversible, after the organized renewing blood supply, might recover cell function in theory, but because reperfusion injury and protect, still be difficult to recovery in the function of the later half blanking bar tissue of revascularization.Therefore,, not only need to recover as early as possible blood supply (perfusion again), also need drug application prevention and protective tissue to avoid again dabbling damage in the treatment of cardiovascular and cerebrovascular ischemic disease.
The ischemic disease majority of cardiovascular and cerebrovascular be since behind the blood vessel endothelium injury thrombosis or the thrombus at a distance back infraction that comes off cause, as acute myocardial infarction (AMI) and cerebral apoplexy.But so-called " ischemic " can be generalized concept more, also can produce identical phenomenon as the low perfusion state of blood (as shock).Therefore, reperfusion injury can relate to many tissue and organs such as the heart, brain, liver, kidney, lung, digestive tube, and its consequence can cause damage and the necrosis and the nonfunction of related tissue and organ, and serious sequela and very high mortality ratio are arranged.But the present clinical control medicine that still do not have.Therefore the medicine of researching and developing the ischemia resisting reperfusion injury is very necessary.
Ischemical reperfusion injury also can betide the logical again of blood flow after the transplantation of surgical operation and histoorgan.As using the extracorporeal circulation technology in the heart surgical procedure,, be difficult to avoid heart is caused damage to the control ischemic of heart and perfusion again.Other after one's own heart, when liver, renal transplantation, organ blood flow logical again behind ischemic after a while also has the problem of ischemical reperfusion injury.
Ischemical reperfusion injury is no matter be to occur in brain, the heart or other organ, and the damage that causes usually and the pathomechanism of damage have many common ground: (1) ischemical reperfusion injury causes histiocytic apoptosis and necrosis; (2) the attached wall of capillary endothelium oedema and neutrophil leucocyte stops up and causes the no resurgent phenomenon between flush phase again; (3) white corpuscle is assembled toward the ishemic part chemotactic, and induces pro-inflammatory cytokine to produce; (4) local oxyradical produces too much, the peroxidation of cytolemma lipid, cell membrane damage, tissue edema; (5) intracellular calcium overload etc.Ischemical reperfusion injury is the cascade process of the rapid multimachine system of multistep that is mutually related.At present the protection medicine at each link of the pathomechanism of ischemical reperfusion injury has: (1) calcium channel blocker, as nimodipine; (2) stabilizing cell membrane medicine is as citicoline; (3) antioxidant radical generates and radical scavenger, as vitamin-E; (4) suppress toxicity of excitatory amino acid and do medication, as glutamate receptor antagonistic phencyclidine.These medicines all have tangible ischemia resisting reperfusion injury and protect in animal model experiment, but clinical efficacy all is unsatisfied with.May be single with their mechanism of action, the number of mechanisms that can not resist ischemical reperfusion injury is relevant suddenly with multistep, and the someone advocates to use the different drug regimen of multiple mechanism of action to treat to improve curative effect.Therefore research and develop the shortcoming that the ischemia resisting reperfusion injury medicine with multiple mechanism of action might be able to overcome the good medicine of present no result of treatment.
The lipid acid of the terminal side chain that the present invention describes is that a class can not can not be synthesized in the human body through the metabolic lipid acid of plastosome β-Yang Hua, has only trace to enter in the human body with food.Wherein 12-methyl-tetradecanoic acid and 13-methyl-tetradecanoic acid are present in the cytolemma of various bacteria at occurring in nature, be the important composition of keeping the bacterial cell membrane function (Satio K. etc., J.Biochem., 1960,47:699-719).Faung ST[Faung ST. in 1996 etc., thrombus research, Thromb.Res., 1996,81 (1): 91-100] can cause accumulative thrombocytolysis when reporting this compound high density, suppress hematoblastic gathering and adhesion function during lower concentration.Anticoagulant and activation improve ischemic tissue's microcirculation thereby reduce blood viscosity, alleviate the no resurgent phenomenon when pouring into again, and ischemical reperfusion injury is shielded.Also can prevent simultaneously the restenosis after the blood flow filling is led to.
