A number of studies have highlighted the importance of the correct choice of the ethanol percentage in terms of maximizing the quality of herbal liquid preparations. A Swiss study found that 55% ethanol was the optimum percentage for the extraction of the essential oil from chamomile (Matricaria chamomilla).¹ Higher percentages of ethanol did not extract any additional oil, and the solids content of the extract was decreased, indicating that other components were being less efficiently extracted. More recently, Meier found that 40% to 60% ethanol was the optimum range for achieving the highest extraction efficiency for the active components of a variety of herbs.² For example, at 25% ethanol, none of the saponins in ivy leaves (Hedera helix) were extracted, but at 60% ethanol, they were maximally extracted. Similarly, the alkylamides, which give the oral tingling sensation from Echinacea, are better extracted at higher ethanol percentages. Extracts of milk thistle (Silybum marianum) prepared in 25% ethanol will not contain any silymarin because it is insoluble at this concentration.

Practitioners should keep this consideration in mind when assessing a high-ethanolic extract of an herb. In many cases, the product may be more active (because of the correct choice of a high ethanol percentage), thus less liquid needs to be prescribed for an effective dose. The patient’s ethanol intake may actually be lower than when prescribed a higher quantity of a low-ethanol extract of the same herb.

Higher ethanol percentages do not always confer higher activity. French researchers found that Viburnum prunifolium bark extracted at 30% ethanol was five times more spasmolytic compared with a 60% extract.³

The basic guidelines for the choice of the ethanol percentage to optimize the activity of the final liquid extract are as follows:

• 25%: Water-soluble constituents such as mucilage, tannins, and some glycosides (including some flavonoids and a few saponins)

• 45% to 60%: Essential oils, alkaloids, most saponins, and some glycosides

• 90%: Resins and oleoresins

Glycetracts or glycerites are herbal liquid preparations made using glycerol and water instead of ethanol and water. Glycetracts are useful preparations when the active components are water soluble, for example, marshmallow root (Althaea officinalis), because they do not contain alcohol, and the sweetness of the glycerol gives them a better taste. However, the importance of these preparations should not be overrated. Glycerol is a poor solvent for many of the active components found in herbs, and glycetracts are less stable compared with alcoholic extracts (see the later discussion). Moreover, because of the viscosity of glycerol, concentrated preparations are difficult to make by percolation. The manufacture of 1:1 or 1:2 glycetracts therefore invariably requires the use of a concentration step involving the application of heat or vacuum, which risks deterioration of the product.

Some practitioners are concerned about possible exposure of their patients to the toxic effects of ethanol, such as during pregnancy. However, these toxic effects are dose related and do not occur for the small quantities of alcohol involved. For adverse effects to arise after ethanol intake, the blood alcohol level must rise to a certain level. A 5-ml dose of herbal extract contains as much ethanol as does approximately one sixth of a standard glass of beer or wine. The liver rapidly metabolizes such a small intake of ethanol, and consequently its effect on the blood alcohol level might not even be measurable. Only a much higher intake of ethanol will overload the liver’s metabolizing capacity and lead to significant blood alcohol levels. Moreover, the body is naturally conditioned to a small exposure to ethanol from ripe fruit and the natural fermentation of food. Refrigeration has minimized this exposure in industrialized countries. However, human beings, be they children or adults, have evolved and adapted to levels of ethanol intake through food that are similar to those from herbal extracts.

Only a small minority of patients are genuinely sensitive to ethanol. In other individuals, a presumed sensitivity is only an exaggerated reflex response to the medicine, which can usually be alleviated by prescribing lower doses at a greater frequency, taken with food or water. Recovering alcoholics and Muslims are advised to take tablet preparations. Patients with mild liver conditions should not be adversely affected by a small ethanol intake.

Herbal liquid preparations based on alcohol can exhibit superior bioavailability. Results of a double-blind, placebo-controlled, crossover study on children with chronic obstructed airways were reported in the “Industry News” section of the Zeitschrift für Phytotherapie.⁴ The therapeutic effects of ethanolic and ethanol-free galenical extracts of ivy leaves (Hedera helix) were compared. Spirometric testing showed a significant improvement in lung function for both products, which was superior to conventional bronchodilators. However, results indicated that the addition of alcohol to the preparation yielded an increase in the bioavailability of active components. The dose of the alcohol-free preparation needed to be adjusted to a higher level to obtain the same effect.

