LV12200B - Antidiabeic agent - Google Patents

Antidiabeic agent Download PDF

Info

Publication number
LV12200B
LV12200B LVP-97-131A LV970131A LV12200B LV 12200 B LV12200 B LV 12200B LV 970131 A LV970131 A LV 970131A LV 12200 B LV12200 B LV 12200B
Authority
LV
Latvia
Prior art keywords
insulin
ochf2
agent
substances
administration
Prior art date
Application number
LVP-97-131A
Other languages
Latvian (lv)
Other versions
LV12200A (en
Inventor
Janīna BRIEDE
Māra STIVRIŅA
Egils BISENIEKS
Jānis ULDRIĶIS
Natālija MAKĀROVA
Jānis POIKĀNS
Gunārs DUBURS
Kārlis HEIDEMANIS
Original Assignee
Gunārs DUBURS
Egils BISENIEKS
Janīna BRIEDE
Māra STIVRIŅA
Jānis POIKĀNS
Jānis ULDRIĶIS
MAKAROVA,Natālija
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Gunārs DUBURS, Egils BISENIEKS, Janīna BRIEDE, Māra STIVRIŅA, Jānis POIKĀNS, Jānis ULDRIĶIS, MAKAROVA,Natālija filed Critical Gunārs DUBURS
Priority to LVP-97-131A priority Critical patent/LV12200B/en
Priority to PCT/LV1998/000005 priority patent/WO1999001432A1/en
Publication of LV12200A publication Critical patent/LV12200A/en
Publication of LV12200B publication Critical patent/LV12200B/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
    • C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Description

LV 12200LV 12200

Antidiabētisks līdzeklisAntidiabetic agent

Izgudrojums attiecināms uz medicīnu, konkrēti uz ārstnieciskiem preparātiem, kuri domāti cukura diabēta ārstēšanai un var atrast šai jomā praktisku pielietojumu. 5 Ir zināms, ka cukura diabēta ārstēšanai izmanto insulīnu, sulfonilurīnvielas atvasinā jumus un biguanīdus. Tomēr insulīns darbojas relatīvi īslaicīgi un, ilgstoši lietojot, pat izraisa cukura diabēta padziļināšanos un stāvokļa saasināšanos, bet sulfoniluiīnvielas atvasinājumi un biguanīdi ir mazāk efektīvi un tos nevar lietot bērnu un pusaudžu vecumā. Tie izraisa arī citas blakusparādības. 10 Bez tam, iepriekšminētie līdzekļi ir dārgi un to iegūšana tehnoloģiski sarežģīta. Šī izgudrojuma mērķis ir jauna pretdiabēta līdzekļa radīšana, kuram būtu augsta efektivitāte, pēc iespējas ilgstoša darbība uri maza toksicitāte.The invention relates to medicine, in particular to therapeutic preparations for the treatment of diabetes and can find practical application in this field. It is known that insulin, sulphonylureas and biguanides are used to treat diabetes. However, insulin is relatively short-lived and, even on prolonged use, even causes diabetes to worsen and exacerbate, while sulphonylurea derivatives and biguanides are less effective and cannot be used in children and adolescents. They also cause other side effects. 10 In addition, the aforementioned means are expensive and technologically difficult to obtain. The object of the present invention is to create a new anti-diabetic agent with high efficacy, low toxicity for as long as possible.

Izgudrojumu realizē, izmantojot 4-aril-2,6-dimetil-1,4-dihidropiridīn-3,5-dikarbonskābju alkoksialkil- un fenoksialkilēsterus ar sekojošu formulu: 15The invention is carried out using alkoxyalkyl and phenoxyalkylesters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid having the following formula:

