KP 2647 The unique dietary supplement supported by

KP 2647™ The unique dietary supplement supported by science Kunpoong Bio Co. , Ltd. Kunpoong@kunpoong. co. kr, http: //kpbio. com

Biological Efficacy of KP 2647 1. The unique dietary supplement for Anti-Lipocyte Differentiation supported by science

Scientific Literature on KP 2647 TM prevent PPAR-gamma expression in introduced Fat-liver by fed ethanol Euk-Ok Kang, Young-Joon Jin, Ji-Gweon Park, Gi-Ok Kim, Se-Jae Kim Department of Technology Innocation Center, Cheju National University KP 2647 TM is a natural compound from based on mid-molecular weight Chitosan, that extracted from the shells of crutaceans. Chitosan is the deacetylated form of chitin that is wild distributed in microorganism, fungi, crutaceans And plants. Whereas the polysaccharide used for purpose of industrial medical, biomedical, and diet, but mid-molecular weight Chitosan did unknown. We studied the effect of polymeric Chitosans (US and Norway origin) and KP 2647 TM on suppression of lipid droplet in ethanol-induced Liver injury. Blood-glucose, total cholesterol level and lipid droplet formation in liver were significantly reduced in fed KP 2647 TM group than other group. The FAS (fatty acid synthease), PPAR-a, PPAR-r and HMG-Co. A reductase m. RNA were lower expressed in fed KP 2647 TM mice liver. In particular, expression of PPAR-r was corrected with reduced droplet in liver. These result suggest that KP 2647 TM is prevent the formation of liver-lipid-droplet in fed ethanol mice. “Proceeding of Current Biotechnology and Bioengineering (XIII)” : October 22 -24, 2003 COEX, Seoul, Korea, Proceeding P. 642 The Korean Society for Biotechnology and Bioengineering http: //www. ksbb. or. kr, T. 02 -556 -2164

Carbohydrate, Fat, Alcohol Glucose Acetyl- Co. A Malonyl Co. A FAS 3 -hydroy-3 -methygutatyl Co. A (HMG-Co. A) statin HMG-Co. A reductase Fatty acid mevalonate TG Isopententy phosphate Gernyl-p Farnzyl-p Choresterol PPARs

PPRE sequence

KP 2647 protect the differentiation of lipocyte. FAS PPAR-r -actin M 1 2 3 4 5 6 7 8 1: normal (preadipocyte) 2: insun (adipocyte) 3: insulin+chitosan A 10 ug 4: 50 ug 5: 100 ug 6: +chitosan B 10 ug 7: 50 ug 8: 100 ug 9: insulin+KP 2647 10 ug 10: 50 ug 11: 100 ug 9 10 11

Table. Comparison Data between normal Chitosan and KP 2647 In terms of Liver and body weight (Rat)

A B C 1: 2: 3: 4: 5: Normal Feed 7. 5% Et. OH+Chitosan A 7. 5% Et. OH+Chitosan B 7. 5% Et. OH+KP 2647 Fig. Comparison between normal Chitosan and KP 2647 in terms of HDL, Total Cholesterol and Blood Glucose Level

NORMAL 7. 5% Eto. H+20 mg Normal Chitosan A 7. 5% Eto. H

7. 5% Eto. H+20 mg Normal Chitosan B 7. 5% Eto. H+20 mg KP 2647 Fig. Comparison between normal Chitosan and KP 2647 (Microscope of rat liver-tissue)

Normal Feed 7. 5% Eto. H p n 7. 5% Eto. H+20 mg Chitosan k 7. 5% Eto. H+20 mg KP 2647

PPAR- HMG-Co. A FAS PPAR- -actin KP 47 26 n n sa ito Ch H sa ito Ch Et. O l o ntr Co g mg mg 20 20 m 20 B A

PPAR- KP 2647 Chitosan B Chitosan A 7. 5% Et. OH Normal Feed 50 Kb Poncer (loading control) Fig. Gene Expression profile on PPAR between normal Chitosan and KP 2647

Abstract • • Chitosan polymer does not affect to the gene expression concerning the lipocyte related gene PPAR-r. KP 2647 reduce the level of total choresterol and blood glucose level. KP 2647 inhibit the formation fatty-liver significantly. KP 2647 significantly inhibit the PPAR-r gene (which directly related to lipocyte) expression. Conclusion KP 2647 as a dietary supplement can protect the fatty-liver formation Through PPAR-r gene expression inhibition.

Future direction on KP 2647 1. 2. 3. Cardiovascular desease mice Gene Expression study on Human Body Lipid PPAR-r target molecule

Biological Efficacy of KP 2647 2. The unique dietary supplement for Penile Erectile Dysfunction supported by science

Born of KP 2647™ § § KP 2647™ was originally investigated as a potential immune booster. Although KP 2647™ failed as a potent immune boosting health food ingredient, researchers in Kunpoong Bio became excited when it shows significant ability to release nitric oxide, which produces cyclic guanosine monophosphate (c-GMP) to induce erection. According to this matter, many of the men in the clinical trials reported the frequent occurrence of unaccustomed erections and improved sexual performance.

