Only One Clinically-Proven Hyaluronic Acid for 'Beauty from Within'

Transcription

1 Hyabest (S) LF-P Only One Clinically-Proven Hyaluronic Acid for 'Beauty from Within' Nov, 2015

2 Kewpie Corporation Founded in 1919 in Tokyo, Japan. Started business with mayonnaise and jam. Corporate slogan Food, for ages group consolidated sales approx. US$ 5 billion.

3 Business Category of Kewpie Corporation Condiments Products Processed Foods Fine Chemical Products Top producer in Japan Egg Products Delicious & Highest quality Excellent health to every generation Functional ingredients (Food, Cosmetics, Medicines) Delicatessen Products About 9% of all eggs produced in Japan are transformed into Kewpie products Facilitated by national production network and area-wise mobility in Japan

4 Application of Hyaluronic Acid Medical Food Cosmetic

5 What is Hyaluronic Acid Chemical Structure Hyaluronic acid Acidic mucopolysaccharides Polymer of N-acetylglucosamine and D-glucuronic acid MW: Up to 2,000kDA It naturally exists in human body specially abundant in skin, eye, joints, etc

6 Natural synthesis of Hyaluronic Acid (HA) decreases as you get aged. Skin Dermis Collagen Dermis won t retain moisture. Dry Skin! Enlarged Aged Hyaluronic Acid (HA) HA decreased That s why HA should be replenished to the skin.

7 Volume of HA in the skin (%) Change in the volume of Hyaluronic Acid in the skin Age by Age Age 80% Lost Hyaluronic Acid in the skin turns over every 2-3 days As you get aged natural synthesis of Hyaluronic Acid becomes unable to catch up with its decomposition, consequently its volume staying in the skin gets less. Maria O. Longas, et al, Carbo hydr Res 1987;159:

8 Now, how do you replenish Hyaluronic Acid into your skin? 1. Injection? 2. Cosmetics? 3. Dietary Supplment? Most of ladies may rely on #2 cosmetics, which are applied from outside of the skin. But we recommend more natural way to get the Beauty from Within as #3 dietary supplement.

9 Is Hyaluronic Acid (HA) really effective by oral ingestion? I don t think HA is effective by oral ingestion, because HA should not be absorbed to the body due to its big molecular size. Plastic Surgeon Certainly! HA may not be absorbed to the body via small intestine, but Doctor, you may forget about the HA abosorption via large intestine..

10 Time course of radioactive quantitation in the blood after oral & intravenous administration of C 14 -labeled HA in SD rats. Oe, M. et al. (2014) Sci.World J., 10/2014,

11 Time course of radioactivity change by whole body radioluminograms after oral administration of C 14 -labeled HA in SD rats. 8 hrs 24 hrs 96 hrs Oe, M. et al. (2014) Sci.World J., 10/2014,

12 C 14 -labeled HA by oral administration was found to be absorbed to the body, and distributed to the skin in male SD rats. Skin 24 hrs Oe, M. et al. (2014) Sci.World J., 10/2014,

13 Time course of radioactivity in selected organs by whole body radioluminograms after oral administration of C 14 -labeled HA in SD rats. Oe, M. et al. (2014) Sci.World J., 10/2014,

14 HA is permeable through human intestinal cells. HA HA HA HA little bit difficult.. Intestinal cells HA HA HA Tight junction Small size HA can pass the intestinal Human Caco-2 Cell monolayers through the tight junction.

15 Detected Intensity HA may be degraded to di-, tetra-, or hexa-saccharides of HA by Hyaluronidase secreted from intestinal bacteria in cecus. Di-saccharides Di-saccharides Tetra-saccharides HA Standard Tetra-s Hexa-s Hexa-saccharides HA Standard Cecal contents Cecal contents + HA Fig.1 HPLC profile of HA molecular change after mixing with cecal contents Kurihara, H. et al. (2014) 14 th Jpn Soc. Anti-Aging Med., Poster Session P104.

16 Pharmacokinetics of Hyaluronic Acid in the Body Oral intake of HA MW of HA is lowered by acid in a stomach and HA is transferred to intestine Excretion (approx. 10%) Absorbed in intestine and transferred into the blood (90%) Blood Decomposition MW is further lowered in the blood and is metabolized in the liver. Utilized in the body Transferred into the skin from the blood (Emission rate is 2 times higher than in the blood) HA is synthesized in the skin Excretion (breath and urineapprox. 80 %) Excretion from the skin Decomposition HA is decomposed in the skin and transferred in to the blood

