TBC Providing the Missing Piece
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2 Put simplistically, Spring is a twisted collagen hydrolysate molecule. Spring stimulates the body to repair and maintain its own connective tissue. It is not possible to overdose on Spring as the body breaks down any it doesn t use and disposes of it naturally
3 It is a specific Bioactive Collagen Peptides obtained by special enzymatic degradation of collagen Spring comprises peptides ranging from kda (mean M.W. 3.3 kda) Its unique twisted molecule prevents rapid hepatic degradation
4 Unlike other collagen hydrolysates Spring does not act as an antiinflammatory Instead it stimulates the body to repair itself Being entirely natural, the body s own off-switch prevents more tissue than necessary being laid down Spring is effective against OsteoArthritis up to, and including OA4
5 The Joint Cartilage Composition of Joint Cartilage Cell-Stimulation for Cartilage Regeneration Mode of Action Spring ~ 25% Proteoglycans Stimulation ~ 70% Collagen Chondrocyte Production Collagen Proteoglycans Regeneration Miscellaneous (Cells, etc.) Increase of Cartilage Mass
6 Red dead/dying tissue Green live/active tissue Day 1 Week 24 Week 48
7 Progression without Spring Progression with 10g/d Spring
8 Gen 1 Pain killers and anti-inflammatory medicine Addressed symptoms and some short term relief and improved mobility Gen 2 Chondroitin and Glucosamine Has shown to improve joint functioning, mobility and relieve symptoms Gen 3 Spring Effective mobility enhancement and symptom mitigation Evidence of stimulation of growth in cartilage mass
9 Process The Company has been fine tuning the production of Spring for several years Recipe The Company has refined the unique recipe for enzymatic degradation of collagen that produce the specific bioactive collagen peptides that is Spring Research Only Spring has been used by scientists and scholars to produce the positive outcomes on joint health discussed in this presentation
10 Spring is effective on all connective tissue; not just cartilage Investigations continue into the beneficial effects of Spring in various areas of interest: Improvement and maintenance of joint care Improvement of physical performance in active individuals Anti-ageing (skin care and health) Dental care Bone health New products are launched when it is found that altering the molecular weight brings other clinically proven benefits.
11 Because Spring works on all connective tissue, it has many benefits beyond joint health Joint Health Healthy Bones (Osteoporosis) Tissue Strength (tendons, ligaments, musculature) Fibrocartilage (Meniscus / Intervertebral Disks) Beauty (Qyra) (Nutriocosmetics / Cosmeceuticals) Weight Management Dental health
12 Collagen Hydrolysate is easily broken down into component amino acids by the liver. Low dose collagen hydrolysates act as irritants within the body and trigger an anti-inflammatory response. By twisting the molecule Spring prevents the body from breaking it up easily thereby allowing the body to absorb more and for it to be more efficacious. Spring is the only collagen hydrolysate to trigger the body s own rebuilding response.
13 Type II collagen-synthesis [x-fold of control] 2 1,8 Mean MW: kda 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 control Spring Marine-Source Collagen Porcine Hydrolysate Bovine Hydrolysate Collagen ex Chicken mean ± SD, n = 6 performed in triplicate
14 Including Results and Data
15 Absorption Distribution Efficacy Proof of Concept
16 Serum level of hydroxyproline (noml/ml) Significant and continuous increase of collagen-specific amino acids in human blood after collagen peptide supplementation (Beuker et al. 1993) Excellent and rapid absorption of Collagen Peptides after oral uptake (Iwai et al. 2005) Time (min)
17 60 [ 14 C]- Collagen Peptides (Spring) P < 0, [ 14 C]- Proline* *Representative amino acid 0 Time [h] MW ± SD, n = 6
18 Collagen new synthesis of Type II collagen (brown colour) Proteoglycans new synthesis of Aggrecan (green colour) Without Spring With Spring Oesser et al. (2006) Annals of the Rheumatic Diseases
19 Type II collagen-expression [x-fold of control] Type II collagen-synthesis [x-fold of control] 2 * * * * Stimulation with Spring [days] 4 Data represent mean ± SD for n > 6; *p < 0.05 (Mann-Whitney) for untreated control vs. Spring Bello & Oesser (2006) Current Medical Research and Opinions
20 Aggrecan-expression [x-fold of control] Aggrecan-synthesis [x-fold of control] 2 * * * * * Stimulation with Spring [days] Data represent mean ± SD for n > 8; *p < 0.05 (Mann-Whitney) for untreated control vs. Spring Bello & Oesser (2006) Current Medical Research and Opinions
21 RNA Expression (x-oldof control) mean ± SD, n > Aggrecan Type II-Collagen J. Glowacki, (2008 in press) Department of Orthopedic Surgery, Harvard Medical School, Boston Ng et al. (2007) Department of Biomedical Engineering, Columbia University, New York
22 A B Thin section of the knee stained with Haematoxylin-eosin. Exemplary illustration of different OA grades (A) OA-Grade 0 at the begin of the study (B) OA-Grade 4 at the end of the study (9 months) of an untreated subject Histopathological score (0-4) * 0 = no apparent changes 1 = loss of superficial zone 2 = defects limited above tidemark 3 = defects extending to calcified cartilage 4 = exposure of subchondral bone * S. Kamekura et al. (2005) Osteoarthritis and Cartilage 13:
23 Grade of OA P < Control Placebo Spring Beginning of Treatment (6 month) End of Treatment (9 month) Data represent mean ± SD for n = 12; p < 0.05 (Mann-Whitney) for untreated control vs. Spring Oesser et al. (2007) Osteoarthritis & Cartilage
