CN104869988B - The purposes of 3 carboxyl N ethyl ns, the ammonium of N dimethyl propylenes 1 or its pharmaceutically acceptable salt in treatment atherosclerosis - Google Patents
The purposes of 3 carboxyl N ethyl ns, the ammonium of N dimethyl propylenes 1 or its pharmaceutically acceptable salt in treatment atherosclerosis Download PDFInfo
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- 201000001320 Atherosclerosis Diseases 0.000 title claims abstract description 18
- 150000003839 salts Chemical class 0.000 title claims abstract description 14
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical class CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 title abstract 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 title abstract 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title abstract 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 title abstract 3
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 8
- 235000021317 phosphate Nutrition 0.000 claims description 7
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract description 4
- 239000010452 phosphate Substances 0.000 abstract description 4
- PJSQQYJIMPYNHW-UTMFBWBUSA-N [NH4+].[NH4+].[NH4+].[NH4+].[O-]C(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O Chemical compound [NH4+].[NH4+].[NH4+].[NH4+].[O-]C(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O PJSQQYJIMPYNHW-UTMFBWBUSA-N 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
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- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
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- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 210000002414 leg Anatomy 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
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- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
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- 230000000489 anti-atherogenic effect Effects 0.000 description 2
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 2
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- -1 hydrogen salt Chemical class 0.000 description 2
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- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- PHIQHXFUZVPYII-LURJTMIESA-O (S)-carnitinium Chemical compound C[N+](C)(C)C[C@@H](O)CC(O)=O PHIQHXFUZVPYII-LURJTMIESA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
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- 238000002965 ELISA Methods 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
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- 208000002193 Pain Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 206010054880 Vascular insufficiency Diseases 0.000 description 1
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- 229960004203 carnitine Drugs 0.000 description 1
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- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
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- 210000003205 muscle Anatomy 0.000 description 1
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- 230000002107 myocardial effect Effects 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- PPQFUDZMTNGHBJ-UHFFFAOYSA-N propanoic acid;dihydrate Chemical compound O.O.CCC(O)=O PPQFUDZMTNGHBJ-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
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- 238000007619 statistical method Methods 0.000 description 1
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- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 208000023577 vascular insufficiency disease Diseases 0.000 description 1
- 208000020854 vein disease Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Urology & Nephrology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to 3 carboxyl N ethyl ns, the ammonium of N dimethyl propylenes 1 and its pharmaceutically acceptable salt:3 carboxyl N ethyl ns, the ammonium difumarate of N dimethyl propylenes 1 and 3 carboxyl N ethyl ns, purposes of the ammonium dihydric phosphate of N dimethyl propylenes 1 in prevention and treatment atherosclerosis.
Description
Technical field
The present invention relates to 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums or its pharmaceutically acceptable salt, it is used for
Prevent and treat atherosclerosis (atherosclerosis).The pharmacy of 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums
Above the example of acceptable salt is:3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums difumarate and 3- carboxy-Ns-second
Base-N, N- dimethyl propylene -1- ammonium dihydric phosphates.
Background technology
Atherosclerosis is the complicated chronic inflammation processes for the vascular wall that process lasts decades.Its feature is oxidation
Low-density lipoprotein (LDL) is accumulated, the plump sexual involution of cell death increase and arterial wall, its cause vessel diameter narrow and because
This hinders blood flow.It can occur in any region of body, but be when it develops in the blood vessel of heart or brain
It is most important.Narrow be due to artery liner formation plaque (plaques) (raised patch) (raised patches).This
A little plaques are by OxLDL ELISA, rotten muscle cell, fibr tissue, blood platelet, cholesterol agglomerate, macrophage, T
Lymphocyte and frequently calcium composition.Atherosclerotic lesion generally develops and is most commonly in turbulent blood flow region
People with high cholesterol concentration.The number and thickness of plaque with age, cause the loss of vascular smooth inner membrance and helped
The formation of long thrombus (blood clotting).Sometimes thrombus fragment comes off and forms embolus, and it is advanced by blood flow and blocked smaller
Blood vessel, therefore cause the ischemia injury of tissue.
