Salmon ovary outer membrane hydrolysate Salmon Ovary-based Peptides （ＳＯＰ )

1. Salmon ovary outer membrane hydrolysateSalmon Ovary-based Peptides（ＳＯＰ) KYOWA PHARMA CO. LTD.

2. History of Placenta ① Ancient Greece (BC 400): Hippocrates (Father of Medicine) confirmed natural healing power of Placenta Ancient China (Tang period – 4000 years ago): Placenta presented in a ancient Chinese medical book China (Ming period): A Chinese herbalism book presented Human Placenta curative properties such as tonicity, menstrual regulation effect, postpartum disorder improvement and lactogenic action USSR in 1933 Dr. Filatov developed tissue therapy with Placenta

3. History of Placenta ② Japan (Kaga region) Placenta was deemed as drug conferring immortality Medical application of Placenta in Japan: Dr. K. MITSUBAYASHI (Gynecology professor of Kyoto University): Development of Placenta formulation “Vita-X” (drug improving forcing, galactopoiesis, hematopoietic function, etc.) Dr. K. HIEDA (Pathology professor of Kurume University):Development of Placenta injectable solution “Laennec”: For neuralgia, rheumatism, sirrhosis, chloasma, frozen shoulder, menopausal syndrome and tonicity Medical application of Placenta covered by insurance in Japan: For hepatic dysfunction, menopausal syndrome, agalactorrhea, etc.

4. Ｂａｃｋｇｒｏｕｎｄ　ｏｆ　ｄｅｖｅｌｏｐｍｅｎｔ ① Beneficial effects of Placenta - Concentrated source of nutrition - Human growth factor - Cellular stimulant activity - Improvement of menopausal syndrome Example of human placenta: After ＢＳＥ problems, placenta derived from pigs is used for cosmetic and medicinal products.

5. Concentrated source of nutrition • Provides nutrition to the baby & the mother itself. • The child’s brain, eyes, muscles, bones, organs, glands, nerves, skin, tissues and fluids are entirely make from the nutrients taken from its mother’s bloodstream via the placenta.

6. Human growth factor • The hormone can promotes tissue repair. • Create cell regeneration in the bones. • Re-generate tissue for muscle & vital organs. • Can support immune system in combating infection and disease.

7. Cellular stimulant activity • placenta also has metabolic and endocrine activity. • produces, among other hormones, progesterone's which is important in maintaining the pregnancy. • maintain the uterine lining as well as inhibit the production

8. Improvement of menopausal syndrome • With concentrated source of nutrition's, it can improved the menopausal syndrome. • Make looks younger.

9. Ｂａｃｋｇｒｏｕｎｄ　ｏｆ　ｄｅｖｅｌｏｐｍｅｎｔ ② - Avoidance of animal ingredient’s use (quadruped) for health and cosmetic products in Europe - Safety issue (diseases characteristic of animal) - Shifting to marine-derived ingredients for the safety - Use of biomass in a positive manner (for environmental care) 　　 ↓ Focus on salmon ovary outer membrane (disposal part of salmon) for its “baby protective action” similar to placenta action ↓ Development of Salmon ovary outer membrane hydrolysate = Salmon Ovary Peptides (SOP)

10. ＳＯＰ Safety data Residual pesticides Heavy metals Hormones

11. Physical aspect of SOP Origin and production: SOP is freeze-dried salmon （Salmonidae） ovary-based peptides, obtained by enzymatic decomposition Aspect: Slightly yellow-brown powder having a characteristic odor Molecular weight distribution: ６００～１５００ Mean molecular weight: ６００～８００

12. Very special ingredient！ Patented product！ Extraction of amino-acid constituents from fish ovary outer membrane by enzymatic decomposition. Patent in Japan No. ３６９１４９７ International patents In China ＺＣ　０３１４８６９９．１ In Hong-Kong ０４１０５５３１．１ In Korea ９２８９９／２００３ In USA １０／７３３．６２７

13. Physical aspect

14. SOP Analysis data (in 100g) 日本食品分析センター

15. Amino acids profile comparative chartbetween SOP and Pig Placenta extract （Unit: mol%）

16. Amino acids profile comparisonbetween SOP and Animal origin Placenta extract SOP profile Human Placenta profile Pig Placenta profile

17. Safety of SOP LD５０ > 2,500mg/kg Nothing abnormal detected on Performance status, Weight and Necropcy Nothing abnormal detected on Biochemical examination of blood

18. Clinical trial results on the drink containing SOP menopausal symptoms-improving effect

19. Various effects of Placenta - Activation of cell division - Activation of metabolism - Hormonal adjustment - Improvement of immunity/resistance - Improvement of metabolism/blood circulation - Suppression of inflammation - Regulation of autonomic nerves (ataractic effect) - Improvement of menopausal syndrome - Elimination of radical oxygen Activation and regulation of physical function and detoxification

20. Placenta-like function of SOP Composition: Similar to human or pig placenta Function: Similar to Animal Placenta - Inhibition of functional decline for liver and pancreas (antitoxic effect) - SOD-like function - Inhibition of tyrosinase activation - Inhibition of visceral fat accumulation On the base of this function, we realized a clinical trial.

