LAMPIRAN A PERHITUNGAN PEMBUATAN LARUTAN SEDIAAN UJI DAN VOLUME PENYUNTIKANNYA Volume penyuntikan : 0,5 ml/ 20 g bb mencit. mg/kg bb Untuk mencit 20 g = 20 g x mg = 0,02 mg/20 g bb 000 g Konsentrasi larutan = 0,02 mg/0,5 ml = 0,04 mg/ml 2. 2,5 mg/kg bb Untuk mencit 20 g = 20 g x 2,5 mg = 0,05 mg/20 g bb 000 g Konsentrasi larutan = 0,05 mg/0,5 ml = 0, mg/ ml 3. 5 mg/kg bb Untuk mencit 20 g = 20 g x 5 mg = 0, mg/20 g bb 000 g Konsentrasi larutan = 0, mg/0,5 ml = 0,2 mg/ ml 4. 0 mg/kg bb Untuk mencit 20 g = 20 g x 0 mg = 0,2 mg/20 g bb 000 g Konsentrasi larutan = 0,2 mg/0,5 ml = 0,4 mg/ml 63
LAMPIRAN B CONTOH PERHITUNGAN % HAMBATAN NYERI SENYAWA UJI Rumus : % hambatan nyeri = fk fr x 00 % fk fr = frekuensi geliat pada kelompok uji atau kelompok pembanding fk = frekuensi rata-rata geliat pada kelompok kontrol Perhitungan : Senyawa Uji N-benzoil-N -feniltiourea Dosis mg/kg BB: % hambatan nyeri : Mencit = 47 85 x 00 % = 42,8 % 47 Mencit 2 = 47 86 x 00 % = 4,50 % 47 Mencit 3 = 47 89 x 00 % = 39,46 % 47 Mencit 4 = 47 88 x 00 % = 40,4 % 47 Mencit 5 = 47 93 x 00 % = 36,73 % 47 Rata-rata % hambatan nyeri N-benzoil-N -feniltiourea dosis mg/kg BB = ± 40,00 % 64
LAMPIRAN C SPEKTRA INFRA MERAH N-BENZOIL-N -FENILTIOUREA DAN TIGA TURUNANNYA PADA PENELITIAN TERDAHULU Spektrum infra merah N-fenil-N -benzoiltiourea (Wijaya, 2006) 65
Spektrum infra merah N-(p-klorobenzoil)-N -feniltiourea (Nobsina, 2006) 66
Spektrum infra merah N-(p-metilbenzoil)-N -feniltiourea (Wijaya, 2006) 67
Spektrum infra merah N-(p-klorobenzoil)-N -(p-tolil)tiourea (Setiawati, 2006) 68
LAMPIRAN D PERHITUNGAN NILAI KONVERSI NATRIUM DIKLOFENAK PADA MENCIT Dosis lazim natrium diklofenak = 50 mg (Tan & Rahardja, 2007). Faktor konversi pada mencit = 0,0026 (Laurence & Barcarach, 964) Berat rata rata mencit dewasa = 20 g (Laurence & Barcarach, 964) Konversi dosis natrium diklofenak pada mencit = 50x0,0026=0,3 mg/20 gbb Dosis diklofenak per kgbb mencit= 0,3/20 x 000 = 6,5 mg/kgbb 69
LAMPIRAN E PERSAMAAN REGRESI LINIER PADA SIFAT FISIKA KIMIA SUBSTITUEN SENYAWA UJI E.. Nilai Lipofilik - log ED 50 versus π Regression Residual Total a. Predictors: (Constant), phi ANOVA b.047.047 3.234.24 a.029 2.04.076 3 b. Dependent Variable: loged50 a. Summary Adjusted Std. Error of R R Square R Square the Estimate.786 a.68.427.2034 Predictors: (Constant), phi (Constant) phi Unstandardized a. Dependent Variable: loged50 a Standardized B Std. Error Beta t Sig. -.472.04-4.550.045.239.33.786.798.24 Berdasarkan tabel di atas, diperoleh nilai: R = 0,786 F = 3,234 Persamaan regresi dari nilai lipofilik (- log ED 50 versus π) adalah: y = 0,239 π - 0,472 () 70
E.2. Nilai Lipofilik - log ED 50 versus π, π 2 a. Summary Adjusted Std. Error of R R Square R Square the Estimate.936 a.876.629.09680 Predictors: (Constant), phi2, phi Regression Residual Total a. Predictors: (Constant), phi2, phi b. Dependent Variable: log.ed50 ANOVA b.066 2.033 3.545.352 a.009.009.076 3 (Constant) phi phi2 Unstandardized a. Dependent Variable: log.ed50 a Standardized B Std. Error Beta t Sig. -.542.096-5.68.2.683.325 2.243 2.02.283 -.350.242 -.543 -.446.385 Berdasarkan tabel di atas, diperoleh nilai: R = 0,936 F = 3,545 Persamaan regresi dari nilai lipofilik (- log ED 50 versus π, π 2 ) adalah: y = 0,683 π - 0,350 π - 0,542 (2) 7