GLYCEROL-WATER COMBINATIONS

Recently, glycerol-water preparations have become popular, resulting from some perceived disadvantages of ethanol-water combinations (see the previous discussion). A less important reason in real terms is that glycerol is seen to be less toxic than is ethanol. However, glycerol is chemically classified as an alcohol and is also toxic at high levels. The 26th edition of Martindale’s Extra Pharmacopoeia states that large doses of glycerol by mouth can exert systemic effects such as headache, thirst, and nausea. The injection of large doses may induce convulsions, paralysis, and hemolysis. A 2.6% solution of glycerol will cause 100% hemolysis of red blood cells. Glycerol has an irritant effect on the gastric mucosa when given at concentrations greater than 40%, and large oral doses of glycerol caused signs that were misdiagnosed as cardiac arrest in one elderly patient with hypertension.⁵ The authors concluded that these elderly patients were liable to be dehydrated and that the effects from glycerol ingestion on an empty stomach may be acute.⁵

However, it must be stressed that, similar to ethanol, the low intake of glycerol involved in using herbal preparations will not cause negative health effects.

Most importantly, glycerol or glycerol-water combinations are poor solvents for many of the active components found in herbs. For example, essential oil components, resins, and many saponins will not extract well into glycerol-water combinations. Some companies have developed a special process to overcome this problem. The herb is first extracted with an ethanol-water mixture. The ethanol is then removed and replaced with glycerol. However, quantitative and qualitative analyses have been initiated using highperformance liquid chromatography (HPLC), which show that if this process is not performed correctly, considerable losses of activity can result. The removal of the ethanol may cause loss of volatile components and may also cause precipitation of active components because they are no longer soluble once the ethanol is removed or the glycerol is added. These problems can sometimes be overcome but only with great care in manufacture, dealing with each problem on a case-by-case basis.

Glycerol is a poor preservative. Several instances of homemade or commercial herbal preparations have developed bacteria or mold growths. Additionally, few studies have been conducted on the long-term chemical stability of glycerol-based herbal products.

MACERATION

As previously mentioned, the two most common extraction methods used to prepare herbal liquid products are maceration and percolation. With either technique, the solvent is termed the menstruum, and the inert, fibrous, or other insoluble material remaining after the menstruum has done its work is called the marc.

With maceration:

• The menstruum is usually an ethanol-water mixture.

• The herb is maintained in contact with the menstruum for a relatively long period.

• The process is conducted at ordinary room temperature.

• After straining, the liquid remaining in the marc is pressed out and mixed with the strained liquid. (The marc often soaks up a considerable quantity of menstruum that can only be satisfactorily recovered by pressing.)

The form of the herb varies. Although the whole herb is sometimes used, the cut herb and in some cases the powdered herb are more often used. The required amount of herb (say 1 kg) is placed in a vessel; the required amount of menstruum is also put in the vessel (say 5 L, to make a 1:5 tincture); and the vessel is closed to prevent the loss of alcohol. The vessel is shaken and the contents turned regularly, preferably daily, for a length of time that depends on the herb, but is usually from 7 to 10 days. The direction to shake or stir daily must be strictly adhered to so as to disperse the saturated layer of menstruum that surrounds the marc, thereby allowing fresh liquid to come into contact with the marc. After the prescribed time, the liquid is drained from the residue or marc. When draining is completed, the marc is put in a press to obtain that part of the menstruum that the marc absorbed.

The pressing of the marc can be done in various ways. One of the most basic is to enclose the marc in a cloth and then to manually squeeze out the menstruum. The best way of exerting pressure is to put the marc into a press. The expressed liquid is mixed with the strained liquid and the mixture left to stand until it is clear, whereupon it is filtered. Normally, no final adjustment to a definite volume is required. The reason for this omission is that the final volume of liquid extract depends on the type and efficiency of the press. Additionally, the liquid retained in the marc is of the same concentration as is the liquid that was strained off. Thus the act of making the volume up to a set amount, for example, the same amount of menstruum that was originally used, would give a final product of varying concentration, depending on the amount of menstruum left in the marc after pressing. Moreover, any adjustment would destroy the ratio of the tincture, which must be preserved for dose consistency.

PERCOLATION

In the majority of instances, percolation is considered the best method for obtaining a solution of the active principles of herbs. Briefly, percolation consists of allowing a liquid, the menstruum, to trickle slowly through a column of the herb that has been previously ground into a more or less fine powder. The liquid is carried out in a vessel called a percolator in such a way that every solid particle is, in turn, submitted to the solvent action of the gravitating fluid.