Atherosclerosis and its clinical manifestation are morbidity and mortality main causes in modern society.It is related to coronal dynamic
The atherosclerotic heart disease of arteries and veins (coronary cardiopathy) is dead most common reason, accounts for all dead three points
One of.The atherosclerosis (apoplexy) for interfering with the blood supply of brain is the third-largest most common cause of death, with cancer
Afterwards.Vascular insufficiency is another clinical manifestation of atherosclerosis, and it is such as led to by reducing other major arteries
Blood flow in the artery of kidney, leg and intestines causes a large amount of serious diseases.
Unfortunately, atherosclerosis does not produce symptom, until serious to being enough limit blood stream to the destruction of artery
It is dynamic.The blood flow limitation of cardiac muscle is flowed to as caused by atherosclerosis can cause angina pectoris or myocardial infarction (heart
Onste).The blood flow limitation for flowing to leg muscle causes Charcot's syndrome (pain occurs in motion process leg, and passes through
Rest is alleviated).Blood supply narrows to the artery of brain may cause transient ischemic attack (symptom of apoplexy and sign duration
No more than 24 hours) and dizzy breaking-out, or finally cause apoplexy in itself.
3- carboxy-Ns, N, N- trimethyl propyl- 1- ammoniums (GBB) are known to be in most cases used as carnitine bioprecursor, its
It is the key molecule in energy metabolism of myocardial regulation, and originally it be characterized as being a kind of noxious material, it accelerates breathing, causes stream
Saliva and shed tears, pupil amplification, vessel retraction and cardiac arrest (LINNEWEH, W.Gamma- in the diastole
Butyrobetain,Crotonbetain und Carnitin im tierischen Stoffwechsel.Hoppe-
Seylers Zeitschrift fur physiologische Chemie.1929, volume 181, the 42-53 pages).Meanwhile, slightly
3- carboxy-Ns are had shown that in the paper a little later delivered, N, the administration of N- trimethyl propyl- 1- ammoniums does not induce any toxic action,
Because its toxicity is low-down (LD5O 7000mg/kg,s.c.)(ROTZSCH,W.Iber die Toxizitat des
Carnitins und einiger verwandter Stoffe.Acta biol.med.germ.1959, volume 3,28-36
Page).
WO2010/149654A disclosed in 29 days October in 2010 (GRINDEKS JSC) proposes 3- carboxy-Ns, N, N- tri-
The combination of methyl propyl- 1- ammoniums and 3- (2,2,2- trimethyls hydrazine) propionate dihydrate is used to treat atherosclerosis.However,
It does not report exclusive use 3- carboxy-Ns, and N, N- trimethyls propyl- 1- ammoniums treat the effect of atherosclerosis.
04 month 2011 WO2011/048201A disclosed in 28 days (GRINDEKS JSC) disclose 3- carboxy-Ns, N, N- tri-
The new derivative of methyl propyl- 1- ammoniums, 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums, it is with cardioprotective activity
Noval chemical compound.
Apolipoprotein E gene knocks out (ApoE-/-) mouse is being used for of being commonly used to assess the anti-atherogenics of test substances
The experimental model of the atherosclerosis of hardening activity.
The content of the invention
The present invention relates to treat atherosclerosis by reducing the gross area and volume of atherosclerotic lesion.
By using 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums or its pharmaceutically acceptable salt:3- carboxy-Ns-second
Base-N, N- dimethyl propylene -1- ammoniums difumarate or 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium biphosphate salts for treating
(perhaps through lipid and cholesterol metabolic is changed) realizes the suppression for lesion process.
The therapeutically effective amount of 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums or its pharmaceutically acceptable salt is about
0.01 to 500mg/kg/ days, preferably 0.1 to 100mg/kg/ days.
Wondrous and it was unexpectedly observed that 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums and its is pharmaceutically acceptable
Salt:3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums difumarate or 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1-
Ammonium dihydric phosphate possesses significant study of anti-atherogenic effect.
3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums, 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium fumaric acid
The anti-atherosclerotic activity of hydrogen salt or 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium dihydric phosphates can be by commenting
Estimate these compounds for the influence of the aorta face part covered by atherosclerotic lesion to determine.
