karya tulis ilmiah pengaruh gel ekstrak daun...

20
i KARYA TULIS ILMIAH PENGARUH GEL EKSTRAK DAUN KENIKIR (COSMOS CAUDATUS H.B.K) TERHADAP PENYEMBUHAN LUKA EKSISI TIKUS PUTIH JANTAN (RATTUS NOVERGICUS STRAIN WISTAR) Oleh: MONICA ROSELLINI 201310330311162 UNIVERSITAS MUHAMMADIYAH MALANG FAKULTAS KEDOKTERAN 2017

Upload: others

Post on 22-Oct-2020

8 views

Category:

Documents


0 download

TRANSCRIPT

  • i

    KARYA TULIS ILMIAH

    PENGARUH GEL EKSTRAK DAUN KENIKIR (COSMOS CAUDATUS

    H.B.K) TERHADAP PENYEMBUHAN LUKA EKSISI TIKUS PUTIH

    JANTAN (RATTUS NOVERGICUS STRAIN WISTAR)

    Oleh:

    MONICA ROSELLINI

    201310330311162

    UNIVERSITAS MUHAMMADIYAH MALANG

    FAKULTAS KEDOKTERAN

    2017

  • ii

    PENGARUH GEL EKSTRAK DAUN KENIKIR (COSMOS CAUDATUS

    H.B.K) TERHADAP PENYEMBUHAN LUKA EKSISI TIKUS PUTIH

    JANTAN (RATTUS NOVERGICUS STRAIN WISTAR)

    KARYA TULIS AKHIR

    Diajukan kepada

    Universitas Muhammadiyah Malang

    untuk Memenuhi Salah Satu Persyaratan

    dalam Menyelesaikan Program Sarjana

    Fakultas Kedokteran

    Oleh:

    Monica Rosellini

    201310330311162

    UNIVERSITAS MUHAMMADIYAH MALANG

    FAKULTAS KEDOKTERAN

    2017

  • iii

  • iv

    PERNYATAAN ORISINALITAS

    Karya tulis akhir ini adalah karya saya sendiri, dan semua sumber baik yang

    dikutip maupun dirujuk telah saya nyatakan dengan benar.

    Nama : Monica Rosellini

    NIM : 201310330311162

    Malang, 27 Juli 2017

    Penulis

  • v

  • vi

    KATA PENGANTAR

    Assalamu’alaikum Warahmatullah Wabarakatuh

    Puji syukur kehadirat Allah SWT Yang Maha Pengasih lagi Maha

    Penyayang dan atas karunia-Nya, penulisan tugas akhir ini dapat selesai dengan

    baik. Shalawat serta salam selalu tercurahkan kepada Rasulullah Muhammad

    shalallahu alaihi wasallam, keluarganya dan para sahabatnya yang telah berjasa

    membawa syiar dakwah Islam ke seluruh dunia.

    Penelitian tugas akhir ini berjudul “PENGARUH GEL EKSTRAK DAUN

    KENIKIR (COSMOS CAUDATUS H.B.K) TERHADAP PENYEMBUHAN

    LUKA EKSISI TIKUS PUTIH JANTAN (RATTUS NOVERGICUS STRAIN

    WISTAR)”. Tugas akhir ini diajukan untuk memenuhi persyaratan Pendidikan

    Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang.

    Penulis menyadari tugas akhir ini masih jauh dari kata sempurna, oleh

    karena itu, penulis sangat mengharapkan saran dan masukan yang membangun.

    Semoga karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi

    semua pihak.

    Wassalamu’alaikum Warahmatullah Wabarakatuh

    Malang, 22 Mei 2017

    Penulis

  • vii

    UCAPAN TERIMA KASIH

    Allah SWT yang telah memberikan rahmat, karunia, kesehatan, dan

    lindungan sehingga penulis dapat menyelesaikan tugas akhir ini.

    dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran

    Universitas Muhammadiyah Malang atas ilmu dan bimbingannya selama di

    Fakultas Kedokteran UMM.

    dr. Moch. Ma’roef, Sp.OG, selaku Pembantu Dekan I Fakultas

    Kedokteran UMM atas kesediaan waktu, kesabaran dalam membimbing,

    dan penyampaian ilmu yang sangat bermanfaat bagi masa depan para

    mahasiswa FK UMM.

