Skip to main content
main-content
Erschienen in: Inflammopharmacology 3/2018

07.05.2018 | Commentary

Is the pharmaceutical industry’s preoccupation with the monotherapy drug model stifling the development of effective new drug therapies?

verfasst von: Ian Edwin Cock

Erschienen in: Inflammopharmacology | Ausgabe 3/2018

Einloggen, um Zugang zu erhalten

Abstract

Drug discovery and development is heavily biased towards the development of monotherapies. Screening, testing, and evaluation of mono-entity drugs are generally much simpler than drug combinations, and are generally easier to get approval from the regulatory authorities for their clinical use. However, monotherapy drugs may not have optimal activity, may have associated toxicities, or may lose activity over time as their target develops resistance. Drug combinations, often developed from existing monotherapies, may have improved efficacy and/or be less toxic. Furthermore, the existing drugs which have lost efficacy due to the development of resistance can often be re-activated by combining them with other chemical entities. Thus, whilst the current climate for drug approval, registration, and clinical use drives the majority of drug development research towards the development of monotherapies, combinations are often a substantial improvement on the original drug. This commentary examines monotherapy and combinational therapy models and discusses the benefits and limitations of each model.
Literatur
Zurück zum Zitat Adams BM, Banks HT, Kwon HD et al (2005) Dynamic multidrug therapies for HIV: optimal and STI control approaches. J Comput Appl Math 184(1):10–49 CrossRef Adams BM, Banks HT, Kwon HD et al (2005) Dynamic multidrug therapies for HIV: optimal and STI control approaches. J Comput Appl Math 184(1):10–49 CrossRef
Zurück zum Zitat Adel SPR, Prakash J (2010) Chemical composition and antioxidant properties of ginger root ( Zingiber officinale). J Med Plant Res 4(24):2674–2679 CrossRef Adel SPR, Prakash J (2010) Chemical composition and antioxidant properties of ginger root ( Zingiber officinale). J Med Plant Res 4(24):2674–2679 CrossRef
Zurück zum Zitat Ahmed A, Azim A, Gurjar M et al (2014) Current concepts in combination antibiotic therapy for critically ill patients. Indian J Crit Care Med 18:310–314 CrossRefPubMedPubMedCentral Ahmed A, Azim A, Gurjar M et al (2014) Current concepts in combination antibiotic therapy for critically ill patients. Indian J Crit Care Med 18:310–314 CrossRefPubMedPubMedCentral
Zurück zum Zitat Airaksinen S, Karajalainen M, Kivikero N et al (2005) Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation. AAPS Pharmscitech 6:E311–E322 CrossRefPubMedPubMedCentral Airaksinen S, Karajalainen M, Kivikero N et al (2005) Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation. AAPS Pharmscitech 6:E311–E322 CrossRefPubMedPubMedCentral
Zurück zum Zitat Akihisa T, Takahashi A, Kikuchi T et al (2011) The melanogenesis-inhibitory, anti-inflammatory, and chemopreventative effects of liminoids in n-hexane extract of Azadirachta indica A. Juss. (Neem) seeds. J Oleo Sci 60:53–59 CrossRefPubMed Akihisa T, Takahashi A, Kikuchi T et al (2011) The melanogenesis-inhibitory, anti-inflammatory, and chemopreventative effects of liminoids in n-hexane extract of Azadirachta indica A. Juss. (Neem) seeds. J Oleo Sci 60:53–59 CrossRefPubMed
Zurück zum Zitat Akram M, Uddin S, Ahmed A et al (2010) Curcuma longa and curcumin: a review article. R J Biol Plant Biol 55(2):65–70 Akram M, Uddin S, Ahmed A et al (2010) Curcuma longa and curcumin: a review article. R J Biol Plant Biol 55(2):65–70
Zurück zum Zitat Arrowsmith J (2011) Trial watch: phase III and submission failures: 2007–2010. Nat Rev Drug Discov 10(2):87 CrossRefPubMed Arrowsmith J (2011) Trial watch: phase III and submission failures: 2007–2010. Nat Rev Drug Discov 10(2):87 CrossRefPubMed