Proposed Mechanism of Action (In terms of nitric oxide release) § § The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (c. GMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. KP 2647™ has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of nitric oxide (NO), which is responsible for degradation of c. GMP in the corpus cavernosum. When sexual stimulation causes local release of NO by KP 2647™ causes increased levels of c. GMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. KP 2647™ at recommended doses has no effect in the absence of sexual stimulation, which is same as sildenafil citrate (viagra).

NO Production & Proposed Mechanism of KP 2647 NANC KP 2647 NO Endotherial cells Guanylate cyclase c. GMP GTP & GMP relax Penile Erection

Clinical Trials with patients of erectile dysfunction • Patients : 65 cases (avg. 45. 1± 6. 4 years old) • Dosage : 300 mg & 450 mg for total 2 weeks (1 week as serial) • Data were pooled analyzed using 5 categories for sexual functions among International Index of Erectile Function-5 (IIEF-5). Fig 1. Effect of KP 2647 on mean domain score of IIEF-5. The clinical effect of KP 2647 was significantly higher than that of pretreatment mean domain score (p<0. 01) Fig 2. Clinical efficacies evaluated by improvement of mean IIEF-5 score according to each treatment with KP 2647. “Effect of KP 2647 TM in Patients with Erectile Dysfunction” H. Chung 1) , S. L. Park 2) , S. C. Kim 2) , C. W. Sung 2) , J. W. Lee 2) Chung Euro & Derma Clinic, Seoul, Korea 1) Central Research Institute of Kunpoong Bio, Korea 2)

Dosage, Safety and Side-Effect Recommended Dosage The recommended dosage of KP 2647™ is 600 milligrams per day. Maximum dose level for most patients is 3, 000 milligrams per day, according to Kunpoong Bio. Safety According to the Acute oral toxicity test, The overall results indicate that LD 50 of KP 2647 is above 2 g/kg B. W. in this test. (TBH-000039, (Dr. ) Park Hark Soo, Korea Testing & Research Institute for Chemical Industry) Side-Effect The most common side effects on hypersensitive patients of KP 2647™ include pruritus, headaches, facial flushing, hemophthalmia, and indigestion, . if one was dosed over 20, 000 milligrams per day. If one desires to be dosed over 10, 000 milligrams per day, a combination of KP 2647™ and a vasodilating drug like nitroglycerin might result in a drop in blood pressure. This is due to the molecule’s action of enhancing the smooth muscle relaxing effects of nitric oxide.

Acute oral toxicity test Report (TBH-000039, (Dr. ) Park Hark Soo, Korea Testing & Research Institute for Chemical Industry)

Cytotoxicity test Report (TBH-000038, (Dr. ) Park Hark Soo, Korea Testing & Research Institute for Chemical Industry)

Certificate of Analysis Commercial Name KP 2647™ API (Active Principle Ingredient) Water-Soluble Chitosan Assay (as tot. Glucosamine) 22% Maltodextrin Rest of Them (as career) Appearance Bright Yellow Powder Solubility (p. H 3 -10) Pass Viscosity 10 cps Moisture 10% Ash 0. 5% Heavy Metal 5 mg/kg Total Plate Count 1 x 103/g Yeast and Mould 1 x 10/g Packaging 10 kgs in Carton Box

Solubility and Stability of KP 2647 (in H 2 O & Ethyl alcohol)

Applications of KP 2647 § § Health Food in Capsule or Tablet All kinds of Beverages (includes alcoholic beverage as well) § Bars § Cereals

Contact Japan CBC Co. , Ltd. Fine Chemicals & Foods Division Osaka Foods & Feedstuff Group Ehime Bldg. , 1 -7 -7, Kawaramachi, Chuo-ku, Osaka Italy A. C. E. F. spa 29017 Fiorenzuola D’arda (Piacenza) via Umbria 8/14 T. 0523 24 19 11 F. 0523 24 19 37 Integratori@acef. it T. (81 6) 6206 5047 F. (81 6) 6222 0606 Tashiro@cbc. co. jp Taiwan Progen International Co. , Ltd. 7 FL-3, No. 2. Sec. 2, HSIN Sheng South Rd. Taipei, Taiwan ROC (T. 02 2351 5492) Spain & Portugal Nutraceuticos Portal del Rey, 3 – Oficina 10 01001 Vitoria T. 945 125 002 F. 945 124 807 Baceiredo@nutraceuticos. net Manufactured by Kunpoong Bio Co, Ltd. 903, Wooree Venture, 684 -2, Deungchon, Gangseo, Seoul, Korea T. (82 2) 3662 8565, F. (82 2) 3662 8385 Kunpoong@kunpoong. co. kr Kpbio. com