1 R=C2H5; R1=OCHFr2 II r=ch2ch2ch3; R1=OCHF2-2 III R=CH(CH3)2; R1=OCHF2-2 IV R=C6H5; R1=OCHF2-2 V R=C2H5; R1=N02-3 VI R=CH2CH2CH3; R1=N02-3 Ķīmiskajiem savienojumiem l-IV [1] un V, VI [2] agrāk atklāta vazodilatējošā aktivitāte. 30 Līdzīga aktivitāte ir arī preparātiem nifedipīnam (VII) un riodipīnam (VIII) (foridonam), kuri mūsu izgudrojuma gadījumā izmantoti salīdzināšanai kā klīnikas praksē lietotie preparāti.1 R = C 2 H 5; R1 = OCHFr2 II r = ch2ch2ch3; R1 = OCHF2-2 III R = CH (CH3) 2; R1 = OCHF2-2 IV R = C6H5; R1 = OCHF2-2V R = C2H5; R1 = NO2-3 VI R = CH2CH2CH3; R1 = N02-3 Chemical compounds 1-IV [1] and V, VI [2] have previously been found to have vasodilating activity. Similarly, preparations for nifedipine (VII) and riodipine (VIII) (foridone), which are used in our invention for comparison as clinical practice, are also similar.

Nifedipīns (VII, R=N02) Riodipīns (VIII, R=OCHF2) 40 -2-Nifedipine (VII, R = NO2) Riodipine (VIII, R = OCHF2) 40-2-

Izgudrojuma aprakstā minētos savienojumus l-VI sintezē ar iznākumu 55-62%, kondensējot attiecīgi aizvietoto benzaldehīdu ar acetetiķskābes alkoksi- vai fenoksietilēsteriem amonjaka klātienē, lietojot metodi [1],In the description of the invention, the compounds I-VI are synthesized with a yield of 55-62% by condensation of the substituted benzaldehyde with the alkoxy or phenoxyethyl esters of acetic acid in the presence of ammonia by the method [1],

Insulīna nepietiekamība organismā izraisa ogļhidrātu un lipīdu vielu maiņas traucējumus, radot hiperglikēmiju un hiperlipidēmiju.Insulin deficiency in the body causes disorders of carbohydrate and lipid metabolism, resulting in hyperglycaemia and hyperlipidemia.

Pasaulē aktīvi meklē jaunas sintētiskas antidiabētiskas vielas, kuras koriģētu lipīdu un ogļhidrātu vielu maiņu, novēršot glikozes vielu maiņu pa sorbitālo ceļu, bloķējot aldola reduktāzi vai α-glikozilāzi, kā arī taukskābju β-oksidāciju.The world is actively looking for new synthetic antidiabetic agents that correct lipid and carbohydrate metabolism by preventing sorbitol metabolism by blocking aldol reductase or α-glucosylase, as well as β-oxidation of fatty acids.

Patentējamo vielu hipoglikēmisko īpašību izpēti veica, izmantojot normālas žurkas (masa 180-220 g), kuras 18 stundas badināja. Pārbaudāmās vielas ievadīja džādās devās perorāli (p/o), un glikozes līmeni žurku asinīs noteica pēc 3 stundām no ievadīšanas brīža (skat. 1. tab.). Atskaitei izmantoja insulīnu, nifedipīnu un riodipīnu. Žurkām izraisīja eksperimentālo cukura diabētu ar streptozotocīnu (ST), ievadot to astes vēnā 50 mg/kg. Glikozes līmeni asinīs noteica pirms ST ievadīšanas un 3 st. pēc pētāmo vielu ievadīšanas, kā arī pēc 4 dienām. Eksperimentus veica ar badinātām žurkām.The study of the hypoglycemic properties of the patented substances was carried out using normal rats (180-220 g weight) that starved for 18 hours. The test substances were administered orally (p / o) and the glucose level in the rat blood was measured after 3 hours from the time of administration (see Table 1). The report used insulin, nifedipine, and riodipine. In rats, experimental diabetes mellitus was induced by streptozotocin (ST) at a dose of 50 mg / kg in the tail vein. Blood glucose levels were determined prior to ST administration and 3 hrs. and after 4 days. Experiments were carried out with fasted rats.

