This document discusses the potential of oral lumbrokinase (DLBS 1033) as a fibrinolytic drug. It summarizes research showing that DLBS 1033 increases autolytic and fibrinolytic activity, inhibits platelet aggregation, reduces proinflammatory factors, and improves blood flow in clinical studies of ischemic stroke, atherosclerosis, and angina patients. The document concludes that due to its antithrombotic, antiplatelet, and fibrinolytic mechanisms, lumbrokinase presents a challenging opportunity as a fibrinolytic oral drug.
This document discusses the potential of oral lumbrokinase (DLBS 1033) as a fibrinolytic drug. It summarizes research showing that DLBS 1033 increases autolytic and fibrinolytic activity, inhibits platelet aggregation, reduces proinflammatory factors, and improves blood flow in clinical studies of ischemic stroke, atherosclerosis, and angina patients. The document concludes that due to its antithrombotic, antiplatelet, and fibrinolytic mechanisms, lumbrokinase presents a challenging opportunity as a fibrinolytic oral drug.
This document discusses the potential of oral lumbrokinase (DLBS 1033) as a fibrinolytic drug. It summarizes research showing that DLBS 1033 increases autolytic and fibrinolytic activity, inhibits platelet aggregation, reduces proinflammatory factors, and improves blood flow in clinical studies of ischemic stroke, atherosclerosis, and angina patients. The document concludes that due to its antithrombotic, antiplatelet, and fibrinolytic mechanisms, lumbrokinase presents a challenging opportunity as a fibrinolytic oral drug.
This document discusses the potential of oral lumbrokinase (DLBS 1033) as a fibrinolytic drug. It summarizes research showing that DLBS 1033 increases autolytic and fibrinolytic activity, inhibits platelet aggregation, reduces proinflammatory factors, and improves blood flow in clinical studies of ischemic stroke, atherosclerosis, and angina patients. The document concludes that due to its antithrombotic, antiplatelet, and fibrinolytic mechanisms, lumbrokinase presents a challenging opportunity as a fibrinolytic oral drug.
A CHALLANGING OPPORTUNITY Moh Hasan Machfoed Department of Neurology School of Medicine Airlangga University Dr. Soetomo Hospital Surabaya Mobil Phone: 0812-353-8163 E-mail: m-hasan-m@telkom.net 1
Atherothrombosis Perspective 2
Atherothrombosis is the leading cause of death worldwide
1. Vascular Thrombosis Obstruction cant be open automatically Insufficiency of Autolytic
activity 2. Neither Anticoagulant oral nor anti pletelet increase Autolytic activity Different
mechanism 3. Fibrinolytic oral is needed to increase Autolytic activity common sense Lumbrokinase (Fibrinolytic oral) has opportunity for these cases
DLBS 1033: MECHANISME OF ACTION
Fibrinolytic
Stimulating the vascular endothelial cells to secrete
endogenous t-PA
Anticoagulation Antiplatelet
Specific binding to fibrinogen Decrease
concentration of fibrinogen
Decrease the levels of Gmp-140, TXB2 and 5-HT
Inhibiting platelet activation and vasoconstriction
Positive Pleotrophic Effects
In addition, DLBS1033 also has Positive Pleiotropic Effects via down regulate expression of genes related to vascular remodeling: Anti inflammatory activities: (NF-KB, P-Selectin, TNF-, & VCAM-1) Plaque stabilization: MMP9 VSMC inhibition of proliferation & migration: JAK1/STAT1 Kurnia et al, 2011
FIBRINOLYTIC ACTION
Trisina et al, 2011
DLBS 1033 FIBRINOLYTIC ACTIVITY
(FIBRIN DISC METHOD)
Fibrinoliytic activity
0h
1h
3h
6h
> 24 h
Trisina et al, 2011
DLBS 1033: CLOT LYSIS ACTIVITY
Clot lysis activity defined as percentage of destroyed blood clot weight after incubated with samples compared to the initial frozen weight. DLBS1033 yielded in the increased thrombolytic activity compared to control Suhartono et al, 2008
DLBS 1033: ANTI PLATELET AGGREGATION ACTIVITIES
In vitro study using human blood with platelet aggregation activators
(ADP and thrombin). DLBS1033 totally inhibits platelet aggregation at concentration above 60 mg/ml Trisina et al, 2011
Changes in coagulation and t-PA after the treatment
of cerebral infarction with lumbrokinase Case: Acute cerebral infarction (acute ischemic stroke) Onset before treatment around 3 + 1 days
Sample size: n = 51, 47-88 years old
