Chapter 34 Botanical Medicine—Understanding Herbal Preparations
Introduction
The clinical application of botanical medicine involves the use of various herbal preparations. That being the case, it is imperative that practitioners and physicians using herbal medicines understand the differences among the various forms. Commercial herbal preparations are whole fresh and dried herbs, teas, tinctures, fluid extracts, and tablets or capsules. In addition, juices, purified compounds, and specific fractions of plants (e.g., volatile oil preparations) can also be considered herbal medicines. Each form has advantages and disadvantages and varying ways of expressing its medicinal strength. Any form may be an effective medicine as long as it can deliver an effective dosage of active compounds. The following section reviews the major extraction forms, discusses the benefits of standardized botanical extracts, and emphasizes the importance of delivering a clinically effective level of active compounds regardless of the form of the herbal preparation.
Types of Extracts
An extract is a concentrated form of an herb obtained by mixing the crude herb with an appropriate solvent (such as alcohol or water, or both). A major advance in the herb industry has been the improvement in extraction and concentration processes.
When an herbal tea bag is steeped in hot water, it is actually a type of herbal extract known as an infusion. The water is serving as a solvent in removing some of the medicinal properties from the herb. Teas are often better sources of bioavailable compounds than powdered herbs, but are relatively weak in action compared with tinctures, fluid extracts, and solid extracts. These forms are commonly used by the lay public and herbal practitioners for medicinal effects.
Tinctures are typically made using an alcohol and water mixture as the solvent. The herb is soaked in the solvent for a specified amount of time, depending on the herb. This soaking is usually from several hours to days; however, some herbs may be soaked for much longer periods of time. The solution is then pressed out, yielding the tincture.
Fluid extracts are similar to, but more concentrated than, tinctures. Although they are most often made from hydroalcoholic mixtures, other solvents may be used (e.g., vinegar, glycerin, propylene glycol). Commercial fluid extracts are usually made by distilling off some of the alcohol, typically by using methods that do not require elevated temperatures, such as vacuum distillation and counter-current filtration. However, some small manufacturers produce fluid extracts in a similar manner to tinctures via percolation at room temperature.
A solid extract is produced by further concentration of the extract by the mechanisms described earlier for fluid extracts, as well as by other techniques such as thin-layer evaporation. The solvent is completely removed, leaving a viscous extract (soft solid extract) or a dry solid extract depending on the plant, portion of the plant, solvent, and drying process (if any) used. The dry solid extract, if not already in powdered form, can be ground into coarse granules or a fine powder. A solid extract can also be diluted with alcohol and water to form a fluid extract or tincture.
Strengths of Extracts
The potencies or strengths of herbal extracts are generally expressed in two ways. If they contain known active principles, their strengths are commonly expressed in terms of the content of these active principles. Otherwise, the strength is expressed in terms of their concentration. For example, tinctures are typically made at a 1:5 to 1:10 concentration. This means one part of the herb (in grams) is soaked in five parts solvent (in milliliters of volume), meaning there is five times the amount of solvent (alcohol/water) in a tincture as there is herbal material. Fluid extracts are typically 1:1.
A 4:1 concentration means that one part of the extract is equivalent to, or derived from, four parts of the crude herb. This is the typical concentration of a solid extract. A quantity of 1 g of a 4:1 extract is concentrated from 4 g of crude herb.
Typically, 1 g of a 4:1 solid extract is equivalent to 4 mL of a fluid extract and 20 to 40 mL of a tincture. Some solid extracts are concentrated as high as 100:1, meaning it would take nearly 100 g of crude herb, or 100 mL of a fluid extract, or 1 L of a tincture, to provide an equal amount of herbal material in 1 g of a 100:1 extract.