Eksperimentālie dati parāda, ka žurkām izteikts cukura diabēts attīstās 48 st. pēc ievadīšanas ar visām raksturīgām pazīmēm: 3-4 kārtīgu glikozes daudzuma pieaugumu asinīs, 5-10% svara zudumu, glikozūriju, ketonu parādīšanos urīnā u.c. (skat. 2. tab.). No tabulas redzams, ka, izmantojot patentējamās vielas, vairākkārt samazinās glikozes līmenis asinīs.Experimental data show that diabetes mellitus in rats develops at 48 h. after administration with all the characteristic features: 3-4 fold increase in blood glucose, 5-10% weight loss, glycosuria, urinary ketones, etc. (see Table 2). The table shows that the use of proprietary substances reduces blood glucose levels several times.

Faktu kopsavilkums un secinājumi: 1) šo līdzekļu antidiabētiskā darbība atšķiras no insulīna darbības; insulīns strauji samazina glikozes daudzumu asinīs, bet patentējamo vielu antidiabētiskās īpašības parādās pēc apmēram 24-48 stundām, un aktivitāte saglabājas vairākas dienas; šis fakts var nodrošināt prolongētu efektu, lietojot preparātu tikai 2-3 reizes nedēļā; 2) vielas ir maz toksiskas; LD50 atrodas diapazonā 400-4000 mg/kg; 3) vadoties no toksikoloģiskiem pētījumiem un fakta, ka šīs vielas lietojamas mazās devās, izriet, ka šos preparātus var lietot bērni un pusaudži; 4) minētajiem antidiabētiskajiem līdzekļiem iespējama perorāla lietošana, atšķirībā no insulīna, kurš ir efektīvs tikai injekciju formā. -3- LV 12200 1. tabulaSummary of facts and conclusions: (1) The antidiabetic action of these agents is different from that of insulin; insulin rapidly decreases blood glucose levels, while the antidiabetic properties of the patentable substances appear after about 24-48 hours and the activity remains for several days; this can provide a prolonged effect when used only 2-3 times a week; 2) the substances are not toxic; LD50 is in the range 400-4000 mg / kg; (3) It follows from toxicological studies and the fact that these substances are used at low doses, that these preparations can be used by children and adolescents; 4) Oral administration of these antidiabetic agents is possible, unlike insulin, which is effective only in the form of injections. -3- EN 12200 Table 1

Savienojumu l-VIII1 ietekme uz glikozes daudzumu žurku asinīs mg% (M±m) pēc vienreizējas vielu ievadīšanas 5 Savienojums Ievadītā doza, mg/kg Glikozes līmenis asinīs, mg% (M±m) Izejas līmenis 3 st. pēc preparāta ievadīšanas 1 0,05 53,64±2,7 52,70±2,3 0,5 58,25±2,9 48,15±0,62 1,5 60,69±4,1 48,23±2,22 10 II 0,05 69,81 ±2,8 51,98±2,82 0,5 70,09±4,9 61,10±6,1 1,5 69,16±5,2 58,33±0,72 III 0,5 74,08±5,0 59,70±4,9 1,5 75,46±3,8 61,68±1,62 15 IV 0,5 80,66±3,2 72,57±6,3 3,0 78,67±3,9 58,33±1,32 V 0,05 69,03±3,4 65,62±4,2 0,5 77,60±4,8 66,83±2,7 1,5 77,99±1,3 67,61 ±1,72 20 3,0 80,79±6,4 80,01±6,3 VI 0,05 87,61 ±1,2 72,81 ±2,83 0,5 84,81 ±0,8 73,66±0,73 1,5 83,95±1,3 65,17±2,93 3,0 85,85±2,4 68,67±4,62 25 Insulīns 5 U/kg s.c. 74,13±3,3 25,94±3,93 1Effect of Compounds l-VIII1 on glucose in the blood of rats at a dose of mg% (M ± m) after single administration 5 Compound Dose in mg / kg Blood glucose, mg% (M ± m) Exit level 3 h. after administration of the preparation 1 0.05 53.64 ± 2.7 52.70 ± 2.3 0.5 58.25 ± 2.9 48.15 ± 0.62 1.5 60.69 ± 4.1 48, 23 ± 2.22 10 II 0.05 69.81 ± 2.8 51.98 ± 2.82 0.5 70.09 ± 4.9 61.10 ± 6.1 1.5 69.16 ± 5, 2 58.33 ± 0.72 III 0.5 74.08 ± 5.0 59.70 ± 4.9 1.5 75.46 ± 3.8 61.68 ± 1.62 15 IV 0.5 80, 66 ± 3.2 72.57 ± 6.3 3.0 78.67 ± 3.9 58.33 ± 1.32 V 0.05 69.03 ± 3.4 65.62 ± 4.2 0.5 77.60 ± 4.8 66.83 ± 2.7 1.5 77.99 ± 1.3 67.61 ± 1.72 20 3.0 80.79 ± 6.4 80.01 ± 6.3 VI 0.05 87.61 ± 1.2 72.81 ± 2.83 0.5 84.81 ± 0.8 73.66 ± 0.73 1.5 83.95 ± 1.3 65.17 ± 2, 93 3.0 85.85 ± 2.4 68.67 ± 4.62 25 Insulin 5 U / kg sc 74.13 ± 3.3 25.94 ± 3.93 1

