TENSIDYSS. Blood pressure regulator. Marine Ingredients developer for high health benefits
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1 Marine Ingredients developer for high health benefits TENSIDYSS Blood pressure regulator MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
2 CONTENTS PROCESS OF BY PRODUCTS UPGRADING TENSIDYSS COMPOSITION ASSESSMENT OF ANTI HYPERTENSIVE EFFECTS - MECHANISMS OF HYPERTENSION AND REGULATION - IN VIVO STUDIES : RAT PHYSIOLOGICAL STUDY AND CLINICAL STUDY SAFETY EVALUATION TENSIDYSS CHARACTERISTICS CONCLUSION
3 Marine Ingredients developer for high health benefits PROCESS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
4 UPGRADING BY-PRODUCTS MACKEREL FLESH CONTROLLED ENZYMATIC HYDROLYSIS CENTRIFUGATION FILTRATION CONCENTRATION DRYING GRINDING TENSIDYSS
5 Marine Ingredients developer for high health benefits COMPOSITION MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
6 COMPOSITION TENSIDYSS = hydrolysate derived from mackerel proteins Glutamic acid 13.50% Aspartic acid 9.00% Lysine 8.50% Leucine 8.00% Alanine 7.20% Glycine 7.00% Proline 5.50% Valine 5.20% Arginine 4.50% Threonine 4.50% Isoleucine 4.30% Serine 4.00% Phenylalanine 4.00% Histidine 3.00% Tyrosine 3.00% Methionine 2.50% Tryptophan 0.80% Cysteine 0.75% Peptides : Daltons
7 Marine Ingredients developer for high health benefits ASSESSMENT OF ANTI HYPERTENSIVE EFFECTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
8 MECHANISMS OF HYPERTENSION Renin-angiotensin system Angiotensinogen Angiotensin I Angiotensin II + Renin Angiotensin I Conversion Enzyme Bradykine (ACE) (vasodilatator) Vasoconstriction Blood Pressure
9 REGULATION OF HYPERTENSION Renin-angiotensin system Angiotensinogen ACE inhibitor Renin Angiotensin I Angiotensin II - ACE + Bradykine (vasodilatator) - Vasoconstriction + - Blood Pressure
10 ACE inhibitors Drug (chemical substance) : Captopril Several natural substances - prevent the conversion of angiotensine I to angiotensine II. - measure of blood pressure regulators activity = IC 50 (concentration of ACE inhibitor required to inhibit 50% of the ACE activity IC 50 of Captopril = 0,62 ng/ml)
11 Natural products present in foods with an blood pression regulator activity Peptides from: - fishes (sardines, bonites, hake) by Matsui et al., Jujita et al., Byun et al. - milk by IMPLVO et al. - maize by Suh & Whang
12 Peptides with a blood pression regulator activity Peptidic sequence Source Peptidic sequence Source LKP Dried bonito KVLAGM Sardine IKP Dried bonito HQAAGW Sardine IY Dried bonito VKAGF Sardine LKPMN Dried bonito LKVGVKQY Sardine IWH Dried bonito LKL Sardine IWHHT Dried bonito YALPHA Squid GHF Bonito bowels GYALPHA Bonito bowels
13 PRECLINICAL STUDY: RAT PHYSIOLOGICAL STUDY Study N 1 Iroyuki Fujita et al. LKPNM: a prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology 44 (1999) Experience: comparison of Kasuobushi Oligopeptide (KO or LKPNM) antihypertensive activity with Captopril. Protocol: - 30 Spontaneously Hypertensive Rats= SHR (Systolic blood pressure > 130 mm Hg and diastolic blood pressure> 85 mm Hg) - Oral administration of 2 different substances at different dosages (4, 8 and 15mg/kg for the peptide and 1.25,2.5 and 5mg/kg for Captopril) - Measurement of rats blood pressure (mmhg)
14 PRECLINICAL STUDY: RAT PHYSIOLOGICAL STUDY Results: Fig.1 Antihypertensive activity of LKPNM and Captopril after oral administration in SHR - Anti hypertensive effect of both substances in quasi simultaneous time : 2 h after administration and for 5h. LKPNM has practically the same activity than Captopril. Remark : Captopril (chemical substance) is efficiant at low doses, unlike natural substances.
15 PRECLINICAL STUDY: RAT PHYSIOLOGICAL STUDY Study N 2 Won-Kyo Jung et al. Angiotensin I-converting enzyme inhibitory peptide from yellofih sole (limanda aspera) frame protein and its antihypertensive effect in spontaneously hypertensive rats. Food Chemistry 94 (2006) Experience: comparison of yellofih sole peptide (YFP) antihypertensive effect with Captopril Protocol: - Study on spontaneously hypertensive rats - Oral administration of 2 hypotensive substances - Measurement of blood pressure (mmhg) HIGHER CS CONTENT COMPARED TO CARTILAGE POWDER
16 Results: PRECLINICAL STUDY: RAT PHYSIOLOGICAL STUDY -The activity is maintained during 9h after ingestion. - Peptide effect very similar to Captopril.
