LV14273B - Novel salts of acetylsalicylic acid - Google Patents
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- LV14273B LV14273B LVP-09-117A LV090117A LV14273B LV 14273 B LV14273 B LV 14273B LV 090117 A LV090117 A LV 090117A LV 14273 B LV14273 B LV 14273B
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Abstract
Description
IZGUDROJUMA NOZARE UN TEHNIKAS LĪMENISFIELD OF THE INVENTION AND TECHNICAL FIELD
Aprakstītais izgudrojums kopumā attiecas uz acetilsalicilskābes sāļiem, īpaši uz jauniem un ūdenī šķīstošiem acetilsalicilskābes sāļiem un to iegūšanas paņēmienu. Acetilsalicilskābe ir ļoti plaši lietotas zāles, kas pazīstama galvenokārt ar tās pretsāpju īpašībām. Tās pielietošanas diapazonu lielā mērā ierobežo zemā šķīdība ūdenī (aptuveni 0,3%). Bez Li, Na, Mg un Ca sāļiem ir aprakstīti ari vairāki sāļi ar bāziskām aminoskābēm [US 4, 265,888], Katram no šiem sāļiem ir zināmas priekšrocības un trūkumi, tāpēc ir vēlama jaunu acetilsalicilskābes sāļu iegūšana ar potenciāli vēl labākām īpašībām.The present invention relates generally to the salts of acetylsalicylic acid, in particular to the novel and water-soluble salts of acetylsalicylic acid and the process for their preparation. Acetylsalicylic acid is a very widely used drug known mainly for its analgesic properties. Its application range is largely limited by its low water solubility (about 0.3%). In addition to the Li, Na, Mg and Ca salts, several salts with basic amino acids have been described [US 4, 265,888]. Each of these salts has certain advantages and disadvantages, so it is desirable to obtain new acetylsalicylic acid salts with potentially even better properties.
IZGUDROJUMA KOPSAVILKUMSSUMMARY OF THE INVENTION
Šī izgudrojuma būtība ir jauna tipa acetilsalicilskābes sāļu atrašana ar zināmiem betaīna tipa savienojumiem. Negaidīti un pārsteidzoši mēs atradām, ka acetilsalicilskābe veido stabilus, ūdenī šķīstošus, kristāliskus sāļus ar zināmiem betaīniem, kas paši ir higroskopiskas vielas.The essence of this invention is the discovery of a novel type of acetylsalicylic acid salts with known betaine-type compounds. Unexpectedly and surprisingly, we have found that acetylsalicylic acid forms stable, water-soluble, crystalline salts with known betaines, which are themselves hygroscopic.
Tātad šī izgudrojuma mērķis ir iegūt acetilsalicilskābes sāļus, kas labi šķīst ūdenī, bet tajā pašā laikā ir ļoti stabili un ilgi uzglabājami.Thus, it is an object of the present invention to obtain acetylsalicylic acid salts which are highly water soluble but at the same time very stable and long storage.
Šī izgudrojuma papildu mērķis ir piedāvāt šādu sāļu iegūšanas paņēmienu.It is a further object of the present invention to provide a process for the preparation of such salts.
Tā kā betaīna tipa savienojumiem, kas ir iekļauti jaunajos acetilsalicilskābes sāļos, pašiem piemīt dažādas farmakoloģiskās aktivitātes, jaunaiem acetilsalicilskābes sāļiem var būt papildu labvēlīgas aktivitātes tām, kas piemīt acetilsalicilskābei vai betaīniem, tostarp jaunas farmakoloģiskas aktivitātes.Because betaine-like compounds included in the new acetylsalicylic acid salts themselves have different pharmacological activities, new acetylsalicylic acid salts may have additional beneficial activities to those of the acetylsalicylic acid or betaines, including new pharmacological activities.
IETEICAMIE IZGUDROJUMA REALIZĀCIJAS VARIANTIRECOMMENDED EMBODIMENTS OF THE INVENTION
Turpmāki aprakstīti piedāvātā izgudrojuma dažādu sāļu un paņēmienu piemēri.The following describes examples of various salts and methods of the present invention.
