Phytotherapies – Efficacy, Safety, and Regulation

<p>List of Contributors xvii</p>
<p>Preface xxi</p>
<p>1 Phytotherapies Past, Present, and Future 1<br />Iqbal Ramzan and George Q. Li</p>
<p>1.1 Overview of Phytotherapy 1</p>
<p>1.1.1 Definition 1</p>
<p>1.1.2 International Trend in the Usage of Complementary Medicines 2</p>
<p>1.2 Preclinical Research on Phytotherapies 3</p>
<p>1.2.1 Pharmacognosy and Quality Standardization of Phytotherapies 3</p>
<p>1.2.2 Pharmacological Studies and Identification of Bioactive Compounds 4</p>
<p>1.2.3 Application of Proteomics and Metabolomics in Phytotherapy Research 5</p>
<p>1.3 Clinical Research on Phytotherapies 6</p>
<p>1.3.1 Efficacy of Popular Phytotherapies 6</p>
<p>1.3.2 Chinese Herbal Medicines 7</p>
<p>1.3.3 Food Nutrition and Translational Research 7</p>
<p>1.4 Safety of Phytotherapies 8</p>
<p>1.5 Profile of Research in Complementary Medicine 9</p>
<p>1.5.1 International Profile 9</p>
<p>1.5.2 Australian Profile of Research in Complementary Medicines 10</p>
<p>1.6 Summary and Future Directions 12</p>
<p>References 12</p>
<p>2 Quality Control and Quality Assurance of Phytomedicines: Key Considerations, Methods, and Analytical Challenges 18<br />Wai ]Ping Yau, Cheong Hian Goh, and Hwee ]Ling Koh</p>
<p>2.1 Introduction 18</p>
<p>2.2 Key Considerations in Qc/Qa of Phytomedicines 20</p>
<p>2.2.1 Identification and Good Agricultural and Collection Practices (GACP) 20</p>
<p>2.2.2 Contamination 22</p>
<p>2.2.3 Substitution 25</p>
<p>2.2.4 Adulteration 25</p>
<p>2.2.5 Contents and Standardization 26</p>
<p>2.2.6 Stability 26</p>
<p>2.2.7 Processing 26</p>
<p>2.3 Methods for Qc/Qa of Phytomedicines 27</p>
<p>2.3.1 Macroscopic Evaluation 27</p>
<p>2.3.2 Microscopic Evaluation 27</p>
<p>2.3.3 Physicochemical Analysis 29</p>
<p>2.3.4 Chemical Fingerprinting 29</p>
<p>2.3.5 DNA Fingerprinting 35</p>
<p>2.3.6 Omics Technology 36</p>
<p>2.4 Challenges 37</p>
<p>2.5 Conclusions 40</p>
<p>References 40</p>
<p>3 Preclinical (In Vivo) and Laboratory (In Vitro) Evidence of Phytomedicine Efficacy 49<br />Mohi Iqbal Mohammed Abdul and Tom Hsun ]Wei Huang</p>
<p>3.1 Introduction to Development of Drugs from Nature 49</p>
<p>3.2 Use of In Vitro and in Vivo Models in Herb Drug Research: Learning Thus Far 50</p>
<p>3.2.1 In Vitro Assays 50</p>
<p>3.2.2 In Vivo Assays 51</p>
<p>3.3 Cardiovascular ] and Stroke ]Related Diseases: In Vitro and In Vivo Focus 53</p>
<p>3.3.1 Cardiovascular Diseases 53</p>
<p>3.3.2 Stroke 55</p>
<p>3.4 Conclusions 60</p>
<p>References 61</p>
<p>4 Clinical Efficacy Trials with Natural Products and Herbal Medicines 65<br />Christina L. Nance</p>
<p>4.1 Introduction 65</p>
<p>4.2 Trials in Various Disease States 66</p>
<p>4.2.1 Profile: RCT of Natural Product in Rheumatoid Arthritis (RA) 66</p>
<p>4.2.2 Asthma 67</p>
<p>4.2.3 Cancer 68</p>
<p>4.2.4 Cardiovascular Disease 68</p>
<p>4.2.5 Diabetes 69</p>
<p>4.2.6 Dermatology 70</p>
<p>4.2.7 Gastroenterology 70</p>
<p>4.2.8 Viral Infections 72</p>