17 What is Health Function of Oral Ingested HA on Skin?

18 Mechanism of photo-aging Ultra-violet rays Creases Sagginess Free-radical Decline in the volume of epidermis Collagen in the skin Active oxygen Accelerated formation of crossbridged collagen dermis Enlarged Collagen Degrading flexibility and elasticity of dermis Hyaluronic Acid Reference: Aging of the skin and formations of creases (FREGRANCE JOURNAL, , 24-29) : Function of Hyaluronic Acid in the interstitial connective tissue(fregrance JOURNAL, , 22-28)

19 Study design of Preventive effct from skin UV irradiation in mice Animals: male hairless mice HOS:HR-1 (4 weeks old) UV irradiation source: lump GL20SE (SANKYO DENKI) Oral administration of HA (LF-P) or control 200mg/kg BW (week) Randomly divided Total irradiation: 2.8J/cm 2 UV(-) control group (n = 6) UV(+) control group (n = 6) UV(+) HA (LF-P) group (n = 5) Evaluation Photograph Data of Hyabest(S) LF-P are extracted from publication Kawada, C. et al. (2015) J. Photochem. Photobiol. B. Biol. 153,

20 Skin wrinkles caused by UV irradiation Preventive effect of Hyabest (S) LF-P Wrinkle Score Epidermis Thickness(μm) 0.22± ±0.4 UV(-) control 3.94± ±6.5 UV(+) control 2.93± ±2.3 Data of Hyabest(S) UV(+) HA LF-P are extracted 50μm Kawada, C. et al. (2015) J. Photochem. Photobiol. B. Biol. 153, from publication

21 Amount of Skin Moisture Amount of Skin Moisture Skin moisture change by UV irradiation Preventive effect of Hyabest (S) LF-P CM units UV(-) control UV(+) control UV(+) HA CM units ## ## * Data of Hyabest(S) LF-P are extracted from publication ##,* ## ##, ## * ## ## ## ## ## ## ## (Week) UV(-) control UV(+) control UV(+) HA HA UV(-) UV(+) Data are shown as Mean ±SE(n=5, 6) # UV(-) controlp < ## UV(-) controlp < *UV(+) control(p < Skin Moisture Amount in mice at 3 weeks (UV irradiaion & HA oral administration) Hyabest(S)LF-P prevented skin moisture from reducing by UV irradiation in mice. Kawada, C. et al. (2015) J. Photochem. Photobiol. B. Biol. 153,

22 Amount of HAS-2 gene expression (Relative value to GAPDH) HA-related gene expression in the skin Preventive effect of Hyabest (S) LF-P 5 4 Data of Hyabest(S) LF-P are extracted from publication UV(-)control UV(+)control UV(+)HA20 万 control control HA UV(-) UV(+) Hyabest(S)LF-P enhanced gene expression of HAS-2 which is related to HA synthesizing enzyme. Kawada, C. et al. (2015) J. Photochem. Photobiol. B. Biol. 153,

23 Study design of Therapeutic effect against skin UV irradiation Animals: male hairless mice HOS:HR-1 (4 weeks old) UV irradiation source: lump GL20SE (SANKYO DENKI) 0 12 Oral administration of HA (LF-P) or control 200mg/kg BW (4 weeks) 16 (week) Randomly divided Total irradiation: 4.7J/cm 2 (12 weeks) UV(-) control group (n = 8) Randomly divided Evaluation Photograph UV(+) control group (n = 8) UV(+) HA group (n = 7) Kawada, C. et al. (2013) Jpn. Pharmacol. Ther. 41(7):

24 Skin wrinkles caused by UV irradiation Therapeutic effect of Hyabest (S) LF-P UV(-) control UV(+) control UV(+) HA Kawada, C. et al. (2013) Jpn. Pharmacol. Ther. 41(7): µm

25 Skin moisture change by UV irradiation Therapeutic effect of Hyabest (S) LF-P CM units 80 UV(-) control CM units ## UV(+) control ## UV(+) HA 70 * * (Weeks) Data are shown as Mean ±SE(n=7, 8) ## UV(-) control(p < 0.01 ) *UV(+) control(p < 0.05) Kawada, C. et al. (2013) Jpn. Pharmacol. Ther. 41(7): ## UV(-) control UV(+) control UV(+) HA Skin Moisture Amount in mice at 3 weeks (HA oral administration)

26 Agarose Gel Electrophorasis Profile of Hyaluronic acid from UV irradiated skin Oral administration of Hyabest(S)LF-P enhanced the biosynthesis of bigger molecular size of HA. Kawada, C. et al. (2013) Jpn. Pharmacol. Ther. 41(7):

