reinhardweidhase--国际血浆代用品市场的发展趋势

Parenteral Drug Congress 2013Medicinal Products forPlasma Substitution Experiences, Peculiarities,Market TrendsNanjing,June 21st 2013Prof. Dr. Reinhard WeidhaseSerumwerk Bernburg AG, GermanyParenteral Drug Congress 2013Main Topics1. General Remarks2. The Active Pharmaceutical IngredientsGelatine and Hydroxyethyl Starch3. The Characteristics of Hydroxyethylstarch4. Clinical Particulars and Market TrendsParenteral Drug Congress 2013History of PlasmasubstitutionYear Source Investigators1878 Saline SANDER1881 Saline LANDERER1915 Gelatine HOGAN1937 PV-Alcohol BRAUN/JORNS1940 PV-Pyrrolidone REPPE/WEESE/ HECHT 1944 Dextrane GRNWALL/INGELMANNParenteral Drug Congress 2013History of PlasmasubstitutionYear Source Investigators1951/52 modified GEL CAMPBELL/TOURTELOTTE1957 Oxyethylstarch WIEDERSHEIM1962 Urea-linked GEL SCHMIDT-THOME1962 HES THOMPSON/WALTONSince 1970 several variations of HESby different companies2011 Monograph for HES of Pharm. Eur. Parenteral Drug Congress 2013Developments in Serumwerk Bernburg AGYear Source 1959 Dextranes for clinical use 1979 Modified Gelatine in saline 1991 Modified Gelatine in balanced solution 1994 HES 200/0.5 based on potato starch2004 HES 130/0,42 based on potato starchin saline and in balanced solution as well 2008 New plant for Manufacturing of HESParenteral Drug Congress 2013Substances for colloidal volume replacementSourcesBiological Origin Non-Biological OriginSynthetic PolymersPVPHuman Origin Other Biological OriginDextran (Microbes)Gelatine (Animal)Starch (Plants)Human PlasmaHSAParenteral Drug Congress 2013Requirements for Volume Replacement Products1. Isooncotic and isoosmotic properties2. Adequate volume efficacy3. Safe elimination4. Metabolization and no storage in tissues5. No additional pharmacological effects6. Sterile and free of pyrogens7. No Influence on plasma viscosity8. Stabile to temperature changes9. Long shelf life10.Acceptable (low) price to customersParenteral Drug Congress 2013Parenteral Drug Congress 2013Solutions for Infusion Based on Gelatine Peculiarities concerning Manufacturing, Structure and Administration Parenteral Drug Congress 2013Parenteral Drug Congress 2013Parenteral Drug Congress 2013Parenteral Drug Congress 2013Substances for colloidal volume replacementSourcesBiological Origin Non-Biological OriginSynthetic PolymersPVPHuman Origin Other Biological OriginDextran (Microbes)Gelatine (Animal)Starch (Plants)Human PlasmaHSAParenteral Drug Congress 2013Solutions for Infusion with Hydroxyethyl Starch Peculiarities concerning Manufacturing, Structure and Administration HES Specifications in the European Market/10% /2007HES Monograph to PHARM. EUR.!Native Sources for StarchesMolecular Weight DistributionPeculiarities of HESHES Storage in Rat LiverRelationship Between Colloid Content and Volume Effect of an HES SolutionConcentration of HES 200/0.5Initial volume effectRating3% 0.4 0.6 hypo-oncotic6% 0.8 1.0 iso-oncotic10% 1.2 1.4 hyper-oncoticCumulation in PlasmaCumulation of HES 200/0.5 versus HES 130/0.42 after repeated administrationElimination of HES- Molecular Weight and Renal ThresholdSerumUrineParenteral Drug Congress 2013Volume Replacement TherapyClinical Particulars and Market Trends Parenteral Drug Congress 2013VitaHES, solution for infusion Hydroxyethyl Starch 130: 60 g / lSodium chloride: 9 g / lMolecular Weight (Mw) : 130000 DaltonsMolar Substitution (MS) : 0.4Therapeutic indications (SmPC section 4.1)Treatment and prophylaxis of hypovolaemia and shockSummary of Product Characteristics VitaHESIndicationParenteral Drug Congress 2013VitaHES, solution for infusion Contraindications (SmPC section 4.3) Hypersensitivity to hydroxyethyl starch or to any of the excipients Hyperhydration states including pulmonary edema Renal failure with oliguria or