1. piemērs. 4-trimetilamoniobutanoāta acetilsalicilskābes aditīvais sāls γ-Butirobetaīna dihidrātu (1,81 g, 10 mmol) un acetilsalicilskābi (1,80 g, mmol) izšķīdina etanolā (20 ml). Šķīdumu koncentrē vakuumā pie aptuveni 40 °C līdz sīrupa konsistencei, kas atdziestot kristalizējas. Kristālisko masu saberž ar acetonu (50 ml), nofiltrē, noskalo ar acetonu un žāvē vakuumā istabas temperatūrā. Bezkrāsainu kristālu ar k.t. 120-122 °C iznākums ir 3,04 g (93,5%). Viela ir ūdenī šķīstoša, stabila parastos apstākļos.Example 1: The acetylsalicylic acid addition salt of 4-trimethylammoniobutanoate γ-Butyrobetaine dihydrate (1.81 g, 10 mmol) and acetyl salicylic acid (1.80 g, mmol) are dissolved in ethanol (20 mL). The solution is concentrated in vacuo at about 40 ° C to a syrupy consistency which crystallizes upon cooling. The crystalline mass is triturated with acetone (50 mL), filtered, rinsed with acetone and vacuum dried at room temperature. Colorless crystals with k.t. 120-122 ° C, yield 3.04 g (93.5%). The substance is water soluble, stable under normal conditions.
’H-KMR spektrs (CDC13, 200 MHz, δ): 1,93-2,12 (2H, m, CH?CH?CH?); 2,33 (3H, s, COCH3); 2,40 (2H, t, J = 7,0 Hz, CH2COO~); 3,09 (9H, s, Me3N); 3,24-3,37 (2H, m, CH2N); 7,16 (1H, dd, J = 1,1 un 8,1 Hz, H-3); 7,38 (1H, ddd, J = 1,1, 7,6 un 7,6 Hz, H-5); 7,56 (1H, ddd, J = 1,8, 7,6 un 8,1 Hz, H-4); 7,79 m.d. (1H, dd, J = 1,8 un 7,6 Hz, H-6).1 H-NMR Spectrum (CDCl 3 , 200 MHz, δ): 1.93-2.12 (2H, m, CH? CH? CH?); 2.33 (3H, s, COCH 3 ); 2.40 (2H, t, J = 7.0 Hz, CH 2 COO -); 3.09 (9H, s, Me 3 N); 3.24-3.37 (2H, m, CH 2 N); 7.16 (1H, dd, J = 1.1 and 8.1 Hz, H-3); 7.38 (1H, ddd, J = 1.1, 7.6 and 7.6 Hz, H-5); 7.56 (1H, ddd, J = 1.8, 7.6 and 8.1 Hz, H-4); 7.79 md (1H, dd, J = 1.8 and 7.6 Hz, H-6).
Ci6H23NO6. Aprēķināts, %: C 59,07; H 7,13; N 4,30.Ci 6 H2 3 NO 6 . Calculated,%: C, 59.07; H, 7.13; N, 4.30.
Atrasts, %: C 59,17; H 7,20; N 4,23.Found,%: C, 59.17; H, 7.20; N, 4.23.
Jauno sali raksturo pulvera rentgenogramma (Cu Ka- radiacija) ar maksimumiem pie šādām 2Θ vērtībām: 5,10; 13,58, 13,83; 15,02; 15,17; 17,89; 19,33; 19,87; 21,85; 22,05; 23,32; 23,56; 23,92; 24,75; 25,55; 25,80; 27,05; 27,91; 30,25 ± 0,2°.The new island is characterized by a powder X-ray (Cu K a - radiation) with peaks at the following 2Θ values: 5.10; 13.58, 13.83; 15.02; 15.17; 17.89; 19.33; 19.87; 21.85; 22.05; 23.32; 23.56; 23.92; 24.75; 25.55; 25.80; 27.05; 27.91; 30.25 ± 0.2 °.
