Scientifically Concentrated TCM Herbal Extracts-Part I
Brion Research Institute of Taiwan
Sun Ten Pharmaceutical Co., Ltd.
Translated by Sun Ten ITD
Traditional Chinese medicine (TCM) is the cultural heritage of the Chinese people, developed and cultivated by our ancestors through thousands of years of clinical experience. Their great contributions have been vital to the health and well-being of the Chinese people and have also played a crucial role in setting the foundation for TCM. By using various raw materials comprised of animals, minerals, and plants, our ancestors have been able to formulate countless different remedies in relation to a symbiotic system consisting of an emperor, minister, deputy, and ambassador, all designations for distinct natural herbal ingredients. Each TCM remedy has its own specific composition of herbs, functions, indications, dosage forms, and clinical applications. The information regarding these TCM remedies were documented and scattered amongst an assortment of TCM literatures which were generally deprived of analytical data, strict quality control, and product specifications. As a result, TCM remains a relatively ambiguous idea to the international medical mainstream. This is why it is exceptionally significant to modernize TCM by starting with selection of raw materials, controlled manufacturing processes, and strict quality control. These necessary modifications will guarantee the safety, consistency, and efficacy of the TCM final products.
During the first century, a pioneer in Rome named Galenus began treating ailments with herbal extracts as a form of medication. His acquisitions of these herbal extracts were based on a crude process in which the extracts were obtained by soaking natural herbs in alcohol. Western medication has changed dramatically since Galenus?time and has evolved into much more convenient dosage forms nowadays such as granules, tablets, capsules, liquids, and injections, all with specific and distinct properties. In contrast, TCM is derived from different natural resources whose properties amongst each batch can and will fluctuate, causing it to be much more volatile and inconsistent. The home decoctions of these herbal resources into honey pills or ground powders tend to have large dosage amounts which are not only inconvenient to consume, but also incapable of meeting product consistency and stability standards. Thus, developing scientific methods of producing concentrated TCM herbal extracts with conformed specifications is the only way to facilitate the recognition and acceptance of TCM into the international medical mainstream.
1. What are Scientific Concentrated TCM Herbal Extracts?
The definition of scientific concentrated TCM herbal extracts simply refers to herbal extracts which are in compliance with modern scientific standards. This requires the usage of pharmacopoeia-specified herbs, manufacturing processes which yield products of the greatest therapeutic effects, and highly sophisticated QC (quality control) analytical equipment to ensure the quality of the TCM products.
TCM herbal extracts utilizes authentic pharmacopoeia-specified herbs grown in uncontaminated locations, harvested during the right seasons, processed using the correct procedures, and stored under optimal conditions. These raw materials must also contain specific levels of active constituents before they are accepted and used in the manufacturing processes. These selected raw materials are measured, decocted, and concentrated according to precise Standard Operation Procedures (SOP) with reasonable application of extraction ratios and suitable addition of excipients. The manufacturing processes are conducted entirely under Good Manufacturing Practices (GMP), resulting in the production of high-quality TCM herbal extracts in convenient dosage forms which are fully capable of meeting modern medical demands. By following the QC standards for modern medicine, every batch of each product is analyzed for botanical identification, chemical analysis, heavy metal analysis, microbiological analysis, quantitative tests, consistency tests, and stability tests, delivering to the public safe and high-quality TCM products.
In 1930, Mr. Onzo Nagakuro pioneered the usage of concentrated Kempo herbal extracts in Japan. Due to the fact that they were convenient, easy to take, and quality controlled, these concentrated herbal extracts quickly became popular in Japan. During the 1950, Dr. Hong-yen Hsu, a native of Zhang Hua, Taiwan (1917-1991), who was at the time, the director of the Taiwan Food and Drug Control Board, visited Nagakura Pharmaceutical Company and was intrigued by their manufacturing processes of concentrated herbal extracts and its great convenience. Dr. Hsu decided to bring the idea of concentrated herbal extracts back to Taiwan and began its production at Sun Ten Pharmaceutical while referring to the essence of ancient decoction processes of each different herbal ingredient documented in literatures. This marked the beginning of a new era in the TCM field in Taiwan.