Determining Quality
Before the 1980s, the quality of the extract produced was often difficult to determine because many of the active principles of the herbs were unknown. However, advances in extraction processes, coupled with improved analytic methods, reduced this problem of quality control.1,2 The concentration method of expressing the strength of an extract does not accurately measure potency because there may be great variation among manufacturing techniques and raw materials. By using a high-quality herb (i.e., rich in active compounds), it is possible to have a more potent dried herb, tincture, or fluid extract compared with the solid extract that was made from a lower quality herb. Standardization of herbal extracts for key active constituents has been suggested to be the solution to this problem.3
Standardized Extracts: The Best Solution
Standardized extracts (also referred to as guaranteed potency extracts) refer to an extract guaranteed to contain a “standardized” level of active compounds or key chemical marker. Stating the content of active compounds or key chemical marker rather than the concentration ratio allows for more accurate dosages to be made. However, the complex composition of an herbal medicine makes it unwise to ignore the other constituents.
The best scenario for determining the quality of an herb is the level of active components or key biological markers, along with taking into consideration the complete chemical profile. Regardless of the herb’s form, it should be analyzed to ensure that it contains these components at an acceptable standardized level. More accurate dosages can then be given. This form of standardization has emerged as the preferred method, but it is not without its shortcomings. Chief among them is that assigning too much importance to individual components rather than the entire chemical profile leads to the assumption that controlling for the level of marker compounds is equivalent to controlling the entire pharmacologic effect of the herbal medicine. However, stating the content of active constituents versus drug concentration ratio does allow for more accurate dosages to be based on active constituents and provides the greatest degree of consistency and assurance of quality, especially if attention is also given to the other constituents.
Although referred to in terms of active constituents, it must be kept in mind that these are still whole extracts and not isolated constituents. For example, a Uva ursi extract standardized for its arbutin content, say 10%, still contains all of the synergistic factors that enhance the active ingredient’s function.
Techniques Used in the Production of Herbal Products
A tremendous range of sophistication exists in processing herbs, from crude herb to highly concentrated standardized extracts. Nonetheless, there are some common stages. Some of the processes in the production of herbal products and the machines that perform these functions are discussed in the following section.3
Collection/Harvesting
When plants are collected from their natural habitat, they are said to be “wild-crafted.” When they are grown using commercial farming techniques, they are said to be “cultivated.” Collection of plants from cultivated sources ensures that the plant collected is the one that is desired. When an herb is wild-crafted, there is a greater chance of picking the wrong herb and of variation in potency. However, some herbal practitioners believe that wild-crafted herbs are inherently superior because growth in their natural habitat produces an herb with constituents and properties more consistent with traditional use. The use of analytic techniques can be employed to guarantee that the plant collected is the one desired and that its concentrations of medicinal constituents are within an acceptable range.
Herbs from all over the world are marketed in the U.S. marketplace. Herb collectors vary from uneducated natives to self-proclaimed “herbalists” to trained botanists.
The mode of harvesting varies from hand labor to sophisticated equipment. The mode is not as important as the time of year. A plant should be harvested when the part of the plant being used contains the highest possible level of active compounds. Again, this is ensured by using analytic techniques.
Drying
After harvesting, most herbs have a moisture content of 60% to 80% and cannot be stored without drying. Otherwise, important compounds could break down or microorganisms could contaminate the material, or both. As many of the desired compounds are heat labile, the majority of herbs require relatively mild conditions for drying. Commercially, most plants are dried within a temperature range of 100°F to 140°F. During drying, the plant constituents must not be damaged or suffer losses that would prevent them from conforming to accepted standards. With proper drying, the herb’s moisture content is reduced to less than 14%.
Garbling
Garbling refers to separation of the portion of the plant to be used from other parts of the plant, dirt, and other extraneous matter. This step is often done during collection. Although there are machines that perform garbling, garbling is usually performed by hand.
Grinding
Grinding or mincing an herb means mechanically breaking down either leaves, roots, seeds, or other parts of a plant into small pieces ranging from larger course fragments to fine powder. Grinding is employed in the production of crude herbal products, as well as in the initial phases of extracts.