Jaunās sāls struktūra ir apstiprināta ar monokristāla rentgenstruktūranalīzi. Kristāli ir monoklīni, šūnas parametri eksperimenta temperatūrā T = - 85 °C ir šādi: a= 13,2154(6) A, b= 7,5092(3) A, c= 17,6451(9) Α, β= 104,728(2)°, šūnas tilpums V = 1693,5(1) A3, telpiskā grupa P2]/a. 4-trimetilamoniobutanoāta acetilsalicilāta kristāla struktūras fragments:The structure of the new salt is confirmed by single crystal X-ray structure analysis. The crystals are monocular, the cell parameters at the experimental temperature T = - 85 ° C are as follows: a = 13.2154 (6) A, b = 7.5092 (3) A, c = 17.6451 (9) Α, β = 104.728 (2) °, cell volume V = 1693.5 (1) A 3 , space group P2] / a. Crystal fragment of 4-trimethylammoniobutanoate acetylsalicylate:
C6C6
2. piemērs. Z-kamitīna acetilsalicilskābes aditīvais sālsExample 2: Addition salt of Z-carnitine acetylsalicylic acid
Z-Kamitīnu (1,61 g, 10 mmol) un acetilsalicilskābi (1,80 g, 10 mmol) izšķīdina etanolā (20 ml) un šķīdumu koncentrē vakuumā pie aptuveni 40 °C līdz sīrupa konsistencei, kas atdziestot kristalizējas. Kristālisko masu saberž ar acetonu (50 ml), nofiltrē, noskalo ar acetonu un žāvē vakuumā istabas temperatūrā. Bezkrāsainu kristālu ar k.t. 90-94 °C iznākums ir 3,17 g (93%). Viela ir ūdenī šķīstoša, stabila parastos apstākļos.Z-Camitine (1.61 g, 10 mmol) and acetylsalicylic acid (1.80 g, 10 mmol) are dissolved in ethanol (20 mL) and the solution is concentrated in vacuo at about 40 ° C until the syrup is crystallized upon cooling. The crystalline mass is triturated with acetone (50 mL), filtered, rinsed with acetone and vacuum dried at room temperature. Colorless crystals with k.t. 90-94 ° C. Yield: 3.17 g (93%). The substance is water soluble, stable under normal conditions.
’H-KMR spektrs (CDC13, 200 MHz, δ): 2,32 (3H, s, COCH3); 2,53 (2H, d, J = 6,6 Hz, CH2COOH; 3,18 (9H, s, Me3N); 3,38-3,45 (2H, m, CH2N); 4,59 (1H, kvint, J = 6,1 Hz, CHOH); 7,15 (1H, dd, J = 1,1 un 8,1 Hz, H-3); 7,37 (1H, ddd, J = 1,1; 7,6 un 7,6 Hz, H-5); 7,56 (1H, ddd, J = 1,8; 7,8 un 7,8 Hz, H-4); 7,79 m.d. (1H, dd, J = 1,8 un 7,8 Hz, H-6).1 H-NMR Spectrum (CDCl 3 , 200 MHz, δ): 2.32 (3H, s, COCH 3 ); 2.53 (2H, d, J = 6.6 Hz, CH 2 COOH; 3.18 (9H, s, Me 3 N); 3.38-3.45 (2H, m, CH 2 N); , 59 (1H, quint, J = 6.1 Hz, CHOH); 7.15 (1H, dd, J = 1.1 and 8.1 Hz, H-3); 7.37 (1H, ddd, J = 1.1; 7.6 and 7.6 Hz, H-5); 7.56 (1H, ddd, J = 1.8; 7.8 and 7.8 Hz, H-4); 7.79 md (1H, dd, J = 1.8 and 7.8 Hz, H-6).
0ι6Η23ΝΟ7. Aprēķināts, %: C 56,30; H 6,79; N 4,10.0ι 6 Η 23 ΝΟ 7 . Calculated,%: C, 56.30; H, 6.79; N, 4.10.
Atrasts: %: C 55,67; H 6,85; N 4,12.Found:%: C 55.67; H, 6.85; N, 4.12.
