1. A process for the preparation of (R)- or (S)-aminocarnitine inner salt, the salts and a derivatives thereof, said derivative being selected from the group consisting of \u2014NHR, \u2014NHCSR, \u2014NHCOOR, \u2014NHCSOR, \u2014NHCONHR, \u2014NHCSNHR, -NHSOR, \u2014NHSONHR, \u2014NHSO2R, \u2014NHSO2NHR, wherein R is a C1-C20 saturated or unsaturated, straight or branched alkyl group, optionally substituted with a A1 group, wherein A1 is selected from the group consisting of halogen atom, C6-C14 aryl, heteroaryl, aryloxy, heteroaryloxy, groups, being optionally substituted with one or more C1-C20 saturated or unsaturated, straight or branched alkyl or alkoxy group, andor halogen atom, said process comprising:
a) treating (R)- or (S)-nitryloxycarnitine with sodium or potassium phthalimide, then with lithium or sodium azide to give respectively (R)- or (S)-azidocarnitine;
b) hydrogenating the (R)- or (S)-azidocarnitine obtained in step a) to give respectively (R)- or (S)-aminocarnitine and, if desired
c) salifying the (R)- or (S)-aminocarnitine and, if desired
d) transforming the (R)- or (S)-aminocarnitine into one of said derivatives.
2. The process according to claim 1, wherein the aminocarnitine obtained is further purified.
3. The process according to claim 2, wherein said purification is by treatment with ion exchange resins or through electrodialysis.
4. The process according to claim 1, wherein the aminocarnitine is later converted into a non-deliquescent salt.
5. The process according to claim 4, in which said salt is sulphate.
6. The process according to claim 1, wherein a polar aprotic solvent medium is used in step a).
7. The process according to claim 6, wherein said solvent is N-methyl-pyrrolidone, dimethylacetamide or dimethylformamide.
8. A process for the preparation of derivatives of (R)- or (S)-aminocarnitine, which comprises:
a) transforming the (R)- or (S)-nitryloxycarnitine respectively in (R)- or (S)-azidocarnitine;
b) hydrogenating the (R)- or (S)-azidocarnitine obtained in step a) to give respectively (R)- or (S)-aminocarnitine,
c) transforming of the (R)- or (S)-aminocamitine of step b) into a non-deliquescent, non-hygroscopic salt thereof;
d) releasing of the aminic function of the corresponding salt, by treating with alkaline metal or alkaline earth metal hydroxides or carbonates, in situ, in a solvent suitable for the subsequent functionalization;
e) optionally removing the insoluble products thus obtained; and
f) in-situ functionalizing the released aminic function.
9. The process according to claim 8, wherein said derivatives are acylated or ureic.
10. The process according to claim 9, wherein said derivatives are (R)- or (S)-N-acetylaminocarnitine or (R)- or (S)-N-tetradecyl carbamoyl aminocarnitine.
11. The process according to claim 9, wherein the salt of (R)- or (S)-aminocarnitine is treated with a base, then with an appropriate isocyanate to give the corresponding ureic derivative.
12. The process according to claim 9, wherein the (R)- or (S)-aminocarnitine salt is treated with a base, then with an appropriate acylating agent to give the corresponding acylic derivative.
13. The process according to claim 8, wherein the salt of (R)- or (S)-aminocarnitine is sulphate.
14. The process according to claim 8, wherein, in step c), said salt is sulphate.
15. A process for the preparation of (R)- or (S)-aminocarnitine inner salt, the salts and a derivative thereof, said derivative being selected from the group consisting of \u2014NHR, \u2014NHCSR, \u2014NHCOOR, \u2014NHCSOR, \u2014NHCONHR, \u2014NHCSNHR, \u2014NHSOR, \u2014NHSONHR, \u2014NHSO2R, \u2014NHSO2NHR, wherein R is a C1-C20 saturated or unsaturated, straight or branched alkyl group, optionally substituted with a A1 group, wherein A1 is selected from the group consisting of halogen atom, C6-C14 aryl, heteroaryl, aryloxy, heteroaryloxy, groups, being optionally substituted with one or more C1-C20 saturated or unsaturated, straight or branched alkyl or alkoxy group,andor halogen atom, said process comprising:
a) transforming the (R)- or (S)-nitryloxycarnitine respectively in (R)- or (S)-azidocarnitine;
b) hydrogenating the (R)- or (S)-azidocarnitine obtained in step a) to give respectively (R)- or (S)-aminocarnitine and, if desired
c) transforming the (R)- or (S)-aminocamitine of step b) into a non-deliquescent, non-hygroscopic salt thereof; and, if desired
d) transforming the (R)- or (S)-aminocarnitine into one of said derivatives.