In addition, [Ishida-Okawara etc. such as Ishida-Okawara, J Antibio. (Tokyo), 1991,44 (5): 524-532] find that 12-methyl-tetradecanoic acid can suppress polymorphonuclear leukocyte and discharge myeloperoxidase (MPO), and reduce the generation of oxyradical, reduce the MPO activity and can effectively reduce neutrophil infiltration, the reaction that reduces inflammation, and then microcirculation improvement situation reduce tissue injury.[Yang P etc. such as Yang P, Prostate, 2003,55 (4): 281-291] report that this compounds can also suppress the 5-lipoxygenase activity, inhibition to the 5-lipoxygenase in the membrane phospholipid metabolic process, can reduce the generation of leukotrienes pro-inflammatory cytokine, anti-inflammatory action is arranged, useful to the tissue inflammation reaction that alleviates ischemical reperfusion injury.
Comprehensive above-mentioned bibliographical information; illustrate that this compounds can suppress thrombocyte and leukocyte function in blood vessel; EV histiocytic membrane stabilizing action is arranged again and suppress the effect of 5-lipoxygenase activity; can alleviate the permeability of cytolemma; alleviate oedema and inflammatory reaction, show as the provide protection of many target spots too many levels.This compounds that studies have shown that of the present invention has good ischemia resisting reperfusion injury and protect.
This compounds does not have serious toxic action to laboratory animal, Klein[Klein RA. etc., Lipids, 1980,15 (8): 572-579] give the rat successive administration after 25 days, do not have considerable change with control group comparison body weight, liver spleen brain and fat etc. are organized does not also have obvious pathological change.Pittet etc. [Pittet PG. etc., Proc.Nutri.Soc., 1977,36:116A] do not find the overt toxicity reaction for volunteer's administration.Our experiment shows the body weight to animal maximum tolerated dose 5g/kg, does not all cause animal dead.Illustrate that this compounds has the drug safety of becoming reconciled.
Summary of the invention
Saturated and unsaturated fatty acids and the derivative thereof that a class has terminal side chain, its general formula following (I, II, III) structure of to the effect that disclosing of the present invention.
Wherein n is 0～18 integer, and m is the even-integral number of 0～2a, and a is the unsaturated double-bond number that structure allows, and two key numbers are 0～8.End group must be sec.-propyl or the sec-butyl or the tertiary butyl.
R wherein
1Be one of following group or structure:
-OH is saturated or unsaturated fatty acids.
-NH
2,-amino acid ,-glucose.The optional position that allows by structure is connected with acyl group formation amido linkage or ester bond.
-ONa ,-OK is the sodium salt and the sylvite of lipid acid, also can be other salt that pharmaceutically allows.
-OCH
3,-OC
2H
5,-OC
3H
7,-OC
4H
9,-OC
5H
11, being the alcohol ester of saturated or unsaturated fatty acids, propyl ester wherein, butyl ester and pentyl ester can be isomer arbitrarily, as propyl ester and isopropyl ester; Positive butyl ester, isobutyl ester and secondary butyl ester; N-pentyl ester, isopentyl ester, tert-pentyl ester and secondary pentyl ester.The fatty acid ester that forms with the alcohol of short carbon chain mostly is the lower oily matter of fusing point, easily is embedded in the microbial film lipid bilayer structure, and the stability of film is increased.
-glycerol ,-propylene glycol, the ester that any hydroxyl of acyl group and alcohol forms is as forming monoglyceride or triglyceride or triglyceride level with glycerine.
Compound of the present invention also is present in the cytolemma component of occurring in nature various bacteria and fungi, can therefrom extract branched chain fatty acid by the method mass production of biological fermentation.Also can be by the method preparation of chemosynthesis.
It is for oral administration that compound of the present invention can be made into tablet, capsule, granule and pill etc., also can make oil solution, suspension, and microemulsion, and lipomuls etc. are for drug administration by injection.Drug administration by injection especially intravenous injection or intravenous drip administration is a more suitably clinical application method, and anxious because of cerebral apoplexy or the heart stalk patient state of an illness, oral administration is had any problem and absorbed slower.Some is oily matter for a compound of the present invention, can with nutritive ingredient such as oil, Yelkin TTS, G ﹠ W are emulsified into stable lipomul, can intravenous injection administration safely and fast by the high-fat emulsion carrier.Wherein the oil in the lipomul can be soybean oil, fish oil, and long chain fatty acid ester in the olive wet goods also can be a long chain fatty acid ester in the synthetic.