Test group (n = 31) Lumbrokinase po, tid + dextran Control group (n = 20) Dextran
Treatment duration : 28 days
Clinical Hemorheology and Microcirculation 2000; 23: 213 8
Changes in the Plasma Fibrinogen Level after the
treatment of cerebral infarction with lumbrokinase Plasma Fibrinogen Level between Treatment and Control Groups
* p < 0.05 vs week-0
Clinical Hemorheology and Microcirculation 2000; 23: 213 8
Changes in coagulation and t-PA after the treatment
of cerebral infarction with lumbrokinase Plasma t-PA Activity between Treatment and Control Groups
* p < 0.05 vs week-4, **p < 0.01 vs week-1&2
Clinical Hemorheology and Microcirculation 2000; 23: 213 8
Lumbrokinase significantly potentiated the activity of adenylate cyclase, increased the
cAMP level in vivo, remarkably inhibited the rise of rat platelet intracellular Ca2+
Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011
Adhesion Molecules: Anti-inflamation
P-selectin leukocytes recruitment
atherosclerotic plaque formation Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011
VCAM-1 adhesion of lymph, monocy, eosin, basoph
plaque formation Kurnia and Tjandrawinata. Medicinus 24(1):18-24, 2011
CLINICAL USES OF DISOLF
Based on the mechanism of action and pleiotropic effect DISOLF can be given to the cases as follows: 1. Ischemic Stroke 2. Atherosclerosis 3. Acute Limb Ischemia 4. Deep Vein Thrombosis (DVT) 5. Venous Thromboembolism (VTE) 6. Pulmonary Emboli 7. Heart diseases
Double Blind Randomized clinical trial on
Bleeding Profile and Clinical Outcome Ischemic stroke patients Clinical outcome results on 90th day Clinical Outcome Barthel Index Score: - Aspirin - Clopidogrel - DLBS 1033 SSGM : - Aspirin - Clopidogrel - DLBS 1033
Baseline
Day-90
Delta
83,75 75,20 79,21
98,10 91,85 97,79
14,35 16,65 18,58
<0,001 0,001 <0,001
31,30 28,75 29,21
36,15 33,90 35,95
4,85 5,15 6,74
< 0,001 0,002 <0,001
Aspirin, Clopidogrel and DLBS 1033 showed significant statistical difference to
improve clinical outcome on stroke patients, based on Barthel Index Score and SSGM after 90 days of administration. Setyopranoto et al, 2012
Ziyuan, 2009
Zhang et al, 2013
Wang et al, 2013
Policherla et al, 2015
DISOLF affected CIMT Reduction
Open study of DLBS1033 on the progression of CIMT in atheroscrelotic subjects (n = 18): DLBS1033 significantly reduced carotid intima-media thickness ( CIMT )
Gunawan H, 2012. The effect of DLBS1033 on the progression of CIMT in subjects with atherosclerosis. Jakarta
The Effect of Disolf (DLBS 1033) in
Peripheral Arterial Disease (PAD) Randomized Clinical Controlled Trial, 20 number of subject, for 2 weeks evaluation Measurement : ABI ( Ankle Brachial Index ) Dose: DISOLF 3 x 1 Versus Placebo A low ABI indicate narrowing or blockage of the arteries in the legs, increasing the risk of circulatory problems
Ndraha S et al. Depart of Intern Med UKRIDA
Christian University, Jakarta-indonesia 2013
34
Results after 2 weeks
CONCLUSION: DBLS 1033 showed to improve ABI in patients
with intermittent claudication.
Oral Lumbrokinase in Stable Angina Pectoris
36
Improved Myocardial Perfusion in Stable
Angina Pectoris by Oral Lumbrokinase: A Pilot Study M. Kasim, A. A. Kiat, M. S. Rohman, Y. Hanifah, and H. Kiat, Improved myocardial perfusion in stable angina pectoris by oral lumbrokinase: a pilot study, Journal of Alternative and Complementary Medicine, vol. 15, no. 5, pp. 539544, 2009.
10 stable angina pectoris patients were randomly
selected from proved Coronary artery disease (CAD) population in National Cardiovascular Center Harapan Kita. Diagnosis of CAD confirmed by MSCT or coronary angiography examination.
MRI PERFUSION IMAGING (MPI) Improved Perfusion
after 1 month in lumbrokinase in SAP (70%)
CONCLUSION: Lumbrokinase reduction in the degree and
extent of inducible myocardial ischemia without bleeding complication
Dose: Adults 1-2 tablets 3 times a day, - 1 hour before meals. Warning and attention: Only used on medical advice During the use of this product, please consult the doctor on
a regular basis
CONCLUSION With the action mechanisms as antipletelet agregation, antithrombosis, fibrinogenolytic and thrombolytic, Lumbrokinase (DLBS 1033) can be used as a Challenging Fibrinolytic Drug