However, at the time, this new idea of convenient, decoction-free concentrated herbal extracts was difficult for the TCM field to accept. Yet, driven by his determination and good-faith, Dr. Hsu, continued to uphold and pursue this new idea of concentrated herbal extracts by elevating the quality of raw herbal materials used, improving the production technology, and enhancing the quality control of the products despite its costs. Furthermore, he employed capable and experienced professionals from the TCM field to promote concentrated TCM herbal extracts through education. Finally, after ten years of cultivation and perseverance, concentrated TCM herbal extracts had become an established conception in Taiwan, and as a result, Dr. Hong-yen Hsu was hailed as the “Father of Scientific Concentrated Herbal Extracts.” (Fig. 1)
To further advance the quality of raw herbal materials and its production processes, Dr. Hsu founded the Brion Research Institute of Taiwan in 1972, which remains as the only private TCM research center in Taiwan. In 1976, Dr. Hsu established the Oriental Healing Art Institute in Los Angeles, USA to further propagate TCM theory and knowledge to the Western world.
During the 1970's, concentrated TCM herbal extracts gradually became the primary TCM product in Taiwan. The government began monitoring the production conditions of concentrated TCM herbal extracts and set testing specifications to ensure the quality of the TCM products. Government regulations also required every TCM manufacturing plant to be GMP certified; and by the late 1980Õs, the first group of TCM manufacturers received GMP certifications. By 1986, the Health Department required TLC (Thin Layer Chromatography) analytical data for new and renewal product license applications. In 1990, besides TLC analytical data, the Health Department also required general description and biochemical analysis for product license applications. Regulations continued to tighten and by the year 2000, new product license applications and renewal applications required quantitative analysis in addition to all other mandatory tests. On March 1st of 1995, the Taiwanese government implemented a full-scale public health insurance system which included the reimbursement of GMP certified concentrated TCM herbal extracts, signifying its acceptance and recognition into TaiwanÕs medical mainstream.
II. GMP and GAP Introduction
1. Good Manufacturing Practices (GMP)
In order to ensure product quality, it is imperative to possess strict operational guidelines in addition to first-rate equipment and production technology. Thus, on May 26th, 1982, the Taiwan Health Department established and announced the guidelines for Good Manufacturing Practices (GMP). GMP compliance was in full effect by 1988. The GMP guidelines consist of the following key points:
1.1 Sanitation and Environment
- The location of the manufacturing plant should be clean and free of excess pollution.
- Production, processing, and packaging sites should maintain a safe distance from surrounding buildings to avoid unnecessary contamination and fire hazards.
- The manufacturing plant must be well built, durable, and kept clean.
- Production, processing, and packaging sites must be completely segregated from offices, reception areas, laboratories, cafeterias, and restrooms to prevent unnecessary contamination.
- Avoid usage of any materials containing asbestos.
- Storage areas for finished products, containers/lids, labeling/packaging materials, and the warehouse for storing raw materials should be kept in an orderly fashion with adequate spacing and proper marking to prevent any confusion and/or contamination.
- Equipments used for production, processing, packaging, and storage should be designed to be accessible, maneuverable, and convenient to clean and maintain.
- Production equipments used for various dosage forms should be arranged systematically to maintain a smooth flow of production processes.
1.4 Organization and Personnel
- Quality control and manufacturing departments should be independent of each other.
- Each department requires qualified and experienced key personnel with specific responsibilities.
- Each department must have sufficient personnel to maintain the execution and supervision of the production, processing, packaging, and storage of each product.
1.5 Production Control
- In order to maintain the consistency between each batch, designated personnel will devise a Master File for the production processes of each product. This Master file will be examined by an auditor to confirm its credibility which also needs to be reviewed and approved by the Quality Assurance Manager.
- The Master File of each product should contain the following:
a. Product Information: name, contents, dosage form, unit weight/volume, the name and unit weight/volume of every active ingredient, and if applicable, per tablet/capsule weight.
b. Raw materials Used: names, characteristics, specifications.
c. Production batch size: the unit weight/volume of each raw material used; reasonable marginal differences are allowed but should be noted and explained in the Master File.
d. Theoretical Production Yield: Estimated production yield and variances.
e. Product containers, lids, and packaging material specifications.
f. Complete Batch Manufacturing Records, sampling and testing method SOPs, product specifications, and special cautions.