Often the material must be pre-chopped or minced before feeding it into a grinder. In the process of grinding, a number of machines can be used, but the most widely used is the hammer mill. These machines are simple in design. The hammers, arranged radially, follow the rotation of the shaft to which they are attached, breaking up the material that is fed into the machine from above. On the walls of the chamber is a grid, which determines the size of the material that is passed through it. Other types of grinders include knife mills and teeth mills.
Extraction
The process of extraction is used in making tinctures, fluid extracts, and solid extracts. Extraction in the context of this textbook refers to separating, by physical or chemical means, the desired material from a plant with the aid of a solvent. In the U.S. health food industry, most extracts use alcohol and water mixtures as solvents to remove soluble compounds from the herb. The exceptions are liposterolic extracts, which are produced either through the use of lipophilic solvents or with the aid of hypercritical carbon dioxide (carbon dioxide gas compressed to a liquid by high pressures).
Most extracts that are produced by small manufacturers use maceration procedures. The simplest process consists of soaking the herb in the alcohol/water solution for a period of time and then filtering it. For many botanicals, this process yields a lower quantity of active constituents at a higher price because of the cost of the solvent. Because tinctures are 1:5 concentrates, 80% of the bottle is alcohol and water and only 20% is herbal material. In essence, the cost of the alcohol is a major portion of the retail price of tinctures.
Larger manufacturers use more elaborate techniques to ensure that the herb is fully extracted and the solvent is reused. For example, counter-current extraction is often used. In this process, the herb enters the column of a large percolator composed of several columns. The material to be extracted is pumped through the different columns at a specific temperature and flow speed, where it continuously mixes with solvent. The extract-rich solvent then passes into another column, while fresh solvent once again comes into contact with herbal material as it is passed into a new chamber. In this process, complete extraction of health-promoting compounds can be performed. The extract-rich solvent is then concentrated by the following techniques.
Concentration
After extraction of the herb, the resulting solutions can be concentrated into fluid extracts or solid extracts. In large manufacturing operations, techniques and machines such as thin-layer evaporators are used to ensure that the extracted plant components are not damaged. These machines work by evaporating the solvent and leaving the plant compounds. The solvent vapors pass into a condenser whereby they return to a liquid for reuse. The result is separation of the extracted materials from the solvent so that the final product is a pure extract, and the solvent can be used again and again.
Drying of Extracts
Many practitioners prefer the extract dried to a solid form because it is more chemically stable and lower in cost (alcohol is often more expensive than the herb). In addition, tinctures, fluid, and soft extracts can more easily be contaminated by bacteria and other microorganisms. Liquid forms of extracts also promote reactions that eventually break down some active constituents. A number of drying techniques are employed, including freeze-drying and spray drying (atomization). The result is a dried powdered extract that can then be put into capsules or tablets.
Analytic Methods
Improvements in analytic methods have definitely led to improvements in harvesting schedules, cultivation techniques, storage, stability and concentration of active compounds, and product purity. All of these gains have resulted in tremendous improvements in the quality of currently available herbal preparations.
Methods currently used in evaluating herbs and their extracts include the following:
Organoleptic
Organoleptic means the “impression of the organs.” Organoleptic analysis involves the application of sight, smell, taste, touch, and occasionally even sound to identify the plant. Typically, the initial sight of the plant or extract is so specific it is easily recognized. If this is not enough, perhaps the plant or extract has a characteristic odor or taste. Organoleptic analysis represents the simplest, yet the most human, form of analysis.
Microscopic Evaluation
Microscopic evaluation is indispensable in the initial identification of herbs, as well as in identifying small fragments of crude or powdered herbs. It is also important in the detection of contaminants and adulterants (e.g., insects, animal feces, mold, fungi). Every plant possesses a characteristic tissue structure, which can be demonstrated through study of tissue arrangement, cell walls, and configuration when properly mounted in stain reagents and media.