16. The process according to claim 15, wherein the aminocarnitine obtained is further purified.
17. The process according to claim 16, wherein said purification is by treatment with ion exchange resins or through electrodialysis.
18. The process according to claim 15, wherein, in step b), said salt is sulphate.
19. The process according to claim 15, wherein a polar aprotic solvent medium is used in step a).
20. The process according to claim 19, wherein said solvent is N-methyl-pyrrolidone, dimethylacetamide or dimethylformamide.
21. The process according to claim 19, wherein in step a) (R)- or (S)-nitryloxycarnitine is treated with sodium or potassium phthalimide, then with lithium or sodium azide.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A machine for filling bottles (2) with solid forms (3) of pharmaceutical products, in particular capsules, pills, pastilles, andor tablets, the machine comprising a conveying device (4, 5, 7) for moving forward, one after the other, a plurality of bottles (2) along a given path (P); and a dosing device (4), which is arranged along the path (P), comprises a tank (21) for containing the solid forms (3), and is provided with a plurality of discharge ducts (32) of the solid forms (3) from the containing tank (21) into relative bottles (2); and being characterised in that it comprises, furthermore, for each discharge duct (32), a respective deviating device (35), which is mobile between a first operating position, in which the deviating device (35) is arranged so as to allow the solid forms (3) to be fed along the discharge duct (32) and into the relative bottle (2), and a second operating position, in which the deviating device (35) is arranged so as to prevent the solid forms (3) from being fed along the discharge duct (32) and into the relative bottle (2).
2. A machine according to claim 1, wherein each deviating device (35) is defined by a portion of the relative discharge duct (32) which is mobile between said first and second operating positions.
3. A machine according to claim 1, wherein each deviating device (35) comprises a deviating member, which is mobile inside the relative discharge duct (32) between said first and second operating positions, and an opening, which is obtained trough the discharge duct (32), so as to discharge the solid forms (3) outside of the discharge duct (32) itself when the deviating member is arranged in its second operating position.
4. A machine according to claim 1 and comprising, furthermore, a recirculating device (27) for recirculating in the tank (21) the solid forms (3) which are discharged outside of each discharge duct (32) when the relative deviating device (35) is arranged in its second operating position.
5. A machine according to claim 4, wherein the recirculating device (27) comprises a collecting container (28) suited to receive the solid forms (3) discharged outside of the discharge ducts (32) when the relative deviating devices (35) are arranged in their second operating positions, and feeding means (29) for transferring the solid forms (3) from the collecting container (28) to the tank (21).
6. A machine according to claim 1 and comprising, furthermore, a counting device (46) for calculating the passage of a given number of solid forms (3) along each discharge duct (32) and, for each deviating device (35), a respective actuating means (36) suited to move the deviating device (35) between said first and second operating positions according to a signal coming from the counting device (46).
7. A machine according to claim 6, wherein the counting device (46) comprises a detecting device (48; 90), which is mounted along each discharge duct (32), so as to detect the passage of each solid form (3) along the discharge duct (32) itself, and an electronic control unit (47), which is connected to the detecting devices (48; 90) and to the actuating devices (36), so as to move each deviating device (35) to its second operating position when the number of solid forms (3) fed through the relative discharge duct (32) is equal to a value stored in the electronic control unit (47).
8. A machine according to claim 1 and comprising, furthermore, a collecting store of the incomplete solid forms (3); each deviating device (35) being mobile, furthermore, to a third operating position, in which the deviating device (35) is arranged so as to prevent the solid forms (3) from being fed along the relative discharge duct (32) and into the relative bottle (2) and to allow the solid forms (3) to be fed to the collecting store.
9. A machine according to claim 8, wherein each discharge duct (32) is provided, furthermore, with a measuring device (90) for measuring the weight of the solid form (3) fed each time along the discharge duct (32) itself; the deviating device (35) being moved to the third operating position, when the weight of the solid form (3) measured by the measuring device (90) is lower than a given threshold value.
10. A machine according to claim 1, wherein each discharge duct (32) is provided, furthermore, with a stop device (43), which is mobile between a stop position of the solid forms (3) along the discharge duct (32) and a release position of the solid forms (3) into the relative bottle (2).