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Abstrak :
Tablet Cepat Hancur (TCH) telah dikembangkan bagi pasien yang sulit menelan tablet konvensional atau kapsul terutama untuk obat-obat yang mempunyai dosis besar seperti sediaan herbal. Ekstrak herbal umumnya mempunyai karakteristik lengket, higroskopis sehingga mempunyai flowabilitas dan kompresibilitas yang buruk, selain itu mempunyai rasa tidak enak dan dosis besar, karena itu dibutuhkan suatu metode dan eksipien yang dapat mengatasi karakteristik tersebut agar didapatkan TCH yang aman, berkhasiat dan disukai konsumen. Dilakukan penelitian pembuatan sediaan TCH dengan bahan aktif ekstrak buah oyong (Luffa acutangula (L) Roxb) yang hancur dan larut dengan cepat di saliva. Digunakan eksipen yang dibuat dengan cara ko-proses maltodekstrin suksinat (MDS), polivinilpirolidon (PVP) dan manitol (Mnt) rasio 1: 1: 8; 2: 1: 7 dan 3: 1: 6. Massa TCH dibuat dengan 3 metode, yaitu eksipien tunggal ko-proses MDS, PVP dan Mnt ditambahkan ekstrak dan dilakukan spray drying (formula F1, F2, F3), eksipien ko-proses dikeringkan dengan spray dryer dan ekstrak ditambahkan secara fisik (formula F4, F5, F6), eksipien (tanpa ko-proses) dan ekstrak dicampur secara fisik (formula F7, F8, F9), kemudian masing-masing massa tablet dikempa, selanjutnya TCH yang dihasilkan dikarakterisasi dan dievaluasi. Terhadap TCH juga dilakukan uji stabilitas dipercepat, uji hedonik serta uji khasiat pada hewan coba. Fraksi aktif ekstrak buah oyong dilakukan uji antisindrom metabolik, uji toksisitas akut, skrining fitokimia dan standardisasi ekstrak. Hasil penelitian menunjukan bahwa TCH formula F2 mempunyai performans sediaan tablet terbaik dan memenuhi karakteristik farmakope. Studi stabilitas dipercepat tidak terlihat adanya perubahan fisik, uji hedonik TCH F2 disukai oleh konsumen. Fraksi aktif ekstrak buah oyong terbukti berkhasiat sebagai antisindrom metabolik pada hewan coba, dikategorikan praktis tidak toksik dan memenuhi persyaratan standardisasi ekstrak. Senyawa Cucurbitacin diduga sebagai zat berkhasiat dalam buah oyong, berat molekul senyawa ini ditemukan dalam ekstrak dan serum darah hewan uji yang diberi TCH. Fraksi aktif buah oyong telah berhasil dibuat TCH menggunakan eksipien tunggal MDS-PVP-Mnt rasio 2:1:7 dengan metode koproses - spray drying dan dapat dijadikan alternatif antisindrom metabolik.

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Fast Disintegrating Tablet (FDT) has been developed for patients who have difficulty swallowing conventional tablets or capsules especially medicines which have a high dose. Herbal extracts generally have characteristics of sticky, hygroscopic and therefore have poor flowability and compressibility. In addition, it possesses faintly aromatic odor and somewhat unpleasant taste, so that it took a special method and excipient that could cover these characteristics in order to fulfill with requirements of quality, safety, efficacy and preferred by consumers. FDT using the squash (Luffa acutangula (L) Roxb) fruit extract are disintegrated and dissolve rapidly in saliva is proposed. Excipient used is made by the coprocess maltodextrin succinate (MDS), polyvinylpyrrolidone (PVP) and mannitol (Mnt) ratio of 1: 1: 8; 2: 1: 7 and 3: 1: 6 then characterized. The mass of FDT was made by three methods are co-process excipient was added the extract and sprayed drying (formulas F1, F2, F3), co-process and sprayed drying of excipient then physically added the extract (formula F4, F5, F6), physically mixed the extract with excipient without co-process (formula F7, F8, F9), then each mass of FDT was compressed then the resulting FDT was characterized and evaluated. The hedonic test and the efficacy test in experimental animals have done and some testings on anti-metabolic syndrome, acute toxicity, phytochemical screening and standardization were also carried out to the active fraction of squash fruit extract. The results indicated that the FDT F2 formula showed the best pharmaceutical performance and meet the characteristics of pharmacopoeia. In the short-term stability testing, FDT did not appear to physical changes, while in the hedonic testing resulted acceptable palatability. Cucurbitacin compound which was found in the squash fruit extract and in the blood serum of animals treated by FDT was suspected as active substance, pharmacological experiments confirm its therapeutic efficacy and safety. In conclusion, the active fraction of squash fruit had successfully created FDT using a single excipient of MDS-PVP-Mnt (ratio of 2: 1: 7) with co-process - spray drying method and can be an alternative as antimetabolic syndrome.