Savienojumi VII (nifedipīns) un VIII (riodipīns) analoģiskos apstākļos nedod statistiski 30 ticamu glikozes līmeņa izmaiņu asinīs. 2 p < 0,05 attiecībā pret izejas līmeni 3 p < 0,01 attiecībā pret izejas līmeni -4- 2. tabulaCompounds VII (nifedipine) and VIII (riodipine) do not give statistically reliable blood glucose changes under similar conditions. 2 p < 0.05 to output level 3 p < 0.01 to output level -4- Table 2

Glikozes daudzuma izmaiņas mg% (M±m) žurkām ar eksperimentālo cukura diabētu dažādos laikos pēc vielu l-VIII1 vienreizējas ievadīšanasChanges in glucose content in mg% (M ± m) rats with experimental diabetes mellitus at different times after single-dose administration of substances 1-VIII1

Savienojums Ievadītā doza, mg/kg Glikozes daudzuma izmaiņas asinīs mg% (M±m) pēc vielu ievadīšanas Izejas līmenis pēc 48 st. diabēta pēc 3 st. pēc 4 dienām I 0,05 199,28±6,4 180,35±34,9 76,53±7,42 0.5 153,45±4,3 106,03±3,2 77,06±11,92 1,5 178,65±4,8 129,14±6,7 71,30±2,82 II 0,05 442,46±31,4 386,45±19,3 51,36±4,22 0,5 293,48±22,6 182,44±18,2 57,63±3,62 1,5 226,29±3,82 193,05±22,8 66,12±6,82 III 0,5 188,58±9,7 185,35±10,8 162,82±35,6 1,5 161,15±1,2 119,52±3,4 104,87±7,32 IV 3,0 194,81 ±13,4 187,59±2,7 123,72±18,032 V 0,5 323,27±3,2 237,54±4,32 (pēc 24 st.) 1,5 236,88±1,5 219,27±7,3 (pēc 24 st.) VI 0,05 156,44±2,8 84,41 ±5,32 (pēc 24 st.) 0,5 192,84±3,4 177,78±2,3 (pēc 24 st.) Insulīns 1 U/kg s.c. 216,15±19,2 130,04±25,032 (pēc 1 st.) Kontrole, 0,9% NaCI 1 ml, p.o. 417,0±30,9 408,4±48,6 1Compound Injected dose, mg / kg Changes in blood glucose mg% (M ± m) after administration of substances Exit level after 48 h. diabetes after 3 h. after 4 days I 0.05 199.28 ± 6.4 180.35 ± 34.9 76.53 ± 7.42 0.5 153.45 ± 4.3 106.03 ± 3.2 77.06 ± 11.92 1.5 178.65 ± 4.8 129.14 ± 6.7 71.30 ± 2.82 II 0.05 442.46 ± 31.4 386.45 ± 19.3 51.36 ± 4.22 0 , 5 293.48 ± 22.6 182.44 ± 18.2 57.63 ± 3.62 1.5 226.29 ± 3.82 193.05 ± 22.8 66.12 ± 6.82 III 0, 5 188.58 ± 9.7 185.35 ± 10.8 162.82 ± 35.6 1.5 161.15 ± 1.2 119.52 ± 3.4 104.87 ± 7.32 IV 3.0 194.81 ± 13.4 187.59 ± 2.7 123.72 ± 18.032 V 0.5 323.27 ± 3.2 237.54 ± 4.32 (after 24 h) 1.5 236.88 ± 1.5 219.27 ± 7.3 (after 24 h) VI 0.05 156.44 ± 2.8 84.41 ± 5.32 (after 24 h) 0.5 192.84 ± 3.4 177.78 ± 2.3 (after 24 h) Insulin 1 U / kg sc 216.15 ± 19.2 130.04 ± 25.032 (at 1 h) Control, 0.9% NaCl in 1 mL, p.o. 417.0 ± 30.9 408.4 ± 48.6 1

