Eclectic Medical Publications

Excerpts from
Complex Herbs - Complete Medicines

Copyright 2003
by Francis Brinker, N.D.

[excerpts]
No reproductions allowed without written consent from the author.
Preface

What is an herb? In botany the understanding of herb is a plant with a fleshy rather than a woody stem, which, after the plant has bloomed and set seed, dies down to the ground. However, the word “herb” has other meanings that expand the concept. The word is derived from the Old Sanskrit bharb, meaning “to eat;” this eventually became the Latin berba, used for “fodder.” The early English used the word herb as synonymous with vegetables. Later, this was restricted to parts of vegetables that grow above ground. In medicine an herb refers to a plant whose properties allow its use therapeutically. Some are also used as seasonings. In the culinary arts, compared to spices herbs are mild fresh or dried leaves, while spices involve more pungent seeds, roots, fruits, flowers, and bark. Generally, an herb is a plant or plant part valued for its medicinal, savory, or aromatic properties. In all of these cases, an herb is a fresh or dried plant or its useful part. Herbs descriptions all involve the intact substance of the plant, including its fiber but sometimes excluding the water. A plant extract is not an herb.

What is a drug? The term drug has different meanings in different times and contexts. Legal definitions and common understandings vary. Most people consider drugs as medicines or substances of abuse, as nonfood items that affect function and sometimes behavior. Herbs and their products are caught in the middle of this web of nomenclature. In the following discussions of herbal medicines, confusion may arise as to the proper designation of these products. A brief explanation is necessary to help guide the reader through this maze. The word ‘drug’ was derived from the Dutch work droog, meaning “dried,” and from the Anglo-Saxon drigan, indicating “to dry.” As recently as 100 years ago in the pharmaceutical profession, drugs were understood as the dried herbs from which medicinal extracts were produced. This is apparent in the many quotations taken from writings by the president of the American Pharmaceutical Association at that time, the Eclectic pharmacist John Uri Lloyd.

During this same period naturopaths were calling themselves drugless practitioners and using common dried herbs and their water extracts, considering them as foods. By naturopathic reckoning, toxic herbs, alcoholic tinctures, concentrated extracts and isolated compounds from botanical remedies were drugs. This belief was supported by the fact that during this time botanical agents comprised half of medications listed in the United States Pharmacopoeia (USP), the official American drug compendium. In addition, the USP contained many isolated compounds derived from plants. In the naturopathic context most nonaqueous derivatives of herbs used as official drugs were undesirable. Synthetic medications, referred to as “coal tar derivatives,” were anathema.

With the passage of time, many alcoholic extracts became accepted by naturopathic doctors as also providing in large part the desirable complex nature of the whole herb. Such preparations as juice, teas, and tinctures can be considered native extracts. Native extracts are liquid fractions prepared by simple extraction procedures from the fresh or dried herb and consumed without further alteration of this form. Another term often used to describe these native extracts is “crude extracts.” Nontoxic herbs and their native extracts are no longer considered as drugs, and their use remains commonplace among the general public. Ultimately, they became so popular that a law was passed to assure continuing access to these and other nutrients. In 1994 the Dietary Supplement Health and Education Act (DSHEA) included herb products under the official designation as dietary supplements in the United States. Herbs and their derivatives are now being included in the National Formulary, a publication of the USP Convention, even though they are not considered as drugs.

The past 50 years has seen an increased medicalization of American culture, along with an increased reliance upon synthesized pharmaceutical medications. Those botanical derivatives that are now officially designated as drugs in the USP are almost exclusively concentrated subfractions or isolated components, many of which have been altered at the molecular level for patent purposes. Even the use of concentrated extracts remains rare in American medicine, compared to European nations and Germany in particular. The emphasis on pharmaceutical extracts of botanicals in Europe has led to increasing clinical studies of these concentrates and has allowed for their official approval there as drugs. These phytopharmaceutical drugs are often concentrated subfractions of native extracts, produced by multiple purification steps using toxic chemical solvents. Yet, when these products are imported to the United States, they qualify under the DSHEA regulations as dietary supplements and are referred to as herbs. Such concentrated fractions for all intents and purposes are increasingly like conventional pharmaceutical drugs, the isolated compounds typically preferred in American medical practice.

The reduction of an intact complex herb to a native extract using water and/or ethanol represents the first level of fractionation of botanicals. A diminished complexity results, but these traditional selective liquid extracts are quite appropriate for specific conditions. The reduction of a native extract to a concentrated fraction allows a lower dose in exchange for even more limited activity. The final stage of reduction to a purified chemical compound provides a greater selective strength. Typically, an isolate is more rapidly absorbed and reaches greater tissue concentrations, but the greater bioavailability and potency is often associated with elevated risks as well.

Each person is confronted with important life choices each day. When it comes to health care and medicinal agents, such choices abound. Each individual must decide whether their preference should be for the greatest nutrient and phytochemical complexity as found in the whole herb and in a somewhat reduced content with native extracts. Or, are the concentrated fractions or their isolated drug constituents more desirable? It becomes more confusing when the extract is called a herb and the fraction is referred to as an extract. It is exasperating when the fraction is marketed as an herb. Dried herb, extract, fraction or isolate, each at some time likely to be called a drug, all have a living plant as their source. How close to the source do you want to be? This book provides information to help understand the differences, so that decisions can be made with a better grasp of the issues involved.