<p>4.3 Natural Product: Green Tea 73</p>
<p>4.3.1 Green Tea Catechin, Epigallocatechin Gallate (EGCG) 73</p>
<p>4.4 Egcg Clinical Trials 75</p>
<p>4.4.1 Polyphenon E 75</p>
<p>4.4.2 Safety, Toxicity, and Pharmacokinetics 75</p>
<p>4.4.3 Metabolism 76</p>
<p>4.4.4 Clinical Studies 76</p>
<p>4.4.5 Cancer Studies 77</p>
<p>4.5 Human Clinical Study: Egcg and Hiv ]1 Infection 78</p>
<p>4.5.1 Translational Medicine: EGCG: Bench ]to ]Bedside 78</p>
<p>4.5.2 Phase I Clinical Trial: Polyphenon E in HIV ]1 Infection 79</p>
<p>4.6 Conclusion 80</p>
<p>References 80</p>
<p>5 Novel Formulations and Drug Delivery Systems for Phytotherapies 89<br />Shengpeng Wang, Meiwan Chen, Qi (Tony) Zhou, and Hak ]Kim Chan</p>
<p>5.1 Limitations of Conventional Formulations for Herbal Medicines 89</p>
<p>5.1.1 Barriers in Physicochemical and Biological Properties 89</p>
<p>5.1.2 Challenges in Quality and Safety Assurance 90</p>
<p>5.1.3 Conventional Formulations Limit the Therapeutic Efficacy of Herbal Medicines 90</p>
<p>5.2 Crucial Issues of Developing Novel Delivery Systems for Herbal Medicines 91</p>
<p>5.2.1 How Novel Delivery Systems Follow the Tradition? 91</p>
<p>5.2.2 Pharmacokinetic Research on Delivery Systems for Herbal Medicines 92</p>
<p>5.2.3 Safety Considerations on Delivery Systems for Herbal Medicines 92</p>
<p>5.3 Novel Delivery Systems of Herbal Medicines 93</p>
<p>5.3.1 Pulmonary Delivery of Herbal Medicines 93</p>
<p>5.3.2 Nanocarriers of Herbal Medicines for Drug/Gene Delivery 94</p>
<p>5.3.3 Surface Modification of Nanocarriers by Herbal Medicines 95</p>
<p>5.3.4 Herbal Medicines as Photosensitizers for Photodynamic Therapy 95</p>
<p>5.4 Summary 96</p>
<p>References 97</p>
<p>6 Phytotherapies Used by Indigenous Populations 101<br />Bradley S. Simpson and Susan J. Semple</p>
<p>6.1 Introduction 101</p>
<p>6.2 Phytotherapies of Indigenous Australians 103</p>
<p>6.2.1 Introduction 103</p>
<p>6.2.2 Philosophy and Knowledge Transmission 104</p>
<p>6.2.3 Ailments Treated with Medicinal Plants 106</p>
<p>6.2.4 How Plant Medicines Have Been Used 107</p>
<p>6.2.5 Methods of Plant Preparation 109</p>
<p>6.2.6 Prized and Commonly Used Plants in Australian Indigenous Medicine 111</p>
<p>6.3 Challenges of a Changing Environment 114</p>
<p>6.3.1 Safety of Australian Phytotherapies 115</p>
<p>6.3.2 Development and Regulation of Australian Indigenous Medicines 116</p>
<p>6.3.3 Integration of Traditional and Western Medicine in Indigenous Populations 117</p>
<p>6.4 Conclusions 117</p>
<p>References 118</p>
<p>7 Phytotherapies from Traditional Chinese Medicine 122<br />Michael Rieder</p>
<p>7.1 Traditional Chinese Medicine 122</p>
<p>7.2 Key Concepts in Traditional Chinese Medicine 124</p>
<p>7.3 Herbal Medicine and Traditional Chinese Medicine 126</p>
<p>7.4 Issues in the Development of Phytotherapy from Traditional Chinese Medicine 130</p>
<p>7.5 Phytotherapies Developed from Traditional Chinese Medicine 131</p>
<p>7.6 Huang Qin Tang and the Development of Phy906 134</p>