    dr. Rahayu, Sp.S, selaku Pembantu dekan II Fakultas Kedokteran

    UMM yang senantiasa bersabar dalam membimbing dan mengajarkan

    ilmunya kepada kami.

    dr. Iwan Sys Indrawanto, Sp.KJ, selaku Pembantu Dekan III, yang

    penuh semangat dalam menyampaikan ilmu dan motivasi yang membangun

    semangat kami selama menjalani pendidikan di Fakultas Kedokteran.

    dr. Moch. Aleq Sander, M.Kes., Sp.B., FinaCS selaku pembimbing 1,

    atas kesabaran, kebaikan hati, serta kesediaan dalam meluangkan waktu

    dalam membimbing hingga dapat menyelesaikan penelitian ini dengan baik.

    dr. Thontowi Djauhari N.S, M. Kes, selaku pembimbing 2, atas

    kesabaran, kebaikan hati, serta kesediaan dalam meluangkan waktu dalam

    membimbing penulis hingga dapat menyelesaikan penelitian ini dengan

    baik.

  • viii

    dr. Annisa’ Hasanah, M.Si., selaku penguji tugas akhir ini, atas segala

    nasihat, masukan, dan arahan yang sangat bermanfaat dalam proses

    penyelesaian tugas akhir ini dan kesediaan waktu beliau, sehingga tugas

    akhir ini dapat diselesaikan dengan baik.

    Kedua orang tua saya, yang tidak pernah lelah mendoakan, berikhtiar

    dalam tirakatnya untuk saya, memberikan dukungan moril dan materiil, dan

    senantiasa hadir dalam setiap detik perjuangan hidup saya.

    Kakak saya, dr. Syailendra Fii Sulaiman, dan seluruh keluarga yang

    senantiasa memberikan dukungan tak terputus kepada saya.

    Sahabat-sahabat tercinta, Inas Khoirunnisa, Nungki Samahah, Amirah

    Muhammad Abdullah, Elda Cintya, Mira Wiji Lestari, Galih Bayu Prakoso,

    Umar Thalib, dan Azmiyah Febri yang telah sangat banyak membantu

    proses penyelesaian tugas akhir ini hingga tidak dapat dijelaskan satu per

    satu.

    Seluruh staf TU dan laboran, Pak Yono, Bu Endah, Mba Citra, Mba

    Nuke, Mas Miftah, Mas Nyono dan Pak Joko yang bersedia membantu

    setiap tahapan proses penelitian hingga penyelesaian tugas akhir ini.

    Sejawat FK UMM angkatan 2013, Gluteus Maximus, bantuan dan

    kerjasamanya. Semoga kelak dapat menjadi dokter-dokter profesional yang

    barokah, sukses dunia akhirat, dan senantiasa dalam ketaatan kepada Allah

    SWT.

    Semua pihak yang terlibat secara langsung maupun tidak langsung,

    terima kasih atas bantuan dan dukungannya.

  • ix

    DAFTAR ISI

    Halaman

    HALAMAN JUDUL ........................................................................................... i

    KATA PENGANTAR ........................................................................................ ii

    UCAPAN TERIMAKASIH .............................................................................. iii

    ABSTRAK ....................................................................................................... viii

    ABSTRACT ........................................................................................................ ix

    DAFTAR ISI ........................................................................................................ x

    DAFTAR TABEL.............................................................................................. xii

    DAFTAR GAMBAR ........................................................................................ xiii

    DAFTAR SINGKATAN .................................................................................. xiv

    BAB 1 PENDAHULUAN .................................................................................. 1

    1.1 Latar Belakang ................................................................................... 1 1.2 Rumusan Masalah .............................................................................. 3 1.3 Tujuan Penelitian ................................................................................ 3

    1.3.1 Tujuan Umum ........................................................................... 3

    1.3.2 Tujuan Khusus .......................................................................... 3

    1.4 Manfaat Penelitian .............................................................................. 3

    1.4.1 Manfaat Akademik .................................................................... 3

    1.4.2 Manfaat Klinis ........................................................................... 3

    1.4.3 Manfaat Masyarakat .................................................................. 4

    BAB 2 TINJAUAN PUSTAKA .......................................................................... 5

    2.1 Kulit.................................................................................................... 5 2.1.1 Anatomi Kulit Manusia ............................................................. 5 2.1.1.1 Epidermis ...................................................................... 5