The second part of this book looks at examples of herbs whose products are popular in America. The uses of the different types of product forms are discussed from a historical perspective. This is intended to show both how our understanding of the herb, its extracts, and its fractions and isolated components has developed and how the uses of the various forms are in some ways similar and in other ways different. Emphasis on the acknowledged activities and uses for each of the forms provides a means for recognizing the unique features of each. While each form has some features that are similar, each also needs to be understood in terms of its own peculiar nature to appreciate its optimal applications in health care. Since the whole is greater than the sum of its parts, the potential found in the living plant remains the basis for each different form.

Introduction

MEDICINE AS FOOD
[The following is taken from end of this first section of the Introduction.]

Ultimately, the standard of high quality is the fresh plant part that contains the desirable features. This is the form that rightfully deserves to be described by the plant name. Whatever is made from the fresh part should be described in relation to this form. Dr. Ed Alstat likes to use a common food to illustrate this issue. Grapes (Vitis vinifera) are known to be powerful contributors to health as demonstrated by Johanna Brandt and her “grape cure,’ in which the whole fresh grape was consumed with its skin, pulp, and seeds. Visit any grocery store and find in the fruit aisle fresh red and green grapes with and without seeds. Another aisle has raisins, dark and golden. Moving through the store you can find white and Concord grape juices. In the condiment aisle will be red wine vinegar. In the freezers are found frozen concentrated grape juices. Many states allow a liquor section where many varieties and vintages of wine will be available, along with distilled brandy. Now, if grapes were like most herbs, these products would all be called “grapes.” Does it matter if it’s raisins or red wine that you put on your bran for breakfast?

What are some of the differences in these various forms of grapes? In 2000 Karadeniz and others found that compared to fresh Thompson Seedless grapes (Vitis vinifera cv. sultanina), loss of the major phenolic acids were on the order of 90% in sun-dried raisins and air-dried dark or golden (treated with sulfur dioxide - SO2) raisins made from these grapes, with golden raisins retaining the most. Procyanidins and catechins in the raisin samples were completely degraded, while the flavonol content was not greatly influenced. Spanos and Wrolstad in 1990 looked at juice processing of Thompson Seedless grapes. They found that SO2 addition gave higher levels of phenolic acids and procyanidins but not quercetin glycosides, while enzymatic clarification hydrolyzed the latter two. Heating during bottling and concentration reduced procyanidins, while storing concentrates for 9 months at room temperature markedly lowered phenolic acids and completely destroyed procyanidins and quercetin glycosides. Seedless grapes lack certain anti-oxidants to begin with. Of the 30 types of oligomeric procyanidins in grape seeds, Souquet and others found in 1996 that these are limited to the 7 in the skins of Merlot grapes (V. vinifera var. Merlot). Furthermore, the grape skin and seeds with their procyanidins and the skin’s anthocyanins, phenolic acids, and flavonols are removed in the production of white wine. These phenolics make up important taste and health components that vary among Bordeaux red wines such as Merlot, as described in 1984 by Salagoity-Auguste and Bertrand. Sources, parts, and processing matter greatly.

Karadeniz F, et al. Polyphenolic compostition of raisins. J. Agric. Food Chem., 48:5343-50, 2000
Salagoity-Auguste M-H & Bertrand A. Wine phenolics – Analysis of low molecular weight components by high performance liquid chromatography. J. Sci. Foood Agric. 35:1241-7, 1984
Souquet J-M, et al. Polymeric proanthocyanidins from grape skins. Phytochem. 43(2):509-12, 1996
Spanos GA & Wrolstad RE. Influence of processing and storage on the phenolic composition of Thompson Seedless grape juice. J. Agric. Food Chem. 38:1565-71, 1990

The Challenge Of Complexity –
Distinctions Between Herb Products

Table 1.Herb Product Continuum from Most to Least Complex

The order in this list follows a steady reduction in content of plant compounds that may serve as adjuvants, agonists, antagonists, buffers, emulsifiers, enzymes, fiber, metabolism inducers and inhibitors, preservatives, stabilizers, synergists, etc. In general, some carriers (solvents, fillers, binders), preservatives, stabilizers, flavors, and/or other additives are present in most forms listed below. These additives usually range in relative content from the lesser amount with herbs (such as capsules) to greater amounts in native extracts (such as ethanol), simplified fractions and isolates.

MOST COMPLEX

LEAST COMPLEX

HERB – intact plant or utilized structures retaining fiber and complete phytochemical content

• Common name(s) – describes herb or, sometimes, several similar herbs
• Scientific name – identifies plant species distinct from generically similar plants
• Plant part – medicinally active portion(s); often distinct parts have different activities
• Fresh – recently separated from entire living plant; cells and tissues still alive and growing
• Frozen –plant content preserved by suspending animation with extremely low temperature
• Dried (1.freeze-dried > 2.shade > 3.oven > 4.sun) – removal of water to minimize changes by:
  1. freezing plant and slowly heating to remove water vapor in vacuum;
  2. slowly drying away from intense light;
  3. rapidly drying in high heat
  4. rapidly drying in intense light
• bulk – dry herb parts in whole uncut form cut/sifted –dry herb parts chopped into slices or small pieces to increase surface area
• powdered – dried herb parts ground into fine powder to greatly increase surface area