- To ensure the product consistency and quality of each batch, specific departments should be responsible for the assessment and validation of the production process SOPs of each product including validation and qualification of related procedures, equipment, and facilities. All the validation and qualification SOPs must be recorded for future references.
1.6 Reporting and Documentation Control
- A set of standard operation procedures should be devised and followed for: inspection and acceptance of packaging and labeling materials, labeling, storage, management, sampling, and analysis.
- To ensure products quality, stability tests are conducted in order to determine the expiration dates and the products shelf life.
1.7 Records of Distribution
- All production controls and distribution records of every batch for each product must be kept for at least one year after the product expiration date.
- For every batch produced, there must be a Batch Manufacturing Record documenting the complete information on the production and quality controls, including a copy of the Master File which is reviewed and released by authorized signatory and dates.
- Batch Manufacturing Records including production, packaging, labeling, and quality control should be reviewed by the QA manager to ensure the SOPs were followed and that each product conforms to product specifications before being released for distribution.
- Distribution records should include: product name, contents, dosage, batch number, recipient names and shipping address, quantity, and the release date.
2. Good Agricultural Practices (GAP)
Good Agricultural Practices (GAP) for herbal materials is a set of guidelines intended to elevate the quality, safety, and efficacy of raw herbs collected and used for medicinal purposes. GAP can be simply interpreted as the combination of medical and agricultural science with primary focuses on identification and authentication of raw herbs, propagation materials, cultivation technology, harvesting methods, and post-harvest operations. The standardization of these procedures will ultimately result in the production of high-quality products. In 1992 and 1997 respectively, Japan and the European Union successfully implemented GAP and were both rewarded with positive results. Currently, China has just begun the implementation of GAP; thus, it is impossible to employ a full-scale regulation of herbal materials immediately. There are only approximately ten different herbs involved in GAP programs with several under experimental stages (Fig. 2). Therefore, TCM manufacturers are unable to attain GAP certified herbal materials for the production of TCM products under the current conditions.
Regulation can be achieved through various means including cultivation methods, which are also vital in determining the quality of the herbs. Amongst the different cultivation methods, there is a unique method called the “quasi-wild” cultivation method in which seedlings of selected species are grown and then moved to a designated location for out-door growth. Generally speaking, GAP is a proven and effective system used to standardize and control raw materials. The GAP for herbal materials consists of the following factors:
2.1 Ecological Environment
- Production sites for medicinal herbs must have suitable and apporpriate environmental conditions including air, soil, and water conditions that meet the national standards.
- National Standards Pertaining to China: Atmospheric Condition – B level Standard; Soil Condition – B level Standard; Water Condition for Irrigation – Agricultural Irrigation Water; Water for Animal Consumption – Human Drinking Water Quality.
2.2 Seeds and Propagating Materials
- Botanical identification of medicinal herbs and the selection of high-quality species.
- Standardization of seeds and propagating materials to cultivate high-quality medicinal herbs.
- Disease control to prevent plant diseases/pests within seeds and propagation materials during the production, storage, and shipping processes.
2.3 Cultivation Procedures
- Provide good irrigation/drainage processes in accordance to each medicinal herb's requirement to optimize soil condition and ventilation.
- Maintain quality and stability by applying field management (i.e. topping, nipping buds, pruning and shading) to control growth and development processes of medicinal herbs.
- Fertilizers used should be primarily organic and the amount should be in accordance with the herb and its soil conditions. (Refer to Table 1)
- Usages of fertilizers that are not publicly hazardous and have been thoroughly decomposed are permitted (i.e. farm fertilizers such as animal refuse, compost).
- The usage of urban life garbage, industrial wastes, and hospital refuses as fertilizer is strictly prohibited.
- The usages of low-residue, low-toxicity, and highly effective pesticides are allowed only if necessary and should be primarily organic in nature.