Abstrak :
Senyawa turunan eugenol diduga dapat menginhibisi Bcl-2 pada sel kanker kolorektal HT29. Penelitian ini bertujuan untuk memperoleh senyawa baru turunan eugenol yang dapat menghambat sel kanker kolorektal HT29 secara in vitro dan menurunkan ekspresi Bcl-2 pada mencit yang mengalami pre-klamsia terhadap kolon secara in vivo. Penelitian ini diawali dengan melakukan desain senyawa turunan secara in silico. Hasil senyawa hit disintesis di laboratorium. Uji secara in vitro, uji apoptosis dan uji in vivo dilakukan berturut-turut pada hasil senyawa sintesis. Hasil in silico, dari skrining secara farmakofor dengan rancangan acak lengkap menggunakan 220 senyawa desain. Berdasarkan fitur farmakofor dengan cut off 5 fitur dihasilkan 23 senyawa. Hasil skrining farmakofor dilakukan docking menghasilkan delapan senyawa yaitu senyawa 4 rsquo;- 2-kloro-3-hidroksipropil -2 rsquo;-metoksifenil 2-hidroksibenzoat 57, 4 rsquo;- 2-kloro-3-hidroksi-propil -2 rsquo;-hidroksifenil 2-hidroksibenzoat 167, S -4 rsquo;- 2,3-dihidroksipropil -2 rsquo;-metoksifenil 2-hidroksibenzoat 59, R -4 rsquo;- 2,3-dihidroksipropil -2 rsquo;-metoksifenil 2-hidroksibenzoat 60, 4 rsquo;-alil-2 rsquo;-metoksifenil 4-amino-2-hidroksibenzoat 71, 4 rsquo;-alil-2 rsquo;-hidroksifenil 4-amino-2-hidroksibenzoat 181, 4 rsquo;-alil-2 rsquo;-metoksifenil 3,4,5-trihidroksibenzoat 86 dan 4 rsquo;-alil-2 rsquo;-metoksifenil 3,5-diihidroksi-4-metoksibenzoat 91 dengan energi ikatan lebih negatif dari standar. Delapan senyawa hasil skrining disintesis melalui reaksi esterifikasi, adisi halogen, hidroksilasi dan demetilasi. Hasil sintesis diuji aktivitas penghambatannya secara in vitro terhadap sel HT29 kanker kolon. Aktivitas penghambatan terhadap sel HT29 menunjukkan nilai IC50 antara 82.98 g/mL - 8.455 g/mL. Nilai IC50 tersebut lebih negatif dibandingkan senyawa penuntun eugenol. Hubungan Kuantitatif Struktur Aktivitas terhadap sel line HT29 menghasilkan persamaan Log 1/IC50 = -0.865-0.210 LogP 2 1.264 logP -0.994CMR n=10; r=0.706; SE:0.21; F=0.497, sig=7.86 . Persamaan menunjukkan variabel log P dan CMR berpengaruh terhadap IC50. Sifat hidrofobisitas log P lebih berperan dibandingkan dengan sifat sterik CMR . Hasil uji in vivo terhadap mencit Mus musculus menunjukkan senyawa turunan 59 memiliki nilai HE dan IHK mendekati kontrol positif. Peningkatan dosis pemberian menyebabkan peningkatan degradasi Bcl-2 pada jaringan mendekati kontrol normal. Hasil penelitian menunjukkan bahwa senyawa baru turunan eugenol 59 yang diperoleh dapat menghambat kanker kolorektal secara in vitro dan in vivo.

