LAMPIRAN A PERHITUNGAN PROSENTASE HASIL
Reaksi: →
Piroksikam + O-benzoil M : 0,010 mol B : S :
0,010 mol -
O-(benzoil)piroksikam 0,017 mol
-
0,010 mol
0,010 mol
0,007 mol
0,010 mol
BM O-(benzoil)piroksikam
= 472.0
Berat teoritis O-(benzoil)piroksikam
= 0,010 mol × 472.0 = 4.72gram
Hasil O-(benzoil)piroksikam yang didapat Jadi, persentase hasil =
= 1.821 gram
Berat senyawa hasil sintesis x 100 % Berat senyawa secara teoritis =
1.821 x 100 % 4.72
= 38.58 % = 39 %
54
LAMPIRAN B PERHITUNGAN BERAT
Piroksikam
= mol x BM = 0.010 mol x 331.4 = 3.314 gram
benzoil klorida
= mol x BM = 0.017 mmol x 140.5 = 2.3885 gram
Volume O-benzoil klorida
=
berat
ρ =
2.3885 1.36
= 1.75 ml ≈ 2 ml Piridin
= mol x BM = 0.025 mol x 79,10 = 1,9775 gram
Volume piridin
=
=
berat
ρ 1,9775 0,9827
= 2,0123 ml ≈ 2 ml
55
LAMPIRAN C PERHITUNGAN % HAMBATAN NYERI SENYAWA UJI O(BENZOIL)PIROKSIKAM DAN SENYAWA PEMBANDING PIROKSIKAM
Rumus :
% hambatan nyeri =
fK − fT
× 100 %
fK fT = frekuensi geliat rata-rata pada kelompok uji atau kelompok pembanding fK = frekuensi geliat rata-rata pada kelompok kontrol Perhitungan : O-(benzoil)piroksikam
Piroksikam
Dosis 0.625 mg/kg BB
Dosis 0.625 mg/kg BB
% Hambatan nyeri = 173.4 - 155 × 100%
% Hambatan nyeri = 173.4 - 133.2 × 100%
173.4
173.4
= 10.61 %
= 23.18%
Dosis 1.25 mg/kg BB
Dosis 1.25 mg/kg BB
% Hambatan nyeri = 173.4 - 139 × 100% 173.4 = 19.83 %
% Hambatan nyeri = 173.4 - 90.8 × 100% 173.4 = 47.63 %
Dosis 2.5 mg/kg BB
Dosis 2.5 mg/kg BB
% Hambatan nyeri = 173.4 - 118 × 100% 173.4 = 31.94 %
% Hambatan nyeri = 173.4 - 70.6 × 100% 173.4 = 459.28 %
Dosis 5 mg/kg BB
Dosis 5 mg/kg BB
% Hambatan nyeri =
% Hambatan nyeri =
56
173.4 - 98
173.4 - 70.6
× 100%
173.4
× 100%
173.4 = 43.48%
= 59.28 %
Dosis 5 mg/kg BB
Dosis 10 mg/kg BB
% Hambatan nyeri = 173,4 - 71 × 100% 173.4 = 59.05 %
% Hambatan nyeri = 173.4 - 69.6 × 100%
173.4
= 59.86 %
57
LAMPIRAN D HASIL UJI HSD ANTARA KELOMPOK SENYAWA UJI O(BENZOIL)PIROKSIKAM, SENYAWA PEMBANDING PIROKSIKAM, DAN KONTROL CMC-NA 0,5% Post Hoc Tests Multiple Comparisons Dependent Variable: GELIAT Tukey HSD
LAMPIRAN ANOVA Geliat
Between Groups Within Groups Total
Sum of Squares 71332.436 15806.400 87138.836
df 10 44 54
Mean Square 7133.244 359.236
F 19.857
Sig. .000
Multiple Comparisons Dependent Variable: Geliat LSD 95% Confidence Interval (I) Dosis
0.625A
(J) Dosis Mean Difference (I-J) 42.40000(*) 62.60000(*)
Std. Error 11.98727 11.98727
Sig. .001 .000
Lower Bound 18.2413 38.4413
Upper Bound 66.5587 86.7587
5A
62.60000(*)
11.98727
.000
38.4413
86.7587
10A
63.60000(*)