Jauno sāli raksturo pulvera rentgenogramma (Cu Ka- radiācija) ar maksimumiem pie šādām 2Θ vērtībām: 5,09; 12,62; 13,48; 13,84; 15,04; 17,82; 19,15; 19,77; 21,84; 22,56; 23,33; 24,40; 23,92; 25,17; 25,43; 26,14; 27,24; 29,50; 30,36 ± 0,2°.The new salt is characterized by a powder radiograph (Cu K a - radiation) with peaks at the following 2Θ values: 5.09; 12.62; 13.48; 13.84; 15.04; 17.82; 19.15; 19.77; 21.84; 22.56; 23.33; 24.40; 23.92; 25.17; 25.43; 26.14; 27.24; 29.50; 30.36 ± 0.2 °.
Jaunās sāls struktūra ir apstiprināta ar monokristāla rentgenstruktūranalīzi. Kristāli ir monoklīni, šūnas parametri eksperimenta temperatūrā T = - 85 °C ir šādi: a= 13,1342(6) A, b = 7,6396(3) A, c = 17,737(1) Α, β = 104,535(2)°, šūnas tilpumsThe structure of the new salt is confirmed by single crystal X-ray structure analysis. The crystals are monocular, the cell parameters at the experimental temperature T = - 85 ° C are as follows: a = 13.1342 (6) A, b = 7.6396 (3) A, c = 17.737 (1) Α, β = 104.535 (2 ) °, cell volume
V - 1722,8(2) A3, telpiskā grupa P2j. £-kamitma acetilsalicilata kristālā struktūras fragments:V - 1722.8 (2) A 3 , P2j. Crystalline structure fragment of £ -chammax acetylsalicylate:
C5a C6aC5a C6a
3. piemērs. 3-ftrimetiIamonioamino)propanoāta acetilsalicilskābes adifivais sālsExample 3: Addition salt of 3-trimethylammonioamino) propanoate with acetylsalicylic acid
3-(Trimetilarnonioamino)propanoāta dihidrātu (SNN - Meldonium) (3,64 g, 20 mmol) un acetilsalicilicskābi (3,60 g, 20 mmol) maisot izšķīdina karstā propanolā2 (30 ml) un silda 20 minūtes pie aptuveni 50-55 °C. Sildīšanu pārtrauc un šķīdumu maisa istabas temperatūrā 3 stundas. Masu maisa pie 0 °C vēl 3 stundas, nogulsnes nofiltrē un noskalo ar aukstu propanolu-2 (2x15 ml). Iegūto produktu pārkristalizē no propanola-2. Bezkrāsainu kristālu ar k.t. 104-106 °C iznākums 4,12 g (63%).3- (Trimethylarnonioamino) propanoate dihydrate (SNN - Meldonium) (3.64 g, 20 mmol) and acetylsalicylic acid (3.60 g, 20 mmol) are dissolved in hot propanol2 (30 mL) and heated for 20 minutes at about 50-55 ° C. Stop heating and stir the solution at room temperature for 3 hours. The mass is stirred at 0 ° C for a further 3 hours, the precipitate is filtered off and rinsed with cold propanol-2 (2 x 15 mL). The product obtained is recrystallized from propanol-2. Colorless crystals with k.t. 104-106 ° C, 4.12 g (63%).
’H-KMR spektrs (CDC13, 200 MHz, δ): 2,34 (3H, s, COCH3); 2,51 (2H, t, J =1 H-NMR Spectrum (CDCl 3 , 200 MHz, δ): 2.34 (3H, s, COCH 3); 2.51 (2H, t, J =
6,4 Hz, CH2COO’); 3,26 (2H, t, J = 6,4 Hz, CH2N); 3,33 (9H, s, Me3N); 7,17 (1H, dd, J = 1,1 un 7,8 Hz, H-3); 7,39 (1H, ddd, J = 1,1; 7,6 un 7,6 Hz, H-5); 7,58 (1H, ddd, J = 1,7; 7,6 un 7,8 Hz, H-4); 7,81 m.d. (1H, dd, J = 1,7 un 7,6 Hz, H-6).6.4 Hz, CH 2 COO '); 3.26 (2H, t, J = 6.4 Hz, CH 2 N); 3.33 (9H, s, Me 3 N); 7.17 (1H, dd, J = 1.1 and 7.8 Hz, H-3); 7.39 (1H, ddd, J = 1.1; 7.6 and 7.6 Hz, H-5); 7.58 (1H, ddd, J = 1.7; 7.6 and 7.8 Hz, H-4); 7.81 md (1H, dd, J = 1.7 and 7.6 Hz, H-6).