NATIVE EXTRACTS (Complex Fractions) – primary soluble portion of phytochemicals removed from the herb by a liquid solvent and/or heat and/or pressure, used to draw multiple types of compounds out of herb tissue matrix and into solution

• Fresh extracts: liquid portions taken from living plant tissues
  • fresh juice – recently expressed watery liquid from one or more plant parts
  • freeze-dried juice – fresh juice frozen, then water slowly removed under a vacuum
  • frozen concentrate – juice with most water removed, then frozen
  • stabilized juice – bottled juice sealed under a vacuum, usually pasteurized (heated)
  • preserved juice – juice with additives (like alcohol) to prevent fermentation/degradation
  • green (specific) tincture – fresh plant part extracted at fresh herb weight to solvent volume ratio of 1:1 using a water/alcohol mixture
  • homeopathic mother tincture – fresh plant extract at 1:10 ratio with water/alcohol mixture
• Liquid extracts of dried plant part: complex mixture of plant compounds removed with a solvent
  • decoction – solution from simmering cut herb in water at low heat for > 15 minutes
  • infusion – solution from soaking cut herb in hot (boiled) water for 5-15 minutes
  • cold infusion – solution from soaking cut herb in water at room-temperature for hours
  • tincture – extract of dried plant part, dry herb weight to solvent volume ratio usually 1:4 or 1:5, soaked in water/alcohol solvent for up to 14 days
  • spagyric extract – water/alcohol plant extract with ash from burnt plant marc added back
  • fluid extract – water/alcohol extract of powdered plant part, weight to volume ratio 1:1, first soaked and then slowly percolated over several days
• Solid extract – powder obtained from liquid extract by removing solvent with heat and drying
  • standardized concentrate – contains most dissolved compounds found in a primary solvent extract and a consistent marker compound content, having ratio of original dry herb weight to final extract weight 2:1 – 10:1, along with excipients

SIMPLIFIED FRACTIONS (Extract Subfractions) – secondary extracts of complex fractions to concentrate select compounds; specific chemical portions separated from extracts

• Standardized derivatives – multiple solvent extractions concentrate active component(s) to specific content; ratio of dry herb to final extract weight 10:1 – 50:1
• Fixed or aromatic oils – lipid fraction removed by solvents (both) or cold pressure (fixed), or distilled with heat (aromatics); concentration ratio of dry herb to oil 50:1 – 100:1

ISOLATED CONSTITUENTS (Isolates; Purified Compounds) – phytochemicals that have been separated from their complex natural matrices; single molecular components removed from complex mixtures, often by fractionation followed by precipitation

• Crystalline drug salts – single constituents altered through chemical processes that result in formation of drugs with ionic bonds that will dissolve in liquids

Table 2. Product Content Trends When Moving From Whole Herb to Fractions to Isolates

COMPARATIVE DOSES

Concentrates

A mistaken assumption is constantly being promoted that a therapeutic equivalency exists between a certain weight of a whole herb and extracts made from that same weight. Based on the fact that any extract provides only a fraction of the total herb, and only some of any total component content, this clearly is not the case. Even if the whole herb contained only one biologically active component (a situation that is virtually unknown), no commercially employed extraction process will completely exhaust the herb of its content of the active compound. The most common means of making herbal liquid extracts (referred to as tinctures) is with a process known as maceration. When herbs are soaked (macerated) in a solvent made of a mixture of water and alcohol (ethanol), the extraction process stops when the concentration of a compound in the solvent equals the concentration remaining in the extracted herb (equilibrium), known as the marc. Relatively complete extraction of certain components in the herb can only occur under these conditions if the amount of solvent is great and little herb is used, resulting in an extract that is extremely weak. Even this will only occur if the compounds in the herb are completely soluble in the ratio of water to alcohol used. When using a water/alcohol mixture as the extracting solvent, a complete solubility, and therefore extraction, does not occur for any single compound, much less all of the components simultaneously.

The process that most closely approaches complete extraction of certain components of the herb is called percolation. Percolation is typically applied to the manufacture of concentrated fluid extracts. By allowing a slow, steady flow of solvent to pass through the ground herb loosely packed in a column, the fresh solvent added to the top of the column is much more effective in extracting the components than when it reaches the bottom of the column where it is concentrated with extracted components. Even using this method, to completely remove the remaining active components from the herb in the bottom of the column, the final portion of extract is so dilute that it must be concentrated after the extraction is complete. This process employs the application of heat to drive off the excess solvent and reduce the volume. Heating the extract is destructive to many compounds, thereby changing the content and rendering the extract less complex and less potent. As a consequence the extract does not provide all of the original component content and activity present in the whole herb amount that was extracted. Study of the essential oil content in thyme and its extracts has shown in general that the greater the degree of concentrating the extract, the lower the percentage of original content of the whole herb is contained in the final extract.