<p>7.7 Ginseng 136</p>
<p>7.8 Moving Forward 138</p>
<p>References 138</p>
<p>8 Integrating Traditional Greco ]Arab and Islamic Diet and Herbal Medicines in Research and Clinical Practice 142<br />Bashar Saad</p>
<p>8.1 Introduction 142</p>
<p>8.2 Food Therapy in Greco ]Arab and Islamic Medicine 147</p>
<p>8.2.1 Honey 148</p>
<p>8.2.2 Olive Oil 149</p>
<p>8.2.3 Dates 151</p>
<p>8.2.4 Carob (Ceratonia siliqua) 152</p>
<p>8.2.5 Fig (Ficus carica) 153</p>
<p>8.2.6 Pomegranate (Punica granatum) 153</p>
<p>8.2.7 Garlic (Allium sativum) and Onion (Allium cepa) 154</p>
<p>8.2.8 Edible Wild Plants 154</p>
<p>8.3 Medicinal Plants 157</p>
<p>8.3.1 Black Seed (Nigella sativa) 160</p>
<p>8.3.2 Fenugreek (Trigonella foenum ]graecum) 167</p>
<p>8.3.3 Sage (Salvia officinalis) 168</p>
<p>8.3.4 Khella (Ammi visnaga) 168</p>
<p>8.3.5 Milk Thistle (Silybum marianum) 168</p>
<p>8.3.6 Marjoram (Origanum majorana) 171</p>
<p>8.3.7 Garlic (Allium sativum) and Onion (Allium cepa) 172</p>
<p>8.3.8 Tayun (Inula viscose) 172</p>
<p>8.3.9 Rocket (Eruca sativa) 172</p>
<p>8.3.10 Nettle (Urtica dioica) 173</p>
<p>8.3.11 Peppermint (Mentha piperita) 173</p>
<p>8.3.12 Chamomile (Chamomilla recutita) 174</p>
<p>8.3.13 Coriander (Coriandrum sativum) 175</p>
<p>8.3.14 Anise (Pimpinella anisum) 175</p>
<p>8.3.15 Rosemary (Rosmarinus officinalis) 175</p>
<p>8.3.16 Devil s Dung (Ferula asafetida) 176</p>
<p>8.3.17 Ginger (Zingiber officinale) 176</p>
<p>References 177</p>
<p>9 Evolution of Herbal Medicines in Europe and its Relationship with Modern Medicine 183<br />Elizabeth M. Williamson and Kelvin Chan</p>
<p>9.1 Background 183</p>
<p>9.2 Historical Perspective 184</p>
<p>9.3 European Herbal Medicine: Relationship with Modern Medicine 194</p>
<p>9.4 Summary 194</p>
<p>References 196</p>
<p>10 Chemical Classification and Chemistry of Phytotherapeutics Constituents 199<br />Pei H. Cui and Colin C. Duke</p>
<p>10.1 Introduction 199</p>
<p>10.2 Phytochemicals 201</p>
<p>10.2.1 Alkaloids 201</p>
<p>10.2.2 Flavonoids 205</p>
<p>10.2.3 Glycosides and Saponins 208</p>
<p>10.2.4 Phytosterols 209</p>
<p>10.2.5 Fatty Acids 212</p>
<p>10.2.6 Essential Oils 214</p>
<p>10.2.7 Terpenes 214</p>
<p>10.3 Other Phytochemicals 215</p>
<p>10.4 Medicinal Effects Relating to Dietary Intake 217</p>
<p>10.4.1 Anti ]oxidants 217</p>
<p>10.4.2 Omega ]3 Long Chain Fatty Acids and Derivatives 220</p>
<p>10.5 Natural Products as Leads for Drug Development 223</p>
<p>10.5.1 Catechol Moiety of Piceatannol: Implication and Significance 224</p>
<p>10.5.2 SAR Studies for Drug Development 226</p>
<p>10.6 Summary 230</p>
<p>References 230</p>
<p>11 Therapeutic Potential of Ginsenosides in Management of Atherosclerosis 236<br />Xiao ]Jing Zhang, Huanxing Su, Yi–Tao Wang, and Jian–Bo Wan</p>
<p>11.1 Introduction 236</p>
<p>11.2 Chemical Diversity of Ginsenosides and Distribution 238</p>
<p>11.3 Anti ]Atherosclerotic Effects of Ginsenosides 240</p>
<p>11.4 Underlying Mechanisms of Ginsenosides Against Atherosclerosis 244</p>