Zurück zum Zitat Babu NP, Pandikumar P, Ignacimuthu S (2011) Lysosomal membrane stabilisation and anti-inflammatory activity of Clerodendrum phlomidis L.f., a traditional medicinal plant. J Ethnopharmacol 135(3):779–785 CrossRefPubMed Babu NP, Pandikumar P, Ignacimuthu S (2011) Lysosomal membrane stabilisation and anti-inflammatory activity of Clerodendrum phlomidis L.f., a traditional medicinal plant. J Ethnopharmacol 135(3):779–785 CrossRefPubMed
Zurück zum Zitat Banno N, Akihisa T, Yasukawa K et al (2006) Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri. J Ethnopharmacol 107(2):249–253 CrossRefPubMed Banno N, Akihisa T, Yasukawa K et al (2006) Anti-inflammatory activities of the triterpene acids from the resin of Boswellia carteri. J Ethnopharmacol 107(2):249–253 CrossRefPubMed
Zurück zum Zitat Biswas K, Chattopadhyay I, Banerjee RK et al (2002) Biological activities and medicinal properties of neem ( Azadirachta indica). Curr Sci 11:1336–1345 Biswas K, Chattopadhyay I, Banerjee RK et al (2002) Biological activities and medicinal properties of neem ( Azadirachta indica). Curr Sci 11:1336–1345
Zurück zum Zitat Byeon SE, Chung JY, Lee YG et al (2008) In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J Ethnopharmacol 119:145–152 CrossRefPubMed Byeon SE, Chung JY, Lee YG et al (2008) In vitro and in vivo anti-inflammatory effects of taheebo, a water extract from the inner bark of Tabebuia avellanedae. J Ethnopharmacol 119:145–152 CrossRefPubMed
Zurück zum Zitat Carey AN, Fisher DR, Joseph JA et al (2013) The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutr Neurosci 16(1):13–20 CrossRefPubMed Carey AN, Fisher DR, Joseph JA et al (2013) The ability of walnut extract and fatty acids to protect against the deleterious effects of oxidative stress and inflammation in hippocampal cells. Nutr Neurosci 16(1):13–20 CrossRefPubMed
Zurück zum Zitat Cock IE (2014) The early stages of rheumatoid arthritis: new targets for the development of combinational drug therapies. OA Arthritis 2(1):5 Cock IE (2014) The early stages of rheumatoid arthritis: new targets for the development of combinational drug therapies. OA Arthritis 2(1):5
Zurück zum Zitat Cock IE (2015a) The genus Aloe: phytochemistry and therapeutic uses including treatments for gastrointestinal conditions and chronic inflammation. In: Rainsford KD et al (eds) Novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases, progress in drug research 70. Springer, Basel, pp 179–235 CrossRef Cock IE (2015a) The genus Aloe: phytochemistry and therapeutic uses including treatments for gastrointestinal conditions and chronic inflammation. In: Rainsford KD et al (eds) Novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases, progress in drug research 70. Springer, Basel, pp 179–235 CrossRef
Zurück zum Zitat Dale J, Alcorn N, Capell H et al (2007) Combination therapy for rheumatoid arthritis: methotrexate and sulfasalazine together or with other DMARDs. Nat Clin Pract Rheumatol 3(8):450–458 CrossRefPubMed Dale J, Alcorn N, Capell H et al (2007) Combination therapy for rheumatoid arthritis: methotrexate and sulfasalazine together or with other DMARDs. Nat Clin Pract Rheumatol 3(8):450–458 CrossRefPubMed
Zurück zum Zitat El SN, Karakaya S (2009) Olive tree ( Olea europaea) leaves: potential beneficial effects on human health. Nutr Rev 11(1):632–638 CrossRef El SN, Karakaya S (2009) Olive tree ( Olea europaea) leaves: potential beneficial effects on human health. Nutr Rev 11(1):632–638 CrossRef