17 CLINICAL STUDY Study N 3 Kawasaki et al. Antihypertensive effect of Valyl-Tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects. Journal of Human Hypertension (2000) 14, Protocol: - VY Group receives sardine peptide. - Placebo Group. - Study during 11 weeks (measurement of blood pressure every week).
18 CLINICAL STUDY Results: Measurement of systolic (SBP) and diastolic (DBP) blood pressure in both groups. - Placebo Group : constant pressions - VY Group : significant lowering just after sardine peptide ingestion - No side effects
19 Marine Ingredients developer for high health benefits SAFETY EVALUATION MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
20 SAFETY EVALUATION Study N 4 Kawasaki et al. Antihypertensive effect and safety evaluation of vegetable drink derived from sardine protein hydrolysates on mildly hypertensive, high-normal and normal blood pressure subjects. Journal of Human Hypertension (2000) 14, Test N 1: Peptides effects on normotensive subjects Protocol: - 63 subjects (mildly hypertensive and normotensive subjects) separated in 2 groups : the test group and the control group - Test group: 195g of vegetable drink with 0,5g of sardine peptides once a day for 13 weeks. - Control group : same protocol with a drink without sardine peptides. Results: No blood pressure changes in normotensive subjects, no adverse effects.
21 SAFETY EVALUATION Test N 2: Effect of an excessive ingestion of peptides on hypertensive, mildly hypertensive and normotensive subjects. Protocol: - 25 subjects separated in 2 groups : the test group and the control group - Test group : receives 3 times the amount of test N 1, that is to say 585g of vegetable drink (1,5g of sardine peptides) once a day for 14 days. - Control group: same protocol with a drink without sardine peptides. Results: - We notice a normal lowering of blood pressure in subjects with hypertension and with mild hypertension, without adverse effects. - No lowering is noticed in normotensive subjects.
22 Marine Ingredients developer for high health benefits TENSIDYSS CHARACTERISTICS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
23 %ACE Inhibition TENSIDYSS CHARACTERISTICS ACE inhibition curve of TENSIDYSS Gel filtration profile of TENSIDYSS and ACE inhibition activity of the different fractions 90% 80% 70% 60% 50% 40% 30% 20% IC 50 = 0,25 (+/- 0,06) mg / ml 10% 0% 0 0,2 0,4 0,6 0,8 1 1,2 mg peptides / ml Results from an internal study
24 TENSIDYSS Characteristics Our study permitted to develop an internal analysis method (which was the subject of a scientific publication), to verify that each batch have this activity of inhibition of angiotensin conversion enzyme. Our study also demonstrate that several peptides have this activity in our hydrolysate (peptides of 2 to 5 amino acids = low molecular weight) Publication : Véronique Lahogue et al. (2009) A HPLC-UV method for the determination of angiotensin I- converting enzyme (ACE) inhibitory activity.food Chemistry118 (2010);
25 TENSIDYSS Characteristics TENSIDYSS, like other fish peptides studied before (Sardine, tuna, hake), presents also an activity of blood pressure regulation TENSIDYSS, controlled at each batch guarantees this ACE activity thanks to our analysis method -TENSIDYSS, like for all peptides which have this activity, we can notice: -A normal lowering of blood pressure in subjects with hypertension and with mild hypertension, without adverse effects. -No lowering is noticed in normotensive subjects.
26 FORMULATIONS WITH TENSIDYSS TENSIDYSS can be formulated with: Fish oils (modest reduction in systolic and diastolic pressures - Protective effect on the cardiovascular system.) Co-Q10 (antioxidant lowering blood pressure) Calcium from food source could help maintain normal blood pressure and protect the cardiovascular system (link scientifically demonstrated between hypertension and poor calcium metabolism) Plant extracts: Horsetail, olive leaves, hawthorn, etc
27 Marine Ingredients developer for high health benefits CONCLUSION MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS MARINE BIOTECHNOLOGICAL INGREDIENTS
28 CONCLUSION NATURAL PRODUCT BLOOD PRESSION REGULATOR ACTIVITY WITHOUT ADVERSE EFFECTS DAILY RECOMMENDED DOSE: 500mg 1g /day Scientific bibliography available on request
29 Conclusion Hermes Consilium Hermes Consilium d.o.o. Blaž Gorjup Managing Director (E) (W) Valjhunova 11, SI-1000 Ljubljana, Slovenija (T) (F)
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