<p>11.4.1 Regulation of Blood Lipid Profile 244</p>
<p>11.4.2 Anti ]oxidant Activity 251</p>
<p>11.4.3 Anti ]vascular Inflammation 252</p>
<p>11.4.4 Effect on Vascular Cells 255</p>
<p>11.4.5 Anti ]platelet Effects 257</p>
<p>11.4.6 Anti ]angiogenesis Effects 257</p>
<p>11.5 Conclusions and Future Perspectives 258</p>
<p>Acknowledgments 258</p>
<p>References 258</p>
<p>12 Phytotherapy Pharmacophores for Major Cellular Drug Targets 268<br />Jennifer A. Ong, Paul W. Groundwater, and David E. Hibbs</p>
<p>12.1 Introduction 268</p>
<p>12.2 What is a Pharmacophore? 269</p>
<p>12.3 Pharmacophore Models of Cardiovascular Drugs 270</p>
<p>12.4 Pharmacophore Models for Anticancer Drugs 285</p>
<p>12.5 Pharmacophore Models for Anti ]Inflammatory Drugs 290</p>
<p>12.6 Pharmacophore Models for Anti ]Infective Drugs 297</p>
<p>12.7 Pharmacophore Models for Neurological Drugs 299</p>
<p>12.8 Pharmacophore Models for Miscellaneous Drugs 305</p>
<p>12.9 Conclusions 309</p>
<p>References 309</p>
<p>13 Use of Kava as a Phytotherapeutic Agent and Kava ]Related Hepatotoxicity 312<br />Dong Fu and Iqbal Ramzan</p>
<p>13.1 Introduction 312</p>
<p>13.2 Active Components in Kava 313</p>
<p>13.3 Therapeutic Applications of Kava 314</p>
<p>13.4 Pharmacology of Kava 314</p>
<p>13.4.1 Anti ]psychotic Effects of Kava 314</p>
<p>13.4.2 Anti ]cancer Effects of Kava 316</p>
<p>13.5 Side Effects of Kava 317</p>
<p>13.6 Hepatotoxicity of Kava 318</p>
<p>13.6.1 Inhibition of Cytochrome P450 Enzymes Activities 318</p>
<p>13.6.2 Reduction of Liver Glutathione 319</p>
<p>13.6.3 Induction of Hepatic Inflammatory Responses 320</p>
<p>13.6.4 Inhibition of Cyclooxygenase Enzyme Activity 320</p>
<p>13.6.5 Inhibition of Hepatic Transporters 321</p>
<p>13.6.6 Damage of Hepatic Mitochondria 321</p>
<p>13.7 Summary and Future Challenges 322</p>
<p>References 323</p>
<p>14 Phytotherapies as New Drug Sources: Gossypol and Curcumin 330<br />Vivian Wan Yu Liao, Rajeshwar Narlawar, David E. Hibbs, and Paul W. Groundwater</p>
<p>14.1 Botanical Sources of Gossypol and Curcumin 330</p>
<p>14.2 Stereoisomerism, Tautomerism, and Reactivity 332</p>
<p>14.2.1 Stereoisomerism 332</p>
<p>14.2.2 Tautomerism 333</p>
<p>14.2.3 Reactivity 333</p>
<p>14.3 Biological Activity of Gossypol and its Analogues 337</p>
<p>14.3.1 Antifertility 337</p>
<p>14.3.2 Anticancer 338</p>
<p>14.3.3 Antiviral 341</p>
<p>14.3.4 Antimalarial 345</p>
<p>14.3.5 Other Biological Activity 346</p>
<p>14.4 Biological Activity of Curcumin and its Analogues 346</p>
<p>14.4.1 Introduction 346</p>
<p>14.4.2 Anticancer 348</p>
<p>14.4.3 Anti ]inflammatory and Antioxidant 354</p>
<p>14.4.4 Curcumin in Neurodegenerative Diseases 357</p>
<p>14.4.5 Antimalarial 359</p>
<p>14.4.6 Other Biological Activity 360</p>
<p>References 360</p>
<p>15 Phytotherapies for the Management of Obesity and Diabetes 370<br />Michel Rapinski and Alain Cuerrier</p>
<p>15.1 Introduction 370</p>
<p>15.2 Plants from the North American Pharmacopoeia 372</p>