    2.1.1.2 Dermis ........................................................................... 7

    2.1.1.3 Hipodermis atau Subkutis .............................................. 7

    2.1.2 Fungsi Kulit ............................................................................... 8

    2.1.3 Anatomi Kulit Tikus ............................................................... 11

    2.2 Luka.................................................................................................. 13

    2.2.1 Pembagian Jenis Luka ............................................................. 13

    2.2.2 Penyembuhan Luka ................................................................. 15

    2.2.3 Faktor Yang Mempengaruhi Penyembuhan Luka .................. 18

    2.3 Kenikir.............................................................................................. 19

    2.3.1 Klasifikasi Kenikir .................................................................. 19

    2.3.2 Morfologi Kenikir ................................................................... 20

    2.3.3 Kandungan Daun Kenikir ....................................................... 21

    2.3.4 Quercetin dalam Kenikir ......................................................... 21

    2.3.4.1 Pengaruh Quercetin Sebagai Antioksidan .................. 22

    2.3.4.2 Pengaruh Quercetin Terhadap Penyembuhan Luka .... 23

    2.4 Sediaan Gel ...................................................................................... 24

    2.4.1 HPMC ..................................................................................... 25

    BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN .. 26

    3.1 Kerangka Konseptual Penelitian ...................................................... 26

    3.2 Hipotesis Penelitian .......................................................................... 27

    BAB 4 METODE PENELITIAN ..................................................................... 28

  • x

    4.1 Jenis dan Rancangan Penelitian ....................................................... 28

    4.2 Lokasi dan Waktu Penelitian ........................................................... 28

    4.3 Populasi dan Sampel ........................................................................ 28

    4.3.1 Populasi ................................................................................... 28

    4.3.2 Sampel ..................................................................................... 28

    4.3.3 Teknik Pengambilan Sampel ................................................... 28

    4.3.4 Estimasi Besar Sampel ............................................................ 28

    4.4 Karakteristik Sampel Penelitian ........................................................ 30

    4.5 Variabel Penelitian ............................................................................ 30

    4.6 Definisi Operasional .......................................................................... 31

    4.7 Alat dan Bahan penelitian ................................................................. 32

    4.7.1 Alat ........................................................................................... 32

    4.7.2 Bahan ........................................................................................ 34

    4.8 Prosedur Penelitian............................................................................ 35

    4.9 Alur Penelitian .................................................................................. 41

    4.10 Analisis Data ................................................................................... 41

    BAB 5 HASIL PENELITIAN DAN ANALISIS DATA ................................ 43

    5.1 Hasil Penelitian ................................................................................ 43

    5.2 Analisis Data .................................................................................... 45

    BAB 6 PEMBAHASAN .................................................................................... 47

    BAB 7 KESIMPULAN DAN SARAN ............................................................. 53

    7.1 Kesimpulan ...................................................................................... 53

    7.2 Saran ................................................................................................. 53

    DAFTAR PUSTAKA ........................................................................................ 54

    LAMPIRAN ....................................................................................................... 57

  • xi

    DAFTAR TABEL

    Tabel

    Halaman

    2.1 Perbandingan Anatomi Kulit Tikus dan

    Manusia.……...……….…………….11

    2.2 Perbandingan Kandungan Tumbuhan

    Kenikir….……………….…………….20

    4.1 Formulasi

    Gel.....................................................................................................37

    4.2 Formulasi Basis Gel

    ..........................................................................................38

    5.1 Data Luas Luka Eksisi Pada Tikus

    Putih...........................................................43

    5.2 Uji Normalitas Shapiro-

    Wilk…………..............................................................46

    5.3 Uji

    Homogenitas.................................................................................................46

    5.3 Uji Analisis Statistik

    ANOVA...........................................................................47

    5.3 Uji Post Hoc

    Bonferroni.....................................................................................47

  • xii

    DAFTAR GAMBAR

    Gambar

    Halaman

    2.1 Anatomi Kulit

    Manusia………………………………………………………..….8

    2.2 Histologi Kulit

    Tikus………………………………...……………….……....….12

    2.3 Jenis

    Luka……………………...…………………………………………......….14

    2.4 Mekanisme Penyembuhan

    Luka........................................................................... 18

    2.5 Daun Kenikir (Cosmos Caudatus

    H.B.K).............................................................20

    2.5 Struktur

    Quercetin.................................................................................................22

