CN100364540C - Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis - Google Patents
Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis Download PDFInfo
- Publication number
- CN100364540C CN100364540C CNB2006100575358A CN200610057535A CN100364540C CN 100364540 C CN100364540 C CN 100364540C CN B2006100575358 A CNB2006100575358 A CN B2006100575358A CN 200610057535 A CN200610057535 A CN 200610057535A CN 100364540 C CN100364540 C CN 100364540C
- Authority
- CN
- China
- Prior art keywords
- hepatitis
- dihydro
- benzothiazepine
- medicine
- cis
- 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.)
- Expired - Fee Related
Links
- 208000006454 hepatitis Diseases 0.000 title claims abstract description 15
- 231100000283 hepatitis Toxicity 0.000 title claims abstract description 14
- LHBHZALHFIQJGJ-CABCVRRESA-N (2s,3s)-3-hydroxy-2-(4-methoxyphenyl)-3,5-dihydro-2h-1,5-benzothiazepin-4-one Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](O)C(=O)NC2=CC=CC=C2S1 LHBHZALHFIQJGJ-CABCVRRESA-N 0.000 title description 3
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 15
- 229960003920 cocaine Drugs 0.000 claims abstract description 13
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 208000005374 Poisoning Diseases 0.000 claims description 4
- 231100000572 poisoning Toxicity 0.000 claims description 4
- 230000000607 poisoning effect Effects 0.000 claims description 4
- 208000001378 Carbon Tetrachloride Poisoning Diseases 0.000 claims description 3
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 abstract description 5
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 abstract description 5
- 239000004480 active ingredient Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 208000019423 liver disease Diseases 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 108010082126 Alanine transaminase Proteins 0.000 description 4
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 4
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 238000013245 carbon tetrachloride model Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a new purpose of (25-cis)-(+)-2.3-dihydro-3-hydroxy-2-(4-methoxphenyl)-1, 5-benzothiazatropylidene-4-(5H)-ketone (abbreviation is shun nei) in the preparation of medicine for curing hepatitis. Medicine which uses shun nei as active ingredients can effectively cure cocaine toxic hepatitis and carbon tetrachloride toxic hepatitis.
Description
Technical field
The present invention relates to the purposes of a kind of chemical compound in medicine, specifically, be (2S-is suitable)-(+)-2,3-dihydro-3-hydroxyl-2-(4-anisyl)-1, the purposes of 5-benzothiazepine-4 (5H)-ketone (abbreviating as) in the medicine of preparation treatment hepatitis along interior.
Background technology
In the middle of gastral disease, hepatopathy is the disease kind of serious harm people ' s health.China has 1.2 hundred million hepatitis B virus lifelong carriers at present approximately, and wherein 3,000 ten thousand people can be transformed into chronic hepatitis, liver cirrhosis, hepatocarcinoma, and annual people because of hepatopathy death has 300,000 people approximately.In recent years, along with improving constantly of living standards of the people, the fatty liver by being addicted to drink and causing with some other factor also increases day by day.When health was caused damage, China was used for the treatment of the expense of hepatopathy every year up to 40,000,000,000 yuans, and national economy and social development has also been caused very big influence.Owing to still lack the method for specific treatment hepatitis at present, the new drug of exploitation treatment hepatopathy is very urgent and important.
(2S-is suitable)-(+)-2,3-dihydro-3-hydroxyl-2-(4-anisyl)-1,5-benzothiazepine-4 (5H)-ketone (abbreviate as along interior) are our up-to-date a kind of chemical compounds that screens, the still unmanned medical value of finding it.
Summary of the invention
The purpose of this invention is to provide along interior new purposes, i.e. new application in the medicine of preparation treatment hepatitis.
Another object of the present invention provides a kind of medicine for the treatment of hepatitis.
The inventor according to the hepatoprotective method of " new drug preclinical study guideline " (1993, national Bureau of Drugs Supervision) etc. to along in carried out pharmacology and pathological study.
The inventor finds, carries out lumbar injection and oral administration in suitable, and obvious effects is all arranged, and serum functional parameter and pathological index all improve significantly.
With along in when treating, it can be with form oral administrations such as powder, granule, tablet, capsule, pill and liquid preparations; Also can be non-through enteral administration with forms such as injection, suppository, percutaneous preparation, inhalant.Along interior effective agent, be by with suitable medicinal blend, be mixed with as mixing such as excipient, binding agent, penetrating agent, lubricant.
Dosage changes with patient's the state of an illness, route of administration, patient's age and body weight.Under the oral administration situation, dosage is generally adult 100～1000mg/kg/ days, is preferably 250～500mg/kg/ days.
Advantage of the present invention is: along the interior chemical compound that can treat the research of cocaine poisoning hepatitis.Cocaine is popular drugs in a kind of world wide.2002 the end of the year China major drug-related cases of 100 kilograms of cocaine smugglings have just taken place.Hepatitis is the lethal major reason of cocaine poisoning.Also do not treat at present the generally acknowledged medicine of cocaine poisoning hepatitis in the world.All is to find first along acting on of interior antitoxin product cocaine on internal and international.Also is to find first along acting on of interior anti-carbon tetrachloride poisoning hepatitis on internal and international.