<p>15.3 Pharmacological Screening: Providing Empirical Evidence for Phytotherapies 379</p>
<p>15.3.1 Diabetes 379</p>
<p>15.3.2 Obesity 384</p>
<p>15.4 Community ]Based Participation: Developing Phytotherapies from Traditional Knowledge 385</p>
<p>15.5 Conclusions 387</p>
<p>References 387</p>
<p>16 Phytotherapeutics for Cancer Therapy 394<br />Daniel M. ]Y. Sze, Hao Liu, Maureen V. Boost, Raimond Wong, and Stephen Sagar</p>
<p>16.1 Introduction 394</p>
<p>16.2 Anticancer Phytotherapeutics With Nk Enhancement 395</p>
<p>16.2.1 Effects of Clinically Useful Phytocompounds on Cancer Patients NK Cell Immunity, Quality of Life (QoL), and Overall Survival 395</p>
<p>16.2.2 Commonly Used Phytotherapeutics in Cancer Management 395</p>
<p>16.2.3 Phytotherapeutic Formulae for Cancer via NK Modulation 409</p>
<p>16.3 Conclusions 423</p>
<p>References 425</p>
<p>17 Phytomedicines for Fatty Liver Disease and Functional Gastrointestinal Conditions 429<br />George Q. Li, Moon ]Sun Kim, Fangming Jin, and Jun ]Lae Cho</p>
<p>17.1 Introduction 429</p>
<p>17.2 Phytomedicines for Fld 430</p>
<p>17.2.1 Introduction and Pharmacotherapy 430</p>
<p>17.2.2 Treatment of Fatty Liver with Herbal Medicines 433</p>
<p>17.2.3 Common Herbs Used in Fatty Liver Management 433</p>
<p>17.3 Phytomedicines for Ibs 439</p>
<p>17.3.1 Introduction and Pharmacotherapy 439</p>
<p>17.3.2 Treatment of IBS in Traditional Medicine 440</p>
<p>17.3.3 Common Herbs Used in the Management of IBS 440</p>
<p>17.4 Phytomedicines for Constipation 444</p>
<p>17.4.1 Treatment of Constipation with Herbal Medicines 445</p>
<p>17.4.2 Common Herbs Used in the Management of Constipation 446</p>
<p>17.5 Summary and Future Perspectives 448</p>
<p>References 448</p>
<p>18 Phytomedicines for Inflammatory Conditions 464<br />Sigrun Chrubasik ]Hausmann</p>
<p>18.1 Traditional Medicines for Inflammatory Conditions in Europe 464</p>
<p>18.2 Twenty ]First ]Century Update on Paids 465</p>
<p>18.3 Oral Extracts from Salix Species 465</p>
<p>18.3.1 Efficacy 467</p>
<p>18.3.2 Safety 467</p>
<p>18.4 Oral Extracts from Harpagophytum procumbens 468</p>
<p>18.4.1 Efficacy 469</p>
<p>18.4.2 Safety 469</p>
<p>18.5 Oral Avocado Soybean Unsaponifiables 469</p>
<p>18.5.1 Efficacy 470</p>
<p>18.5.2 Safety 473</p>
<p>18.6 Oral Extracts From Tripterygium wilfordii 473</p>
<p>18.6.1 Efficacy 473</p>
<p>18.6.2 Safety 474</p>
<p>18.7 Oral Paids Containing Unsaturated Fatty Acids 475</p>
<p>18.7.1 Efficacy 475</p>
<p>18.7.2 Safety 475</p>
<p>18.8 Other Oral Paids 476</p>
<p>18.9 Topical Paids 477</p>
<p>18.9.1 Efficacy 478</p>
<p>18.9.2 Safety 478</p>
<p>References 478</p>
<p>19 Phytotherapies for Infectious Diseases: Are These Really Useful? 483<br />Gail B. Mahady, Gabrielle Escalante, Pooja Mikkilineni, Laura J. Mahady, Temitope O. Lawal, and Bolanle A. Adeniyi</p>
<p>The History of Medicine 483</p>
<p>19.1 Introduction 484</p>
<p>19.2 Historical Precedent for Natural Products as Antimicrobial Drugs 486</p>