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Compounds derived from eugenol are thought to inhibit Bcl 2 in HT29 colorectal cancer cells. The aim of this study was to obtain new compounds of eugenol derivatives that could inhibit in HT29 cell invitro test and decrease of Bcl 2 expression in mice pre clammed on colon with invivo test. This research begins by designing in silico derivative compounds. The result of the hit compound is synthesized in the laboratory. In vitro tests, apoptotic test and in vivo test were performed successively on the result of the synthesis compound. In silico yield, from a complete randomized pharmacophore screening using 220 design compounds. Based on the pharmacophore features with cut off 5 features produced 23 compounds. The results of pharmacophore screening conducted docking which yielded eight compounds of compound 4 rsquo 2 chloro 3 hydroxypropyl 2 rsquo metohoxyphenyl 2 hydroxybenzoat 57, 4 rsquo 2 chloro 3 hidroxy propyl 2 rsquo hydroxyphenyl 2 hydroxybenzoat 167, S 4 rsquo 2,3 dihydroxypropyl 2 rsquo methoxyphenyl 2 hydroxybenzoat 59, R 4 rsquo 2,3 dihydroxypropyl 2 rsquo methoxyphenyl 2 hydroxybenzoat 60, 4 rsquo allyl 2 rsquo methoxyphenyl 4 amino 2 hydroxybenzoat 71, 4 rsquo allyl 2 rsquo hydroxyphenyl 4 amino 2 hydroxybenzoat 181, 4 rsquo allyl 2 rsquo methoxyphenyl 3,4,5 trihydroxybenzoat 86 dan 4 rsquo allyl 2 rsquo methoxyphenyl 3,5 dihydroxy 4 methoxybenzoat 91 with energy binding more negative than standard. The eight compounds of the screening are synthesized by esterification reaction, addition with halogen, hydroxylation. And demetylation The synthesis results were tested in vitro inhibitory activity against HT29 colon cancer cells. The inhibitory activity against HT29 cells shows an IC50 value between 82.98 g mL 8,455 g mL. The value of IC50 is better than the eugenol guiding compound. Quantitative Relation of Structure Activity against cell line HT29 with equation Log 1 IC50 0.865 0.210 LogP 2 1.264 logP 0.994CMR n 10 r 0.706 SE 0.21 F 0.497, sig 7.86 . This equation showed that log P and CMR have effect with IC50. Hydrophobicity log P more of effect compared than steric parameters CMR . In vivo test of Mus musculus that showed compound derivative 59 based on HE and IHK values approaching positive control. Increased dosage of administration leads to an increase in Bcl 2 degradation in tissues near normal control. The results showed that the new compound derived eugenol 59 obtained can inhibit colorectal cancer in vitro and in vivo.

Abstrak :
Hipertensi merupakan penyakit penyerta yang paling umum ada pada penderita COVID-19. Faktor risiko seperti genetik, sosiodemografi, dan kondisi klinis awal diduga dapat memengaruhi kerentanan individu terhadap hipertensi dan COVID-19. Salah satu gen yang berhubungan dengan hipertensi adalah gen ACE. Penelitian ini bertujuan untuk mengkaji variasi genetik gen ACE dalam hubungannya dengan risiko kerentanan dan penanganan penyakit hipertensi dan COVID-19 menggunakan model populasi Palu-Sulawesi Tengah. Penelitian ini merupakan studi observasional dengan desain cross-sectional. Data faktor non-genetik diperoleh dari rekam medis dan kuesioner. Identifikasi variasi genetik dilakukan pada 4 lokasi pada gen ACE, yaitu rs1799752 (I/D) dengan metode PCR, dan rs4331 (A/G), rs4341 (G/C), dan rs4343 (G/A) dengan rhAmp SNP genotyping. Data faktor genetik dan non-genetik kemudian disusun menjadi model instrumen translasional. Studi melibatkan 136 subjek, dan analisis variasi genetik menunjukkan genotipe dominan untuk rs1799752 adalah II (50%), rs4331 adalah GG (51%), rs4341 adalah GG (100%), dan rs4343 adalah AA (65%). Varian alel D rs1799752, alel A rs4331, dan alel G rs4343 menunjukkan hubungan dengan kerentanan terhadap hipertensi, COVID-19, dan keparahan COVID-19. Analisis regresi menunjukkan bahwa jenis kelamin, usia, riwayat