11.98727
.000
39.4413
87.7587
1.25A 2.5A
58
0.625B
-22.00000
11.98727
.073
-46.1587
2.1587
1.25B
-6.00000
11.98727
.619
-30.1587
18.1587
2.5B
14.80000
11.98727
.224
-9.3587
38.9587
5B
35.60000(*)
11.98727
.005
11.4413
59.7587
10B
62.20000(*)
11.98727
.000
38.0413
-40.20000(*)
11.98727
.002
-64.3587
-42.40000(*)
11.98727
.001
-66.5587
20.20000 20.20000 21.20000
11.98727 11.98727 11.98727
.099 .099 .084
-3.9587 -3.9587 -2.9587
-64.40000(*)
11.98727
.000
-88.5587
-48.40000(*)
11.98727
.000
-72.5587
-27.60000(*)
11.98727
.026
-51.7587
86.3587 16.0413 18.2413 44.3587 44.3587 45.3587 40.2413 24.2413 -3.4413
5B
-6.80000
11.98727
.573
-30.9587
17.3587
10B
19.80000
11.98727
.106
-4.3587
-82.60000(*)
11.98727
.000
-106.7587
-62.60000(*)
11.98727
.000
-86.7587
Kontrol 1.25A
0.625A 2.5A 5A 10A 0.625B 1.25B 2.5B
-20.20000
11.98727
.099
-44.3587
43.9587 58.4413 38.4413 3.9587
5A
.00000
11.98727
1.000
-24.1587
24.1587
10A
1.00000
11.98727
.934
-23.1587
-84.60000(*)
11.98727
.000
-108.7587
-68.60000(*)
11.98727
.000
-92.7587
-47.80000(*)
11.98727
.000
-71.9587
-27.00000(*)
11.98727
.029
-51.1587
25.1587 60.4413 44.4413 23.6413 -2.8413
-.40000
11.98727
.974
-24.5587
-102.80000(*)
11.98727
.000
-126.9587
-62.60000(*)
11.98727
.000
-86.7587
Kontrol 2.5A
0.625A 1.25A
0.625B 1.25B 2.5B 5B 10B
-20.20000
11.98727
.099
-44.3587
23.7587 78.6413 38.4413 3.9587
2.5A
.00000
11.98727
1.000
-24.1587
24.1587
10A
1.00000
11.98727
.934
-23.1587
-84.60000(*)
11.98727
.000
-108.7587
25.1587 60.4413
Kontrol 5A
0.625A 1.25A
0.625B
59
1.25B
11.98727
.000
-92.7587
-47.80000(*)
11.98727
.000
-71.9587
-27.00000(*)
11.98727
.029
-51.1587
-.40000
11.98727
.974
-24.5587
-102.80000(*)
11.98727
.000
-126.9587
-63.60000(*)
11.98727
.000
-87.7587
1.25A
-21.20000
11.98727
.084
-45.3587
23.7587 78.6413 39.4413 2.9587
2.5A
-1.00000
11.98727
.934
-25.1587
23.1587
5A
-1.00000
11.98727
.934
-25.1587
-85.60000(*)
11.98727
.000
-109.7587
-69.60000(*)
11.98727
.000
-93.7587
-48.80000(*)
11.98727
.000
-72.9587
-28.00000(*) -1.40000
11.98727 11.98727
.024 .908
-52.1587 -25.5587
-103.80000(*)
11.98727
.000
-127.9587
23.1587 61.4413 45.4413 24.6413 -3.8413 22.7587 79.6413 46.1587
2.5B 5B 10B Kontrol 10A
0.625A
0.625B 1.25B 2.5B 5B 10B Kontrol 0.625B
0.625A 1.25A
22.00000
11.98727
.073
-2.1587
64.40000(*)
11.98727
.000
40.2413
84.60000(*)
11.98727
.000
60.4413
84.60000(*)
11.98727
.000
60.4413
85.60000(*)
11.98727
.000
61.4413
16.00000
11.98727
.189
-8.1587
88.5587 108.758 7 108.758 7 109.758 7 40.1587
2.5B
36.80000(*)
11.98727
.004
12.6413
60.9587
5B