The process of percolation, as laid down in various pharmacopeias, is carried out as follows: the crude herb is reduced to a degree of fineness, which is specified for each case, and it is moistened with an amount of the menstruum, again specified for each case. The herb is evenly moistened with this amount of menstruum and then placed in a closed vessel for 4 to 24 hours. This procedure is used to allow the particles of the herb to absorb the menstruum and to swell to a certain degree. If dried herb was placed directly into the percolator and then brought into contact with the menstruum, it may in some cases swell sufficiently to completely obstruct the flow of the menstruum through the percolator. After the designated time, the moist powder is passed through a coarse sieve to break up any masses formed.

Before the percolator is packed, the bottom of the percolator must be loosely plugged with a wad of some material such as glass wool to prevent the powder from falling through the outlet and blocking it. The moist herb is now introduced into the percolator, each layer of 2 to 3 cm in thickness being lightly pressed down by means of a suitable implement. The technique of packing the percolator is fundamental to the quality of extract at the end. The percolator is now placed in position, and a sufficient quantity of the menstruum is poured on. If all the conditions have been properly observed, the menstruum will penetrate the wetted powder equally until it has passed to the bottom of the percolator.

The outlet is closed, and the percolator is now covered to prevent evaporation and left to stand (usually for 24 hours) to allow the herb to macerate in the menstruum. This maceration facilitates the extraction process. Percolation is then commenced by opening the outlet to such a degree that the liquid drops from it at a rate of 10 to 30 drops per minute. A layer of menstruum must be constantly maintained above the powder. Percolation is continued until three quarters of the volume of finished product has been collected or until the herb is exhausted. The fluid collected from the percolator is called the percolate. When the percolation is finished, the marc is often removed from the percolator and pressed, the expressed liquid is then mixed with the percolate, and a sufficient amount of menstruum is added to produce the required volume. In the case in which the marc is completely exhausted by percolation, pressing the marc is not required. The resulting percolate is then filtered.

This percolation process is sometimes described as cold percolation because it is conducted at room temperature without the application of heat.

WHY ARE 1:2 HERBAL LIQUIDS GENERALLY RECOMMENDED?

Even using percolation, manufacturing a 1:1 liquid extract (1 kg of dried herb extracted into 1 L of liquid) is difficult without using some form of concentration step. This problem occurs because the bulky nature of most herbs means that the volume of 1 kg generally far exceeds the volume of 1 L of liquid. Additionally, many manufacturers are not interested in the labor-intensive and costly requirements of doing percolation properly. Hence 1:1 liquid extracts are produced inefficiently because phytochemicals are lost or changed during a concentration step, or the herb is poorly extracted in a vain attempt to produce a highly concentrated product by limiting the amount of solvent, or both.

This problem was the main reason why herbalists throughout the world in the 1970s moved to adopt tinctures as their preferred liquid products. However, because traditional dose information was typically based on high-quality 1:1 extracts, the use of these more dilute preparations resulted in a reduction of the actual dose given to patients.

Approximately 20 years ago the author of this text chose 1:2 liquid extracts made by cold percolation as a preferred preparation because they represented the best of both worlds. Similar to tinctures, liquid extracts do not need heating or a concentration step in their manufacture, thus no risk occurs to the delicate balance of the phytochemical spectrum of the original herb. However, liquid extracts are sufficiently concentrated to allow the convenient use of pharmacologically effective doses. A true, well-extracted 1:1 liquid extract cannot be made without using a concentration step (meaning that at least 2 L of percolate needs to be produced for every 1 kg of herb, which is then concentrated back to 1 L). In contrast, 1:2 extracts can achieve high-extraction efficiencies.

The argument holds that 1:2 extracts are relatively new, are not mentioned in the British Herbal Pharmacopoeia 1983 (BHP) or other pharmacopeias, and therefore should not be used. In fact, 1:2 extracts are mentioned in nineteenth century texts ^6,⁷ and are described in the seventh edition of the German pharmacopeia (Deutsches Arzneibuch [DAB], published in 1968).⁸ The seventh edition of the DAB actually defines a liquid extract as a 1:2 extract.⁹ Therefore the precedent for their use is ample.

FRESH PLANT TINCTURES

In recent times, the use of tinctures made from the fresh plant has become popular among some herbalists. The belief is often that a fresh plant tincture better reflects the plant’s “vitality” or “energy” and therefore will be a more therapeutic preparation. Other practitioners believe that a fresh plant tincture will better preserve the delicate active components of the plant.

On the other hand, the following observations need to be considered:

• The evidence from phytochemical analysis that fresh plant tinctures contain better levels of active components than do dried plant tinctures is generally lacking. In fact, fresh plant tinctures are usually prepared in a low-alcohol environment (see later discussion), which means that some less polar (more lipophilic) components may be only poorly extracted. Furthermore, the enzymatic activity of the plant material may not be inhibited in this low-alcohol environment, meaning that key phytochemicals may actually be decomposed during the maceration process. This fact was dramatically illustrated by Bauer, who found that cichoric acid in fresh plant preparations of Echinacea purpurea was largely decomposed by enzymatic activity.¹⁰ Therefore what can be found in the living Echinacea plant was not preserved in the fresh plant tincture.