Physical/Chemical Analysis
In crude plant evaluation, physical methods are often used to determine the solubility, specific gravity, melting point, water content, degree of fiber elasticity, and other physical characteristics. Various chemical/physical methods are also used to determine the percentage of active principles, alkaloids, flavonoids, enzymes, vitamins, essential oils, fats, carbohydrates, protein, ash, acid-insoluble ash, or crude fiber present.
Chromatography
The most sophisticated analytic processes involve more highly technologic assays to determine quality. Advanced techniques such as thin-layer chromatography, high-pressure liquid chromatography, capillary electrophoresis, and nuclear magnetic resonance are used to precisely separate, identify, and quantify molecules. The readings from these machines provide a chemical “fingerprint” as to the nature of chemicals contained in the plant or extract.4 These techniques are invaluable in the effort to identify herbs, as well as to standardize extracts.
Quality Control in Herbal Products
Quality control refers to processes involved in maintaining the quality or validity of a product. Regardless of the form of herbal preparation, some degree of quality control should exist. Without quality control, there is no assurance that the herb contained in the bottle is the same as what is stated on the outside. One of the key solutions to the quality control problem that exists in the United States is for manufacturers and suppliers of herbal products to adhere to quality control standards and good manufacturing practices. With improvements in the identification of plants by laboratory analysis, consumers should at least be guaranteed that the right plant is being used. Consumers, health food stores, pharmacists, herbalists, and physicians who use or sell herbal products should ask for information from the suppliers of herbal products on their quality control process. What do they do to guarantee the validity of their product? As more consumers, retailers, and professionals begin demanding quality control from the suppliers, manufacturers will use more quality control processes.
Currently, only a few manufacturers adhere to complete quality control and good manufacturing practices. Companies supplying standardized extracts currently offer the greatest degree of quality control; hence, these products typically offer the highest quality. The production of standardized extracts seeking registration in Europe may serve as a model for quality control processes for all forms of herbal preparations (Box 34-1). In general, it is believed that if the active components of a particular herb are known, whatever the form of the herb product, the herb should be analyzed to ensure that it contains these components at a medicinally appropriate level. More accurate dosages can then be given. Products should also be subjected to bacteriologic counts and be free of contaminants.
BOX 34-1 List of Quality Control Steps Necessary for the Registration of Plant-Based Drug Formulation
1. Selection of suitable plant material
2. Botanical investigation using organoleptic and microscopic techniques
3. Chemical analysis using appropriate laboratory equipment
4. Screening for biological activity
5. Analysis of active fractions of crude extracts
6. Isolation of active principles
7. Determination of chemical structure of active principles
8. Comparison with compounds of similar structure
9. Analytic method developed for formulation
10. Detailed pharmacologic evaluation
11. Studies performed to determine activity and toxicity of formulation
12. Studies on absorption, distribution, and elimination of herbal compounds
13. Clinical trials performed to determine activity in humans
The Issue of “Phytoequivalence”
It is often difficult to translate the effectiveness of a particular form of an herbal product to another form. For example, how many milk thistle (Silybum marianum) seeds are required to produce the same effects as those demonstrated in clinical studies conducted on milk thistle extracts standardized to contain 70% silymarin? Or does an extract of St. John’s wort that is standardized to contain 0.3% hypericin and 3% to 5% hyperforin, but whose remaining chemical profile is substantially different from the clinically proven St. John’s wort, produce the same benefits? The real answers to these questions require investigations into phytoequivalence and pharmacokinetics.
The concept of phytoequivalence dictates that if a particular extract demonstrates certain clinical results, a second extract can only be considered as being equivalent if it possesses the same chemical profile as the first extract. This definition of phytoequivalence requires that not just the level of marker compounds or key active constituents, or both, be the same, but that the extracts be identical in the complete spectrum and quantity of all constituents. However, assuring identical chemical equivalence may not assure true therapeutic equivalence if pharmacokinetic factors are not taken into consideration regarding how the herbal medicine is delivered. True phytoequivalence may not be related to having identical extracts but rather to being able to produce the same pharmacokinetic pattern.