57.60000(*)
11.98727
.000
33.4413
84.20000(*)
11.98727
.000
60.0413
0.625A 1.25A
-18.20000 6.00000 48.40000(*)
11.98727 11.98727 11.98727
.136 .619 .000
-42.3587 -18.1587 24.2413
81.7587 108.358 7 5.9587 30.1587 72.5587
2.5A
68.60000(*)
11.98727
.000
44.4413
92.7587
5A
68.60000(*)
11.98727
.000
44.4413
92.7587
10A
69.60000(*)
11.98727
.000
45.4413
93.7587
-16.00000
11.98727
.189
-40.1587
8.1587
2.5A 5A 10A 1.25B
10B Kontrol 1.25B
44.4413 23.6413 -2.8413
-68.60000(*)
0.625B
60
2.5B
20.80000
11.98727
.090
-3.3587
44.9587
5B
41.60000(*)
11.98727
.001
17.4413
65.7587
10B
68.20000(*)
11.98727
.000
44.0413
-34.20000(*)
11.98727
.007
-58.3587
-14.80000
11.98727
.224
-38.9587
92.3587 10.0413 9.3587
2.5A 5A
27.60000(*) 47.80000(*) 47.80000(*)
11.98727 11.98727 11.98727
.026 .000 .000
3.4413 23.6413 23.6413
51.7587 71.9587 71.9587
10A
48.80000(*)
11.98727
.000
24.6413
-36.80000(*)
11.98727
.004
-60.9587
-20.80000
11.98727
.090
-44.9587
72.9587 12.6413 3.3587
Kontrol 2.5B
0.625A 1.25A
0.625B 1.25B 5B 10B
.090
-3.3587
44.9587
11.98727
.000
23.2413
-55.00000(*)
11.98727
.000
-79.1587
-35.60000(*)
11.98727
.005
-59.7587
6.80000
11.98727
.573
-17.3587
2.5A
27.00000(*)
11.98727
.029
2.8413
51.1587
5A
27.00000(*) 28.00000(*)
11.98727 11.98727
.029 .024
2.8413 3.8413
-57.60000(*)
11.98727
.000
-81.7587
51.1587 52.1587 33.4413 17.4413 3.3587
0.625A 1.25A
10A 0.625B 1.25B
-41.60000(*)
11.98727
.001
-65.7587
2.5B
-20.80000
11.98727
.090
-44.9587
10B
26.60000(*)
11.98727
.032
2.4413
-75.80000(*)
11.98727
.000
-99.9587
-62.20000(*)
11.98727
.000
-86.3587
-19.80000
11.98727
.106
-43.9587
50.7587 51.6413 38.0413 4.3587
2.5A
.40000
11.98727
.974
-23.7587
24.5587
5A
.40000
11.98727
.974
-23.7587
24.5587
10A
1.40000
11.98727
.908
-22.7587
-84.20000(*)
11.98727
.000
-108.3587
-68.20000(*)
11.98727
.000
-92.3587
-47.40000(*)
11.98727
.000
-71.5587
25.5587 60.0413 44.0413 23.2413
Kontrol 10B
11.98727
71.5587 30.8413 11.4413 30.9587
Kontrol 5B
20.80000 47.40000(*)
0.625A 1.25A
0.625B 1.25B 2.5B
61
5B
18.20000
11.98727
.136
-5.9587
-2.4413 78.2413 64.3587 106.758 7 126.958 7 126.958 7 127.958 7 42.3587
1.25B
34.20000(*)
11.98727
.007
10.0413
58.3587
2.5B
55.00000(*) 75.80000(*)
11.98727 11.98727
.000 .000
30.8413 51.6413
102.40000(*)
11.98727
.000
78.2413
79.1587 99.9587 126.558 7
Kontrol Kontrol
0.625A 1.25A 2.5A 5A 10A 0.625B
5B 10B
-26.60000(*)
11.98727
.032
-50.7587
-102.40000(*)
11.98727
.000
-126.5587
40.20000(*)
11.98727
.002
16.0413
82.60000(*)
11.98727
.000
58.4413
102.80000(*)
11.98727
.000
78.6413
102.80000(*)
11.98727