Zurück zum Zitat Feltonstein MW, Schühly W, Warnick JE et al (2004) Anti-inflammatory and anti-hyperalgesic effects of sesquiterpine lactones from Magnolia and Bear’s foot. Pharmacol Biochem Behav 79(2):299–302 CrossRef Feltonstein MW, Schühly W, Warnick JE et al (2004) Anti-inflammatory and anti-hyperalgesic effects of sesquiterpine lactones from Magnolia and Bear’s foot. Pharmacol Biochem Behav 79(2):299–302 CrossRef
Zurück zum Zitat Franklin SJ, Dickinson SE, Karlage KL et al (2014) Stability of sulforaphane for topical formulation. Drug Dev Ind Pharm 40(4):494–502 CrossRefPubMed Franklin SJ, Dickinson SE, Karlage KL et al (2014) Stability of sulforaphane for topical formulation. Drug Dev Ind Pharm 40(4):494–502 CrossRefPubMed
Zurück zum Zitat Fu Y, Zhou H, Wang S et al (2014) Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses. PLoS One 9:e98137 CrossRefPubMedPubMedCentral Fu Y, Zhou H, Wang S et al (2014) Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses. PLoS One 9:e98137 CrossRefPubMedPubMedCentral
Zurück zum Zitat Gayathri B, Manjula N, Vinaykumar KS et al (2007) Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. Int Immunopharmacol 7(4):473–482 CrossRefPubMed Gayathri B, Manjula N, Vinaykumar KS et al (2007) Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. Int Immunopharmacol 7(4):473–482 CrossRefPubMed
Zurück zum Zitat Grzanna R, Lindmark L, Frondoza CG (2005) Ginger—an herbal medicinal product with broad anti-inflammatory actions. J Med Food 8(2):125–132 CrossRefPubMed Grzanna R, Lindmark L, Frondoza CG (2005) Ginger—an herbal medicinal product with broad anti-inflammatory actions. J Med Food 8(2):125–132 CrossRefPubMed
Zurück zum Zitat Gyurkovska V, Alipieva K, Maciul A et al (2011) Anti-inflammatory activity of Devil’s claw in vitro systems and their active constituents. Food Chem 125(1):171–178 CrossRef Gyurkovska V, Alipieva K, Maciul A et al (2011) Anti-inflammatory activity of Devil’s claw in vitro systems and their active constituents. Food Chem 125(1):171–178 CrossRef
Zurück zum Zitat Hernández-Ortega M, Ortiz-Moreno A, Hernández-Navarro MD, et al (2012) Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper ( Capsicum annuum L.) J Biomed Biotechnol ( Article ID 524019) Hernández-Ortega M, Ortiz-Moreno A, Hernández-Navarro MD, et al (2012) Antioxidant, antinociceptive, and anti-inflammatory effects of carotenoids extracted from dried pepper ( Capsicum annuum L.) J Biomed Biotechnol ( Article ID 524019)
Zurück zum Zitat Hodge G, Hodge S, Han P (2002) Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 48:209–215 CrossRefPubMed Hodge G, Hodge S, Han P (2002) Allium sativum (garlic) suppresses leukocyte inflammatory cytokine production in vitro: potential therapeutic use in the treatment of inflammatory bowel disease. Cytometry 48:209–215 CrossRefPubMed
Zurück zum Zitat Jang MH, Lim S, Han SM et al (2003) Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci 93:367–371 CrossRefPubMed Jang MH, Lim S, Han SM et al (2003) Harpagophytum procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. J Pharmacol Sci 93:367–371 CrossRefPubMed
Zurück zum Zitat Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14(2):141–153 PubMed Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14(2):141–153 PubMed
Zurück zum Zitat Khdair A, Chen D, Patil Y et al (2010) Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance. J Control Release 141:137–144 CrossRefPubMed Khdair A, Chen D, Patil Y et al (2010) Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance. J Control Release 141:137–144 CrossRefPubMed
Zurück zum Zitat Kim JH, Kim SJ (2014) Overexpression of microRNA-25 by withaferin A induces cyclooxygenase-2 expression in rabbit articular chondrocytes. J Pharmacol Sci 125:83–90 CrossRefPubMed Kim JH, Kim SJ (2014) Overexpression of microRNA-25 by withaferin A induces cyclooxygenase-2 expression in rabbit articular chondrocytes. J Pharmacol Sci 125:83–90 CrossRefPubMed