<p>19.3 Are Phytotherapies Useful for the Treatment of Infectious Diseases? 487</p>
<p>19.3.1 Cranberry (Vaccinium macrocarpon Ait) 488</p>
<p>19.3.2 Turmeric (Curcuma longa L.) as an Antimicrobial Agent 492</p>
<p>19.3.3 Ginger (Zingiber officinale L.) as an Antimicrobial Agent 494</p>
<p>19.4 Naturally Occurring Compounds that may Reduce Zoonosis 495</p>
<p>19.5 Synergistic and Additive Effects with Antibiotics 496</p>
<p>19.6 New Emerging Infectious Diseases and those with no Known Treatments 496</p>
<p>19.7 Sars 497</p>
<p>19.8 Reducing Mrsa Carriage 498</p>
<p>19.9 Conclusions 499</p>
<p>References 500</p>
<p>20 Phytomedicines for CNS Disorders: Safety Issues for use with Antiepileptic Drugs 504<br />Sophia Yui Kau Fong, Rosina Yau Mok, Qiong Gao, Yin Cheong Wong, and Zhong Zuo</p>
<p>20.1 Introduction 504</p>
<p>20.2 Methodology of Systematic Literature Search 506</p>
<p>20.3 Pharmacokinetic Interactions 506</p>
<p>20.3.1 Carbamazepine 507</p>
<p>20.3.2 Phenytoin 507</p>
<p>20.3.3 Valproate 510</p>
<p>20.3.4 Diazepam 511</p>
<p>20.3.5 Phenobarbitone 511</p>
<p>20.3.6 Newer Generations of Antiepileptic Drugs 512</p>
<p>20.4 Pharmacodynamic Interactions 512</p>
<p>20.4.1 Antiepileptic Effects 513</p>
<p>20.4.2 Sedative Effects 517</p>
<p>20.4.3 Anxiolytic Effects 520</p>
<p>20.4.4 Memory Impairment Effects 520</p>
<p>20.4.5 Motor Incoordination Effects 523</p>
<p>20.5 Conclusions 524</p>
<p>References 524</p>
<p>21 Phytotherapies: Drug Interactions in Cancer 536<br />Andrew J. McLachlan and Stephen J. Clarke</p>
<p>21.1 Introduction 536</p>
<p>21.2 Use of Herbal and Complementary Medicines by People Living with Cancer 537</p>
<p>21.3 Mechanisms of Phytotherapy Drug Interactions 538</p>
<p>21.4 Selected Examples of Phytotherapy Medicines that have the Potential to Cause Drug Interactions in Cancer 540</p>
<p>21.4.1 Black Cohosh (Cimicifuga racemosa) 540</p>
<p>21.4.2 Echinacea (Echinacea purpurea) 541</p>
<p>21.4.3 Fenugreek (Trigonella foenum graecum) 541</p>
<p>21.4.4 Ginkgo Biloba 542</p>
<p>21.4.5 Asian Ginseng (Panax ginseng) 542</p>
<p>21.4.6 Green Tea (Camellia sinensis) 543</p>
<p>21.4.7 Kava Kava (Piper methysticum Forst. f.) 544</p>
<p>21.4.8 Liquorice (Glycyrrhiza uralensis) 544</p>
<p>21.4.9 Milk Thistle (Silybum marianum) 544</p>
<p>21.4.10 St. John s Wort (Hypericum perforatum) 545</p>
<p>21.4.11 Valerian (Valeriana officinalis) 546</p>
<p>21.5 Future Perspectives: Need for Evidence and Advice to Cancer Patients and Physicians 546</p>
<p>21.6 Conclusions 547</p>
<p>Acknowledgments 547</p>
<p>Conflict of Interest 547</p>
<p>References 547</p>
<p>22 Quality Use of Medicines: Considerations in Phytotherapy 554<br />Lynn Weekes</p>
<p>22.1 Introduction 554</p>
<p>22.1.1 Judicious Use 554</p>
<p>22.1.2 Appropriate Selection 555</p>
<p>22.1.3 Safe and Effective Use 555</p>
<p>22.1.4 The QUM Paradigm 555</p>
<p>22.2 Relevance of Qum for Herbal Medicines 556</p>
<p>22.2.1 Is the QUM Framework Relevant for Herbal Therapies? 556</p>
