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490 As shown in Figure 8, compared with the average annual number of deaths in the five years before 2020, there were 13,925 more deaths from Alzheimer's disease and 44,729 more deaths from all dementias, including Alzheimer's, in 2020

(2000), Horm Res 53(Suppl 3), PubMed 10971106 Statistics from preclinical literature AOD-9604 = modified fragment of hGH 177191 + N-terminal Tyr (sequence Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe), molecular weight 1815.1 Da Developed at Metabolic Pharmaceuticals (Australia) based on the work of professor Frank Ng (Monash University) in the 1990s Standard experimental dose in obesity clinical trials: 1 mg/day subcutaneously (Phase 2b, Heffernan et al.) Mechanism: stimulation of 3-adrenergic receptors in adipose tissue, increased lipolysis and fatty acid oxidation without activation of the hGH receptor (no IGF-1 increase) Phase 2b clinical trial (2007, 300 patients): weight reduction ~2.8 kg vs placebo over 12 weeks FDA status: NDI rejection (2014) as a dietary supplement

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The clinical implication: these peptides don't mask symptoms

(14) (14) Preparation Fmoc-Glu(otBu)-Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly-Leu-Val-WangResin Fmoc-Glu(otBu)-Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly-Leu-Val-WangResin (13)Fmoc-Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly-Leu-Val-WangResin(20DMF)5203DMF3DMF2Fmoc-Glu(otBu)-OH1.1gDIEA0.4mlTBTU0.56gHOBT0.2gDMF10ml1.53DMF3DMF2Fmoc-Glu(otBu)- Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly-Leu-Val-WangResin In the Fmoc-Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly-Leu-Val-WangResin of step (13), add decapping reagent ( 20% piperidine in DMF), reacted at room temperature for 5 minutes, drained, re-added capping agent and reacted at room temperature for 20 minutes, washed 3 times with isopropanol, washed 3 times with DMF, washed 2 times with distilled DMF, drained , add Fmoc-Glu(otBu)-OH1.1g, DIEA0.4ml, TBTU0.56g, HOBT0.2g, DMF10ml, react at room temperature for 1.5 hours, dry with a vacuum pump, wash with isopropanol for 3 times, DMF for 3 times, repeat The steamed DMF was washed twice and dried to obtain Fmoc-Glu(otBu)-Pro-Pro-Pro-Gly-Lys(Boc)-Pro-Ala-Asp(otBu)-Asp(otBu)-Ala-Gly- Leu-Val-Wang Resin