27 Role of Hyaluronic Acid played in anti-photo-aging Ultra-violet rays Hyaluronic Acid: *Blocks free-radicals from attacking Collagen! *Removes active oxygen! epidermis Free-radical Active oxygen Collagen will be protected from damages Anti-aging effect is expected dermis Enlarged Collagen Hyaluronic Acid Reference: Aging of the skin and formation of creases(fregrance JOURNAL, , 24-29) Function of Hyaluronic Acid in the interstitial connective tissue(fregrance JOURNAL, , 22-28)

28 Randomized Clinical Trial Oral intake of Hyabest (S) LF-P( Hyaluronic Acid ) Test sample: Hyabest (S) LF-P supplement (120mg / day) Placebo: Crystalline cellulose * Test subjects: Japanese female from age 35 to 60, 22persons / group Test methods: Double-blind test (parallel 2groups) Measured item: Cheek skin moisture Measured device: CORNEOMETER CM825 Kawada, C. et al. (2015) J. Clin. Biochem. Nutr. 56(1) 66-73

29 Improvement effect of oral intake of Hyabest (S) LF-P( Hyaluronic Acid ) on skin moisture Skin Moisture (a.u.) Prior To Ingestion 3 weeks of Ingestion 6 weeks of Ingestion 2 weeks after ingest. ended Placebo ± ± ± ± 2.23 Hyabest (S) LF-P ± ± 1.64*** ± 2.43*** ± 2.59*** ***: P<0.001 by paired t-test Kawada, C. et al. (2015) J. Clin. Biochem. Nutr. 56(1) 66-73

30 Increased Amount of Skin Moisture Improvement effect of oral intake of Hyabest (S) LF-P( Hyaluronic Acid ) on skin moisture (a.u.) Hyabest (S) LF-P 120mg/day * *p<0.05 PLACEBO Before intake 3week 6week 2week after intake ends Kawada, C. et al. (2015) J. Clin. Biochem. Nutr. 56(1) 66-73

31 Average Score of Luster Improvement effect of oral intake of Hyabest (S) LF-P on Skin Luster & Supple Average Score of Supple LUSTER はり SUPPLE HA LF-P * * Before intake HA LF-P *p< 0.05 vs placebo by Dunnett t test, mean±s.e. 3week 6week 2week after intake ends Kawada, C. et al. (2015) J. Clin. Biochem. Nutr. 56(1) p< 0.10 vs placebo by Dunnett t test, mean±s.e. Before intake 3week 6week 2week after intake ends

32 Improvement effect of oral intake of Hyabest (S) LF-P on Skin Wrinkles Average Score of Wrinkles WRINKLE Before intake placebo HA 300 k week 6week 2week after intake ends Kawada, C. et al. (2015) J. Clin. Biochem. Nutr. 56(1) 66-73

33 Mechanisms of oral ingested HA enhancing skin moisture 1. Ingested HA is degraded into small size by intestinal bacteria 1) 2. Small size HA permeates through intestinal cells tight junction. 2) 3. Carbon-14 labeled HA was orally administered and found distributed to the skin in rats 3),4) 4. Oligo-HA was applied to fibroblasts, which enhanced the biosynthesis of HA. 5) 5.HA facilitates the proliferaion of fibroblasts 6) 6. HA intake enhanced the skin moisture. 7) Possible mechanism: Oral ingested HA is degraded to small size of HA by intestinal bacteria, absorbed to blood stream and distributed to the skin to stimulate HA biosynthesis, which eventually enhances skin moisture. 1)J.Microbiol Biotechnol., 19, 2009, )Biosci. Biotechnol. Biochem., 72, 2008, )J. Agric. Food Chem., 56, 2008, Oe, M. et al. (2014) Sci.World J., 10/2014, )Biochem. J., 343, 1999, )J. Cell. Physiol., 177, 1998, ) Aesthetic Dermatology,17,2007, 33-39

34 Kewpie Hyaluronic Acid quality We believe that our quality is one of the best in the world. Followings are supporting the quality superiority. High purity HA purity 95% No smell, No taste Transparent in water Hyabest (S) LF-P Evidence GMP Control with GLP Lab Original scientific data (including clinical data) Based on cgmp production of pharmaceutical HA,our food / cosmetic grades conform to cgmp

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36 Kewpie was the 1 st company to launch Health Function Labeled Food under new Food Label Law in Japan and we formulated Hyabest(S) for the memorial product.

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40 Hyabest (J)speedily alleviates knee pain Testee : osteoarthritis patients under treatment by physical excercises or drugs,n=21 age 50~70 JKOM score variation (%) # # Time( month) #p<0.05 The ScientificWorld Journal Volume 2012, Article ID , 8 pages Placebo (N=10) Hyabest(J)(N=11) 200 mg/day