Savienojumi VII (nifedipīns) un VIII (riodipīns) analoģiskos apstākļos nedod statistiski ticamu glikozes līmeņa izmaiņu asinīs. 2 p < 0,05 attiecībā pret izejas līmeniCompounds VII (nifedipine) and VIII (riodipine) do not give a statistically significant change in blood glucose under similar conditions. 2 p < 0.05 relative to the output level

Claims (2)

LV 12200 Izgudrojuma formulaEN 12200 Invention Formula 4-Aril-2,6-dimetil-1,4-dihidropiridīn-3,5-dikarbonskābju alkoksialkil- un fenoksialkilēsteri ar kopformulu:Alkoxyalkyl and phenoxyalkyl ester of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid with the formula: R=C2H5; R1=OCHF2-2 R=CH2CH2CH3; R1=OCHF2-2 R=CH(CH3)2; R1=OCHF2-2 R=C6H5; R1=OCHFr2 15 R=C2H5; R1=N02-3 R=CH2CH2CH3; R1=N02-3 kā līdzeklis diabēta ārstēšanai.R = C2H5; R1 = OCHF2-2 R = CH2CH2CH3; R1 = OCHF2-2 R = CH (CH3) 2; R1 = OCHF2-2 R = C6H5; R1 = OCHFr2R = C2H5; R1 = NO2-3 R = CH2CH2CH3; R1 = N02-3 as a remedy for diabetes.
LVP-97-131A 1997-07-03 1997-07-03 Antidiabeic agent LV12200B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
LVP-97-131A LV12200B (en) 1997-07-03 1997-07-03 Antidiabeic agent
PCT/LV1998/000005 WO1999001432A1 (en) 1997-07-03 1998-06-30 Anti-diabetic agent

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
LVP-97-131A LV12200B (en) 1997-07-03 1997-07-03 Antidiabeic agent

Publications (2)

Publication Number Publication Date
LV12200A LV12200A (en) 1999-01-20
LV12200B true LV12200B (en) 1999-04-20

Family

ID=19736322

Family Applications (1)

Application Number Title Priority Date Filing Date
LVP-97-131A LV12200B (en) 1997-07-03 1997-07-03 Antidiabeic agent

Country Status (2)

Country Link
LV (1) LV12200B (en)
WO (1) WO1999001432A1 (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005020977A1 (en) 2003-08-21 2005-03-10 Wisconsin Alumni Research Foundation Alpha-ketoglutarate potentiators of insulin secretion
CN110606822A (en) 2011-11-24 2019-12-24 里克特吉迪翁公司 1,4-dihydropyridine derivatives having HSP modulating activity