In suitable is the chemical compound that sale is arranged on a kind of market.
Along interior english name be:
(2S-cis)-(+)-2，3-Dihydro-3-hydroxy-2-(4-methoxyphenyl)-1，5-benzothiazepin-4(5H)-one。
Molecular formula: C
16H
15NO
3S
Molecular weight: 301.36
CAS registration number: 42399-49-5
Chinese name: (2S-is suitable)-(+)-2,3-dihydro-3-hydroxyl-2-(4-anisyl)-1,5-benzothiazepine-4 (5H)-ketone.
Other title: along interior (abbreviating as) along interior.
Chemical constitution is:
The specific embodiment
The embodiment that provides below is used for further illustrating the present invention, and does not constitute limitation of the scope of the invention.
1. material
Embodiment is used to be provided content 98% along interior by chemical reagent Acros Organics company (U.S.).
Other medicine, reagent and laboratory animal can both be commercial easily.
2. preparation method example
Get along interior 100g, hydroxyethyl-cellulose 10g, tabletting is made tablet, is placed in the vessel of normal temperature drying standby.
3. test method
Laboratory animal is a mice, and body weight is 22～26g, is provided by Department Of Medicine, Peking University's Experimental Animal Center.Duration of test provides the tap water and the normal diet of capacity, and animal housing keeps 22 ℃, automatic ventilation.The grouping of animal is pressed the body weight random packet with processing with mice.Toxic hepatitis modeling group did not give any processing in preceding 3 days, the 4th day subcutaneous injection modeling chemical compound (cocaine or carbon tetrachloride).Along interior+modeling compound component not with various dose along interior filling stomach 4 days, every day 1 time.Behind the 4th day gastric infusion 30 minutes, subcutaneous injection modeling compound solution.The contamination of modeling chemical compound is after 24 hours, and all animal endocanthions are got blood, and disconnected marrow is put to death; leave and take liver at once, weigh, maximum leaf is dipped in 10% the formalin fixing; carry out the observation of liver cardinal principle and leave and take liver specimens, the hepatic pathology intensity of variation is observed in HE dyeing.Utilize the 7170A automatic analyzer, adopt enzyme connection-ultraviolet continuous detecting method, measure the activity of liver function enzyme alanine transaminase (ALT), aspartate transaminase (AST) and lactic acid dehydrogenase (LDH) in the serum.The statistical analysis technique experimental data is represented with mean ± standard deviation.Use the SPSS11.5 statistical software and experimental result is adopted methods analysts such as variance analysis, t check handle, p＜0.05 thinks that group difference has significance, and p＜0.01 thinks that group difference has highly significant.
4. result of the test:
(1) can be along the effect of interior anti-cocaine mice toxic hepatitis referring to table 1.
The effect (serum biochemistry index) of the suitable interior anti-cocaine toxic hepatitis of table 1 (
)
| Along interior dosage mg/kg | ALT(IU/L) | AST(IU/L) | LDH(IU/L) |
| Matched group cocaine model group 50 100 200 | 43.0±8.6 ** 4642.0±1644.9 45.3±2.5 ** 59.0±33.9 ** 44.6±9.4 ** | 135.3±24.3 ** 1111.9±428.4 117.8±9.6 ** 137.6±26.5 ** 127.0±4.4 ** | 1247.8±42.8 ** 3842.3±2597.6 1039.3±274.9 * 1124.3±115.6 * 1082.7±111.2 * |
Compare with the cocaine model group,
*P＜0.05,
*P＜0.01 (n=8)
(2) can be along the effect of interior anti-carbon tetrachloride mice toxic hepatitis referring to table 2.
The effect (serum biochemistry index) of the suitable interior anti-carbon tetrachloride poisoning hepatitis of table 2 (
)
| Along interior dosage mg/kg | ALT(IU/L) | AST(IU/L) | LDH(IU/L) |
| Matched group carbon tetrachloride model group 200 400 800 | 37.0±12.6 * 2681.4±1618.7 2032.4±757.1 883.4±541.8 * 312.2±291.6 ** | 150.4±71.9 * 958.9±541.5 630.6±224.2 347.2±104.7 * 188.6±61.9 * | 1078.2±360.6 * 1537.6±433.9 2821.0±3278.4 1120.6±157.3 * 939.8±96.2 * |
Compare with the carbon tetrachloride model group,
*P＜0.05,
*P＜0.01 (n=8)
Claims (2)
1. (2S-is suitable)-(+)-2,3-dihydro-3-hydroxyl-2-(4-anisyl)-1, the application of 5-benzothiazepine-4 (5H)-ketone in the medicine of preparation treatment cocaine poisoning hepatitis.
