HP DNA Highly Polymerized Deoxyribonucleic Acid HP DNA Highly Polymerized Deoxyribonucleic Acid Definition Marine Biopolymer characterized by Its source Its special method of extraction Its determined physico-chimical properties HP DNA Highly Polymerized Deoxyribonucleic Acid Origin Natural hydrosoluble substance extracted from the milt of wild salmon By non-denaturating technology • protecting the superstructure of polymer • preserving its physiological activity HP DNA Highly Polymerized Deoxyribonucleic Acid Aspect White-cream fibers measuring several centimeters HP DNA Highly Polymerized Deoxyribonucleic Acid Solubility Relatively soluble in water Making a gel with low concentration (1.0 to 3.0 %) insoluble in • alcohol • ethanol • the other oganic solvents HP DNA Highly Polymerized Deoxyribonucleic Acid Metabolism • half-life of 72 hours at rat • elimination after 96 hours:fecal (62,8 %) and urinary (19,4 %) • hepatic degradation in mononucleotides • biliary elimination • the intestine seems to retain polymerized parts of DNA and to be rapidly saturated in part of low molecular weight • the lymphatic tissue seems to accumulate polymerized parts of DNA then to release them rapidly in venous blood HP DNA Highly Polymerized Deoxyribonucleic Acid Pharmacovigilance Followed by laboratory Sterlin-Winthrop from 1985 and 1990 • administration almost without secondary effects • excellent clinical tolerance (superior to 90 %) HP DNA •Highly Polymerized Deoxyribonucleic Acid Antioxidant Properties (1) • It retards and diminishes the formation of dienes conjuges (joined paired),notably by its antiradical activity vis-à-vis the hydroxyl radical (OH°–) HPDR inhibition of free radical formation 90 78 80 72 70 58 60 % of inhibition of DMPO-OH signal 85 65 50 40 30 HPDR 25 20 10 0 0,4 0,8 1,2 1,6 2 HPDR concentration (mg/ml) 2,4 HP DNA •Highly Polymerized Deoxyribonucleic Acid Antioxidant Properties (2) •The capturing of this highly reactive radical by HP DNA accompanies the formation of a stable product, the 8-hydroxyguanosine (8-OHDG), and avoids the formation of a new free radical and thus terminates the process of peroxydation. => HP DNA protects the cells against extra cellular oxidative aggressions. HP DNA Highly Polymerized Deoxyribonucleic Acid Antioxidant Properties (3) • protector effect against lipoperoxydation Ara chidonic Acid oxida tion with and without HPDR Mesu remen t o f con ju gated dienes OD 234 n m 6 5 Arac hidonic Ac id 2,5.10- 3 M 4 Arac hidonic Ac id / HP DR 90 µg/ml 3 2 1 0 0 2 4 6 Day s 8 HP DNA Highly Polymerized Deoxyribonucleic Acid Antioxidant Properties (4) Inhibition of lipid peroxydation by the association of vit E + HPDR in rat hepatocytes overloaded by iron -6 250.10 M 1mg/ml 2 mg/ml 4 mg/ml 1 mg/ml 2 mg/ml 100 90 80 70 Inhibition (%) of production of free malonic dialdehyde 60 50 40 30 20 10 0 Vit E (250.10-6 M) HPDR (mg/ml) Vit E (250.10-6 M + HPDR (mg/ml) 4 mg/ml HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect(1) Open clinical study : HP DNA 8OO mg/j during 30 days • 44 asthenic adults (having no less than 15 of the 60 asthenia symptoms present) compared to 32 normal adults (having less than 15 of the 60 asthenia symptoms present) • 62.7 % of the physical asthenic symptoms • 40 % of the mental asthenic symptoms • The scores observed in the treated asthenic patients directly approached those patients seen as normal • 58 of 60 of asthenia symptoms • many of the most debilitating symptoms • action on asthenia by HP DNA globally is positive in 52.4% of the cases HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (2) Open multi-centered study: HP DNA 800 mg/day during 15days • 688 adults (445 women and 243 men) •spontaneous asthenia showed during the interrogation/isolated or associated with a non evolutionary benign organic pathology Treatment by HP DNA: • Behaviour Rating Scale (61 criteria) - 64.5 % for physical asthenia, - 57.0 % for mental asthenia • improvements more intensively marked when more severe symptoms • global efficacy of the treatment evaluated by researchers in 79.1% of the cases HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (3) Amélioration de l’asthénie physique HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (4) Improvement of psychic asthenia HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (5) Open study • HP DNA 400 mg/day +ascorbic acid 1 g/day during 15 days • 6876 patients Patients did not receive another anti-asthenia treatment (70 % of cases) • fatigue at night (a reduction of more than 50% of the intense symptoms) in 82.5 % of cases • fatigue in the morning in 82.9 % of cases • difficulty concentrating in 76.9 % of cases • trouble sleeping in 75 % of cases • trouble with appetite in 80 % of cases HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (6) Effect of HPDR - Surve y on physical fatigue (1000 doctors) 400 mg/day of HPDR + 1 g/day of vitamin C during 15 days % studied peo ple 90 82,9 82,5 80 76,9 80 75 70 60 Improvment > 50 % Recovery 50 40 33,9 30 25,7 24,3 20,5 20 20 10 0 Eve ning Tire dnes s upon tir ednes s wa king up Difficulty conc entra ting Slee p dis orders Appetite dis orders HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (7) Open clinical trial : ADN-HP 800 mg/day during 1 month • 24 persons of more than 50 years with asthenia of which 16 had anorexia and 8 were chronic alcoholics HP DNA •Highly Polymerized Deoxyribonucleic Acid Anti-asthenia effect (8) Treatment by HP DNA • patients general state in 70 % of cases and mental state in 63% of cases Effect of HPDR on the elderly people (> 50 years) with 800 mg/day of HPDR after 1 month 70 Improvment (in %) 70 68 66 63 64 62 60 58 General Improvment Improvment in psychological behaviour HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on basic arthralgies (1) Multicentric clinical study, in a double blind • 116 patients suffering from chronic spinal problems (for a period of more than 1 month) • HP DNA 800 mg/day during 30 days versus placebo Treatement by HP DNA • 43.6 % intensity of the pain, quantified on the numeric scale of Huskinson (versus 25.4 % with placebo) • 32.6 % degree of functional discomfort (handicap) (versus 25.4 % with placebo) • 43. 3 % importance of the limitation of passive mobilization HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on basic arthralgies (2) Effect of the HPDR on back pain (116 people - average age = 42 years) after 30 days (daily dose of HPDR = 1g/day) 45 40 35 30 25 (%) 20 15 10 5 0 43,3 43,6 39,6 32,7 25,4 25,5 26,9 25,5 HPDR Placebo Reduction in painReduction in the Increase in Overall degree of vertebral column improvment in functional mobility general condition difficulty HP DNA •Highly Polymerized Deoxyribonucleic Acid Chondrostimulating activity (1) Open study • 2960 persons affected by arthrosis, with an average age of 61.1 years old • ADN-HP 400 mg/day + complex of vitamins (B + E) • during 1 or 2 months Treatment by HP DNA • at the end of the first month of treatment: pains in 89.5 % of cases – 21 % were completely relieved – 68.5 % were partially relieved HP DNA •Highly Polymerized Deoxyribonucleic Acid Chondrostimulating activity (2) Effect of HPDR on osteoarthritis (2960 people - average age = 61 years) with 400 mg/j of HPDR + vit B + vit E after 30 days % people studied 83,6 90 80 68,5 70 60 50 40 30 21 20 10 0 Completely relieved pain Partially relieved pain Improved physical performance HP DNA •Highly Polymerized Deoxyribonucleic Acid Chondrostimulating activity (3) In double blind study • 67 persons affected by arthrosis with average disability of the knees and hips • HP DNA 400 mg/day + complex of vitamins (B + E) • versus diclofénac (anti-inflamatory, non-steroid) • during 42 days HP DNA •Highly Polymerized Deoxyribonucleic Acid Chondrostimulating activity (4) Treatment by HP DNA • 39 % pain (versus 35 % with diclofénac) Effect of HPDR on knee or hip osteoarthritis (67 people) of 400 mg/day of HPDR + vit E + vit B after 42 days % of reduction in pain 39 40 35 35 27 30 25 HPDR 20 15 13 Diclofénac 10 5 0 J21 (T0 + 21 days) J42 (T0 + 42 days) HP DNA Highly Polymerized Deoxyribonucleic Acid Chondrostimulating activity (5) Treatment by HP DNA • 16.1 % degree of impotence (versus 26,1 % with diclofénac) Effect of HPDR on knee or hip osteoathritis (67 people) with 400 mg/day of HPDR + vit B + vit E after 42 days % of reduction of infirmity degree 30 26,1 25 20 15,2 16,1 HPDR 15 Diclofénac 10 5 1 0 J21 (T0 + 21 days) J42 (T0 + 42 days) HP DNA •Highly Polymerized Deoxyribonucleic Acid Consolidation of dental joints (1) Study : with a traditional local method • 108 patients affected by periodontal pathology, • HP DNA 1600 mg/day during 3 months With administration of HP DNA • the index of dental mobility to a high of 45.7% • ………………………… to a low of 22.5% HP DNA •Highly Polymerized Deoxyribonucleic Acid Consolidation of dental joints (2) Success treatment for : • 56 % of patients treated by HP DNA and local treatment • 7 % only of patients treated with a traditional local method Effect of HPDR for the treatment o f periodo ntics (g um) with 16 00 mg/day of HPDR after 3 months Review of 10 8 ra ndom observations % s