Zurück zum Zitat Kim SJ, Sancheti SA, Sancheti SS et al (2010) Effect of 1,2,3,4,6-penta- O-galloyl-beta- d-glucose on elastase and hyaluronidase activities and its type II collagen expression. Acta Pol Pharm 67:145–150 PubMed Kim SJ, Sancheti SA, Sancheti SS et al (2010) Effect of 1,2,3,4,6-penta- O-galloyl-beta- d-glucose on elastase and hyaluronidase activities and its type II collagen expression. Acta Pol Pharm 67:145–150 PubMed
Zurück zum Zitat Lafeber M, Spiering W, van der Graaf Y et al (2013) The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease. Am Heart J 166(2):282–289 CrossRefPubMed Lafeber M, Spiering W, van der Graaf Y et al (2013) The combined use of aspirin, a statin, and blood pressure-lowering agents (polypill components) and the risk of vascular morbidity and mortality in patients with coronary artery disease. Am Heart J 166(2):282–289 CrossRefPubMed
Zurück zum Zitat Li XY, Zong SL, Chen FY et al (2012) Three novel immunosuppressive steroidal glycosides from the stems of Stephanotis mucronata. Nat Prod Commun 7(10):1269–1270 PubMed Li XY, Zong SL, Chen FY et al (2012) Three novel immunosuppressive steroidal glycosides from the stems of Stephanotis mucronata. Nat Prod Commun 7(10):1269–1270 PubMed
Zurück zum Zitat Li XJ, Yang YJ, Li YS et al (2016) α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol 179(17):22–26 CrossRefPubMed Li XJ, Yang YJ, Li YS et al (2016) α-Pinene, linalool, and 1-octanol contribute to the topical anti-inflammatory and analgesic activities of frankincense by inhibiting COX-2. J Ethnopharmacol 179(17):22–26 CrossRefPubMed
Zurück zum Zitat Liu Z, Zhong JY, Gao EN et al (2014) Effects of glycyrrhizin and licorice flavonoids on LPS-induced cytokines expression in macrophages. China J Chin Mater Med 39(19):3841–3845 Liu Z, Zhong JY, Gao EN et al (2014) Effects of glycyrrhizin and licorice flavonoids on LPS-induced cytokines expression in macrophages. China J Chin Mater Med 39(19):3841–3845
Zurück zum Zitat Maione F, Russo R, Khan H et al (2016) Medicinal plants with anti-inflammatory activities. Nat Prod Res 30(12):1343–1352 CrossRefPubMed Maione F, Russo R, Khan H et al (2016) Medicinal plants with anti-inflammatory activities. Nat Prod Res 30(12):1343–1352 CrossRefPubMed
Zurück zum Zitat Manglani PR, Arif MA (2006) Multidrug therapy in leprosy. J Indian Med Assoc 104(12):686–688 PubMed Manglani PR, Arif MA (2006) Multidrug therapy in leprosy. J Indian Med Assoc 104(12):686–688 PubMed
Zurück zum Zitat Mohamed AA, Ali SI, El-Baz FK et al (2014) Chemical composition of essential oil and antimicrobial activities of crude extracts of Commiphora myrrha resin. Ind Crops Prod 57:10–16 CrossRef Mohamed AA, Ali SI, El-Baz FK et al (2014) Chemical composition of essential oil and antimicrobial activities of crude extracts of Commiphora myrrha resin. Ind Crops Prod 57:10–16 CrossRef
Zurück zum Zitat Mohan Maruga Raja KK, Mishra SH (2010) Comprehensive review of Clerodendrum phlomidis: a traditionally used bitter. J Chin Integr Med 8(6):510–524 CrossRef Mohan Maruga Raja KK, Mishra SH (2010) Comprehensive review of Clerodendrum phlomidis: a traditionally used bitter. J Chin Integr Med 8(6):510–524 CrossRef
Zurück zum Zitat Morris T, Stables M, Hobbs A et al (2009) Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 183(3):2089–2096 CrossRefPubMed Morris T, Stables M, Hobbs A et al (2009) Effects of low-dose aspirin on acute inflammatory responses in humans. J Immunol 183(3):2089–2096 CrossRefPubMed
Zurück zum Zitat Mutabingwa TK (2005) Atremisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy. Acta Trop 95(3):305–315 CrossRefPubMed Mutabingwa TK (2005) Atremisinin-based combination therapies (ACTs): best hope for malaria treatment but inaccessible to the needy. Acta Trop 95(3):305–315 CrossRefPubMed