<p>22.3 Use of Phytotherapies by Consumers 558</p>
<p>22.4 Consumer Attitudes and Beliefs about Herbal Medicines 559</p>
<p>22.4.1 Holistic View of Health and Well ]Being 559</p>
<p>22.4.2 It is Natural, So it Must be Safe 560</p>
<p>22.5 Applying the Qum Framework to Phytotherapies 561</p>
<p>22.5.1 Judicious Use 561</p>
<p>22.5.2 Appropriate Selection 562</p>
<p>22.5.3 Safe and Effective Use 563</p>
<p>22.5.4 Adverse Reactions 563</p>
<p>22.5.5 Interactions 564</p>
<p>22.5.6 Allergy 565</p>
<p>22.5.7 Safe Formulation 565</p>
<p>22.5.8 Effectiveness 565</p>
<p>22.6 Building Blocks for Quality Use of Herbal Medicines 566</p>
<p>22.6.1 Objective Information and Ethical Promotion 566</p>
<p>22.6.2 Education and Training 568</p>
<p>22.6.3 Systems and Interventions 569</p>
<p>22.6.4 Shared Decision Making 569</p>
<p>22.7 Conclusion 570</p>
<p>References 570</p>
<p>23 Intellectual Property and Patent Issues with Phytotherapy Products 573<br />Gint Silins, Jennifer Tan, and Kelvin Chan</p>
<p>23.1 Introduction 573</p>
<p>23.1.1 Historical and Current Aspects of Intellectual Property 573</p>
<p>23.1.2 Types of Intellectual Property Rights 574</p>
<p>23.1.3 Worldwide IP Laws Have Yet to Be Harmonized 575</p>
<p>23.2 Ip Rights Phyto ]Industry 575</p>
<p>23.2.1 IP Protection for Phytotherapy Products and Phytotherapies 575</p>
<p>23.2.2 Patents 576</p>
<p>23.2.3 Patents as IP Assets 576</p>
<p>23.2.4 Patents for Protecting Phyto ]Inventions 577</p>
<p>23.2.5 Exclusions to Patentability 577</p>
<p>23.3 Brief Overview of Patents and the Patenting Process 578</p>
<p>23.3.1 Patent Searching 578</p>
<p>23.3.2 Patent Ownership 578</p>
<p>23.3.3 Patent Filing 579</p>
<p>23.3.4 Examination and Classification 579</p>
<p>23.3.5 Allowance and Grant 579</p>
<p>23.3.6 Extension of Patent Term 579</p>
<p>23.4 Other Types of IP Rights 585</p>
<p>23.4.1 Trade Secrets 585</p>
<p>23.4.2 Regulatory Exclusivity and Restricted Third ]Party Access 585</p>
<p>23.4.3 Plant Variety Protection 586</p>
<p>23.4.4 Industrial Designs 586</p>
<p>23.4.5 Trademarks 586</p>
<p>23.5 Patenting Trends for Phytotherapeutics 587</p>
<p>23.6 Traditional Knowledge and IP Rights 587</p>
<p>Disclaimer 589</p>
<p>References 590</p>
<p>24 International Regulatory Status of Phytotherapies 593<br />Ernest V. Linek</p>
<p>24.1 Introduction 593</p>
<p>24.1.1 Country Law Sources 594</p>
<p>24.1.2 Common Requirement: Good Manufacturing Practices 594</p>
<p>24.2 Specific Country Regulations 596</p>
<p>24.2.1 Current Regulations in Australia 596</p>
<p>24.2.2 Current Regulations in Canada 597</p>
<p>24.2.3 Current Regulations in China 604</p>
<p>24.2.4 Current Regulations in the European Union (EU) 609</p>
<p>24.2.5 Current Regulations in India 616</p>
<p>24.2.6 Current Regulations in Japan 619</p>
<p>24.2.7 Current Regulations: United Kingdom 622</p>
<p>24.2.8 Current Regulations in the United States 625</p>
<p>24.3 Future of Phytotherapies: World Health Organization (Who) 631</p>
<p>Further Reading 634</p>
<p>Index 635</p>