tudied people 70 70 56 60 50 39 40 Loca l trea tme nt HP DR 30 23 20 10 7 3 0 Trea tment suc cess Trea tment fa ilure Don't know HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on physical performance (1) Study on mice • HP DNA 200mg/day + ascorbic acid 500 mg/day during 5 days => amelioration of a swimming test HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on physical performance (2) Study on dog • HP DNA 400 mg/day ± ascorbic acid 1 g/day • before standard exertion • 50 % the frequency of heart exertion with HP DNA+ vit. C • the recuperation time after exertion: – 50 % with HP DNA alone – 83 % with HP DNA + vitamin C • elevation of cortisolemie 50 minutes after exertion: – 71% with HP DNA alone – 100 % with HP DNA + vitamin C HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on physical performance (3) Study on men • 30 athletes with an average age of 20 years old • HP DNA 800 mg/day + vitamin C 2000 mg/day during 21 days HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on physical performance (4) Effect of the association (1) • recuperation index, calculated by the Ruffier-Dickson Test Effect on recuperation after exercise with 800 mg/day of HPDR + 2000 mg/day of vitamin C during 21 days 80 80 70 60 50 40 20 30 20 10 0 Improvment Discordant results HP DNA •Highly Polymerized Deoxyribonucleic Acid Effect on physical performance (5) Effect of the association (2) • maximum oxygen intake (VO2 max) evaluated using the Cooper test Effect on stamina during exercise HPDR 80 0 mg/da y + vita min C 2000 mg /day during 21 days 39,6 39,4 39,2 39 38,8 38,6 O2 consommatio n during effort (ml/mn/kg) 38,4 38,2 38 37,8 37,6 Average at T0 Average at T0 + 21 days of treatme nt HP DNA •Highly Polymerized Deoxyribonucleic Acid Regenerative action on intellectual development in regard to psychomotor and biometrics of subjects with mental defects Double blind study: HP DNA 200 - 600 mg/day versus placebo during 3 months 256 children between the ages of 6 and 21 years with average to profound mental defects The children have benefited by gaining mental age in cases of: • Exogenous defects with an IQ* > 40 • A real age understanding of between 8 and 14 years * intellectual quotient HP DNA •Highly Polymerized Deoxyribonucleic Acid Immunostimulating activity (1) In mice without spleens 4 weeks before, when injected intraperatonial 0.03 to 0.3 g/kg with HP DNA for 10 days • resistance vis-à-vis a parasitic infection ( time augmented for surveying the animal traits with regard to the evidence) • capacity of the lymphocytes to divide and produce interleukine 2 In vitro, HP DNA exerted a mitogene effect on the splenocytes of naturally immune-depressed mice. HP DNA •Highly Polymerized Deoxyribonucleic Acid Immunostimulating activity (2) Study with patients: • 66 subjects with leucopenia (leucocytes < 3000) • a treatment with HP DNA (800-1200 mg/day for 3 weeks) was effective in 77% of the cases, and the majority just after the first week of treatment HP DNA •Highly Polymerized Deoxyribonucleic Acid Regenerative action vis-à-vis the cicatriciels process In mice, after the realization of experimental wounds, the administration of HP DNA accelerated the cicatrisation: • by proliferative activity • by the number of polypoid epidermal cells In rats, one hour after the administration of 325 mg/kg of aspirin, the taking of HP DNA (10 to 50 mg/kg per os) • prevented the apparition of gastric ulcers from aspirin HP DNA •Highly Polymerized Deoxyribonucleic Acid Powerful radioprotective activity Survival level after irradiation proportional to polymerization degree of injected heterologous DNA At rats • 24 hours after a lethal irradiation of 1000 rœntgens after injection of 300 g of HP DNA => definitive survival At animal, the administration of HP DNA • bone marrow aplasia (anemia and leucopenia) experimental radio-induced • decrease of spermatogenesis secondary to irradiation HP DNA •Highly Polymerized Deoxyribonucleic Acid Potential Applications => To stimulate immunity => To accelerate the cicatrization => To restore the general state => For physical and psychic asthenia => To improve cognitive performances • intellectual quotient • memorization => To improve physical performance • VO2 max • recuperation time => To treat basic arthralgies and arthrosis => To reduce the secondary effects of radiotherapy HP DNA Highly Polymerized Deoxyribonucleic Acid HP DNA, a marine DNA highly polymerized with a strong antioxidant power, with potential applications in health… For asthenia, arthrosis, immunodeficiency, troubles of cicatrisation,…