Succinic acid
Succinic acid
110-15-6
disodium succinate
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The Example of SYNERGISTIC COMPOSITIONS COMPRISING ERYTHROPOIETIN AND SUCCINIC ACID(cas:110-15-6) (SALT)
Release time:2016/8/18 16:38:51


The Example of SYNERGISTIC COMPOSITIONS COMPRISING ERYTHROPOIETIN AND SUCCINIC ACID (SALT)

EXAMPLE 1.

The example shows that co-administration of erythropoietin and succinic acid(cas:110-15-6) results in synergistic stimulation of erythropoiesis in female mice.


Materials. Recombinant human erythropoietin (Epo) was from Institute of Highly Pure Biopreparation, St. Petersburg, Russia.

Treatment. C57B1 female mice 4 weeks aged and 17-20 g weight were treated for 3 days oromucosally with 100 U/kg erythropoietin (Epo), 2.5 mg/kg succinic acid(cas:110-15-6) (SA), combination 100 U/kg Epo plus 2.5 mg/kg SA, or saline (control). The effect of the treatments on erythropoiesis was determined as elevation of blood hemoglobin and hematocrit levels at day 4 in comparison with the control. A Hemoglobin is difference between means of hemoglobin levels in treated and control mice calculated by equiation: A Hemoglobin = 15.5-mean (g/dl). A Hematocrit is difference between means of hematocrit levels in treated and control mice calculated by equiation: A Hematocrit = 34-mean (%). Data are presented in Table 1 and 2 as mean SD (n=5).


Table 1. Hemoglobin levels in female mice at day 4 from treatment beginning. Treatment Hemoglobin, g/dl A Hemoglobin, g/dl Saline (control) 15.5 1. 00 SA 19. 2 0. 9* +3. 7 Epo 16. 4 i 0. 7 +0. 9 Epo + SA 22. 6 i 1. 4*eP° +7. 1 *Differs significantly of control (p<0.01). Differs significantly of Epo (p<0.01). The therapeutic effect achieved with the combination of amounts Epo and SA is 7.1 g/dl increase in hemoglobin level from the control. The sum of effects of amounts Epo and SA administered individually is 4.6 (3.7+0. 9=4.6) g/dl increases in hemoglobin level from the control. Since the therapeutic effect of the combination is greater than the sum of effects of Epo and SA administered individually, the combination is synergistically effective for increasing hemoglobin levels.


Table 2. Hematocrit levels in female mice at day 4 from treatment beginning. Treatment Hematocrit, % A Hematocrit, % Saline (control) 34.0 4. 9 0 SA 37. 4 1. 5 +3. 4 Epo 34. 5 4. 4 +0. 5 51.0~1.1*epo +17. 0 *Differs significantly of control (p<0. 01). eP°Differs significantly of Epo (p<0. 01).


The therapeutic effect achieved with the combination of amounts Epo and SA is 17.0 % increase in hematocrit level from the control. The sum of effects of amounts Epo and SA administered individually is 3.9 (3.4+0. 5=3.9) % increases in hematocrit level from the control. Since the therapeutic effect of the combination is greater than the sum of effects of Epo and SA administered individually, the combination is synergistically effective for increasing hematocrit levels.


EXAMPLE 2.

The example shows that co-administration of erythropoietin and succinic acid(cas:110-15-6) results in synergistic enhancement of erythropoiesis in male mice.


Treatment. C57B1 male mice of 6 weeks aged and 20-25 g weight were treated for 3 days oromucosally with 100 U/kg Epo, 2.5 mg/kg succinic acid(cas:110-15-6) (SA), combination 100 U/kg Epo plus 2.5 mg/kg succinic acid(cas:110-15-6), or saline (control). The effect of the treatments on erythropoiesis was determined as elevation of hemoglobin and hematocrit levels at days 6,10, and 15 from the treatment beginning in comparison with the control. Data are presented in Table 3 and 4 as mean ISO (n=5).
Table 3. Hemoglobin levels in male mice. Treatment Hemoglobin, g/dl 6 day 10 day 15 day Saline (control) 16.24 0. 73 15. 32 1. 6316. 301. 18 SA 16.70~1.02 15.30~1.57 14.84~1. 34 Epo 16. 18 41. 33 14. 76 i1. 22 14. 40 2. 45 Epo + SA 18. 80 0. 47*epo 19.40~1.72*epo 22. 88 4. 00*epo *Differs significantly of control (p<0. 01). eP°Differs significantlyofEpo (p<0.01).
Table 4. Hematocrit levels in male mice. Treatment Hematocrit, % 6 day 10 day 15 day Saline (control) 50. 98 7. 82 46. 58 ~3. 81 45.80~2. 80 SA 46.64~1.98 49. 36 2. 57 44. 82 2. 43 Epo 52. 30 4. 44 51. 56 1. 73 59.16~5.18* Epo + SA 63. 92 7. 04*eP° 59. 88 7. 82*epo 70. 72 9. 77*epo
*Differs significantly of control (p<0. 01). epoDiffers significantly of Epo (p<0.05).
The co-administration of erythropoietin and succinic acid(cas:110-15-6) is synergistically effective for increasing hemoglobin and hematocrit levels in male mice. The therapeutic effects achieved with the combination of amounts Epo and SA at days 6,10, and 15 and calculated by the method described in the example 1 is greater than the sum of effects of amounts Epo and SA administered individually.

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