21. Summary of trial ① • Object: Validation of ＳＯＰ efficacy on improvement of Skin condition, anti-fatigue action and improvement of menopausal syndrome • Subjects： - 17 women aged between 35 and 55 (just before or aftermenopause), having symptoms of menopause such as rough dry skin, insomnia, fatigable, stiff shoulder, etc. - Menopausal Index between 25 and 55 (They have some symptoms of menopause, but not so serious. Medical treatment is not required.) • Exclusion criteria: Subjects hormonally treated

22. Summary of trial ② • Methods Taking a drink containing SOP 500mg per day ・For 17 subjects: during 4 consecutive weeks ・For 4 subjects of them: during 4 consecutive weeks + 1 week of time-out +1 week for retaking SOP drink ・For 4 subjects of them: during 4 consecutive weeks + 1 week of time-out +1 week for retaking Placebo drink

23. Summary of trial ③ • Measurement Measurement timing: Before trial – After 1 week – After 4 weeks – (1 week of time-out) – After 5 weeks (just after time-out) – After 6 weeks Summary of measurement: ・Skin condition was measured in 15 minutes after face-washing by Robo Skin Analyzer 　・Menopausal index 　・Skin condition questionnaire

24. Robo Skin Analyzer Evaluation: - on facial pigmentation - on facial pores

25. Skin condition analysis by Robo SkinSmall pigments on face (observed value and rank) We observed significative diminution of small pigments number and its surface after 1 week and at 4th week. This result shows improvement effect of Ocean Placenta on small pigments. Dr. Y. NOMURA: Director of Nomura Dermatological Clinic Dr. S. HIRASAWA: Director of My City Clinic

26. Large pigments on face (observed value and rank) ⇒ so-called “pigmented spot” We observed slight diminution of large pigments after 1 week and at 4th week, but not significant. According to these results, SOP should have diminution effect of facial pigments in small and large cases. Dr. Y. NOMURA: Director of Nomura Dermatological Clinic Dr. S. HIRASAWA: Director of My City Clinic

27. Facial pores (observed value)Visible pores number We observed slight diminution of visible pores number after 1 week and at 4th week. This result shows tighten effect of Ocean Placenta on visible pores. Dr. Y. NOMURA: Director of Nomura Dermatological Clinic Dr. S. HIRASAWA: Director of My City Clinic

28. Self-evaluation: Change in Menopausal Index and Skin & Physical conditions ① Menopausal Index Self-evaluation by scoring Trial I: 17 subjects Trial II: 8 subjects from them (4 subjects for Placebo group) ② Change in skin and physical conditions ＜Skin condition＞ Inscribing subjective symptom ＜Physical condition＞　 Inscribing subjective symptom

29. Change in Menopausal Index Trial I • Improvement of Menopausal Index on 16 of 17 subjects after 1 week, on 17 of 17 after 2 weeks, on 15 on 17 after 3 weeks and on 17 of 17 after 4 weeks Trial II • During 1 week of time-out: Aggravation of Menopausal Index on 8 of 8 • 1 week after the resumption: Improvement on 4 of 4 for SOP group (for Placebo group: improvement on 2 of 4, aggravation or no change on 2 of 4) This result shows menopausal index improvement effect of SOP after 1 week of use.

30. Change in Menopausal Index ■Trial I After 1 Week After 2 Weeks After 3 Weeks After 4 Weeks 17 subjects

31. Change in Menopausal Index (M.I.) Test period Before After 1 week After 2 weeks After 3 weeks After 4 weeks Change in M.I. Trial I Subjects: 17

32. Change in Skin and physical conditions＜Skin condition ①＞ Trial I (during 4 weeks) (Remarks from the subjects) • Skin dryness was improved after 1 week of use. • During face-washing, skin became smooth at 2nd week. • Skin became velvety at 4th week. • Good blood circulation of face in the morning and clear facial skin at 4th week. • One subject got a cold during the test and took a drug, but she didn’t have any skin problem, such as skin roughness or drug eruption. • Improvement of skin roughness during menstruation

33. Skin condition within 4 weeks

34. Change in Skin and physical conditions＜Skin condition ②＞ Trial II (Remarks from the subjects) At 5th week ‘time-off period”: • Sensation of itching and skin dryness • Not easy to make-up At 6th week: Ocean Placenta group • Improvement of skin brilliance • Improvement of dullness skin color At 6th week: Placebo group • Skin still dried • But skin remains satiny from 4th week

35. Change in Skin and physical conditions＜Physical condition ①＞ Trial I (during 4 weeks) • Easy to sleep from 3rd day • Fatigue reduced after 1 week • Intolerance to cold reduced after 1 week • Improvement of impatience at 4th week • Augmentation of menstrual bleeding

36. Physical condition within 4 weeks

37. Change in Skin and physical conditions＜Physical condition ②＞ Trial II At 5th week ‘time-off period”: • Feeling bleu due to time-off period • Easily-fatigued with shoulder hurt • Difficulty of falling sleep • Sensation of impatience • Intolerance to cold At 6th week: Ocean Placenta group • Good view and shoulder hurt reduced from 3rd day. • Sensation of fatigue reduced • Keeping good mental condition during ill health At 6th week: Placebo group • Sensation of impatience(same as 5th week) • Intolerance to cold • Difficulty of falling sleep

38. Physical condition

39. Resume These results show SOP effects on symptoms of menopause and skin conditionof women of menopausal age. Nearly all of the subjects had a gut feeling of SOP effects on their skin and physical condition from first week. Nearly all of and physical condition from only first week. So, we observed immediate action of SOP and its continuous effect during the dosing. Thanks to SOP’s efficacy, we can hope a wide variety of SOP application, such as beauty supplement or drink, anti-fatigue supplement or drink for women of menopausal age.