While this deficit in the retention of content by concentrating extracts is recognized and acknowledged, an associated error in logic is being propagated in the meantime. This faulty reasoning takes as a standard the effective dose of a concentrated herbal extract and then attempts to determine the equivalent dosage of the whole herb calculated on the basis of the degree of concentration by weight that has occurred. In other words, a 5:1 extract whose dosage quantity (for example, 100 mg) represents components extracted from a greater weight of whole herb (in this case, 500 mg) is regarded as five times more potent (a fallacy). As a consequence, it is believed that to get equivalent activity using the whole herb, five time as much of the herb must be used (a further fallacy). It is on this faulty premise that the proposed dosage equivalency of whole herbs compared to extracts is misrepresented to the public and practitioners alike.

STANDARDIZED EXTRACTS

Confusion in the ranks – Standardization claims for products of popular herbs Echinacea [Example discussing one genus taken from this section.]

A final example of standardization illustrates how its use can be misconstrued in evaluating the quality, and even the identity, of products. In an attempt to assess the validity of label claims, in 2003 Gilroy and others obtained 59 preparations sold as echinacea in the Denver metropolitan area. The investigators decided to use thin layer chromatography (TLC) as a means of determining the legitimacy of content claims for these products. They based the interpretation of their findings on the assumption that the relative content of Echinacea purpurea could be determined by the cichoric acid yield. They also assayed echinacoside as the marker for E. angustifolia to differentiate these two species.

The third commercial echinacea species, E. pallida, also contains echinacoside, therefore this marker could not be used as a means of distinguishing this species from E. angustifolia. Five of the 59 samples were identified on their labels as E. pallida, but the authors state that differentiating between it and E. angustifolia “was never a concern.” Unfortunately, the authors failed to note claims about the part of the plant used. Normally, E. pallida and E. angustifolia roots are the parts used for such products. If this is true for these samples, species identification can be made by the caffeoyl phenolic compound cynarin present in E. angustifolia roots but absent in E. pallida roots (and E. purpurea as well), as shown by Perry and others in 2001.

The roots can also be easily distinguished due to E. pallida root’s lack of the tongue-tingling isobutylamides that typify E. angustifolia (and E. purpurea). Isobutylamides and the polyacetylene or 2-ketoalkenes and 2-ketoalkyne components found in E. pallida are readily demonstrable by TLC. The authors referenced the research by Bauer and Remiger in 1989 that describe these differences with TLC, but surprisingly use this means to only identify the phenolic markers. In addition, Cheminat and others determined in 1988 that cichoric acid was the main phenolic product in E. pallida flowers and leaves, with some was present in the root as well. Likewise, Perry and others in 2001 found cichoric acid in E. angustifolia roots, making this a nonspecific marker for absolutely identifying E. purpurea.

The inadequacy of using the phenolics, cichoric acid and echinacoside, as suitable echinacea markers, as well as not characterizing the processed forms of the samples, come to bear on the issue of evaluating E. purpurea products. The juice of the aerial plant preserved with 22% ethanol is an established remedy, and the most researched echinacea product on the market. In 1999 both Bauer and Kreuter indicated that the enzyme polyphenol oxidase rapidly breaks down cichoric acid in the cold-pressed fresh juice. Kreuter pointed out that clinical research had employed the cold-pressed and unheated E. purpurea plant juice, so only this juice with little or no cichoric acid has been proven clinically effective. When the juice is heated to destroy the enzyme, cichoric acid will be consistently retained. However, in 1999 Bauer found that heat-stabilized juice products had much lower isobutylamide content on average. The isobutylamide components are believed to be more therapeutically active as immune enhancers than the cichoric acid.

Arnason reported that in 1998 Bauer observed that cichoric acid declines in tinctures in six days. Livesey and others indicated in 1999 that cichoric acid diminished in tinctures with 55% alcohol at room temperature after 7 months but was stable in powder during this time even at higher temperatures. Nusslein and others in 2000 showed cichoric acid could be preserved in aqueous extracts over four weeks by adding 50 mM ascorbic acid or 40% ethanol. Thus, it is obviously necessary to characterize the form of the product when assessing relative cichoric acid content, rather than generalizing average content to all forms.

In their evaluation Gilroy and others did not identify these products as powdered root/plant or extracts, but simply reported that 9 were tablets, 32 were capsules, 4 were softgels, and 14 were liquids. Only 21 of the products were standardized, but their forms were not specified. The standardized products had much lower recommended doses, suggesting that these were solid extracts rather than the root. It is obvious that the softgels and liquids were extracts, as were likely some of the tablets and capsules. Whether these were processed as pressed plant juice, its dried powder, or as liquid or solid solvent extracts of fresh or dried roots cannot be deduced. Nonetheless, not all extracts are standardized, so we don’t know from the information given what the forms of the standardized products were. Calling all of the products simply echinacea is inherently misleading, since they represent many possible identities: root, aerial plant, juice, or their solvent extracts and concentrates.

The authors’ premise in assessing the content of the particular caffeoyl phenolic markers is understandable, since these compounds are typically used to “standardize” products of these species. They addressed those products that claimed to be standardized to specific phenolics. Of the nine samples that identified either echinacoside or cichoric acid as markers, none matched the label claim. Rather, seven had on average only 26% of the label claims, and the other two contained no measurable amounts. Ten product labels made claims to be standardized to total phenolics, but this fails to distinguish between particular species markers. In his talk at an international echinacea conference in 1999 Arnason noted that even though the total phenolic content had been the common echinacea standard for years, it was a “completely, utterly useless measure, in the opinion of all the phytochemists in the room, as to the quality of echinacea products.”