Compound of the present invention can be used for the treatment of cerebral ischemia and reperfusion injury, thrombus infraction in the commonly local cerebral artery vessel of the cerebral ischemia disease of indication, present clinically methods of treatment is to use the medicine thrombolysis, as with tissue-type plasminogen activator or urokinase, streptokinase etc.Make the revascularization of obstruction, but perfusion can cause further damage again, compound of the present invention can be prevented and treated the reperfusion injury behind the ischemic, and the part that obtains of cranial nerve dyskinesia and cognition dysfunction is recovered, and reduces the case fatality rate and the sequela of cerebral apoplexy.
Compound of the present invention also can be used for dabbling again injury protection behind the cerebral blood supply insufficiency, logical again behind the controlled blocking blood flow when carrying out carotid artery endothelium surgical blanking as surgery brain tissue injury is protected.And the cerebral ischemia that causes of cardiac arrest and cardio-pulmonary resuscitation (CPR) and the protection of reperfusion injury.Usage generally is administered once for dabbling while or administration more before, also can multiple dosing when needing.
Compound of the present invention reduces reperfusion injury when being used for behind the acute myocardial infarction revascularization, can reduce myocardial infarction area and alleviate the incidence of rapidity heart disorder.Also be used for pouring into myocardial protective effect again after the heart extracorporeal circulation.
The protection of reperfusion injury behind controlled blocking blood flow when compound of the present invention can be used for operation such as lung, liver, kidney, retina and digestive tube, and the ischemic in the migration process of histoorgan and the protection of reperfusion injury.
Ischemic and reperfusion injury when compound of the present invention not only leads to blood flow behind its thromboembolism treatment again have provide protection, can also reduce the incidence of blocking again after blood vessel leads to again.
Compound of the present invention shows very strong ischemia resisting and reperfusion injury and protect by the effect of many target spots to the rapid blocking effect of the pathologic process multistep of ischemic and reperfusion injury, than the medicine of single mechanism of action better result of treatment is arranged.
Embodiment
Synthesizing of embodiment 1:13-methyl-tetradecanoic acid
With dodecanedioic acid mono-methyl 139 grams, isovaleric acid 56 grams, sodium Metal 99.5 0.65 gram is at anhydrous methanol 1400ml, carry out electrolytic reaction under the galvanic current of 2A, be alkalescence, steam and remove methyl alcohol until reaction solution, washing, vacuum fractionation gets 13-methyl-methyl myristate 21 grams.With the above-mentioned 10%NaOH 54ml that uses, methyl alcohol 60ml refluxed 2 hours, steamed and removed methyl alcohol, transferred to pH=2 with 10%HCl, and cold filtration is washed to neutrality, got white solid, vacuum fractionation, and ethyl alcohol recrystallization gets 13-methyl-tetradecanoic acid 14 grams.13-methyl-tetradecanoic acid 14 grams are added in the round-bottomed flask, add the vitriol oil of 40ml Virahol and 1ml, be heated to 90 ℃ and refluxed 2 hours, steam and remove unnecessary Virahol, vacuum fractionation gets 13-methyl-isopropyl myristate 14 grams.
The preparation of embodiment 2:13-methyl-isopropyl myristate fat emulsion injection
6%13-methyl-isopropyl myristate 20% fat emulsion injection prescription is formed: injection soybean oil 200g, 13-methyl-isopropyl myristate 60g, injection Yelkin TTS 12g, glycerol for injection 25g, water for injection add to 1000mL.
Pastille fat emulsion injection preparation technology is: take by weighing the soybean oil of recipe quantity and medicine in the dosing pot, mix with the high speed stamp mill, be heated to 80 ℃, add Yelkin TTS, smash to pieces at a high speed to dissolving fully, make into even settled solution.Other gets recipe quantity water for injection and adds glycerine, puts in another dosing pot, mixes under the condition of nitrogen protection, is heated to 60 ℃.Under high-speed stirring, pastille phosphatide oil solution is slowly added in the aqueous glycerin solution, regulate the pH value to about 8.0 with sodium hydroxide.Homogeneous is to particle (60 ℃ of homogenizing temperatures, homogenization pressure 20MPa) about 0.5 μ m repeatedly through high pressure homogenizer, and with 1 μ m filtering with microporous membrane, can feeds nitrogen in infusion bottle, add butyl rubber plug, the aluminium lid sealing.110 ℃ of rotation sterilization 30min, promptly.