    3.1 Kerangka Konseptual Peneliti..............................................................................

    26

    4.1 Biopsy Punch Medax Epitheasy diameter 5

    mm...................................................33

    4.2 Transparent Dressing

    Tegaderm...........................................................................34

    4.3 Alur

    Penelitian.......................................................................................................41

  • xiii

    5.1 Luas Luka Eksisi Tikus Putih Jantan hari ke

    3......................................................44

    5.2 Luas Luka Eksisi Tikus Putih Jantan hari ke

    6......................................................44

    5.3 Luas Luka Eksisi Tikus Putih Jantan hari ke

    9......................................................44

    5.4 Luas Luka Eksisi Tikus Putih Jantan hari ke

    12....................................................45

    5.5 Luas Luka Eksisi Tikus Putih Jantan hari ke

    15....................................................45

    5.6 Luas Luka Eksisi Tikus Putih Jantan hari ke

    18....................................................45

    5.7 Luas Luka Eksisi Tikus Putih Jantan hari ke

    21....................................................45

    DAFTAR SINGKATAN

    CMC : Carboxymethyl cellulose

    COX : Cyclooxigenase

    EGF : Epidermal Growth Factor

    HPMC : Hydroxypropil Methylcellulose

  • xiv

    IGF : Insulin-like Growth Factor

    LOX : Lypooxigenase

    MMPs : Matrix Metalloproteinases

    PDGF : Plateled-derived Growth Factor

    PMN : Polymorphonuclear

    ROS : Reactive Oxygen Species

    TGF-β : Transforming Growth Factor Beta

    TGF-β1 : Transforming Growth Factor Beta 1

    VEGF : Vascular Endothelial Cell Growth Factor

  • xv

    DAFTAR PUSTAKA

    Allen, L.V., Ansel, H., 2014, Ansel's Pharmaceutical Dosage Forms and Drug

    Delivery Systems, Chapter 10, pp.316-324, Wolters Kluwer, Georgia.

    Australian Tropical Rainforest Plants, 2010, keys.trin.org.au [homepage on the Internet]

    [online], (diunduh 31 Juli 2017), tersedia dari: http://keys.trin.org.au/key-

    server/data/0e0f0504-0103-430d-8004

    060d07080d04/media/Html/taxon/Cosmos_caudatus.htm

    Bunawan, H, Baharum, S, N. & Bunawan S, N, et. al, 2014, ‘Cosmos caudatus

    kunth: a traditional medicinal herb’, J. Pharmacol, 8(3): pp. 420-426

    [online], (diunduh 24 Januari 2017), tersedia dari:

    https://idosi.org/gjp/8(3)14/17.pdf

    Bioinformatics Research Group (BIRG) phyknome.htm [homepage on the

    Internet] Universiti Teknologi Malaysia, 2013, [online], (diunduh 27

    Oktober 2016), tersedia dari:

    http://mapping.fbb.utm.my/phyknome/taxonomy/term/7258

    Cancer Chemoprevention Research Center UGM, 2010, CCRC, Jogjakarta,

    [online], (diunduh 24 Januari 2017), tersedia dari:

    http://ccrc.farmasi.ugm.ac.id/en/?page_id=101

    Cheng, S.H., Barakatun-Nisak, M. Y. & Anthony, J., et. al, 2015, ‘Potential

    medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review’,

    Journal of Research Medical Science, pp 1000-1006 [online], (diunduh

    24 Januari 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746859/

    Chotiah, S, DK Trisharyanti, I & Munawaroh, R, 2015, Ekstrak Etanol Daun

    Kenikir (Cosmos caudatus. (L.) H.B.K. (L.) H.B.K) Sebagai Antibakteri

    Terhadap Streptococcus mutans dan Staphylococcus epidermidis,

    Naskah Publikasi UMS, Universitas Muhammadiyah Surakarta,

    Surakarta [online], (diunduh 24 Januari 2017), tersedia dari:

    eprints.ums.ac.id/36347/1/NASKAH%20PUBLIKASI.pdf

    Dabiri, G., Damstetter, E., Philips, T., 2016, ‘Choosing a Wound Dressing Based

    on Common Wound Characteristics’, Advances in Wound Care, vol. 5,

    http://keys.trin.org.au/key-server/data/0e0f0504-0103-430d-8004%20060d07080d04/media/Html/taxon/Cosmos_caudatus.htmhttp://keys.trin.org.au/key-server/data/0e0f0504-0103-430d-8004%20060d07080d04/media/Html/taxon/Cosmos_caudatus.htmhttp://keys.trin.org.au/key-server/data/0e0f0504-0103-430d-8004%20060d07080d04/media/Html/taxon/Cosmos_caudatus.htmhttps://idosi.org/gjp/8(3)14/17.pdfhttp://mapping.fbb.utm.my/phyknome/taxonomy/term/7258http://ccrc.farmasi.ugm.ac.id/en/?page_id=101https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746859/