• Fresh plant tinctures were never official. Although fresh plant preparations were included in homeopathic pharmacopeias (which is understandable, given the energetic considerations in homeopathy), they were never listed in conventional pharmacopeias other than a few entries for stabilized fresh juices known as succi (singular: succus). Hence the use of a wide range of fresh plant tinctures is travel into unknown territory.

• Because of the water content of fresh plant tinctures, making preparations that are stronger than a 1:5 on a dry-weight basis is difficult. This problem can be readily illustrated by the following example. A leafy, fresh plant material typically contains 80% moisture. Therefore 100 g of this material represents 20 g of dried herb. To make a 1:5 tincture, this 20-g equivalent of dried herb must be mixed with 100 ml of liquid menstruum. However, 80 ml of water already exists from the herb itself. Therefore to preserve the 1:5 ratio, only 20 ml of 96% ethanol can be added. This 20 ml of ethanol is not enough to physically extract the bulky 100 g of fresh plant material. However, what is probably just as detrimental is that the effective ethanol percentage is only 20% (20 ml of ethanol and 80 g [or ml] of water from the fresh plant). This amount is too low to extract lipophilic components and barely enough to preserve the tincture. Some authors suggest using multiple maceration to overcome this problem, whereby the resultant tincture is macerated with a new batch of fresh herb, but this only makes the situation worse, diluting the alcohol to below the level that can stabilize the final tincture.

In summary:

• 100 g of a fresh plant containing 80% moisture is macerated in 20 ml of solvent (alcohol-water).

• The dried herb weight is 20 g.

• The amount of liquid is 80 ml (moisture from the fresh plant)+20 ml (solvent)=100 ml.

• Hence the result is equivalent to a 1:5 tincture on a dry-weight basis (20-g dried herb:100-ml liquid).

• However, the result may be even weaker because of the enzymatic decomposition and the low effective ethanol percentage.

Clearly from the previous discussion, given that the water content of fresh leafy plant material varies from 75% to 90%, the only practical way to make a reliable fresh plant tincture is to work on an equivalent dried herb ratio of 1:10. (Perhaps a 1:5 ratio can be achieved for roots, barks, and seeds that contain less moisture.) However, because the use of 1:10 or even 1:5 tinctures makes therapeutic doses of most herbs difficult, the herbal practitioner who endorses pharmacologic dosing will generally find little advantage in using fresh plant tinctures. Some exceptions occur based on traditional use or instances when the herb is so potent that it is normally used as a tincture (e.g., poke root, Thuja), but these are few.

From the previous discussion, a fresh plant tincture will never be as strong as will a 1:1 or 1:2 liquid extract, provided that:

a. The liquid extract has been made from carefully harvested and dried raw material of high quality.

b. The correct ethanol percentage was used to extract the dried herb.

c. No steps were used in manufacturing (e.g., exposure to high temperatures) that will damage the delicate active component spectrum of the plant.

Dried plant preparations made in such a way will still preserve the “vitality” or “energy” of the original plant, which is embodied in its chemical complexity. Fig. 1-1 gives a visual comparison of a dried plant extract (A) with a fresh plant tincture (B) using a paper chromatography technique known as vertical capillary dynamolysis. Adherents to the anthroposophy movement believe this technique can demonstrate the “vitality” of a preparation under test. Although the analysis of the chromatograms is subjective, the figure does show that a “vitality” to dried plant extracts exists.

Fig. 1-1 A visual comparison of a dried plant extract (A) and fresh plant tincture (B) obtained by a paper chromatography technique (vertical capillary dynamolysis).

Some practitioners use fresh plant preparations that are 1:3 or 1:5 (or even 1:10) based on fresh weight in the mistaken belief that they are using highly active preparations. However, a simple mathematical calculation shows that these practitioners are deceiving themselves. Taking a 1:5 fresh weight ratio as an example and assuming again that the herb contains 80% moisture, the following calculations can be made. If 100 g of fresh herb is macerated in 500 ml of menstruum, the dry-weight equivalent of herb is 20 g, and the total amount of liquid is 500 ml plus the 80 ml from the plant, which equals 580 ml. Hence the so-called 1:5 tincture is actually 1:29 on a dry-weight basis—completely unsuitable for therapeutic herbal doses.