Preparation technology's checking and product stability: prepare 5 batch samples with preparation technology, in pressing/and the detection of long chain fat emulsion injection quality standard, every index is up to specification.Got 25 ℃ of reserved sample observings of above-mentioned 5 batch samples 8 months, except that the pH value has the decline slightly, all the other every indexs do not have considerable change, all meet the requirement of quality standard.
Embodiment 3:13-methyl-tetradecanoic acid and 13-methyl-isopropyl myristate influence focal cerebral ischemia-reperfusion injury in rats model
Model preparation: the acute arteria cerebri media ischemical reperfusion injury of rat line bolt method model (with reference to the method preparation of Longa).Rat is with 2% vetanarcol (40mg/kg, ip) each artery of neck is separated in the anesthesia back, with diameter is that the nylon wire of 0.205mm inserts RICA from RECA, slowly push ahead (18.5 ± 0.5) mm (from the furcation meter) approximately, till the power that is hampered, make arteria cerebri media embolism model (MCAO).Behind the ischemic 2h, under narcosis, extract the bolt line, form perfusion again, administration simultaneously or give solvent.Animal reaches in art and is incubated before postoperative anesthesia is regained consciousness.Being masked as of model success: the hemiplegia based on left fore appears in the clear-headed back of animal.Dead person's rejecting in neurological deficit sign or the 2h does not appear after pulling out line.
Cerebral infarction stereometry: break end rapidly when irritating 24h again and get brain, the section of crown position, 2%TTC dyeing.Infarcted region is white in color, and non-infarcted region takes on a red color.With coloration result shooting input computer, calculate the ratio (%) that the cerebral infarction volume accounts for full brain with the AutoCAD image analysis software.(the results are shown in Table 1)
Cerebral edema is measured: rat model pours into the 24h broken end again and gets brain, blots surface-moisture with filter paper, separates damage brain hemisphere, weighing brain weight in wet base, and 125 ℃ are toasted 48 hours to constant weight, and accurately the weighing dry weight is calculated brain water content.Brain water content=(weight in wet base-dry weight)/weight in wet base * 100%.(the results are shown in Table 1)
Neurological is estimated: press 5 fens systems of Longa standards of grading, postoperative comments 1～3 fen person to be the successfully sign of performing the operation; 0 minute: do not have obvious neurological symptom; 1 minute: can not the full extension left fore; 2 minutes: rotation to the left; 3 minutes: topple over to the left during walking; 4 minutes: can not walk voluntarily.(the results are shown in Table 1)
Table 1 13-methyl-tetradecanoic acid and 13-methyl-isopropyl myristate are to the cerebral infarct volume and the neurologic influence of focal cerebral ischemia-reperfusion injury in rats model
With the solvent control group than * p＜0.05, * * p＜0.01. and sham operated rats are than ##p＜0.01
The mensuration of blood-brain barrier permeability: with 2% Evans Blue (Evan ' s blue, EB) as tracer agent, detect the degree of injury of hemato encephalic barrier.Animal is irritated back 2h again, the tail vein injects 2%EB 2ml/kg, get right side damage zone cerebral tissue and corresponding zone, left side cerebral tissue during execution rapidly, hatch 24h in the formamide soln, the ultraviolet spectrophotometer colorimetric is shown blood-brain barrier permeability with the contained EB of every Borneo camphor tissue wet (μ g/g weight in wet base) scale.(seeing Table 2)
Table 2 13-methyl-tetradecanoic acid is to the blood-brain barrier permeability influence of focal cerebral ischemia-reperfusion injury in rats model
With the solvent control group than * * p＜0.01. and sham operated rats than ##p＜0.01
Brain cell morphological observation: when irritating 24h again, the quick-break head is got brain, get optic chiasma to the crown section of the brain of infundibular stalk, put in 10% formalin fixing, steps such as conventional dehydration, transparent, waxdip, embedding, Hematorylin (hematoxylin) and Yihong (eosin)-HE dyeing are done in the crown section of cerebral tissue, observe brain morphology and change and normal cone neurone density quantification.