- Pesticide usage should be in accordance with national standards in order to maintain good soil quality and prevent contamination including pesticide residues and heavy metal pollution.
2.4 Harvesting and Primary Processing
- Maximize sustainable output: Planned cultivation, collection rotation, and protected growth periods for wild and semi-wild herbs in order to maintain a good ecological environment in the production sites.
- Designated seasons/times and methods to harvest cultivated herbs.
- Remove non-medicinal parts, foreign particles, and rotten/damaged parts when harvesting herbs.
- Use clean machinery free of contamination to harvest herbs.
- Follow standardized SOPs for post-harvest procedures: selection, washing, cutting, and drying.
- Maintain controlled temperature and humidity levels within the processing sites with good ventilation to prevent unnecessary contamination of herbal materials.
2.5 Packaging, Storage, and Shipping
- Standardized SOPs should be followed when packing herbal materials to maintain its standardized quality (elimination of substandard herbal materials).
- Batch records must be clearly indicated on each package and kept with the specific information noted (i.e. name, specifications, origin, batch number, packaging date, manufacturer).
- Packaging material must be clean, dry, and free of pollutants. Do not ship transporting containers in the vicinity of materials which may affect the smell/taste of the herbal materials.
- Storage sites must be dry, clean, and well ventilated to prevent damage and pollution to the herbal materials. Use air conditioning and humidity control devices when necessary.
2.6 Quality Control
- Trained personnel in the QC department with access to specific analyzing equipment should monitor the entire production processes of herbal materials.
- Inspections should take place before packaging to confirm the quality of the herbal materials conform to national standards; Tests include: botanical identification, loss on drying (moisture content), total ash, acid-insoluble ash, seepage, and active constituent/markers.
- Designated personnel along with the head of QC must sign these inspection reports which must be kept on file.
- Inferior herbal materials are not to be sold or distributed.
2.7 Personnel and Equipment
- Personnel responsible for technical matters on production sites must have at least 2 years of education in pharmacy or agronomy.
- Personnel responsible for QC must have at least 2 years of higher education and have QC experience regarding herbal materials.
- Personnel involved in the production processes must have basic training and have general education of pharmacy and agronomy.
- Personnel responsible for packaging, shipping, and storage must have routine medical check-up to prevent contamination of herbal materials.
- All personnel must maintain safety and hygiene.
- Equipment used in production and inspection must be regularly inspected and calibrated.
- SOPs are required for the production and QC of the herbal materials.
- Complete and detailed records must be kept during the entire production processes of each herbal material.
- Records should include the origin of the seeds/propagating materials and the production techniques and processes which include:
a. Planting time, quantity and area, growth of seedlings, transplantation, fertilizer and pesticide used (including time, amount, method).
b. Time of collection, quantity collected – fresh weight and dry weight (After drying), processing, shipping, and storage.
c. Environmental conditions and climate records.
d. Inspection results and evaluation of quality.
- All records should be kept for at least 5 years with designated personnel responsible for the keeping and maintenance of the files.
III. Raw Materials
Traditional Chinese medicine is primarily derived from natural sources comprised of animals, plants, and minerals. The quality of these medicinal resources can be greatly affected by their place of origin, harvesting seasons, and storage conditions. In general, the public judge medicinal herbs solely by their appearances and consider large, beautiful, and expensive herbs as the finest herbs. However, it is extremely difficult to determine the quality or even the authenticity of TCM herbs without the use of analytical equipment, let alone the common eye. Scientific concentrated TCM herbal extracts are manufactured using carefully selected microscopic identified raw materials, which can actually guarantee the safety, quality, and consistency of the final products. The following will explain the relationship between the control of raw materials and product quality.