Gilroy and others assayed phenolic marker content of standardized products as well as those whose identifying label claim was simply the species used in the product. It is interesting to note that, based on their phenolic evaluation approach, 21 of 30 (70%) of the nonstandardized products matched the label species claim, while only 10 of 19 (53%) of the standardized products were presumably the appropriate species. For those products containing cichoric acid, the nonstandardized yielded on average about 2.5 times more than the standardized samples. In the products with echinacoside, the content of nonstandardized samples averaged more than 3 times the yield of those that were standardized. The doses of nonstandardized products were about twice those of standardized.

Finally, Gilroy and others claim that only four of the products (7%) met the four FDA labeling requirements. They observe that the better compliance score for standardized than nonstandardized products was due to the presence of the “Supplements Facts” box. However, products that do not make standardization or structure/function activity claims and companies that have less than 100 employees are exempt from this label requirement. The authors’ conclusion that the “claim of “standardization” does not mean the preparation is accurately labeled, nor does it indicate less variability in concentration of constituents of the herb,” is an appropriate assessement of these echinacea products. One could accurately state that standardization claims provide no basis for determination of quality of these products in terms of therapeutic efficacy. Trying to evaluate echinacea products on the basis of phenolic markers without specifying the plant part and form of each preparation being assessed is meaningless. Even knowing those features is of little value beyond limited characterization of the product. Quality is a function of effect, not just identity.

Arnason JT. North American raw materials: the case for an isobutylamide standardized product. Echin. Past, Present Future Internat. Conf. 1999 Proc., Session Three, pp. 4-5 & slide 40, Skamania, Wash., June 10-12, 1999
Bauer R. Standardization of Echinacea purpurea expressed juice with reference to cichoric acid and alkamides. J. Herbs, Spices Med Plants, 6(3):51-62, 1999
Bauer R & Remiger P. TLC and HPLC analysis of alkamides in echinacea drugs. Planta Med., 55:367-71, 1989
Cheminat A et al. Caffeoyl conjugates from Echinacea species: structures and biological activity. Phytochem., 27(9):2787-94, 1988
Gilroy CM et al. Echinacea and truth in labeling. Arch. Int. Med., 163:699-704, 2003
Kreuter M. Echinacea purpurea substances, characteristics and immunological active principles. Echin. Past, Present Future Internat. Conf. 1999 Proc., Session Two, p. 3 & slide 7, Skamania, Wash., June 10-12, 1999
Livesey J et al. Effect of temperature on stability of marker constituents in Echinacea purpurea root formulations. Phytomed., 6(5):347-9, 1999
Nusslein B et al. Enzymatic degradation of cichoric acid in Echinacea purpurea preparations. J. Nat. Prod., 63:1615-1618, 2000
Perry NB et al. Echinacea standardization: Analytical methods for phenolic compounds and typical levels in medicinal species. J. Agric. Food Chem., 49:1702-6, 2001

Table 3. Echinacea Products of Different Types*

(X = Commercially Available Product) *(See Table 1 and Glossary of Terms from Table 1.)

Table 5. Western Echinacea Root and Derivatives – Summary of Medicinal Uses and Pharmacology

Table 7. Purple Coneflower Plant and Derivatives – Summary of Medicinal Uses and Pharmacology

JOHN URI LLOYD AND BEYOND
[The following three paragraphs are taken from this third section of the Introduction.]

As medical doctors, Eclectics utilized many types of botanical products, often preferring those produced by their pre-eminent pharmacy house, Lloyd Brothers Pharmacists. This company was based on optimizing the Eclectic development of native American plants that led to increased popularity of remedies such as echinacea, saw palmetto and black cohosh. John Uri Lloyd had been hand picked by the renowned Eclectic doctors of the Eclectic Medical Institute of Cincinatti, John King and John Scudder, in 1871 to develop a unique line of remedies designated as Specific Medicines. Lloyd pioneered many pharmaceutical methods including processes (mass action in colloidal chemistry), compounds (atropine sulfate), reagents (Alcresta), and apparatus (cold still processor now on display at the Smithsonian Institution). In the 1880s he taught at the Eclectic Medical Institute and served as its president from 1896-1904. His death in 1936 ultimately led to the demise of the Cincinatti school.

John Uri Lloyd was also an instructor at the Cincinnati College of Pharmacy during the 19th century. Lloyd was elected as president of the American Pharmaceutical Association in 1887 and served as a member of the United States Pharmacopoeia commission in 1890. His book on elixirs served as the basis for what became the official National Formulary. Lloyd’s mastery of botanical extraction issues was recognized officially by his peers. He was awarded the Ebert Prize for innovative research in pharmacy three times (1882, 1891, and 1916). Lloyd was the second recipient of the Remington Medal, American pharmacy’s highest honor, in 1920. Then in 1934 he was presesented with the First Procter International Award. During his career he established the Lloyd Library, endowed for posterity and an important resource to this day. This institution began a publication, Lloydia, which evolved into the current Journal of Natural Products.