3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums can combine use with pharmaceutically acceptable carrier or diluent
In the pharmaceutical preparation comprising the compound or its pharmaceutically acceptable salt.Suitable pharmaceutically acceptable carrier includes lazy
Property solid-filling agent or diluent and sterile aqueous or organic solution.Therefore, for be administered orally, the compound can with it is suitable
Solid or liquid-carrier or diluent combination to form capsule, tablet, pulvis, syrup, solution, suspension etc..If desired,
Pharmaceutical composition can contain additional component such as flavor enhancement, sweetener, excipient etc..For parenterai administration, the compound
It can combine to form the solution or suspension of injectable with sterile aqueous or organic media.Then, the Injectable solution can be with
By vein, it is intraperitoneal, be subcutaneously or intramuscularly administered.
Anti-atherosclerotic activity
By body weight 18-20g ApoE-/-Female mice be maintained at 12 hours it is dark/12 small time circulation air-conditioned room in (22.5 ±
0.5 DEG C, 50 ± 5% humidity), and it is unrestrictedly obtained food and water.
Before the study began, mouse is made to adapt to local condition with week age.During 8 week old, mouse is randomized to either five
Individual equal-sized group (n=10).For inducing experimental atherosclerosis (atherosclerotic lesion in sustainer), institute
There is WESTERN RD (P) diet (Cat 82316) feeding 4 that group animal is provided with Special Diets Services (Britain)
Individual month.During this 4 months, the mouse of different experiments group receives following treat:
1. control group --- drinking water;
2.3- carboxy-Ns, N, N- trimethyl propyl- 1- ammonium groups --- 10mg 3- carboxy-Ns, N, N- front threes in per kg drinking water
Base propyl- 1- ammoniums;
3.3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium groups --- 10mg 3- carboxy-Ns-second in per kg drinking water
Base-N, N- dimethyl propylene -1- ammoniums;
4.3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium difumarate groups --- 17.5mg in per kg drinking water
3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium difumarate;
5.3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium dihydric phosphate groups --- 16.8mg in per kg drinking water
3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium dihydric phosphates.
The dosage of adjustment test substances has 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums with 10mg/kg dosage
There is equimolar.
By the consumptions of every 2 days measurement drinking water and adjust the concentration of supplementation material and determine the agent of test compound
Amount.
After 4 months, injection 1000UI heparin i.p. and lower execution (yellow Jackets, 50mg/kg of anesthesia in mouse peritoneal
i.p.)。
Determine the size of the atherosclerotic lesion in whole sustainer.Sustainer is cleaned from bow portion to furcation
Surrounding tissue, cuts out and is fixed in 4% formaldehyde.It is then that whole sustainer is longitudinally opened, it is pinned on silicon plate and uses the Sudan
IV dyes lipid.Aorta images are obtained using digital camera and calculate diseased region using the softwares of Image-Pro Plus 6.3
The gross area.Atherosclerosis is expressed as percentage of the aorta face relative to total aorta face that lesion is covered
Than.
All analyses to treatment group information by blind observer is set by being carried out.
After Western RD diet by contact 4 months, apoE-/-There is significant atherosclerotic lesion in mouse.The Sudan
IV dyes the total aorta face of area average out to of the atherosclerotic lesion in the analysis shows of sustainer, control group
14-16%.Using 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums that the dosage of 4 months are 10mg/kg, dosage is
17.5mg/kg 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium difumarate, the 3- carboxyls that dosage is 16.8mg/kg -
N- ethyls-N, N- dimethyl propylene -1- ammoniums dihydric phosphate (both rear 3- carboxy-Ns-ethyl-N, N- bis- having with 10mg/kg
The equimolar of methyl propyl- 1- ammoniums) cause atherosclerotic lesion size that there is significant reduction on statistical significance.3- carboxylics
Base-N, N, N- trimethyl propyl- 1- ammoniums (10mg/kg) do not influence on the size of atherosclerotic lesion.
Use 3- carboxy-Ns, N, N- trimethyl propyl- 1- ammoniums, 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums, 3- carboxyls -
N- ethyls-N, N- dimethyl propylene -1- ammoniums difumarate and 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium biphosphates
Salt is to apoE-/-The curative effect that the atherosclerotic lesion region of mouse aorta carries out treatment in 4 months is listed in Table 1 below.