E.3. Nilai Lipofilik dan Elektronik - log ED 50 versus π,σp Summary Adjusted Std. Error of R R Square R Square the Estimate.86 a.74.224.4000 a. Predictors: (Constant), sigmap, phi ANOVA b Regression.056 2.028.434.509 a Residual.020.020 Total.076 3 a. Predictors: (Constant), sigmap, phi b. Dependent Variable: LogEd50 (Constant) phi sigmap Unstandardized a. Dependent Variable: LogEd50 a Standardized B Std. Error Beta t Sig. -.480.2-3.959.58.269.60.882.673.343 -.35.507 -.364 -.69.65 Berdasarkan tabel di atas, diperoleh nilai: R = 0,86 F =,434 Persamaan regresi dari niali lipofilik dan elektronik (- log ED 50 versus π,σp) adalah: y = 0,269 π - 0,35 σp - 0,480 (3) 72
E.4. Nilai Elektronik dan Sterik - log ED 50 versus σp,es a. Summary Adjusted Std. Error of R R Square R Square the Estimate.984 a.968.904.04927 Predictors: (Constant), Es, sigmap Regression Residual Total ANOVA b.073 2.037 5.5.79 a.002.002.076 3 a. Predictors: (Constant), Es, sigmap b. Dependent Variable: LogEd50 (Constant) sigmap Es Unstandardized a. Dependent Variable: LogEd50 a Standardized B Std. Error Beta t Sig. -.92.034-5.64.2 -.040.73 -.042 -.233.855 -.286.052 -.979-5.448.6 Berdasarkan tabel di atas, diperoleh nilai: R = 0,984 F = 5,5 Persamaan regresi dari nilai elektronik dan sterik (- log ED 50 versus σp,es) adalah: y = -0,040 σp - 0,286 Es - 0,92 (4) 73
E.5. Nilai Elektronik dan Sterik -log ED 50 versus σp 2, Es 2 Summary Adjusted Std. Error of R R Square R Square the Estimate.987 a.975.925.04358 a. Predictors: (Constant), Es2, sigma.p.2 ANOVA b Regression.074 2.037 9.458.58 a Residual.002.002 Total.076 3 a. Predictors: (Constant), Es2, sigma.p.2 b. Dependent Variable: log.ed50 (Constant) sigma.p.2 Es2 Unstandardized a. Dependent Variable: log.ed50 a Standardized B Std. Error Beta t Sig. -.92.046-4.50.5 -.446.327 -.24 -.090.473 -.234.042 -.099-5.590.3 Berdasarkan tabel di atas, diperoleh nilai: R = 0,987 F = 9,458 Persamaan regresi dari nilai elektronik dan sterik ( -log ED 50 versus σp 2, Es 2 ) adalah: y = -,446 σp - 0,234 Es - 0,92 (5) 74
E.6. Nilai Sterik - log ED 50 versus Es Summary Adjusted Std. Error of R R Square R Square the Estimate.983 a.966.949.03577 a. Predictors: (Constant), Es Regression Residual Total a. Predictors: (Constant), Es b. Dependent Variable: LogEd50 ANOVA b.073.073 57.256.07 a.003 2.00.076 3 (Constant) Es Unstandardized a. Dependent Variable: LogEd50 a Standardized B Std. Error Beta t Sig. -.92.025-7.830.06 -.287.038 -.983-7.567.07 Berdasarkan tabel di atas, diperoleh nilai: R = 0,983 F = 57,256 Persamaan regresi dari nilai sterik (- log ED 50 versus Es) adalah: y = - 0,287 Es - 0,92 (6) 75
E.7. Nilai Sterik - log ED 50 versus Es 2 Summary Adjusted Std. Error of R R Square R Square the Estimate.972 a.945.98.04558 a. Predictors: (Constant), Es2 ANOVA b Regression.072.072 34.484.028 a Residual.004 2.002 Total.076 3 a. Predictors: (Constant), Es2 b. Dependent Variable: log.ed50 (Constant) Es2 a Unstandardized a. Dependent Variable: log.ed50 Standardized B Std. Error Beta t Sig. -.233.027-8.582.03 -.207.035 -.972-5.872.028 Berdasarkan tabel di atas, diperoleh nilai: R = 0,972 F = 34,484 Persamaan regresi dari niali sterik (- log ED 50 versus Es 2 ) adalah: y = - 0,207 Es 0,233 (7) 76