Since John Uri Lloyd was such an outspoken advocate of botanical remedies and innovative developments respectful of their natural integrity, it is appropriate to consider his observations made during the 65 years that he spent working in this field. This is not merely an acknowledgement of the oft-quoted adage ‘Those who fail to learn from history are doomed to repeat it.’ During his lifetime Lloyd thoughtfully considered the many dilemmas faced by those who were trying to maximize the quality of their various botanical medicine preparations. His opinions ranged far, wide, and deep concerning the many questions that challenge those who look for the best means of addressing complex botanical issues. His articles were published in the leading pharmacy and Eclectic journals of the day, sometimes in series, and often reprinted in other journals or at later dates with editorial comments added.

[Following are a number of excerpted quotes from among the many articles and books Lloyd published from 1876 to 1934. Seventy separate Lloyd citations have been incorporated extensively throughout the text of Complex Herbs – Complete Medicines. Those that follow briefly describe his understanding and beliefs based on extensive laboratory experience in manufacturing botanical extracts as well as from working with Eclectic doctors who explored and developed their applications in clinical practice.]

Value of the whole herb

“From time to time I am confronted with the fact that elaboration in pharmaceutical work is not always improvement, real improvement. I accept without question that the primary object of the pharmacist should be the therapeutical value of his products; elegance of physical appearance being very important considerations, but they are secondary. … I candidly admit that in some instances a crude drug seems to me superior to any known elaborated product of it.”

Herb quality and state

“The quality of drugs is all important, but no general rule can be established to determine quality. … The application of chemical tests is useful in a few instances – a very few. … The quality of drugs must be determined through the personality of the pharmacist, the acuteness and perception of his senses, the experience gained in his labors, the drilling he receives from his methods and the self-instruction that comes from a love of art. … My experience teaches me that some drugs must be worked green, other partly dry, others are best when thoroughly dried, while others yet even become most useful after being aged to a certain extent. Thus, as examples, only green cactus, in my opinion, is of value. Freshly dried Iris versicolor is superior to the green, and Rhamnus purshiana improves by age.”

Water in fresh plants

“The majority of people accept that the function of water in food substances is that of a solvent only, or as an inactive vehicle. … Our works on digestion and on general physiology state that most foods are three-fourths water, and the human body, bones included, over two-thirds water, but yet consider water irrelevant as a nutrient. …

“We call water driven off in the drying of fruit or food of any kind water of separation. May it not be rather the result of structural molecular decomposition? … Should we not look on such water, necessary as it is to life, digestion and tissue replacement, as an integral part of food, instead of simply a carrier of food? It is indeed probable that the student of dietetics must broaden his field and consider foods in their structural entirety, rather than from their analytical created ultimates. …

“Possibly the makers of food products of the future will give less attention to analytical values concerning dead elements and more to vitalized and vitalizing structures in which available water is conspicuous. Possibly it behooves us even now to ask if a closer inquiry into the water molecule, the vitalized or easily vitalized water molecule and its many shadings, may not open up a field for the construction of more rational food products.”

Water extracts

“The endeavor of pharmacists to supply physicians with convenient form of remedies, commendable as all will admit, yet may result in occasional mistakes. There are some drugs that are, in my opinion, more reliable in the form of infusion or decoction than as either a tincture or fluid extract. It is a mistake to use fluid extract of either pomegranate bark, pumpkin seed, or althaea.”

“If I wished to administer to a member of my family pennyroyal, peppermint, sage, boneset, or other of most of the domestic remedies, and many drugs now only known to the profession in fluid extract form, I would surely make “tea” or decoction, and not give a fluid extract or tincture. I am a maker of fluid extracts and other similar preparations, and hence cannot be criticized by fair minded persons for advising physicians of this Society who are largely my patrons to benefit themselves and their patients, as I do now, at my own expense.”

Tincturing fresh herbs

“Great care is required to work fresh plants, and almost every article behaves differently. I am not of the opinion that any one believes “specific medicines” possess any properties not found in the original crude drug. They are only represented by me as superior preparations of very choice materials. First get prime crude drugs, then work with care and use the best processes, and do not believe than any amount of care will make good medicines from worthless drugs.”

“The stepping onward and the transferring of vitality from cell to cell, and from organism to organism in the support of life, seems to depend wholly upon the movements and actions of colloidal bodies. … This includes what may be known as the juices of plants … appearing as a complexity of liquids. … To the homely motto, “Nature abhors a vacuum,” I would add the parallel, “Life structures abhor a crystal.” … A colloid (as afore illustrated) is a substance that has no definite form, and under ordinary conditions at least, is destitute of crystalline structure. … The majority of life structures, created by life processes, are colloidal, as well as are the nourishing principles that carry life energies to their upbuilding and upkeeping. … A study of the action of colloids concerns the very foundation of life, known as vitality.”

“Some people imagine that the tincture from a pound of green herb only represents the strength of a few ounces of the same herb when dried; that the medicinal strength of our pharmaceutical is in proportion to the solid material of the drug from which it is prepared. … I will take issue when they say that the medicinal principles of our herbs are relatively in proportion to the solid and unvolatile materials. … I have also learned that in many cases sufficient exposure to evaporate the water will destroy the medicinal principles of the plant.”