1. Sources of Medicinal Herbs
Most TCM herbs come from different parts of China, one of the largest countries in the world today. However, it is also due to its immense boundaries that homonymic medicinal herbs with completely different sources exist throughout the country. The characteristics and potency of these homonymic herbs differ greatly and can have absolutely different purposes and therapeutic effects. The usage of traditional Chinese medicine and herbs has a history of more than two thousand years and can be dated back as early as the Han dynasty. During this vast period of time, many changes occurred in the TCM field. The first-ever written herbal literature was Shen NongÕs Herbal, which listed 365 different herbs. By Ming dynasty, the great herbal classic, Ben Cao Gang Mu recorded a total of 1892 different types of herbs, an approximately five-fold increase from Shen NongÕs Herbal. However, due to the existence of an immense variety of herbs and the lack of their detailed descriptions in ancient medical literatures, surrogates of various kinds of medicinal herbs began appearing throughout the country, causing chaos and confusion in the TCM field. Remote production regions and regional differences in the usage and naming of different medicinal herbs also contributed to the chaotic circumstances. The constant appearances of homonymic and heteronymous medicinal herbs have greatly affected the precision and efficacy of TCM usage; and because medicinal herbs is the fundamental source of therapy for TCM physicians and the building block of modern scientific TCM, the precise identification and authenticity of each medicinal herb is essential in a products efficacy, safety, and consistency. Thus, the control of the source of medicinal herbs is of the utmost importance.
The identification of the sources of medicinal herbs can be determined by microscopic examination, chemical identification, or the organoleptic examination of external features (Figs. 3?4).
Take Radix Pulsatillae (Bai Tou Weng) as an example. The authentic form of this medicinal herb is actually derived from the root of the Ranunculaceious plant Pulsatilla chinensis (Bunge) Regel. Currently, there are approximately twenty homonymic herbs called Radix Pulsatillae on the market of which Herba Potentillae Chinensis (Wei Ling Cai - Figs. 5?6), derived from the root of the Rosaceous plant Potentilla Chinensis seringe, is most commonly seen.
The true form of Radix Pulsatillae has a yellowish-brown appearance with the cortex around the root-head often decayed. The root-head is also noted for the presence of many microscopic hairs and has 3 microphylls. The cortex appears to be white whereas the xylem takes on a yellowish color. Herba Potentillae Chinensis on the other hand, has a darker, reddish-brown appearance. The root-head is covered with microphylls (8?11 pairs) and the cortex has a light reddish-brown color whereas the xylem takes on a brownish color. Under microscopic examination, Radix Pulsatillae is found to consist of single cells with non-glandular hairs, occasionally found with spiral or double helical streaks. These cells possess rim pits, reticulate and helical tracheae, and has a diameter of 10?72 mm. In contrary, Herba Potentillae Chinensis consists of single cells with many glandular hairs. These cells usually appear in long, curved shapes and are often entangled with each other, forming larger masses. They usually measure up to 4000 mm long and have thick walls which contain calcium oxalate crystals (Fig. 7).
Radix Pulsatillae possesses the effects of clearing heat and toxins, stopping dysentery, and cooling blood. On the other hand, Herba Potentillae Chinensis is used to clear heat, moisten dryness, clean toxins, reduce swelling, stop bleeding, and stop coughing. The UV absorption spectrum also indicates that the two herbs are completely different as well (Fig. 8). Thus, the two herbs are undoubtedly different in nature but appear similar, showing that the usage and selection of the correct medicinal herb is extremely important.
2. Place of Origin and Environment
The climate, soil, and overall environment of a plantÕs place of origin has always been known to play crucial roles on their growth and development. The same medicinal herb grown in different areas may seem similar, but actually differ slightly in their composition and its ratio of constituents. Yet on a closer look, the absolute values of the constituent contents in fact differ greatly; thus, causing herbs derived from different origins to have different flavors, colors, and morphology. For instance, the transplantation of ginseng derived from northeastern China to the mountainous regions in central Taiwan developed radish-like ginseng with great differences in both appearances and composition. Moreover, the most essential and main constituent of the ginseng, ginsenosides, was of much lower value in the Taiwan-grown ginseng when compared with the ginseng grown in northeast China. On the other hand, the berberidaceous plant, Cortex Phellodendri, grown in Taiwan, is known for its high berberine content throughout the world. Likewise, if this berberidaceous plant were to be transplanted to northeast China, the composition and appearances would most definitely be different from the ones grown in Taiwan.