  • xvi

    no.1 [online], (diunduh 5 mei 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717498/

    David, Arkeman, H., 2008, ‘Evaluation Of The Oral Toxicity Of Formaldehyde In

    Rats’, Universa Medicina, Vol 27, pp 107, [online], (diunduh 5 mei

    2017), tersedia dari: www.univmed.org/wp-

    content/uploads/2011/02/david1.pdf

    Dimaio, V., & Dana, S., 2006. Handbook of Forensic Pathology, chapter 7, pp.

    116-117, CRC press, Florida.

    Dorsett-Martin, W., 2004, ‘Rat Models of Skin Wound Healing’, wound repair

    and regeneration : The International Journal of Tissue Repair and

    Regeneration, Volume 12, Issue 6, November 2004, Pages 591–599,

    [online], (diunduh 5 mei 2017), tersedia dari:

    http://onlinelibrary.wiley.com/doi/10.1111/j.1067-

    1927.2004.12601.x/abstract;jsessionid=D9CCF579BD1FF713C87FC96

    4DA297EFB.f04t03

    Dragicevic, N. & Maibach, H.L., 2015, Percutaneous Penetration Enhancers

    Chemical Methods in Penetration Enhancement, chapter 11, pp. 154-

    155, Springer, Berlin.

    Eroschenko, V.P. 2012, Atlas Histologi diFiore ed. 11, chapter 10, pp. 223-227,

    EGC, Jakarta.

    Fiorani M, Guidarelli A. & Blasa M, et. al, 2009, ‘Mitochondria accumulate large

    amounts of quercetin: prevention of mitochondrial damage and release

    upon oxidation of the extramitochondrial fraction of the flavonoid’,

    Journal of Nutritional Biochemistry. pp. 397-404, [online], (diunduh 24

    Januari 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pubmed/19278846

    Gopalakrishnan A, Ram M. & Kumawat S, et. al, 2015, ‘Quercetin Accelerated

    Cutaneous Wound Healing in Rats by Increasing Levels of VEGF and

    TGF-β1’, Indian Journal of Experimental Biology, vol. 54, pp 187-195,

    [online], (diunduh 24 Januari 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pubmed/27145632

    Goweini, M.F., & El Din, N.M., 2005, ‘Effect of Quercetin n Excessive Dermal

    Scarring’, Egyptian Dermatology Online Journal, vol.1, no.1, [online],

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717498/http://www.univmed.org/wp-content/uploads/2011/02/david1.pdfhttp://www.univmed.org/wp-content/uploads/2011/02/david1.pdfhttp://onlinelibrary.wiley.com/doi/10.1111/j.1067-1927.2004.12601.x/abstract;jsessionid=D9CCF579BD1FF713C87FC964DA297EFB.f04t03http://onlinelibrary.wiley.com/doi/10.1111/j.1067-1927.2004.12601.x/abstract;jsessionid=D9CCF579BD1FF713C87FC964DA297EFB.f04t03http://onlinelibrary.wiley.com/doi/10.1111/j.1067-1927.2004.12601.x/abstract;jsessionid=D9CCF579BD1FF713C87FC964DA297EFB.f04t03https://www.ncbi.nlm.nih.gov/pubmed/19278846https://www.ncbi.nlm.nih.gov/pubmed/27145632

  • xvii

    (diunduh 24 Januari 2017), tersedia dari:

    http://www.edoj.org.eg/vol001/00101/05/5.html

    Hanani, E., 2015, Analisis Fitokimia, Bab 2, halaman 10-16, EGC, Jakarta.