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2650013C3 (en) * 1976-10-30 1981-04-02 Bayer Ag, 5090 Leverkusen 1,4-Dihydro-2,6-dimethyl-4- (3-nitrophenyl) -3,5-pyridinedicarboxylic acid isopropyl (2-propoxy-ethyl) ester, process for its preparation and medicinal products containing it
GR851819B (en) * 1984-08-17 1985-11-26 Wyeth John & Brother Ltd
US4757071A (en) * 1984-12-14 1988-07-12 Nisshin Flour Milling Co., Ltd. 1,4-dihydropyridine derivatives, and pharmaceutical compositions containing same, useful for treating cardiovascular diseases
EP0324626A1 (en) * 1988-01-13 1989-07-19 Korea Research Institute of Chemical Technology 1,4-Dihydropyridine derivatives
GB8804439D0 (en) * 1988-02-25 1988-03-23 Pfizer Ltd Dihydropyridines
GR1002248B (en) * 1988-03-08 1996-04-23 Egyt Gyogyszervegyeszeti Gyar 1,4-dihydropyridine derivatives preparation method
ES2193148T3 (en) * 1993-12-10 2003-11-01 Bayer Ag 1,4-DIHYDROPIRIDINES REPLACED WITH PHENYLLUS WITH BRAIN ACTIVITY.
US5405855A (en) * 1993-12-23 1995-04-11 Andrulis Pharmaceuticals Corp. Treatment of insulin resistant diabetes with thalidomine

Also Published As

Publication number Publication date
LV12200A (en) 1999-01-20
WO1999001432A1 (en) 1999-01-14

Similar Documents

Publication Publication Date Title
DD202001A5 (en) PROCESS FOR THE PRODUCTION OF AMINOAETHANOLS
DE1670827B2 (en) 4- (2'-nitrophenyl) -2,6-dimethyl-3,5-di-carbmethoxy-1,4-dihydropyridine
DE3872029T2 (en) RECTALLY ABSORBABLE SHAPE OF L-DOPA.
EP0642349B1 (en) Use of urodilatin in pulmonary and bronchial diseases
US6448450B1 (en) 1-(3,5-dimethoxyphenyl)-2-(4-hydroxyphenyl)-ethylene for diabetes treatment
DE1670572C3 (en) Cinnamylpiperazines and their hydrochlorides, process for their manufacture and medicinal products
LV12200B (en) Antidiabeic agent
DE2166355C2 (en) Use of d, 1-sobrerol in balm therapy of the respiratory tract
AU714086B2 (en) Use of COMT inhibitors for the manufacture of a medicament for the prevention of diabetic vascular dysfunctions
US4361564A (en) Renoprotective treatments employing vasodilator compounds
IS4784A (en) Prevention drug / anti-diabetic drug
DE69022206T2 (en) Preparations for treating ulcers containing aldose reductase inhibitors.
EP0489043B1 (en) Use of the (+)-enantiomer of anipamil
US5047229A (en) Treatment of cardiovascular and cerebral toxicity using calcium modulators
US6004986A (en) Method for treating cerebral vasospasm and cerebral ischemia using iron chelators and pharmaceutical compositions therefor
DE2209526C3 (en) Coronary therapeutic agent in the form of gelatine capsules
US4435574A (en) 2,6-Dimethyl-3,5-dicarbomethoxy-4-(ortho-di-fluoromethylthiophenyl)-1,4-dihydropyridine
DE69108580T2 (en) Optically active derivative of d-2- (6-methoxy-2-naphthyl) propionic acid and pharmaceutical compositions containing it.
DE2428409B2 (en) S, S'-bis (3-hydroxy-4-hydroxymethyl-2-methyl-5-pyridylmethyl) -carbonodithioate, its pharmacologically acceptable salts and medicaments
DE3026053A1 (en) 2-SUBSTITUTED-4-THIAZOLIDONE
DE3046325C2 (en) Pharmaceutical agents with anti-inflammatory, antipyretic and analgesic effects
DE2835043A1 (en) BROMHEXIN DERIVATIVES WITH LOWER MUCOLICANT AND COUGH RELEASE EFFECT AND TOXICITY IN COMPARISON OF BROMHEXIN
DE68901711T2 (en) Antidote.
EP0479874B1 (en) Use of norverapamil and norgallopamil as anti-arteriosclerosis drugs
RU2061481C1 (en) Agent showing antiaggregation activity