The sight substantially that influences cerebral tissue to damage side cerebral morphology: sham operated rats, the big brain volume in both sides is close, solid colour, matter is tough.CIRI24h, the solvent control group, the big brain volume of Ipsilateral increases, and gyrus is flat, and the damage zone color is turned white, and matter is crisp; The tangent plane alba increases, and cortex is squeezed, and cortex and white matter boundary are unclear.Middle dosage and high dose medicament group, the brain both sides do not have significant difference, and are close with sham operated rats.Mirror is seen down: sham operated rats, and the cortical neurogenic cell marshalling is evenly distributed, and is methodically arranged, and size is consistent, and after birth is complete, and endochylema is even, and nuclear membrane is clear, and the chromatin particle is tiny evenly, and a little kernel is arranged; Basal ganglia nerve fiber densification, clear, structural integrity.CIRI24h solvent control model group, pallium part vanished cell, reduced number, arrangement disorder, cell volume is not of uniform size, and form is irregular, triangular in shape, rhombus and irregular shape is arranged, the karyon engrain, size and form differs, and nuclear membrane is unclear, and kernel is not obvious, and the central zone occurs downright bad; The astroglia cell hyperplasia, Glial nodules forms, and empty swooning appears in vasodilation hyperemia around it, and a matter is loose, is netted change etc.; The Basal ganglia liquefactive necrosis, the softening kitchen range of sieve shape forms.Small dose group Ipsilateral cortical neurogenic cell is slightly little, and form is normal substantially, arranges disorder slightly, and nuclear is engrain slightly, and nuclear membrane is clear, and a matter is loose; The slight liquefactive necrosis of Basal ganglia, initially softening kitchen range forms.Middle dosage and high dose group cortical neurogenic cell marshalling, form is normal, does not have obvious difference with sham operated rats; The Basal ganglia nerve fiber is normal substantially, does not see that softening kitchen range forms, but has a matter loose.
Embodiment 4:13-methyl-isopropyl myristate is to the influence of the heart function of isolated rat heart ischemia-reperfusion
Langendorff method perfusion isolated heart, perfusate adopt oxygen-saturated 37 ℃ to revise Rockwell liquid.Locke's solution composition following (g/L) is revised in preparation: NaCl 9.0, and KCl 0.42, CaCl
20.24, NaHCO
30.15 pH 7.4, face with before adding glucose 2.5g/L, in the airtight perfusion bottle of packing into, emit a certain amount of perfusate down, upward linking to each other with oxygen cylinder charges into the oxygen of respective amount, firmly shakes up.Ultra thermostat is kept 37 ℃ of perfusate constant temperature, drains air in the perfusion pipeline.Perfusion pressure is inserted the Glass tubing that communicates with atmosphere at the bottom of the perfusion bottle by one and is kept constant (perfusate identity distance heart 70cm).Core dirty before 30min rats by intraperitoneal injection heparin liquid anti-freezing (2.5mg/100g).The abdominal injection 20% urethanum anesthesia (0.3mL/100g) when dirty of coring, fixing, open the thoracic cavity, cut off Vena cava, aorta and heart surrounding tissue, extract heart rapidly and place the ice Locke's solution to clean to prune, it is standby to wear a cotton thread at aortic root.The aorta sleeve pipe of perfusion pipe end is inserted aorta, fix with the cotton thread ligation of getting ready.Heart can recover to beat in 1min after the perfusate perfusion of oxygenation.
The mensuration heart of heart rate, heart easypro contract power, coronary flow is clamped a little apex of the heart tissue with the frog heart clip of anchor line (string) after recovering to beat, and anchor line (string) turns to the back to link to each other with the muscular tension transmitter by pulley.The effusive perfusate of coronary artery is collected by funnel, contacts with drop transverter two electrodes during drippage.The heart of tension pick-up, the output of drop transverter relaxes and contracts power, drop signal by biological function experimental system record.Before the easypro power that contracts of record heart, regulate the anchor line (string) elasticity that links to each other with tension pick-up, make the about 3g of cardiac preload.Opening entry heartbeat when stablizing behind the perfusion 20min, drop curve (value to start with) are later on every 10min sampling 1min.Stop to pour into 90min again behind the perfusion 30min.After experiment finishes, the curve of each time point is carried out area measure, record heart rate, heart contraction amplitude (g), maximal velocity of contraction, myocardial relaxation power (g), maximum diastolic velocity, coronary flow and (drip/numerical value such as min).As the each point relative value, starting value does 100 to each point value divided by starting value.