Tincturing dried herbs

“Water is intimately connected with the creation of all the component parts of our plants, and experience will teach us that the dissolution of many of these bodies takes place when the water upon which they are indebted for existence, is removed. … Dried plants are exposed to the influences of moisture and the atmosphere; from the time they are gathered until used a constant change is going on. … This imperceptible decomposition may have resulted in the total destruction of the principles that originally give it its therapeutical activity. … Certainly it is true, that it has become a custom to use dry plants for making tinctures; but this fact does not prove they are best adapted to the purpose.”

Fluid extracts

“Percolation was introduced into pharmacy and with this process of extraction came efforts to concentrate liquid representatives of drugs without evaporation, and to these products the terms concentrated tinctures, saturated tinctures and fluid extracts were severally affixed. These preparations were all made with alcoholic menstruums. … Gradually the terms concentrated tinctures and essential tinctures gave way to the term fluid extract. …

“Experienced pharmacists perceive fully the imperfections, to which I will now briefly allude. They are prone to precipitate; they are usually thick with inert matters, both colored and colorless. They are of variable strength, owing both to variation in the quality of crude drugs and the care of the manufacturer.”

“I view fluid extracts as one of the stepping stones to a more perfect pharmacy. … They have … given us portable preparations, but have in many instances crowded our shelves with preparations very much inferior to the decoctions and infusions, or even the crude drugs, that have been displaced.” /p>

“The officinal preparations of plants, such as fluid extracts and tinctures, on which regular medicine depends, … are now, as a rule, nearly black, while there is little, if anything, in most plants in their fresh condition, to produce colored compounds. … The result is that fluid extracts are unstable and unsightly; they are prone to precipitate and disintegrate, and are far from creditable remedies. … /p>

“Unless there be a revival, the practice of plant pharmacy will fall exclusively into the hands of trade manufacturers and chemists (it is fast drifting there now), who … can and will accomplish that which seems now to be generally overlooked. … Do not break up by heroic chemistry the natural compounds in which active agents exist in the plants. Take the opposite course, apply pharmacal skill, but retain these active principles intact, as formulated by nature.”

Alcoholic extracts and dilutions

“Our plant contains oils, resins, gums, mucilage, coloring matter, chlorophyll, alkaloids, glucosides, acids, and other principles. Some are soluble in water, some in alcohol, and some in mixtures of alcohol and water to an extent. … If the principles which are precipitated by alcohol give the extract a portion or all of its medicinal value, it is impaired when we throw these principles out. … Alcohol dissolves oils and resins insoluble in water. When we add an extract made with alcohol or diluted, to either water or syrup, such substances as are insoluble in these menstruums will be precipitated, and often they are valuable.”

Differentiating solvents

“The selection and adaptation of a suitable menstruum that will first abstract and afterward preserve the abstracted therapeutic constituents becomes a perplexing problem. … It should be borne in mind, however, that the products obtained represent, not the drug itself, nor the alkaloidal texture of the drug, but an energetic (alkaloidal) fraction, a product of the drug, more or less modified by the heroic process. The material obtained is a chemically altered, manipulative product, and not a naturally abstracted, textural educt.”

“The solvents considered … as being of possible use in plant pharmacy, as solvents or excluders, either alone or mixed … are classified by group solvent relationships. … Class 1 – Glycerin, Water, Alcohol and Methyl Alcohol. … Class 2 – Acetone, Chloroform, Amylic Alcohol, Acetic Ether and Sulphuric Ether. … Class 3 – Benzol, Carbon Disulphide, Benzin, Turpentine Oil and Liquid Petrolatum. … By means of the neutral solvents named (some substances are soluble in several of the liquids), successively applied, most plants, be they green or dry, may be practically abstracted of their soluble content.”

Solid extracts

“For more concentrated preparations … the evaporation of tinctures, decoctions and infusions resulted. The residues were usually reduced to the consistence of a stiff magma capable of being rolled into pills with or without the addition of an excipient, and to these substances the term extract was applied. … When these extracts were fully dried and powdered, they produced the class known as powdered solid extracts. But it became apparent to thoughtful persons that extracts often did not, as might naturally be supposed, represent the tincture employed, and then it was discovered that the heat applied and accompanying atmospheric influence affected the remedial part of the remedy deleteriously, indeed even in some cases to its utter destruction.

“When a fluid extract is evaporated until the residue reaches a masslike consistence, a prime solid extract results. … Solid extracts, therefore, do not contain any therapeutic qualities in addition to those possessed by the tincture. … At the best, commercial solid extracts are less reliable than either tinctures or fluid extracts, although when care and skill are employed in their preparation active drugs may yield very energetic remedies. … Much harm to pharmacy and to medicine has been done, in my opinion, by thoughtlessly believing that the drug values of tinctures and fluid preparations of many drugs can be carried into a dry condition.”

Herb complexity (structures) vs. derivatives (fragments) and isolates (separates/ultimates)

“Among the earliest remedial agents, as well as the most useful remedies of the present, are plant products and plant agents. … The life of man and the health of man depend on the conservation of energy held in the life forces that are locked in vegetable structures, be they called food or remedy. … They are natural plant structures, which experience has taught, as a crude whole, can influence or conserve life structures. … In the materia medica of intercellular structures, no one chemically-made fragment that can be broken out parallels the drug as a whole, if one knows the whole drug. … Unquestionable evidence taught that fragments created out of drugs by chemistry do not parallel the natural intermolecular structures that establish drugs as remedies.