Ci5H22N2O6. Aprēķināts, %: C 55,21; H 6,79; N 8,58.Ci 5 H 2 2 N 2 O 6. Calculated,%: C 55.21; H, 6.79; N, 8.58.
Atrasts, %: C 55,25; H 6,79; N 8,53.Found,%: C 55.25; H, 6.79; N, 8.53.
Jauno sāli raksturo pulvera rentgenogramma (Cu Ka- radiācija) ar maksimumiem pie šādām 2Θ vērtībām: 5,19; 13,22; 13,82; 14,20; 14,95; 15,36; 15,93; 18,11; 18,97; 19,74; 21,02; 22,15; 23,15; 23,65; 24,31; 25,28; 26,18; 26,58; 27,73; 28,36 ± 0,2°.The new salt is characterized by a powder radiograph (Cu K a - radiation) with peaks at the following 2Θ values: 5.19; 13.22; 13.82; 14.20; 14.95; 15.36; 15.93; 18.11; 18.97; 19.74; 21.02; 22.15; 23.15; 23.65; 24.31; 25.28; 26.18; 26.58; 27.73; 28.36 ± 0.2 °.
Jaunās sāls struktūra ir apstiprināta/pierādīta ar monokristāla rentgenstruktūranalīzi. Kristāli ir monoklīni, šūnas parametri eksperimenta temperatūrā T = - 85 °C ir šādi: a = 19,3399(8) A, b = 7,2400(3) A, c = 35,237(2) A, β = 90,758(2)°, šūnas tilpums V = 4933,5(4) A3, telpiskā grupa P2j/n. 3-(trimetilamonioamino)propanoāta acetilsalicilāta kristāla struktūras fragments:The structure of the new salt has been confirmed / proven by single crystal X-ray structure analysis. The crystals are monocular, and the cell parameters at the experimental temperature T = - 85 ° C are as follows: a = 19.3399 (8) A, b = 7.2400 (3) A, c = 35.237 (2) A, β = 90.758 (2) ) °, cell volume V = 4933.5 (4) A 3 , space group P2j / n. Crystal fragment of 3- (trimethylammonioamino) propanoate acetylsalicylate:
C15cC15c
C11cC11c
C10cC10c
Monokristālu rentgenstruktūranalīzes metode viennozīmīgi pierāda, ka kristāliskajā stāvoklī 3,3,3-trimetilamoniobutānskābes, L-kamitīna un 3-(trimetilamonioamino)propānskābes karboksilgrupas ir protonētas, kas nozīmē protona pārnesi no acetilsalicilskābes un sāls veidošanos. Karboksilgrupas C = O un C - 0 aditīvajam šālim ar acetilsaiicilskābi kristāliskajā struktūrā, 1,194 A un 1,308 A Lkamitīna aditīvajam šālim ar acetilsaiicilskābi kristāliskajā struktūrā un 1,219 A un 1,321 A 3-(trimetilamonio-amino)propānskābes aditīvajam šālim ar acetilsaiicilskābi kristāliskajā struktūrā. Savukārt visās tris struktūrās acetilsalicilskābes karboksilgrupas C=O un C-0 saites ir izlīdzinātas un tām ir vērtības ap 1,26 A.The X-ray monocrystalline analysis method unambiguously demonstrates that in the crystalline state the carboxyl groups of 3,3,3-trimethylammoniobutanoic acid, L-carnitine and 3- (trimethylammonioamino) propanoic acid are protonated, which means proton transfer from acetylsalicylic acid and salt formation. C = O and C - 0 carboxylic acid addition salts with acetylsalicylic acid in the crystalline structure, 1,194 A and 1,308 A Lkamitin addition salts with acetylsalicylic acid in the crystalline structure and 1,219 A and 1,321 A 3- (trimethylammonioamino) propanoic acid in the crystalline structure. In all three structures, however, the C = O and C-0 bonds of the acetylsalicylic acid carboxyl group are aligned and have values around 1.26 A.