Zurück zum Zitat Nambi P, Aiyar N (2003) G protein-coupled receptors in drug discovery. Assay Drug Dev Technol 1(2):305–310 CrossRefPubMed Nambi P, Aiyar N (2003) G protein-coupled receptors in drug discovery. Assay Drug Dev Technol 1(2):305–310 CrossRefPubMed
Zurück zum Zitat Neubauer A (2017) Immunotherapy of cancer with checkpoint inhibitors: not only in malignant melanoma. Der Internist 58(4):409–423 CrossRefPubMed Neubauer A (2017) Immunotherapy of cancer with checkpoint inhibitors: not only in malignant melanoma. Der Internist 58(4):409–423 CrossRefPubMed
Zurück zum Zitat Pan R, Dai Y, Gao X et al (2009) Scopolin isolated from Erycibe obtusifolia Benth stems suppresses adjuvant-induced rat arthritis by inhibiting inflammation and angiogenesis. Int Immunopharmacol 9:859–869 CrossRefPubMed Pan R, Dai Y, Gao X et al (2009) Scopolin isolated from Erycibe obtusifolia Benth stems suppresses adjuvant-induced rat arthritis by inhibiting inflammation and angiogenesis. Int Immunopharmacol 9:859–869 CrossRefPubMed
Zurück zum Zitat Pappová L, Jošová M, Kazimierová I, Sutovska M, Franova S (2016) Combination therapy with budesonide and salmeterol in experimental allergy inflammation. In: Pulmonary infection and inflammation. Springer Publishing, pp 25–34 Pappová L, Jošová M, Kazimierová I, Sutovska M, Franova S (2016) Combination therapy with budesonide and salmeterol in experimental allergy inflammation. In: Pulmonary infection and inflammation. Springer Publishing, pp 25–34
Zurück zum Zitat Pareek A, Suthar M, Rathore GS et al (2011) Feverfew ( Tanacetum parthenium L.): a systematic review. Pharmacog Rev 5(9):103–110 CrossRef Pareek A, Suthar M, Rathore GS et al (2011) Feverfew ( Tanacetum parthenium L.): a systematic review. Pharmacog Rev 5(9):103–110 CrossRef
Zurück zum Zitat Public Assessment Report (2014) Scientific Discussion. TRINOMIA 100/20/2.5 mg hard capsules TRINOMIA 100/20/5 mg hard capsules TRINOMIA 100/20/10 mg hard capsules (acetylsalicylic acid, atorvastatin calcium trihydrate and Ramipril). Registration number in Spain: 74980. EU-procedure number: ES/H/0241/001-003/DC, ES/H/0241/001/E/001-003 Public Assessment Report (2014) Scientific Discussion. TRINOMIA 100/20/2.5 mg hard capsules TRINOMIA 100/20/5 mg hard capsules TRINOMIA 100/20/10 mg hard capsules (acetylsalicylic acid, atorvastatin calcium trihydrate and Ramipril). Registration number in Spain: 74980. EU-procedure number: ES/H/0241/001-003/DC, ES/H/0241/001/E/001-003
Zurück zum Zitat Quinn BA, Dash R, Sarkar S et al (2015) Pancreatic cancer combination therapy using a BH3 mimetic and a synthetic tetracycline. Cancer Res 75:2305–2315 CrossRefPubMedPubMedCentral Quinn BA, Dash R, Sarkar S et al (2015) Pancreatic cancer combination therapy using a BH3 mimetic and a synthetic tetracycline. Cancer Res 75:2305–2315 CrossRefPubMedPubMedCentral
Zurück zum Zitat Ramadan G, Al-Kahtani MA, El-Sayed WM (2014) Anti-inflammatory and antioxidant properties of Curcuma longa (Tumeric) versus Zingiber officinale (Ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation 34(4):291–301 CrossRef Ramadan G, Al-Kahtani MA, El-Sayed WM (2014) Anti-inflammatory and antioxidant properties of Curcuma longa (Tumeric) versus Zingiber officinale (Ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation 34(4):291–301 CrossRef
Zurück zum Zitat Richter M, Winkel AF, Schummer D et al (2014) Pau d-arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway. J Toxicol Sci 2:353–361 CrossRef Richter M, Winkel AF, Schummer D et al (2014) Pau d-arco activates Nrf2-dependent gene expression via the MEK/ERK-pathway. J Toxicol Sci 2:353–361 CrossRef