GALENICAL EXTRACTS AND THE CONCEPT OF SYNERGY

A galenical extract is a traditional pharmacopeial extract of an herb. Guidelines were laid down in the various pharmacopeias (e.g., earlier versions of the British Pharmaceutical Codex) that defined the method of preparation, the extracting solvent (which was usually a combination of ethanol and water), and the ratio of the starting material (the herb) to finished product (the extract). Galenical extracts are usually in liquid form, typically the tinctures and liquid extracts already described in this chapter. However, with the modern trend to solid-dose forms, quite often, a galenical extract is dried to its solid residue and incorporated into a tablet or capsule.

Herbalists often regard galenical extracts as “whole” extracts in that they extract a comprehensive spectrum of the phytochemical content of the plant. Although this practice is generally the case, the reader should keep in mind that alcohol-water mixtures are still selective solvents and do not equally extract everything from the plant that is extractable. Something will always be left behind, depending on the percentage of ethanol that is chosen for the solvent. The ethanol percentages laid down in the pharmacopeias therefore represent what was thought to be the optimum solvent for extracting the widest activity from the herb in question. As mentioned previously, the percentages were often chosen with regard to the particular phytochemical classes known to occur in the plant; for example, a higher ethanol percentage was chosen for herbs containing resins or essential oils and so on as already mentioned.

The main reason why herbalists prefer “whole” or galenical extracts is their belief that the active component is the herb itself. In other words, all of the phytochemicals in the plant act together to confer the therapeutic benefit. According to Sharma:¹¹

… the active ingredient model does not stem from a strength of the scientific method, as often supposed; rather it stems from a weakness—from the inability of the reductionist methods to deal with complex systems.

One of the underlying motivations for using galenical extracts is the concept of synergy. Synergy is an important concept in herbal pharmacology. In the context of a mixture of chemicals (e.g., an herbal extract), synergy applies if the therapeutic action of the chemical mixture is greater than the arithmetic sum of the actions of the mixture’s components. In other words, the whole is greater than the sum of the individual parts. A well-known example of synergy is exploited in the use of insecticidal pyrethrins. A chemical synergist known as piperonyl butoxide, which has little insecticidal activity of its own, interferes with the insect’s ability to break down the pyrethrins, thereby substantially increasing their toxicity. This example emphasizes what is probably an important mechanism behind the synergy observed for medicinal plant components: increased or prolonged levels of key components at the active site. In other words, components of plants that are not active themselves can act to improve the stability, solubility, bioavailability, or half-life of the active components. Hence a particular chemical might, in pure form, have only a fraction of the pharmacologic activity that it has in its plant matrix. This important example of synergy therefore has a pharmacokinetic basis.

An excellent discussion of synergy in the context of herbal therapy was provided by E. M. Williamson.¹² According to the author, “It is almost inescapable that these interactions between ingredients will occur; however, whether the effects are truly synergistic or merely additive is open to question…” In other words, the more likely interaction between the components of a galenical extract is an addition of their pharmacologic effects, rather than true synergy. Even in this case, the “whole” will still be better than a selection of the parts.

As previously inferred, one area in which synergistic interactions probably apply is that of the enhanced bioavailability of key components. Eder and Mehnert discussed the basic issues, and examples can be found in the scientific literature.¹³ The isoflavone glycoside daidzin given in crude extract of Pueraria lobata achieves much greater concentrations in plasma than does equivalent doses of pure daidzin.¹⁴ Ascorbic acid in a citrus extract was more bioavailable than was ascorbic acid alone.¹⁵ Coadministration of procyanidins from Hypericum perforatum (St. John’s wort) significantly increased the in vivo antidepressant effects of hypericin and pseudohypericin. This effect was attributed to the observed enhanced solubility of hypericin and pseudohypericin in the presence of procyanidins. The result also indicates that pure hypericin and pseudohypericin have considerably less antidepressant activity than do their equivalent amounts in St. John’s wort extract.¹⁶

However, synergy can also have a pharmacodynamic basis. One example is the antibacterial activity of major components of lemon grass essential oil. Although geranial and neral individually elicit antibacterial action, the third main component, myrcene, did not show any activity. However, myrcene enhanced antibacterial activities when mixed with either of the other two main components.¹⁷ Sennoside A and sennoside C from senna have similar laxative activities in mice. However, a mixture of these compounds in the ratio 7:3 (which somewhat reflects the relative levels found in senna leaf) has almost double the laxative activity.¹⁸

Additional examples of synergy for galenical extracts are provided by Williamson and include kava, valerian, dragon’s blood, and Artemisia annua.¹²