“Much of the present discouragement of Regular physicians is surely due to the use of fragments only. Unwisely they have ignored the claims of plant structures which in themselves are valuable in medicine, but are neglected and discarded because the test tube and reagent of the chemist cannot create from them bodies like unto the poisonous alkaloids, atropine, strychnine, morphine. These men seek the hurricane; the still, small voice has no part in such medication. … Due credit is given isolated substances in their useful places. … But we value above all the interstructural effect that comes from life-bound structures endowed with their full vital qualities, preserved in assimilable form.”

“Comes now the lesson taught by the half century of turmoil in and among the alkaloids, resins, resinoids, and oleoresins … dispelling of the illusion that a fragment can parallel the whole, if the whole be intelligently comprehended. Eclectic physicians learned from an experience not easily forgotten the lesson that dried fragments of drugs are not representative of drugs.”

“The process of manipulation produces atropine from Belladonna, but the natural alkaloid atropine exists in the drug Hyoscyamus. However, since Hyoscyamus differs greatly in its action from Belladonna, it is a question as to the textural setting of the alkaloidal structure. In addition, there are associated structures that need be considered as influencing partners of every natural drug. This writer ventures to disagree with the view that Atropine parallels Belladonna, or that Hyoscyamine parallels Hyoscyamus, or that either drug parallels the other, as a whole. … The act of manipulation destroys, creates, and recreates, to the third and fourth generation. Nor is this due alone to the heat employed in the manipulation.”

“As men consider structures and not artificial ultimates, it will, we believe, be demonstrated that a study of the dead products broken out of vitalized plant textures is not a study of materials that exist in the plant, but results of the chemistry applied to the plant.”

Strength versus quality

“An error common to a superficial, as well as to a one-sided or fragmentary conception of pharmacy, is that of considering strength and quality as synonymous terms. … The truth is that, although more or less related, the constituent that gives the factor strength is often less important than are the attributes that go to make up quality, which, perhaps more than does strength, leads to high excellence.

“Let us define strength as a dominating something that stands out boldly. … Let us define quality as a balanced combination of other something, with just enough of the toxic agent to make a complex product that, as a whole, has wider functions. … In many familiar directions, such as tea, coffee, spices, tobacco, etc., standards of strength have been differentiated from those of quality.

“For example, the strength of wine lies in its alcoholic proportion, but the quality of wine depends on the attributes imparted by accompanying congeners, such as water, potassium salts, ethers, acids, tannates and such. These, if balanced, the one in proportion to the other, produce wine of varying qualities. … In our opinion, the attempt to standardize a preparation by a single dominating constituent is but a struggle towards a pharmaceutical standard of excellence, in which therapeutic quality should be the ideal.

“Whilst the ultimates broken out of structures are of value in therapy, the structures yielding the ultimates are possessed of qualities that in many directions make them superior to the artificial products. … In a time to come will also follow a scientific comprehension of the pharmacist’s structures now beyond the eye of the talented men engaged in the study of the products broken out of these, as yet, voidless and formless colloidal bodies.”

Standardization

“A standard established by one man, or a committee of men, may be correct from their one viewpoint, but need not necessarily be a standard, that, under different conditions, may prevail in the thought and action of other men. … A chemist or a committee, thinking only of the conspicuous agent, may ignore the milder entities, and in the glare of this one dominating light establish a very one-sided standard, which may neglect unseen qualities that lie beyond the thing that makes the standard of the man of toxic faith.

“Upon the contrary, the one who considers the drug as the balanced whole … may get a therapeutic possibility that … could never have been perceived. From such a view the standard of therapeutic excellence does not necessarily depend upon the … ultimate, but rather upon its subjugation to the associated factors.

“As a result, the person who makes the systematic investigation on these different lines, and finally balances his products in accordance with the evidence at his command, chooses standards peculiarly his own, and very different from the other products. It may even be a better standard of therapeutic excellence than is that based upon the largest possible amount of a conspicuous energetic constituent. … The establishing of a balanced drug complexity, that will act as a unit of value, is the one thing needful. … We believe that standardizers, through an honest misconception of possibilities and probabilities outside their field, are too often inclined to uncharitable error. … The standard of pharmaceutical excellence, in our opinion, … is to be found in the balanced structure of the preparation’s evolution from the crude drug.”

Comparative doses in different types of products from the same herb.

“Among the letters from physicians that come to the writer’s desk for reply, no inquiry is more frequently made than the request for the comparative dose of different preparation of the same drug. At first thought it would seem that a reply would be simple, as it might be if the different preparations were merely extractions of varying strengths. But if we take into consideration the limits and possibilities of solvents, with knowledge of the diversity of products of the same drug that may be produced by different processes, it becomes apparent that comparative doses with the object of producing identical effects cannot always be given.

“It should be borne in mind … that no two plant extracts, made by means of different solvents and processes can be exactly the same. … The choice of menstruum used in extracting a vegetable drug makes a vast difference in the so-called “strength” of the preparation, but much more. It is a difference in the proportions of the therapeutic constituents. It is even possible that constituents dominating one preparation may be absent from another extract of the same drug. Obviously, a comparison of doses that will produce the same therapeutic effect is impossible. It should be understood that … no menstruum will extract all constituents from any plant.”