Zurück zum Zitat Ruhaak LR, Felth J, Karlsson PC et al (2011) Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull 34:774–778 CrossRefPubMed Ruhaak LR, Felth J, Karlsson PC et al (2011) Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull 34:774–778 CrossRefPubMed
Zurück zum Zitat Saklani A, Hegde B, Mishra P et al (2012) NF-κB dependent anti-inflammatory activity of chlorojanerin isolated from Saussurea heteromalla. Phytomedicine 19:988–997 CrossRefPubMed Saklani A, Hegde B, Mishra P et al (2012) NF-κB dependent anti-inflammatory activity of chlorojanerin isolated from Saussurea heteromalla. Phytomedicine 19:988–997 CrossRefPubMed
Zurück zum Zitat Schumacher M, Cerella C, Reuter S et al (2011) Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem ( Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr 6(2):149–160 CrossRefPubMed Schumacher M, Cerella C, Reuter S et al (2011) Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem ( Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway. Genes Nutr 6(2):149–160 CrossRefPubMed
Zurück zum Zitat Spiller F, Alves MK, Vieira SM et al (2008) Anti-inflammatory effects of red pepper ( Capsicum baccatum) on carrageenan- and antigen-induced inflammation. J Pharm Pharmacol 60(4):473–478 CrossRefPubMed Spiller F, Alves MK, Vieira SM et al (2008) Anti-inflammatory effects of red pepper ( Capsicum baccatum) on carrageenan- and antigen-induced inflammation. J Pharm Pharmacol 60(4):473–478 CrossRefPubMed
Zurück zum Zitat Strauss J, Figg WD (2016) Using epigenetic therapy to overcome chemotherapy resistance. Anticancer Res 36(1):1–4 PubMedPubMedCentral Strauss J, Figg WD (2016) Using epigenetic therapy to overcome chemotherapy resistance. Anticancer Res 36(1):1–4 PubMedPubMedCentral
Zurück zum Zitat Su S, Duan J, Chen T et al (2015) Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signalling pathway. Sci Rep 5:13668 CrossRefPubMedPubMedCentral Su S, Duan J, Chen T et al (2015) Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signalling pathway. Sci Rep 5:13668 CrossRefPubMedPubMedCentral
Zurück zum Zitat Süntar I, Akkol EK, Baykal T (2010) Assessment of anti-inflammatory and antiociceptive activities of Olea europaea L. J Med Food 13(2):352–356 CrossRefPubMed Süntar I, Akkol EK, Baykal T (2010) Assessment of anti-inflammatory and antiociceptive activities of Olea europaea L. J Med Food 13(2):352–356 CrossRefPubMed
Zurück zum Zitat Terra X, Montagut G, Bustos M et al (2009) Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 20(3):210–218 CrossRefPubMed Terra X, Montagut G, Bustos M et al (2009) Grape-seed procyanidins prevent low-grade inflammation by modulating cytokine expression in rats fed a high-fat diet. J Nutr Biochem 20(3):210–218 CrossRefPubMed
Zurück zum Zitat Tugwell P, Pincus T, Yocum D et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. N Engl J Med 333(3):137–141 CrossRefPubMed Tugwell P, Pincus T, Yocum D et al (1995) Combination therapy with cyclosporine and methotrexate in severe rheumatoid arthritis. N Engl J Med 333(3):137–141 CrossRefPubMed
Zurück zum Zitat Turner CE, Elshohly MA, Boeren EG (1980) Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod 43(2):169–234 CrossRefPubMed Turner CE, Elshohly MA, Boeren EG (1980) Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod 43(2):169–234 CrossRefPubMed
Zurück zum Zitat Van Voorhis WC, Adams JH, Adelfio R et al (2016) Open source drug discovery with the malaria box compound collection for neglected diseases and beyond. PLoS Pathog 12(7):e1005763 CrossRefPubMedPubMedCentral Van Voorhis WC, Adams JH, Adelfio R et al (2016) Open source drug discovery with the malaria box compound collection for neglected diseases and beyond. PLoS Pathog 12(7):e1005763 CrossRefPubMedPubMedCentral
