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V. N. Khabarov

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Beschreibung

Hyaluronic acid is an essential part of connective, epithelial and neural tissues, and contributes to cell proliferation and migration. It is used as a stimulating agent for collagen synthesis and is a common ingredient in skin-care products, a multi-billion dollar industry, as it is believed to be a key factor in fighting the aging process.

Hyaluronic Acid: Production, Properties, Application in Biology and Medicine consists of six chapters discussing the various issues of hyaluronic acid research. In Chapter 1, a historical analysis recounts the discovery and milestones of the research leading to the practical applications of hyaluronan. Chapter 2 is dedicated to biological role of the hyaluronic acid in nature, in particular in the human body. The chapter starts from the phylogenesis of hyaluronic acid, then describes hyaluronan functions in human ontogenesis and especially the role which hyaluronan plays in extracellular matrix of the different tissues. Chapter 3 describes the methods to manufacture and purify hyaluronic acid, including the analytical means for assessing quality of the finished product. Chapter 4 discusses the structure and rheological properties of hyaluronic acid considering effects on conformation and biological properties related to molecular weight. In Chapter 5, the physical and chemical methods for modifying the structure of hyaluronan are discussed including cross-linking using bi-functional reagents, solid-phase modification and effects of the combined action of high pressures and shift deformation. The final chapter focuses on the products derived from hyaluronic acid, including therapeutics composed of modified hyaluronan conjugated to vitamins, amino acids and oligo-peptides. The biological roles and medical applications of this polysaccharide have been extensively studied and this book provides a wealth of scientific data demonstrating the critical role of hyaluronic acid and its promise as a multifaceted bio-macromolecule.

Approaching hyaluronic acid from multiple angles, this book links relationships between its biological functions, structure and physical–chemical properties. It will be an invaluable resource to researchers, both industrial and academic, involved in all aspects of hyaluronan-based technologies.

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Veröffentlichungsjahr: 2014

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Hyaluronic Acid

Preparation, Properties, Application in Biology and Medicine

Mikhail A. Selyanin, Petr Ya . Boykov and Vladimir N. Khabarov

Martinex International Research Center, Moscow, Russia

 

 

 

 

Translated from the Russian version by Scientific Editor Felix Polyak

 

 

 

 

This edition first published 2015© 2015 John Wiley & Sons, Ltd.

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Library of Congress Cataloging-in-Publication Data

Khabarov, V. N. (Vladimir N.) Hyaluronic acid : preparation, properties, application in biology and medicine / Mikhail A. Selyanin, Petr Ya. Boykov and Vladimir N. Khabarov ; translated from the Russian version by scientific editor Felix Polyak.  pages cm  Includes bibliographical references and index.

 ISBN 978-1-118-63379-3 (cloth)1. Hyaluronic acid. 2. Organic acids. I. Boykov, P. Ya. II. Selyanin, M. A. (Michael A.) III. Title. QP702.H8H9313 2015 612.015782–dc23

    2014038400

A catalogue record for this book is available from the British Library.

ISBN: 978-1-118-63379-3 (HB)

This book is dedicated to our daughters Daria, Maria and Vasilisa

 

Nature is not as you imagine her:She’s not a mold, nor yet a soulless mask-She is made up of soul and freedomShe is made up of love and speech …

F.I. Tyutchev (Russian Poet)

Foreword

In March 2012, I came across a book about hyaluronic acid, which had recently been published in Russian1. I read it with growing interest. I found it extremely educational and insightful, especially the chapters about biology and medical applications of hyaluronic acid (HA). Surprisingly, when I attempted to find other recently published manuscripts, my searches returned no results. I use the word ‘surprisingly’, because there is enormous interest in this compound and an increasing, even exponential growth in the application and use of HA-based products in the cosmetic industry as well as in medicine. There is no doubt that we will see even an broader application of HA to these areas in the near future.

I found this book very thorough in its description and analysis of HA and very well written. It covered all aspects of HA; its history and discovery, its biological role and functions in the body, production and purification, structure and rheological properties, chemical modifications, application in medicine, cosmetology and aesthetic medicine. It should be taken into consideration that the manuscript was written several years ago, so the chapter about HA production could be seen as outdated. Nevertheless, we decided to leave it intact in this version, because it contains important information about HA purification for industrial needs. Additionally, it serves to allow the authors to present their significant achievement with regard to the chemical modification of HA, an accomplishment that has opened the doors to many new products.

As I mentioned, the book was published in Russian, which is why so many potential readers were not able to read it. It did not take much time for me to decide to translate it and try to find a way for English-speaking readers to enjoy the book. I would like to express enormous appreciation to the publishing house John Wiley & Sons, Ltd, for agreeing to publish it.

It is important to mention that the Russian manuscript, in addition to its great scientific value, is written with incredibly beautiful literary flair. I tried with great effort to maintain the original style and to give the English readership the opportunity to enjoy it as much as I did. It took more than a year to translate and edit the book and now it is ready to meet the readers. I would like to express my warmest appreciation to everybody who has helped me to prepare the English manuscript, especially the editors from John Wiley & Sons, who were very supportive in every step during the preparation of the manuscript.