4. piemērs. Antagonisms nikotīnskābes izraisītai ādas vazodilatācijaiExample 4. Antagonism of nicotinic acid vasodilatation of the skin
Modelis. Wistar žurku tēviņus narkotizē ar pentobarbitāla nātrija sāli (50 mg/kg i.p.) un narkozi uztur ar papildu devām (10 mg/kg) ik pēc stundas. Asinsspiedienu mēra kreisajā miega artērijā, EKG reģistrē ar standarta II novadījumu. Asins plūsmu labās auss artērijā mēra ar lāzera Doplera plūsmas mērītāju (OXYFLOW2000, USA). Asins plūsmu, EKG un arteriālo spiedienu reģistrē ar AD Instruments PmverLab sistēmām un saglabā datorā tālākai apstrādei. Pēc 10 min. ilgas bāzes līnijas reģistrācijas pētāmās vielas injicē s.c. skausta rajonā un turpina reģistrāciju vēl 30 min. Vidējos asins plūsmas datus katram dzīvniekam aprēķina, ņemot vērā vidējo asinsspiedienu, un salīdzina ar izejas stāvokli un kontroli. Rezultātus aprēķina no 5 - 8 atsevišķiem eksperimentiem un izteic kā maksimālās asins plūsmas izmaiņas % pret bāzlīniju [Carballo-Jane E et al, JPharmacol Toxicol Methods 2007;56(3):308-316].Model. Wistar male rats are anesthetized with pentobarbital sodium (50 mg / kg i.p.) and anesthetized with additional doses (10 mg / kg) every hour. Blood pressure is measured in the left carotid artery, ECG recorded with standard lead II. Blood flow in the right ear artery is measured with a laser Doppler flow meter (OXYFLOW2000, USA). Blood flow, ECG and arterial pressure are recorded with AD Instruments PmverLab systems and stored on a computer for further processing. After 10 min. long baseline registration test substances are injected s.c. in the withers and continues the registration for another 30 minutes. Mean blood flow data for each animal are calculated from mean blood pressure and compared with baseline and control. Results are calculated from 5 to 8 separate experiments and expressed as% change in maximal blood flow relative to baseline [Carballo-Jane E et al, JPharmacol Toxicol Methods 2007; 56 (3): 308-316].
Statistika. Rezultātus aprēķina kā vidējos ± SEM katrai grupai. Grupas robežās statistiskā analīze tika veikta ar Stjūdenta t-Testu. Atšķirības starp eksperimenta grupām salīdzina, izmantojot vienvirziena ANOVA ar atkārtotu salīdzināšanu (Tukey tests). P <0,05 tiek uzskatīts par nozīmīgu.Statistics. Results are calculated as mean ± SEM for each group. Within the group, statistical analysis was performed by Student's t-test. Differences between experimental groups are compared using one-way ANOVA with repeated comparison (Tukey's test). P <0.05 is considered significant.
RezultātiResults
Nikotīnskābe (NS) devā 15 mg/kg šajā dzīvnieka modelī izsauca nozīmīgu asins plūsmas pieaugumu auss artērijā (1. tabula). 3-(Trimetilamonioamino)propanoāta acetilsalicilskābes aditīvais sāls (TAP-AS), līdzīgi kontrolei (buferētam 0,9% NaCl šķīdumam), izsauca nenozīmīgas izmaiņas asins plūsmā. NS kopā ar TAPAS izsauca novēlotu (lēni pieaugošu) un statistiski nozīmīgi mazāk izteiktu absolūto asins plūsmas pieaugumu, salīdzinot ar NS vienu pašu (1. tabula). TAP-AS spējai antagonizēt nikotīnskābes izsauktu perifero vazodilataciju var but labvēlīgs efekts klīnikā, lai samazinātu nikotīnskābes nevēlamos efektus (ādas sasarkumu u.t.t.).Nicotinic acid (NS) at a dose of 15 mg / kg in this animal model caused a significant increase in blood flow to the ear artery (Table 1). 3- (Trimethylammonioamino) propanoate acetylsalicylic acid addition salt (TAP-AS), similar to control (buffered 0.9% NaCl solution), caused insignificant changes in blood flow. NS together with TAPAS induced a delayed (slowly increasing) and statistically significantly less pronounced absolute increase in blood flow compared to NS alone (Table 1). The ability of TAP-AS to antagonize nicotinic acid-induced peripheral vasodilatation may have a beneficial effect in the clinic in reducing the adverse effects of nicotinic acid (reddening of the skin, etc.).
