ReinhardWeidhase国际血浆代用品市场的发展趋势PPT课件

1、Parenteral Drug Congress 2013Main Topics1. General Remarks2. The Active Pharmaceutical Ingredients Gelatine and Hydroxyethyl Starch3. The Characteristics of Hydroxyethylstarch4. Clinical Particulars and Market Trends第1页/共37页Parenteral Drug Congress 2013History of PlasmasubstitutionYearSourceInvestig

2、ators1878Saline SANDER1881Saline LANDERER1915Gelatine HOGAN1937PV-Alcohol BRAUN/JORNS1940 PV-Pyrrolidone REPPE/WEESE/ HECHT 1944Dextrane GRNWALL/INGELMANN第2页/共37页Parenteral Drug Congress 2013History of PlasmasubstitutionYearSourceInvestigators1951/52modified GEL CAMPBELL/ TOURTELOTTE1957Oxyethylstar

3、ch WIEDERSHEIM1962Urea-linked GEL SCHMIDT-THOME1962HES THOMPSON/WALTONSince 1970several variations of HESby different companies2011Monograph for HES of Pharm. Eur. 第3页/共37页Parenteral Drug Congress 2013Developments in Serumwerk Bernburg AGYearSource1959 Dextranes for clinical use 1979 Modified Gelati

4、ne in saline1991 Modified Gelatine in balanced solution 1994 HES 200/0.5 based on potato starch2004 HES 130/0,42 based on potato starch in saline and in balanced solution as well 2008New plant for Manufacturing of HES第4页/共37页Parenteral Drug Congress 2013Substances for colloidal volume replacementSou

5、rcesBiological OriginNon-Biological OriginSynthetic PolymersPVPHuman OriginOther Biological OriginDextran (Microbes)Gelatine (Animal)Starch (Plants)Human PlasmaHSA第5页/共37页Parenteral Drug Congress 2013Requirements for Volume Replacement Products1.Isooncotic and isoosmotic properties2.Adequate volume

6、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 customers第6页/共37页Parenteral Drug Congress 2013第7页/

7、共37页Parenteral Drug Congress 2013Solutions for Infusion Based on Gelatine Peculiarities concerning Manufacturing, Structure and Administration 第8页/共37页Parenteral Drug Congress 2013第9页/共37页Parenteral Drug Congress 2013第10页/共37页Parenteral Drug Congress 2013第11页/共37页Parenteral Drug Congress 2013Substan

8、ces for colloidal volume replacementSourcesBiological OriginNon-Biological OriginSynthetic PolymersPVPHuman OriginOther Biological OriginDextran (Microbes)Gelatine (Animal)Starch (Plants)Human PlasmaHSA第12页/共37页Parenteral Drug Congress 2013Solutions for Infusion with Hydroxyethyl Starch Peculiaritie

9、s concerning Manufacturing, Structure and Administration 第13页/共37页HES Specifications in the European Market/10%/2007第14页/共37页HES Monograph to PHARM. EUR.!第15页/共37页Native Sources for Starches第16页/共37页Molecular Weight Distribution第17页/共37页Hydroxyethylation of Glucose Molecules at C6- and C2-PositionSu

10、bstitution at Glucose Residues第18页/共37页Peculiarities of HES第19页/共37页C orrel at i on of El i m i nat i on hal f -l i f e and M ol ar Subst i t ut i on of H ES 第20页/共37页C orrel at i on of El i m i nat i on hal f -l i f e and Pat t ern of Subst i t ut i on of H ESAni m al experi m ent s第21页/共37页HES Sto

11、rage in Rat Liver第22页/共37页Relationship Between Colloid Content and Volume Effect of an HES SolutionConcentration of HES 200/0.5Initial volume effectRating3%0.4 0.6hypo-oncotic6%0.8 1.0iso-oncotic10%1.2 1.4hyper-oncotic第23页/共37页 Cumulation in PlasmaCumulation of HES 200/0.5 versus HES 130/0.42 after

12、repeated administration第24页/共37页Elimination of HES- 第25页/共37页 Molecular Weight and Renal ThresholdSerumUrine第26页/共37页Parenteral Drug Congress 2013Volume Replacement Therapy Clinical Particulars and Market Trends 第27页/共37页Parenteral Drug Congress 2013VitaHES, solution for infusion Hydroxyethyl Starch

13、 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 VitaHESIndication第28页/共37页Parenteral Drug Congress 2013VitaHES, sol

14、ution 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 anuria Intracranial bleeding Severe hypernatraemia or severe hyperchloraemia Severely impaired he

15、patic function Congestive cardiac failure Summary of Product Characteristics VitaHES Contraindications第29页/共37页Parenteral Drug Congress 2013VitaHES, solution for infusion Overdose (SmPC section 4.9)The greatest risk associated with an acute overdose is hypervolaemia.In this case, the infusion must b

16、e stopped immediately, and administration of diuretics be considered.Summary of Product Characteristics VitaHES Overdose第30页/共37页Side Effects第31页/共37页Parenteral Drug Congress 2013British Journal of Anaesthesia 98(2): 216 24 ( 2007 )Effects of hydroxyethyl starch administration on renal functionin critically ill patientsY. Sakr, D. Payen, K. Reinhart, F. S. Sipmann, E. Zavala, J. Bewley,G. Marx and J.-L. Vincent第32页/共37页Parenteral Drug Congress 2013Use of colloids in different EU countries第33页/共37页Parenteral Drug Congress 2013Renale SOF