.000
78.6413
103.80000(*)
11.98727
.000
79.6413
* The mean difference is significant at the .05 level. E. HASIL UJI ED50 SENYAWA O-(BENZOIL) ************ PROBIT
ANALYSIS *********
Parameter estimates converged after 14 iterations. Optimal solution found. Parameter Estimates (PROBIT model: (PROBIT(p)) = Intercept + BX): Regression Coeff. Standard Error Dosis
1.42051
.23865
Coeff./S.E. 5.95240
Intercept Standard Error Intercept/S.E. -.60047
.11647
-5.15543
Pearson Goodness-of-Fit Chi Square =
4.580
DF = 3 P = .205
Since Goodness-of-Fit Chi square is NOT significant, no heterogeneity factor is used in the calculation of confidence limits. --------------------------------------
62
************ PROBIT
ANALYSIS *********
Observed and Expected Frequencies
Number of Observed Expected Dosis Subjects Responses Responses 1 2 3 4 5
100.0 100.0 100.0 100.0 100.0
23.2 47.6 59.3 59.3 59.9
27.410 43.138 53.080 60.055 65.263
************ PROBIT
-4.226 4.497 6.205 -.770 -5.401
.01 .02 .03 .04 .05 .06 .07 .08 .09 .10 .15 .20 .25 .30 .35 .40 .45 .50
Dosis .06096 .09483 .12551 .15498 .18399 .21291 .24199 .27138 .30121 .33154 .49328 .67645 .88694 1.13123 1.41730 1.75536 2.15900 2.64676
95% Confidence Limits Lower Upper .00942 .01818 .02757 .03772 .04865 .06042 .07306 .08659 .10104 .11647 .20948 .33332 .49524 .70420 .97055 1.30429 1.71024 2.18134
Prob
.27410 .43138 .53080 .60055 .65263
ANALYSIS *********
Confidence Limits for Effective Dosis
Prob
Residual
.15740 .21986 .27185 .31897 .36331 .40592 .44742 . 48821 .52857 .56872 .77099 .98394 1.21602 1.47598 1.77578 2.13521 2.59056 3.20750
63
.55 .60 .65 .70 .75 .80 .85 .90 .91 .92 .93 .94 .95 .96 .97 .98 .99
3.24472 3.99084 4.94276 6.19267 7.89835 10.35601 14.20151 21.12957 23.25778 25.81340 28.94874 32.90267 38.07543 45.20098 55.81357 73.87463 114.92041
2.70454 3.28447 3.95148 4.75564 5.77336 7.13602 9.10766 12.34752 13.28556 14.38418 15.69576 17.30060 19.32987 22.01714 25.83369 31.94295 44.61689
4.08542 5.35182 7.18809 9.90363 14.07959 20.91657 33.27974 59.85335 68.98909 80.50843 95.41610 115.36368 143.26899 184.81918 252.80311 383.45844 739.72825
Probit Transformed Responses
0.4
0.2
Probit
0.0
-0.2
-0.4
-0.6
-0.8 0.0
0.1
0.2
0.3
0.4
Dosis
64
0.5
0.6
0.7
F. HASIL UJI ED50 SENYAWA PIROKSIKAM ************ PROBIT
ANALYSIS *********
Parameter estimates converged after 10 iterations. Optimal solution found. Parameter Estimates (PROBIT model: (PROBIT(p)) = Intercept + BX): Regression Coeff. Standard Error Dosis
.36400
.04530
Coeff./S.E. 8.03543