Table 3 13-methyl-isopropyl myristate influences global ischemia reperfusion injury isolated rat heart model heart rate
With the solvent control group than * p＜0.05.
This compound is more obvious to the influence of heart rate, and level was slower than solvent control group before heart rate returned to ischemic after irritating again, less generation rapidity heart disorder, and the solvent control group all has rapidity heart disorder (table 3) in various degree.This compound also can increase the amplitude (table 4 and table 5) of irritating back filling arteries and veins flow and heart contraction more in addition.
Table 4 13-methyl-isopropyl myristate influences global ischemia reperfusion injury isolated rat heart model heart contraction amplitude
With the solvent control group than * p＜0.05.
Table 5 13-methyl-isopropyl myristate influences global ischemia reperfusion injury isolated rat heart model coronary flow
With the solvent control group than * p＜0.05.
Claims (7)
1. a class is as shown in the formula (I, II, III) structure, the compound with alkyloyl structure of terminal side chain
Wherein n is 0～18 integer, and m is the even-integral number of 0～2a, and a is the unsaturated double-bond number that structure allows.
R wherein
1Be one of following group or structure:
-OH is saturated or unsaturated fatty acids.
-NH
2,-amino acid ,-glucose
-ONa ,-OK is the sodium salt and the sylvite of lipid acid.
-OCH
3,-OC
2H
5,-OC
3H
7,-OC
4H
9,-OC
5H
11, being the ester of saturated or unsaturated fatty acids, propyl ester wherein, butyl ester and pentyl ester can be isomer arbitrarily.
-glycerol ,-propylene glycol, the ester that any hydroxyl of acyl group and alcohol forms.
2. the described compound of claim 1, they are one of following compounds:
13-methyl-tetradecanoic acid
13-methyl-tetradecanoic acid sodium
13-methyl-methyl myristate
13-methyl-isopropyl myristate
The positive butyl ester of 13-methyl-tetradecanoic acid
13-methyl-tetradecanoic acid monoglyceride
13-methyl-tetradecanoic acid triglyceride
13-methyl-tetradecanoic acid triglyceride level
12-methyl-tetradecanoic acid
12-methyl-methyl myristate
12-methyl-isopropyl myristate
The positive butyl ester of 12-methyl-tetradecanoic acid
12-methyl-tetradecanoic acid monoglyceride
12-methyl-tetradecanoic acid triglyceride
12-methyl-tetradecanoic acid triglyceride level
12-methyl-tridecanoic acid isopropyl ester
14-methyl-pentadecylic acid
15-methyl-hexadecanoic acid
3. according to the compound described in the claim 1, be used for making the purposes of the medicine of treatment people's tissue or organ ischemic and reperfusion injury.
4. tissue described in the claim 3 and organ refer to brain, and its ischemic and reperfusion injury comprise the cerebral ischemia and the reperfusion injury of cerebral apoplexy and cardiac arrest and cardiopulmonary resuscitation postoperative.
5. tissue described in the claim 3 and organ refer to the heart, lung, liver, kidney, retina and digestive tube.Its ischemic and reperfusion injury comprise ischemic and the reperfusion injury in myocardial infarction, intestinal ischemia, hepatic ischemia, thromboembolism treatment, operation on vessels of heart and the histoorgan migration process.
6. according to the described compound of claim 1, when being used for the treatment of ischemic and reperfusion injury, these compounds can be made into pulvis, tablet, capsule, injection, and microemulsion, lipomul.Wherein lipomul mainly comprises water, oil, lecithin and pharmaceutically acceptable other auxiliary material.
7. according to the described compound of claim 1, its source can be chemosynthesis, also can extract from microbial fermentation.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111671725A (en) * | 2018-01-26 | 2020-09-18 | 中国医学科学院阜外医院 | Injection for protecting ischemic myocardium and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111671725A (en) * | 2018-01-26 | 2020-09-18 | 中国医学科学院阜外医院 | Injection for protecting ischemic myocardium and preparation method thereof |
| CN111671725B (en) * | 2018-01-26 | 2023-03-21 | 中国医学科学院阜外医院 | Injection for protecting ischemic myocardium and preparation method thereof |
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Application publication date: 20091014 |