Table 1.3- carboxy-Ns, N, N- trimethyl propyl- 1- ammoniums, 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums, 3- carboxylics
Base-N- ethyls-N, N- dimethyl propylene -1- ammoniums difumarate and 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammonium phosphoric acid
Effect of the dihydric salt for atherosclerotic lesion region
Numerical value is provided with average value ± SEM.Statistical analysis is carried out by Student ' s t-test;*p<0.05 relative to
Control group and #p<0.05 relative to 3- carboxy-Ns, N, N- trimethyl propyl- 1- ammonium groups;N=10.
As a result the percentage relative to control group is expressed as, the value of control group is appointed as 100%.
The result being listed in Table 1 below shows, 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums, 3- carboxy-Ns-ethyl-N,
N- dimethyl propylenes -1- ammoniums difumarate and 3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums dihydric phosphate for
apoE-/-The formation of atherosclerotic lesion in mouse aorta has protective effect.On the contrary, 3- carboxy-Ns, N, N- front threes
Base propyl- 1- ammoniums do not have effect.
Claims (3)
1.3- carboxy-Ns-ethyl-N, N- dimethyl propylene -1- ammoniums or its pharmaceutically acceptable salt, which are used to prepare to prevent and treat, to be moved
The purposes of the medicament of pulse atherosclerosis.
2. purposes according to claim 1, wherein the pharmaceutically acceptable salt is 3- carboxy-Ns-ethyl-N, N- bis-
Methyl propyl- 1- ammonium difumarate.
3. purposes according to claim 1, wherein the pharmaceutically acceptable salt is 3- carboxy-Ns-ethyl-N, N- bis-
Methyl propyl- 1- ammonium dihydric phosphates.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP12198627 | 2012-12-20 | ||
EP12198627.7 | 2012-12-20 | ||
PCT/EP2013/077291 WO2014096133A1 (en) | 2012-12-20 | 2013-12-19 | Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium or a pharmaceutically acceptable salt thereof in the treatment of atherosclerosis |
Publications (2)
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CN (1) | CN104869988B (en) |
AR (1) | AR094084A1 (en) |
BR (1) | BR112015014161B1 (en) |
CA (1) | CA2895574C (en) |
CU (1) | CU20150067A7 (en) |
JO (1) | JO3117B1 (en) |
MX (1) | MX362762B (en) |
PE (1) | PE20151587A1 (en) |
TN (1) | TN2015000236A1 (en) |
WO (1) | WO2014096133A1 (en) |
ZA (1) | ZA201505093B (en) |
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WO2010149654A1 (en) * | 2009-06-25 | 2010-12-29 | Grindeks, A Joint Stock Company | Pharmaceutical composition of gamma-butyrobetaine or a pharmaceutically acceptable salt and meldonium or a pharmaceutically acceptable salt |
WO2010151095A1 (en) * | 2009-06-25 | 2010-12-29 | Tetra, Sia | Novel acetylsalicylic acid salts |
LV14345B (en) * | 2009-10-22 | 2011-07-20 | Grindeks, A/S | 4-[ethyl(dimethyl)ammonio]butanoate and their use in the treatment of cardiovascular diseases |
RS55092B1 (en) * | 2011-04-27 | 2016-12-30 | Grindeks Jsc | Use of 3-carboxy-n-ethyl-n,n-dimethylpropan-1-aminium salts in the treatment of cardiovascular disease |
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CA2895574C (en) | 2019-11-26 |
CN104869988A (en) | 2015-08-26 |
BR112015014161B1 (en) | 2021-02-17 |
MX362762B (en) | 2019-02-06 |
AR094084A1 (en) | 2015-07-08 |
CA2895574A1 (en) | 2014-06-26 |
BR112015014161A2 (en) | 2017-07-11 |
WO2014096133A1 (en) | 2014-06-26 |
MX2015008138A (en) | 2016-04-25 |
TN2015000236A1 (en) | 2016-10-03 |
JO3117B1 (en) | 2017-09-20 |
ZA201505093B (en) | 2016-04-28 |
CU20150067A7 (en) | 2016-01-29 |
PE20151587A1 (en) | 2015-12-05 |
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