E.8. Nilai Sterik -log ED 50 versus Es, Es 2 Summary Adjusted Std. Error of R R Square R Square the Estimate.984 a.968.903.04950 a. Predictors: (Constant), Es2, Es Regression Residual Total ANOVA b.073 2.037 4.969.80 a.002.002.076 3 a. Predictors: (Constant), Es2, Es b. Dependent Variable: log.ed50 (Constant) Es Es2 Unstandardized a. Dependent Variable: log.ed50 a Standardized B Std. Error Beta t Sig. -.200.049-4.04.54 -.230.275 -.788 -.834.557 -.042.20 -.99 -.20.868 Berdasarkan tabel di atas, diperoleh nilai: R = 0,984 F = 4,969 Persamaan regresi dari nilai sterik ( -log ED 50 versus Es, Es 2 ) adalah: y = -0,230 Es - 0,42 Es - 0,2 (8) 77
LAMPIRAN F UJI ANOVA DAN HSD 5 % TERHADAP FREKUENSI GELIAT MENCIT Descriptives Geliat Kontrol p5 p0 induk induk2,5 induk5 induk0 cl cl2,5 cl5 cl0 ch3. ch3.2,5 ch3.5 ch3.0 cl.ch3. cl.ch3.2,5 cl.ch3.5 cl.ch3.0 Total 95% Confidence Interval for Mean N Mean Std. Deviation Std. Error Lower BoundUpper Bound Minimum Maximum 5 47.0000 7.7635 3.20936 38.0894 55.906 40.00 56.00 5 46.2000 4.60435 2.0593 40.4829 5.97 4.00 52.00 5 3.8000 5.3037 2.37487 25.2063 38.3937 24.00 38.00 5 05.8000.92354.86023 03.46 08.884 03.00 08.00 5 88.2000 2.58844.5758 84.9860 9.440 85.00 92.00 5 55.8000 2.38747.0677 52.8356 58.7644 53.00 59.00 5 5.2000 3.34664.49666 47.0446 55.3554 47.00 55.00 5 88.2000 3.448.39284 84.3329 92.067 85.00 93.00 5 59.4000 2.3027.02956 56.545 62.2585 57.00 63.00 5 37.2000 2.28035.0980 34.3686 40.034 35.00 40.00 5 28.6000.408.50990 27.843 30.057 27.00 30.00 5 95.2000.92354.86023 92.86 97.5884 93.00 98.00 5 64.8000.92354.86023 62.46 67.884 62.00 67.00 5 44.0000.87083.83666 4.677 46.3229 4.00 46.00 5 3.0000.584.707 29.0368 32.9632 29.00 33.00 5 85.2000.48324.66332 83.3583 87.047 83.00 87.00 5 68.8000.92354.86023 66.46 7.884 66.00 7.00 5 40.2000.92354.86023 37.86 42.5884 38.00 43.00 5 3.6000 4.03733.80555 26.5870 36.630 25.00 36.00 95 63.684 3.00674 3.822 56.8520 69.4848 24.00 56.00 Geliat Between Groups Within Groups Total Post Hoc Tests ANOVA 8967.305 8 4978.739 500.508.000 756.000 76 9.947 90373.305 94 78
Multiple Comparisons Dependent Variable: FG (Frekuensi Geliat) Tukey HSD (I) Sywuji (J) Sywuji Mean Difference (I-J) Std. Error Sig. 95% Confidence Interval Low er Lower Bound Upper Bound Bou nd Upper Bound Lower Bound kontrol p5 00.80000(*).99473.000 93.5342 08.0658 p0 5.20000(*).99473.000 07.9342 22.4658 induk 4.20000(*).99473.000 33.9342 48.4658 induk2.5 58.80000(*).99473.000 5.5342 66.0658 induk5 9.20000(*).99473.000 83.9342 98.4658 induk0 95.80000(*).99473.000 88.5342 03.0658 cl 58.80000(*).99473.000 5.5342 66.0658 cl2.5 87.60000(*).99473.000 80.3342 94.8658 cl5 09.80000(*).99473.000 02.5342 7.0658 cl0 8.40000(*).99473.000.342 25.6658 ch3 5.80000(*).99473.000 44.5342 59.0658 ch32.5 82.20000(*).99473.000 74.9342 89.4658 ch35 03.00000(*).99473.000 95.7342 0.2658 ch30 6.00000(*).99473.000 08.7342 23.2658 clch3 6.80000(*).99473.000 54.5342 69.0658 clch32.5 78.20000(*).99473.000 70.9342 85.4658 clch35 06.80000(*).99473.000 99.5342 4.0658 clch30 5.40000(*).99473.000 08.342 22.6658 * The mean difference is significant at the.05 level. 79