    Havill, Sonya., 2001, ‘Excision of Biopsy Skin Lesion’, Dermnet New Zealand,

    [online], (diunduh 31 Juli 2017), tersedia dari:

    https://www.dermnetnz.org/topics/excision-of-skin-lesions/

    Hutchinson, J., 2014, ‘Phases of Wound Healing’, Wound Essentials Clinimed,

    [online], (diunduh 31 Juli 2017), tersedia dari:

    http://www.clinimed.co.uk/Wound-Care/Education/Wound-

    Essentials/Phases-of-Wound-Healing.aspx

    Jones, J, 2013, ‘Winter’s concept of moist wound healing: a review of the

    evidence and impact on clinical practice’, Journal of Wound Care, vol.

    14, no.4, pp. 273-276, [online], (diunduh 24 Januari 2017), tersedia dari:

    http://www.magonlinelibrary.com/doi/abs/10.12968/jowc.2005.14.6.267

    94

    Kampfer, H. & Frank, S., 2008, ‘Excisional Wound Healing’, Wound Healing :

    Methods and Protocol, vol. 78, pp 3-15, [online], (diunduh 3 Mei 2017),

    tersedia dari: http://link.springer.com/protocol/10.1385%2F1-59259-

    332-1%3A003

    Kelly, G.S. 2013, ‘Quercetin’, Alternative Medicine Review, vol.16, no.2,

    [online], (diunduh 24 Januari 2017), tersedia dari:

    www.altmedrev.com/publications/16/2/172.pdf

    Khan, A.W., Kotta, S. & Ansari, S.H., et. al, 2013, 'Formation developement,

    optimization and evaluation of aloe vera gel for wound healing',

    Pharmacogn Mag, ed.9, [online], (diunduh 24 Januari 2017), tersedia

    dari: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798142/

    Krinke, G.J., 2000, The Laboratory Rat, Part 5, Chapter 15, halaman 308,

    Elsevier, London.

    Liliwirianis, N., Musa, N.L. & Zain, W.Z., et. al, 2011, ‘Preliminary Studies on

    Phytochemical Screening of Ulam and Fruit from Malaysia’, E-Journal

    of Chemistry, [online], (diunduh 3 Mei 2017), tersedia dari:

    http://www.edoj.org.eg/vol001/00101/05/5.htmlhttp://www.magonlinelibrary.com/doi/abs/10.12968/jowc.2005.14.6.26794http://www.magonlinelibrary.com/doi/abs/10.12968/jowc.2005.14.6.26794http://link.springer.com/protocol/10.1385%2F1-59259-332-1%3A003http://link.springer.com/protocol/10.1385%2F1-59259-332-1%3A003http://www.altmedrev.com/publications/16/2/172.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798142/

  • xviii

    https://www.researchgate.net/publication/258379531_Premilinary_Studi

    es_on_Phytochemical_Screening_of_Ulam_and_Fruit_from_Malaysia

    Menteri Kesehatan Republik Indonesia, 2009, Keputusan Menteri Kesehatan

    Republik Indonesia Nomor. 261/MENKES/SK/IV/2009 tentang

    Farmakope Herbal Indonesia, [online], (diunduh 24 Januari 2017),

    tersedia dari:

    http://perpustakaan.depkes.go.id:8180/handle/123456789/3270

    Menteri Kesehatan Republik Indonesia, 2013, Farmakope Indonesia V, Bab 8,

    halaman 42, Kemenkes, Jakarta.

    Madiyono, B, Moeslichan Mz, S. & Sastroasmoro, S, et. al, 2014, Dasar-dasar

    Metodologi Penelitian Klinis, Edisi 5, bab 5, halaman 352-386, Sagung

    Seto, Jakarta,

    Martin, W.A., & Wysocki, A.B., 2008, ‘Rat Models of Skin Wound Healing’,

    Sourcebook of Models for Biomedical Research, pp. 631-638, [online],

    (diunduh 24 Januari 2017), tersedia dari:

    http://link.springer.com/chapter/10.1007%2F978-1-59745-285-4_65

    Medscape. com [homepage on the internet ] WebMD LLC, 2001 [cited 27

    October 2016], tersedia dari:

    http://www.medscape.com/viewarticle/407568_2

    National Health Care Statistics, 2008, National Hospital Ambulatory Medical

    Care Survey: 2006 emergency department summary, [online], (diunduh

    4 Mei 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pubmed/18958996

    Perdanakusuma, D.S. 2007, ‘Anatomi dan Fisiologi Kulit dan Penyembuhan

    Luka’, From Caring to Curing, Pause Before You Use Gauze, [online],

    (diunduh 24 Januari 2017), tersedia dari:

    https://scholar.google.co.id/citations?user=RdDXiPEAAAAJ&hl=en

    Quinn, M., Sheskey, P.J. & Rowe, R.C., 2009, Handbook of Pharmaceutical

    Excipients, 6th

    Edition, pp. 326-329, RPS Publishing, Washington.