*F<(J,05 pret kontroli **P<0,005 pret kontroli $P<0,05 pretNS* F <{J, 05 versus control ** P <0.005 versus control $ P <0.05 versus control
SecinājumiConclusions
Mēs negaidīti atradām, ka acetilsalicilskābe veido kristāliskus, stabilus un ūdenī šķīstošus sāļus ar dažiem specifiskiem betaīniem, kam var būt plašāka pielietošana nekā acetilsalicil skābei vai betaīniem atsevišķi.We have unexpectedly found that acetylsalicylic acid forms crystalline, stable and water-soluble salts with some specific betaines, which may have broader applications than acetylsalicylic acid or betaines alone.
Claims (7)
Priority Applications (16)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
LVP-09-117A LV14273B (en) | 2009-06-25 | 2009-06-25 | Novel salts of acetylsalicylic acid |
JP2012517421A JP5706409B2 (en) | 2009-06-25 | 2010-06-21 | New salicylate |
PCT/LV2010/000007 WO2010151095A1 (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
NZ597510A NZ597510A (en) | 2009-06-25 | 2010-06-21 | NOVEL ACETYLSALICYLIC ACID SALTS, the salts are 4-trimethylammoniobutanoate, L-carnitine and meldonium |
EP10735094.4A EP2445861B1 (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
US13/377,926 US8889902B2 (en) | 2009-06-25 | 2010-06-21 | Acetylsalicylic acid salts |
UAA201200601A UA106379C2 (en) | 2009-06-25 | 2010-06-21 | Meldonium acetylsalicylic acid addition salts and use thereof as a medicinal agent |
KR1020127001929A KR20120050437A (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
BRPI1009600A BRPI1009600A2 (en) | 2009-06-25 | 2010-06-21 | |
EA201200038A EA021588B1 (en) | 2009-06-25 | 2010-06-21 | Betain salts of acetylsalicylic acid |
CA2766048A CA2766048A1 (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
CN201080028833.9A CN102803199B (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
GEAP201012546A GEP20146015B (en) | 2009-06-25 | 2010-06-21 | Novel acetylsalicylic acid salts |
IL217036A IL217036A (en) | 2009-06-25 | 2011-12-15 | Acetylsalicylic acid addition salt, uses thereof in the preparation of medicaments, pharmaceutical compositions comprising the same and a combination medicinal product comprising such acid addition salt |
ZA2012/00592A ZA201200592B (en) | 2009-06-25 | 2012-01-24 | Novel acetylsalicyclic acid salts |
HK12110406.3A HK1169648A1 (en) | 2009-06-25 | 2012-10-19 | Novel acetylsalicylic acid salts |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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LVP-09-117A LV14273B (en) | 2009-06-25 | 2009-06-25 | Novel salts of acetylsalicylic acid |
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LV14273A LV14273A (en) | 2011-01-20 |
LV14273B true LV14273B (en) | 2011-06-20 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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LVP-09-117A LV14273B (en) | 2009-06-25 | 2009-06-25 | Novel salts of acetylsalicylic acid |
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LV (1) | LV14273B (en) |
UA (1) | UA106379C2 (en) |
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2009
- 2009-06-25 LV LVP-09-117A patent/LV14273B/en unknown
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2010
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Publication number | Publication date |
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UA106379C2 (en) | 2014-08-26 |
LV14273A (en) | 2011-01-20 |
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