24 Bioavailability Impact on Chondrocytes Verification Absorption Distribution Stimulation / Degradation in vivo efficacy Absorption of Spring intact Collagen peptides pass the intestinal wall and reach the blood Spring reaches the Cartilage Collagen Peptides can be detected in articular cartilage Spring stimulates ECM Synthesis Increased synthesis and accretion of collagen and proteoglycans Spring does not induce ECM degradation Protease activity is unaffected Spring halts the progression of OA evidence of therapeutic efficacy after oral administration data suggests cartilage regeneration
25 Investigator Published Subjects Study design Krug open Götz open Oberschelp comparative Seeligmüller open Adam double-blind, crossover Seeligmüller open Beuker, Eck open Beuker, Rosenfeld double-blind Fernández, Pérez comparative Moskowitz double-blind Rippe double-blind Rippe randomized Flechsenhar, Alf open Clark double-blind
26 Study design Subjects took 10 g per day Spring plus other vitamins or placebo 250 patients with symptoms of mild OA of the knee Randomised, double-blind placebo-controlled study over 14 week regime Measurement peak torque at extension with a velocity of 60 /sec peak torque at flexion with a velocity of 60 /sec work at extension with a velocity of 60 /sec work at flexion with a velocity of 60 /sec power at extension with a velocity of 60 /sec power at flexion with a velocity of 180 /sec 26
27 Spring
28 Objective Assess the effects of CH on active individuals with mild forms of joint pain and no diagnosed medical disorder Method A single centre, prospective, randomised, double-blind, placebo-controlled design Student athletes were recruited based on joint pain, but no acute injuries, use of other supplements for joint therapy, or severe symptoms of arthralgia Subject either took 10 grams of Spring or a placebo of xanthan over a 24 week study period A medical history was taken at the baseline, which recorded all use of analgesics, use of alternative therapies, and joint discomfort measured by a visual analogue scale (measured by physician and subject) The same measurements were recorded by subject and physician in each of four subsequent visits No statistical difference between the Spring and control group at baseline 28
29 Measurement 24 Weeks less Baseline p-value Pain at rest (physician report) Spring ±1.78 placebo -0.90± Pain at rest (subject report) Spring -0.81±1.77 placebo -0.39± Pain while walking Spring -1.11±1.98 placebo -0.46± Pain while standing Spring -0.97±1.92 placebo -0.43± Pain carrying objects Spring -1.45±2.11 placebo -0.83± Pain lifting Spring -1.79±2.11 placebo -1.26±
30 Measurement 24 Weeks less Baseline p-value Pain at rest (physician report) Pain at rest (subject report) Pain while walking Pain while standing Pain running a straight line Pain running and changing direction Spring ±1.89 placebo -0.86±1.77 Spring -1.01±1.92 placebo -0.47±1.63 Spring -1.38±2.12 placebo -0.54±1.65 Spring -1.17±2.06 placebo -0.50±1.68 Spring -1.50±1.97 placebo -0.80±1.66 Spring -1.87±2.18 placebo -1.20±
31 Purpose Most clinical studies depend on self-reported symptoms of joint problems and/or X-ray diagnostics Both methods have known limitations The purpose of this study is to study the effects of CH on joint cartilage as measured by MRI and diagnosed by expert technicians The Study The study was conducted at Tufts New England Medical Centre and led by Dr. Timothy McAlindon Subjects were recruited based on a mild form of OA (Kellgren grade 1 or 2) and randomly assigned to a daily regimen of 10 gms of Spring or placebo for an 11 month period A single centre, prospective, randomised, double-blind, placebo-controlled design Final subject readings were completed in November and final results are not complete Results show significant positive effects both in the appearance of greater cartilage density in the test group
32 Pre-Clinical Results Contrary to prior understanding, Spring penetrates the mucosa and is distributed throughout the body The absorbed amino acid sequences in Spring are observed in concentration around and in the joint cartilage Spring both slows the natural deterioration of cartilage and stimulates new growth as observed in the study of STR mice that have naturally developing OA Clinical Results Several studies on hundreds of subjects with OA or severe joint discomfort indicate that a 10 gram/day regime taken over 8-12 week period, significantly reduces symptoms The Penn State study indicated that healthy individuals that experience joint pain from robust physical activity experience statistically significant reduction of pain from the use of Spring over an 8-12 week period The efficacy of Spring is best understood from the most recent study at Tufts which shows that Spring repairs cartilage damage by stimulating new growth 32
33 Clinical trials continue to optimise dosage Clinical trials are ongoing into the effects of Spring on Bone health with initial results indicating a positive effect Clinical trials with a modified version of Spring that is giving good initial results in improving skin tone; repairing and restoring collagen. The company believes in continuous improvement and always seeks to add to the body of knowledge through clinical trials of the highest standards; using high cohort numbers, double blind trials, and conducted at reputable research facilities such as Harvard, Cornard, and Tufts
34 Contact Details TBC Technology in Business Consulting Susan Tainton BSc (Hons) Physiology, Pharmacology, MSc Xenobiotics
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