    https://www.researchgate.net/publication/258379531_Premilinary_Studies_on_Phytochemical_Screening_of_Ulam_and_Fruit_from_Malaysiahttps://www.researchgate.net/publication/258379531_Premilinary_Studies_on_Phytochemical_Screening_of_Ulam_and_Fruit_from_Malaysiahttp://perpustakaan.depkes.go.id:8180/handle/123456789/3270http://link.springer.com/chapter/10.1007%2F978-1-59745-285-4_65http://www.medscape.com/viewarticle/407568_2https://www.ncbi.nlm.nih.gov/pubmed/18958996https://scholar.google.co.id/citations?user=RdDXiPEAAAAJ&hl=en

  • xix

    Rutgers.edu [homepage on the internet] Rutgers The State University of New

    Jersey, 2017 [cited 6 Februari 2017] , tersedia dari:

    http://www.rci.rutgers.edu/~uzwiak/AnatPhys/APFallLect7.html

    Sen, C.K., Gordillo, G.M. & Roy, S., et. al, 2009, ‘Human Skin Wounds : A major

    and snowballing Threat to Public Health and the Economy’, Wound

    Repair Regen, [online], (diunduh 3 Mei 2017), tersedia dari:

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2810192/

    Suriadi, 2004, Penyembuhan Luka edisi 1, Bab 5, halaman 89-90, Sagung Seto,

    Jakarta.

    Sundberg, J.P., Nanney, L.B. & Fleckman, et. al, 2013, ‘Skin and Adnexa’,

    Comparative Anatomy & Histology of Human & Rats, chapter 23, pp

    433-448, [online], (diunduh 3 Mei 2017), tersedia dari:

    http://www.sciencedirect.com/science/book/9780123813619

    Suryo, J., 2009. Rahasia Herbal, Bab 1, halaman 15-18, Mizan, Jakarta.

    Srinivas, C. & Sekar, C. 2012. Textbook on Cutaneous and Aesthetic Surgery,

    chapter 5, pp.62-66, Jaypee Brothers Medical Publisher, London.

    Tortora, G.J. & Derrickson, B.H. 2009, Principles of Anatomy & Physiology 12th

    ed, chapter 5, pp. 148-153, John Wiley & Sons, Asia.

    Waji, R.A. & Sugrani, A, 2009, Flavonoid (Quercetin), Msi, Universitas

    Hasanuddin, Makassar, [online], (diunduh 3 Mei 2017), tersedia dari :

    https://pasche08.files.wordpress.com/2009/05/copy-of-copy-of-makalah-

    quercetin-2003.pdf

    Wang, X., Ge, J. & Tredget, E.E., et. al, 2013, ‘The Mouse Excisional Wound

    Splinting Model, Including Application for Stem Cell Transplantation’,

    Nature Protocols, vol.8, no.2, pp.302-309, [online], (diunduh 13 Januari

    2017), tersedia dari: http://www.nature.com/nprot/journal/v8/n2/full/nprot.2013.002.html

    Weller, R., Hunter, H. & Mann, M. 2015, Clinical Dermatology 5th

    ed., chapter 2,

    pp. 7-17, John Wiley & Sons, West Sussex.

    http://www.rci.rutgers.edu/~uzwiak/AnatPhys/APFallLect7.htmlhttp://www.sciencedirect.com/science/book/9780123813619https://pasche08.files.wordpress.com/2009/05/copy-of-copy-of-makalah-quercetin-2003.pdfhttps://pasche08.files.wordpress.com/2009/05/copy-of-copy-of-makalah-quercetin-2003.pdfhttp://www.nature.com/nprot/journal/v8/n2/full/nprot.2013.002.html

  • xx

    World Alliance for Wound and Lymphedema Care, 2013, ‘Chronic Wounds and

    Lymphoedema: Neglected areas of public health’, [online], (diunduh 3 Mei 2017),

    tersedia dari: http://wawlc.org/about-wawlc/background.html