hipertensi, LDL, asam urat, glukosa darah, dan variasi genetik gen ACE adalah prediktor dalam menilai tingkat risiko hipertensi. Sementara itu, jenis kelamin, trigliserida, HDL, komorbiditas hipertensi, dan variasi genetik gen ACE adalah prediktor dalam menilai risiko terhadap kejadian COVID-19, sementara komorbiditas hipertensi, IMT, asam urat, dan variasi genetik gen ACE adalah prediktor dalam menilai risiko keparahan COVID-19. Asesmen prediksi instrumen translasional menunjukkan bahwa 31% dari kelompok hipertensi berisiko tinggi terhadap kejadian COVID-19 dan 46% memiliki berisiko sangat tinggi untuk mengalami keparahan yang lebih tinggi. Asesmen prediksi instrumen translasional hipertensi menunjukkan bahwa 22% subjek memiliki risiko sangat tinggi dan 23% diantaranya memerlukan penyesuaian pola terapi. Variasi gen ACE rs4331, rs1799752, dan rs4343, bersama dengan faktor risiko non-genetik, dapat digunakan sebagai prediktor untuk kejadian hipertensi, COVID-19, dan keparahan COVID-19. Variasi gen dan faktor non-genetik ini dapat dikembangkan menjadi model pengobatan presisi untuk mengevaluasi tingkat risiko dan penanganan individu terhadap hipertensi, COVID-19, dan keparahan COVID-19 di kalangan populasi Palu-Sulawesi Tengah secara translasional. ......Hypertension is the most common comorbidity in COVID-19 sufferers. Risk factors such as genetics, sociodemographics, and initial clinical conditions are thought to influence an individual's susceptibility to hypertension and COVID-19. One of the genes associated with hypertension is the ACE gene. This study examines the ACE gene's genetic variation in summary with the risk of developing hypertension and COVID-19 using the Palu-Central Sulawesi population model. This research is an observational study with a cross-sectional design. Data on non-genetic factors were obtained from medical records and questionnaires. Identification of genetic variations was carried out at 4 locations in the ACE gene, namely rs1799752 (I/D) using the PCR method, rs4331 (A/G), rs4341 (G/C), and rs4343 (G/A) using rhAmp SNP genotyping. Data on genetic and non-genetic factors are then compiled into a translational instrument model. The study involved 136 subjects, and analysis of genetic variations showed that the dominant genotype for rs1799752 was II (50%), rs4331 was GG (51%), rs4341 was GG (100%), and rs4343 was AA (65%). The variant D allele rs1799753, A allele rs4331, and G allele rs4343 showed an association with susceptibility to hypertension, COVID-19, and severity of COVID-19. Regression analysis showed that gender, age, history of hypertension, LDL, uric acid, blood glucose, and genetic variations of the ACE gene were predictors in assessing the level of hypertension risk. Meanwhile, gender, triglycerides, HDL, comorbid hypertension, and genetic variations of the ACE gene are predictors in determining the risk of COVID-19. In contrast, comorbid hypertension, BMI, uric acid, and genetic variations of the ACE gene are predictors in assessing the risk of COVID-19 severity. -19. The translational instrument prediction assessment showed that 31% of the hypertension group were at high risk of experiencing COVID-19, and 46% were at very high risk of experiencing higher severity. The translational instrument prediction assessment for hypertension showed that 22% of subjects had a very high risk, and 23% of them required adjustment of therapy patterns. ACE gene variations rs4331, rs1799752, and rs4343, together with non-genetic risk factors, can be used as predictors for the incidence of hypertension, COVID-19, and severity of COVID-19. These gene variations and non-genetic factors can be developed into a precision medicine model to evaluate the risk level and individual treatment of hypertension, COVID-19, and the severity of COVID-19 among the Palu-Central Sulawesi population in a translational.