2. (2S-is suitable)-(+)-2,3-dihydro-3-hydroxyl-2-(4-anisyl)-1, the application of 5-benzothiazepine-4 (5H)-ketone in the medicine of preparation treatment carbon tetrachloride poisoning hepatitis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100575358A CN100364540C (en) | 2006-03-14 | 2006-03-14 | Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100575358A CN100364540C (en) | 2006-03-14 | 2006-03-14 | Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1850088A CN1850088A (en) | 2006-10-25 |
| CN100364540C true CN100364540C (en) | 2008-01-30 |
Family
ID=37131600
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100575358A Expired - Fee Related CN100364540C (en) | 2006-03-14 | 2006-03-14 | Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100364540C (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5102999A (en) * | 1989-12-06 | 1992-04-07 | Zambon Group S.P.A. | Process for the preparation of an intermediate of diltiazem |
| CN1160713A (en) * | 1996-02-23 | 1997-10-01 | 田边制药株式会社 | Process for preparing 1,5-benzothiazepine derivative |
| WO1998036733A2 (en) * | 1997-02-24 | 1998-08-27 | Michael Albert Kamm | Topical pharmaceutical composition comprising a cholinergic agent or a calcium channel blocker |
| WO2002049603A1 (en) * | 2000-12-20 | 2002-06-27 | Lg Household & Health Care Ltd. | Compositions for prevention and alleviation of skin wrinkles |
-
2006
- 2006-03-14 CN CNB2006100575358A patent/CN100364540C/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5102999A (en) * | 1989-12-06 | 1992-04-07 | Zambon Group S.P.A. | Process for the preparation of an intermediate of diltiazem |
| CN1160713A (en) * | 1996-02-23 | 1997-10-01 | 田边制药株式会社 | Process for preparing 1,5-benzothiazepine derivative |
| WO1998036733A2 (en) * | 1997-02-24 | 1998-08-27 | Michael Albert Kamm | Topical pharmaceutical composition comprising a cholinergic agent or a calcium channel blocker |
| WO2002049603A1 (en) * | 2000-12-20 | 2002-06-27 | Lg Household & Health Care Ltd. | Compositions for prevention and alleviation of skin wrinkles |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1850088A (en) | 2006-10-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ji et al. | Effect of berberine hydrochloride on grass carp Ctenopharyngodon idella serum bactericidal activity against Edwardsiella ictaluri | |
| CN103609939B (en) | A kind of astragalus polyose and LBP-X composition and method of making the same and application | |
| CN104367987A (en) | Astragalus mongholicus formulation for veterinary use and preparation method thereof | |
| CN103830301A (en) | Flos chrysanthemi with liver tonifying function and application thereof | |
| CN100364540C (en) | Pharmaceutical use of (2s-cis)-(+)-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepine-4(5H)-one for treating hepatitis | |
| CN100382801C (en) | Pharmaceutical use of alpha-(2,4-dichlorobenzyle)-1H-imidazole-1-ethanol for treating hepatitis | |
| Chen et al. | A rare case of amatoxin poisoning in the state of Texas | |
| CN101623284A (en) | Medical composition of compound vitamin C injection | |
| CN1232249C (en) | Application of chalcone for preparing medicnes for treating hepatitis and hepatoma | |
| CN1263506C (en) | Application of laevorotation carnosine in preparaing medication for assistant curing hepatitis and health foods | |
| CN107157924A (en) | Naproxen sodium sodium chloride injection and preparation method thereof | |
| CN101889992B (en) | Application of 2,4-dihydroxy benaophenonel in preparing medicament for treating hepatitis | |
| CN110123824B (en) | Ilicis Pubescentis saponin A1New use of | |
| CN1272008C (en) | Application of diltiazem of hydrochloric acid in preparing antidote | |
| CN108743792A (en) | Be conducive to anti-fatigue traditional Chinese mixture to refresh the mind and preparation method thereof | |
| Parsi et al. | Comparison of Garlic therapeutic effects and standard therapy with De Penicillamine in patients with Lead poisoning | |
| CN1188117C (en) | Application of 1, 3-diphenyl-1, 3-propanedione in preparing medicine for treating hepatitis | |
| CN102091269B (en) | Medicament for treating lead poisoning of ruminant | |
| CN107536836A (en) | The effect of beneficial liver and its application of 6 benayl aminopurines | |
| CN107569484A (en) | A kind of compound for treating hepatitis | |
| Baniasad et al. | Hepatotoxicity due to mushroom poisoning: A case report | |
| CN1660354A (en) | Application of five-finger fig in preparing adjuvant for treating hepatitis and health foods | |
| CN1778309A (en) | Use of arctiin and its aglycon in preparation of medicines for diabetes and nephrosis | |
| CN108272788B (en) | Puerarin is in the drug and pig feed additive for preparing the purposes in the drug for preventing and treating pig virus infection, preventing and treating pig virus infection | |
| CN104983777A (en) | Preparation method for radix astragali and licorice powder and product thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080130 Termination date: 20100314 |