Intercept Standard Error Intercept/S.E. -1.59284 .15956 -9.98283 Pearson Goodness-of-Fit Chi Square = .097
DF = 3 P = .992
Since Goodness-of-Fit Chi square is NOT significant, no heterogeneity factor is used in the calculation of confidence limits. --------------------------------------
************ PROBIT
ANALYSIS *********
Observed and Expected Frequencies
Number of Observed Expected Dosis Subjects Responses Responses 1.00 2.00 3.00 4.00 5.00
100.0 100.0 100.0 100.0 100.0
10.5 19.7 31.7 43.7 59.1
10.956 19.356 30.824 44.557 58.984
************ PROBIT
Residual
-.461 .367 .895 -.843 .070
Prob
.10956 .19356 .30824 .44557 .58984
ANALYSIS *********
65
Confidence Limits for Effective Dosis
Prob .01 .02 .03 .04 .05 .06 .07 .08 .09 .10 .15 .20 .25 .30 .35 .40 .45 .50 .55 .60 .65 .70 .75 .80 .85 .90 .91 .92 .93 .94 .95 .96 .97 .98 .99
Dosis
95% Confidence Limits Lower Upper
-2.01514 -1.26624 -.79108 -.43364 -.14289 .10458 .32157 .51586 .69255 .85520 1.52861 2.06381 2.52297 2.93530 3.31739 3.67996 4.03075 4.37597 4.72120 5.07199 5.43456 5.81665 6.22898 6.68814 7.22334 7.89675 8.05940 8.23609 8.43038 8.64736 8.89484 9.18559 9.54303 10.01819 10.76709
-3.75650 -2.77261 -2.14954 -1.68168 -1.30180 -.97907 -.69667 -.44434 -.21537 -.00512 .85798 1.52995 2.08821 2.56611 2.98191 3.35028 3.68548 4.00014 4.30435 4.60625 4.91312 5.23265 5.57442 5.95239 6.39061 6.93954 7.07182 7.21542 7.37320 7.54929 7.74997 7.98556 8.27496 8.65935 9.26459
-.94046 -.33179 . 05558 .34782 .58623 .78976 .96878 1.12960 1.27638 1.41201 1.98092 2.44707 2.86522 3.26416 3.66088 4.06352 4.47428 4.89375 5.32367 5.76773 6.23186 6.72485 7.25993 7.85836 8.55827 9.44135 9.65494 9.88709 10.14246 10.42780 10.75338 11.13608 11.60678 12.23282 13.22014
66
Probit Transformed Responses
Probit
0.0
-0.5
-1.0
-1.5 1.00
2.00
3.00
Dosis
67
4.00
5.00
LAMPIRAN G SKEMA SINTESIS O-(BENZOIL)PIROKSIKAM O- benzoil klorida (0,017 mol) dalam 10 ml kloroform
Piroksikam (0,010 mol) dalam 30 ml kloroform + piridin (0,05 mol) 4 5 67 45 67 3 8 9 2 1 11
4 5 67
4 5 67 3 8 9 2 1 10
Pada suhu kamar, teteskan perlahan-lahan (0,5jam), sambil diaduk-aduk
Tambahkan etil asetat 30 ml, kocok 3 menit
3 2 1
8 9 11
45 67 8 3 2 9 10 1
Refluks di atas penangas air, KLT tiapjam, sampai noda piroksikam (-)
Cuci dengan air sebanyak 2 kali @ 100 ml
3 2 1
8 9 11
45 67 8 3 2 9 10 1
Uapkan pelarut
Tambahkan NaOH 1N 20 ml
Fasa atas (Etil asetat)
Tambahkan Na-sulfat anhidrat ad hasil sintesis jernih
Uapkan pelarut
Rekristalisasi dengan pelarut etanol
Kristal Hasil Sintesis
68
LAMPIRAN H SERTIFIKAT ANALISIS PIROKSIKAM
69