LAMPIRAN G UJI ANOVA DAN HSD 5 % TERHADAP % HAMBAT NYERI SENYAWA UJI DAN PEMBANDING NATRIUM DIKLOFENAK Descriptives HN.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00 0.00.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 Total 95% Confidence Interval for Mean N Mean Std. Deviation Std. Error Lower Bound Upper Bound Minimum Maximum 5 68.5740 3.3096.4002 64.6864 72.466 64.63 72. 5 78.3660 3.605.649 73.8823 82.8497 74.5 83.67 5 28.0260.3080.58496 26.409 29.650 26.53 29.93 5 40.0020.7638.78880 37.89 42.92 37.4 42.8 5 62.0400.62830.72820 60.082 64.068 59.86 63.95 5 65.740 2.27572.0773 62.3483 67.9997 62.59 68.03 5 40.0020 2.270.94885 37.3676 42.6364 36.73 42.8 5 59.5880.56548.7000 57.6442 6.538 57.4 6.22 5 74.6940.55064.69347 72.7686 76.694 72.79 76.9 5 80.5460.77358.34596 79.5855 8.5065 79.59 8.63 5 35.2340.3080.58496 33.6099 36.858 33.33 36.73 5 55.960.3080.58496 54.299 57.540 54.42 57.82 5 70.0700.2726.56893 68.4904 7.6496 68.7 72. 5 78.900.0757.48083 77.5750 80.2450 77.55 80.27 5 42.0440.00860.4506 40.797 43.2963 40.82 43.54 5 53.960.3080.58496 5.579 54.820 5.70 55.0 5 72.6540.3080.58496 7.0299 74.278 70.75 74.5 5 78.5020 2.74538.22777 75.0932 8.908 75.5 82.99 90 60.966 6.628.754 56.77 63.6760 26.53 83.67 Oneway ANOVA HN Between Groups Within Groups Total 24308.225 7 429.896 404.546.000 254.489 72 3.535 24562.74 89 Multiple Comparisons Dependent Variable: HN (% Hambat Nyeri) Tukey HSD 80
(I) FOR MUL A Mean Difference (I- J) (J) FORMULA Std. Error Sig. 95% Confidence Interval Upper Lower Upper Lower Lower Bound Bound Bound Bound Bound p5 p0-9.79200(*).8904.000-4.0944-5.4896 ind. 40.54800(*).8904.000 36.2456 44.8504 ind.2,5 28.57200(*).8904.000 24.2696 32.8744 ind.5 6.53400(*).8904.000 2.236 0.8364 ind.0 3.40000.8904.30 -.9024 7.7024 cl. 28.57200(*).8904.000 24.2696 32.8744 cl.2,5 8.98600(*).8904.000 4.6836 3.2884 cl.5-6.2000(*).8904.000-0.4224 -.876 cl.0 -.97200(*).8904.000-6.2744-7.6696 ch3. 33.34000(*).8904.000 29.0376 37.6424 ch3.2,5 2.65800(*).8904.000 8.3556 6.9604 ch3.5 -.49600.8904.998-5.7984 2.8064 ch3.0-0.33600(*).8904.000-4.6384-6.0336 cl.ch3. 26.53000(*).8904.000 22.2276 30.8324 cl.ch3.2,5 5.37800(*).8904.000.0756 9.6804 cl.ch3.5-4.08000.8904.083-8.3824.2224 cl.ch3.0-9.92800(*).8904.000-4.2304-5.6256 p0 p5 9.79200(*).8904.000 5.4896 4.0944 ind. 50.34000(*).8904.000 46.0376 54.6424 ind.2,5 38.36400(*).8904.000 34.066 42.6664 ind.5 6.32600(*).8904.000 2.0236 20.6284 ind.0 3.9200(*).8904.000 8.8896 7.4944 cl. 38.36400(*).8904.000 34.066 42.6664 cl.2,5 8.77800(*).8904.000 4.4756 23.0804 cl.5 3.67200.8904.89 -.6304 7.9744 cl.0-2.8000.8904.926-6.4824 2.224 ch3. 43.3200(*).8904.000 38.8296 47.4344 ch3.2,5 22.45000(*).8904.000 8.476 26.7524 ch3.5 8.29600(*).8904.000 3.9936 2.5984 ch3.0 -.54400.8904.000-4.8464 3.7584 cl.ch3. 36.32200(*).8904.000 32.096 40.6244 cl.ch3.2,5 25.7000(*).8904.000 20.8676 29.4724 cl.ch3.5 5.7200(*).8904.00.4096 0.044 cl.ch3.0 -.3600.8904.000-4.4384 4.664 * The mean difference is significant at the.05 level. 8