Standardized Extracts Versus Tinctures
Several misconceptions regarding standardized extracts need to be addressed. One is that standardizing an extract results in the loss of important compounds. This is simply not true for the vast majority of standardized extracts. Chemical analysis of standardized extracts and tinctures, whether it be thin-layer chromatography or high-pressure liquid chromatography, has clearly demonstrated that standardized extracts are not only higher in active compounds but also have a broader range of chemical constituents due to more effective extraction.
Another common misconception is that they are more expensive than alcohol-based tinctures and fluid extracts. Calculations based on the cost of delivery of an effective dosage show that the standardized extract is significantly more cost effective. This is because, as noted earlier, there is less of the herb in tinctures and fluid extracts, resulting in consumers paying extra for alcohol, the bottle, and the cost of shipping.
Final Comments
The effectiveness of any herb or herbal product from a pharmacologic perspective is dependent on providing an effective dosage of active compounds. Regardless of the form of the herbal preparation, clinical effectiveness requires delivery of an active dosage. At this time, standardization or accurate analysis of the content of active constituents or key biological markers is the only real assurance of the delivery of an effective dosage.
This view should not be controversial. Unfortunately, controversy arises from the fact that, from a pharmacologic perspective, it is unlikely that the dosage schedules historically recommended for most herbal tinctures are sufficient to produce significant pharmacologic effects. Although tinctures of such potentially toxic herbs as Gelsemium, aconite, belladonna, and digitalis often produce a pharmacologic effect when given at low dosages, for most common medicinal herbs, it is difficult to produce an adequate and cost-effective response when the herb is administered in tincture form.
The administration of small dosages of herbs in tincture form is an offshoot of the homeopathic and eclectic use of “mother tinctures” and “specific medicines.” The effectiveness of these preparations and their ability to exert pharmacologic effects have not been proved for all but a few botanicals.
The systems of herbal medicine that have been proved to a large extent are based on delivering much higher levels of herbal compounds than those easily obtained via the use of tinctures. Specifically, we are referring to the use of highly concentrated standardized extracts from Europe and the use of herbal preparations in Traditional Chinese Medicine and Ayurveda. In Traditional Chinese Medicine, the typical daily dose of prescribed crude herbal material is approximately 20 g. This high level of dosage is in stark contrast to a much smaller average amount of the herbal material recommended in the British Herbal Pharmacopoeia of 2 to 4 mL of a 1:5 tincture, which provides less than 1 g of herbal material. This difference in dosage may explain the differences in popularity of herbal medicine in China, Japan, India, and Germany compared with its relative obscurity in England, as well as in the United States before the previous decade. The key point is that herbal medicine is not going to be popular if it is not effective. It can be argued that the greater the effectiveness, the greater the popularity.
The tremendous growth noted in the United States since the mid-1980s is, in our opinion, the result of the influx of high-quality standardized extracts into the marketplace. Developments in cultivation, extraction, and concentration processes led to the successful commercial development of these herbal products. Better clinical results were achieved with these herbal medicines because they were able to deliver an effective dose of active constituents.
Although the future looks extremely promising for herbal medicine, ultimately its growth and continued success will be determined by the following:
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2. Karlsen J. Quality control and instrumental analysis of plant extracts. In: Wijeskera R.O.B., ed. The medicinal plant industry. Boca Raton, FL: CRC Press; 1991:99–106.
3. Bonati A. How and why should we standardize phytopharmical drugs for clinical validation? J Ethnopharmacol. 1991;32:195–197.
4. Gong F., Liang Y.Z., Xie P.S., et al. Information theory applied to chromatographic fingerprint of herbal medicine for quality control. J Chromatogr A. 2003;1002:25–40.