As the authors mentioned in their Introduction, we appreciate each and every critical comment, which we will take on board in our efforts to improve upon this first version.

Felix Polyak, PhD

Note

1

The original Russian language version was published in 2012 by Prakticheskaya Meditsina in Moscow: V.N. Khabarov, P.Ya. Boykov, M.A. Selyanin,

Hyaluronic acid

. Moscow: Prakticheskaya meditsina, 2012 (in Russian).

Introduction

‘Biopolymers’ is the common (or general) name for biological macromolecules, which include proteins, nucleic acids and polysaccharides. The existence of the main processes of life is determined by interaction of these substances. Hyaluronic acid possesses one of the leading places among them; it is not accidentally called ‘a wonderful evolution invention’. It would not be easy to come across a monograph dedicated to a single particular compound among scientific publications.

Hyaluronic acid is polysaccharide that was discovered 80 years ago. Even today, it continues to surprise researchers with its unique properties in various areas of chemistry, biology and medicine.

For example, the medical aspects include the study of the hyaluronan role in fertilization, embryogenesis, development of immune responses, wound healing in infectious and oncological diseases, in ageing processes and in aesthetic medicine problem solutions. Hyaluronan is involved in numerous biological processes. It is present in practically all body tissues, where it plays its role in the cell activity regulation or, on the other hand, slows down cell division, migration and is involved in the reorganization of chromatin structure and gene switch.

The natural question is, how did such a variety of physiological and functional properties of this polysaccharide originated, despite its quite simple chemical structure? To clarify this issue even partially, the authors attempted to link the biological functions of hyaluronic acid with the general principles of the structure and physicochemical properties, using a multidisciplinary approach.

The manuscript consists of six chapters. Many issues are discussed with the different levels of complexity and with different degrees of completeness. Every chapter has its own bibliography.

The first chapter describes the history of hyaluronic acid discovery, the main milestones of its research and practical application. The largest chapter, Chapter 2, is dedicated to the biological role of the hyaluronic acid in nature, in particular in the human body. The chapter starts from the phylogenesis of hyaluronic acid, then describes hyaluronan functions in human ontogenesis and especially the role that hyaluronan plays in the extracellular matrix of the different tissues.

The problems of production and purification of hyaluronic acid are discussed in detail in Chapter 3. The comparable data of the commercial products are presented in Chapter 3 as well. The structure and rheological properties are discussed in Chapter 4. The discussion is united by a general idea about cooperative conformational transformations as the main phenomena that manifest bio-specificity of hyaluronic acid as well its unique effect of the relationships of biological properties from molecular mass. The physical and chemical methods of hyaluronan structural modification are presented in Chapter 5. It presents reactions of the macro-molecule cross-linking with bi-functional reagents as well as highly promising method of hyaluronic acid solid state modification. This method, which applies both high pressure and sheer deformation, seems to be very promising both scientifically and practically. The application of the solid state approach allows production of the unique medical products, even now. These preparations, which belong to the class of drug-less (or non-drug) macro-molecular therapeutic products, are prepared from hyaluronan, modified with different vitamins, amino acids and oligopeptides. The final Chapter 6 provides overview of the medical application of hyaluronic acid. In addition to broad application in aesthetic medicine and mesotherapy, hyaluronan has become very popular in such areas as ophthalmology, arthrology, wound healing, immunology, oncology and so on. With better understanding of the biological role of hyaluronan and development of the chemical and physical methods of its derivatization, we can expect increasing role of hyaluronic acid and its products in medicine.

The readers will find that the central part of the book is dedicated to the biological role and medical application of that polysaccharide. The comprehensive scientific material allowed the authors have a new look at the extremely important place of hyaluronic acid in the multi-face world of bio-molecules.

The book is intended for the broad range of the readers – students, professors and researchers, who are interested in the chemistry of biopolymers, molecular biology and medicine.

The authors are extremely grateful for the valuable advice that they received from Professor A. Shilov, Professor N. Milanov, Professor A. Zeleneckiy, Professor A. Shehter, Dr A. Safoyan, Professor I. Samoilenko and Dr V. Volkov. These sincere words are addressed to everybody who helped to prepare this manuscript.

The authors admit that the book is obviously not free from drawbacks, caused by the broad amount of factual material and are grateful in advance for critical comments.

1The History of Hyaluronic Acid Discovery, Foundational Research and Initial Use

1.1 Discovery

In 1934, Karl Meyer and John Palmer wrote in the Journal of Biological Chemistry about an unusual polysaccharide with an extremely high molecular weight isolated from the vitreous of bovine eyes [1]. Being the first to mention it, they gave the new substance the name hyaluronic acid (HA, the modern name ‘hyaluronan’) derived from ‘hyaloid’ (glassy glass-like in appearance) and ‘uronic acid’. While Meyer and Palmer are generally considered to have discovered hyaluronic acid, it is fair to mention that as far back as 1918 Levene and Lopez-Suarez had isolated a new polysaccharide from the vitreous body and cord blood that they called ‘mucoitin-sulfuric acid’ [2]. It consisted of glucosamine, glucuronic acid and a small amount of sulfate ions. It is now clear this substance was actually hyaluronic acid extracted together with a mixture of sulfated glycosaminoglycans.

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