Zurück zum Zitat Van Wyk B, Wink M (2004) Medicinal Plants of the World. Timber Press, Portland, pp 329–430 Van Wyk B, Wink M (2004) Medicinal Plants of the World. Timber Press, Portland, pp 329–430
Zurück zum Zitat Van Wyk BE, van Oudtshoorn B, Gericke N (2009) Medicinal plants of South Africa, 2nd edn. Briza Publications, Pretoria, pp 162–163 Van Wyk BE, van Oudtshoorn B, Gericke N (2009) Medicinal plants of South Africa, 2nd edn. Briza Publications, Pretoria, pp 162–163
Zurück zum Zitat Watts CR, Rousseau B (2012) Slippery elm, its biochemistry, and use as a complementary and alternative treatment for laryngeal irritation. J Investig Biochem 1(1):17–23 CrossRef Watts CR, Rousseau B (2012) Slippery elm, its biochemistry, and use as a complementary and alternative treatment for laryngeal irritation. J Investig Biochem 1(1):17–23 CrossRef
Zurück zum Zitat Weight SS, Purcell EM, Wilcox C et al (1953) Antibiotic combinations and resistance to antibiotics. Development of resistance during repeated subcultures of Staphylococci and certain Streptococci on media containing penicillin, streptomycin, erythromycin, terramycin, and chloramphenicol used singly and in pairs. J Lab Clin Med 42(6):877–895 Weight SS, Purcell EM, Wilcox C et al (1953) Antibiotic combinations and resistance to antibiotics. Development of resistance during repeated subcultures of Staphylococci and certain Streptococci on media containing penicillin, streptomycin, erythromycin, terramycin, and chloramphenicol used singly and in pairs. J Lab Clin Med 42(6):877–895
Zurück zum Zitat Xie YC, Dong XW, Wu XM et al (2009) Inhibitory effect of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice. Int Immunopharmacol 9(2):194–200 CrossRefPubMed Xie YC, Dong XW, Wu XM et al (2009) Inhibitory effect of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice. Int Immunopharmacol 9(2):194–200 CrossRefPubMed
Zurück zum Zitat Xiong Y, Xiao B, Ma X et al (2009) Effects of Gaultheria yunnanensis on adjuvant arthritis in rats. China J Chin Mat Med 34:2516–2519 Xiong Y, Xiao B, Ma X et al (2009) Effects of Gaultheria yunnanensis on adjuvant arthritis in rats. China J Chin Mat Med 34:2516–2519
Zurück zum Zitat Yang MH, Ali Z, Khan IA et al (2014) Anti-inflammatory activity of constituents isolated from Terminalia chebula. Nat Prod Commun 9(7):965–968 PubMed Yang MH, Ali Z, Khan IA et al (2014) Anti-inflammatory activity of constituents isolated from Terminalia chebula. Nat Prod Commun 9(7):965–968 PubMed
Zurück zum Zitat Ye Y, Chen F, Sun H et al (2008) Stemucronatoside K, a novel C21 steroidal glycoside from Stephanotis mucronata, inhibited the cellular and humoral immune response in mice. Int Immunopharmacol 8:1231–1238 CrossRefPubMed Ye Y, Chen F, Sun H et al (2008) Stemucronatoside K, a novel C21 steroidal glycoside from Stephanotis mucronata, inhibited the cellular and humoral immune response in mice. Int Immunopharmacol 8:1231–1238 CrossRefPubMed
Zurück zum Zitat Zhang D, Liu R, Sun L et al (2011) Anti-inflammatory activity of methyl salicylate glycosides isolated from Gaultheria yunnanensis (Franch.) Rehder. Molecules 16:3875–3884 CrossRefPubMedPubMedCentral Zhang D, Liu R, Sun L et al (2011) Anti-inflammatory activity of methyl salicylate glycosides isolated from Gaultheria yunnanensis (Franch.) Rehder. Molecules 16:3875–3884 CrossRefPubMedPubMedCentral
Metadaten
Titel
Is the pharmaceutical industry’s preoccupation with the monotherapy drug model stifling the development of effective new drug therapies?
verfasst von
Ian Edwin Cock
Publikationsdatum
07.05.2018
Verlag
Springer International Publishing
Erschienen in
Inflammopharmacology / Ausgabe 3/2018
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-018-0488-7