The so-called Ògenuine?medicinal herbs (Dao Di Yao Cai) refer to those herbs that are grown under specific natural conditions and ecological environments, which limit their growth and production to particular regions. Obviously, these Ògenuine?herbs are cultivated, harvested, and processed with higher standards, causing them to be known of better quality and efficacy when compared to the same species grown in different locations. Due to the fact that each medicinal herb has its own preferred growth and environmental conditions, there have always been specific regions in which specific herbs flourish which we call their primary place of origin (Fig. 9). The existence of wildlife medicinal herbs in these locations is also not uncommon. However, the increase of population development has caused some medicinal herbs to undergo certain variations, such as the requirement of artificial cultivation in order for them to thrive and flourish.
Based on ancient herbal literatures, the main place of origin for ginseng (Figs. 10?11) was the Shang Dang area. An illustrated and textual ginseng map found in Song dynastyÕs famous herbal literature, Tu Jing Ben Cao, describes Shang Dang Lu Zhou (the present time Chang Ye prefecture) of Shan Xi province as the place of origin of the Panax ginseng meyer. However, during the Qing dynasty, the emperor Qian Long, who was also a fond admirer of ginseng, wrote a poem saying, ÒIn ancient times, Hong-Jing Tao said that ginseng produced from Shang Dang was of best quality; yet, now only ginseng grown in Liao Yang, Ji Lin, and Ning Gu Ta have miraculous effects, whereas Ginseng from Shang Dang are like ordinary herbs.?This poem has clearly showed and suggested that the main place of origin for ginseng has moved from the Shang Dang area in ancient times, to the northeastern regions of China by the Qing dynasty.
Currently, naturally grown ginseng in the wild is extremely scarce and can only be found distributed in Mt. Chang Bai and in the southeastern Xiao Xing An Ling regions of China. Ginseng is a perennial herb with a predisposition of growing in mountain slopes around 500?1000 meters in altitude with leafy and/or needle-leaf plants present to provide a shady, cool, and moist climate. The mass majority of ginseng is cultivated. Before cultivation, ginseng seeds can be dried and stored in a dark, cool place. The embryo of ginseng has two ways of after-maturation, morphological and physiological. Morphological after-maturation requires temperature variation in the range of 10?20 degrees Celsius while physiological after-maturation requires a temperature variation in the range of 2?4 degrees Celsius. Both processes take anywhere from 3?4 months and seeds that do not undergo after-maturation processes will not sprout. In the Fu Song area of Ji Lin province, every ginseng grower will sow seeds harvested, dried, and stored from a year ago. Growers from the Ji An area will sow un-dried seeds that were harvested during August. Both growth processes take 5?7 years before the ginseng are ready to be harvested during September or October.
Temperature conditions during the cultivation of ginseng isnÕt very important, however 11.8?15.2 degrees Celsius is the best range for ginseng sprouts and the proliferation of young roots and root hairs. Moisture should be maintained at a range of 30?45%. The soil conditions on the other hand, are extremely important. Optimal conditions require deep soil layers composed of loose, fertile, sandy loam with very good water drainage. The pH of the soil should be slightly acidic, in the range of 5.6?6.8. Alkaline soil is unsuitable for the growth of ginseng and the continuous cultivation of ginseng in the same area is also not recommended.
Primary places of origin for ginseng is the northeastern regions of China where Ji Lin province offers the highest share of output, occupying more than 70% of the total national productivity of China. Famous places of origin include Fu Song, Ji An, Chang Bai, Jing Yu, and Tong Hua of the Ji Lin province, and Liao Ning, Huan Ren, Kuan Dian, Xin Bin, and Qing Yuan of the Liao Ning province. Other places of origin include Wu Chang, Shang Zhi, Ning An, and Dong Ning of the Hei Long Jiang province, and Beijing, He Bei province, Shan Xi province, Shan Dong province, and Hu Bei province.
3. Harvesting and Processing
There are a vast variety of medicinal plants which are used for therapeutic purposes in the world today. For each medicinal plant, there are different applicable parts, harvest seasons, harvesting methods, processing operations, and drying procedures. The quality of medicinal herbs depends on the amount of active constituents and processing procedures are important in determining the herbs quality. Gao Li once said, ÒHerbs, plants, and insects grow in specific areas while roots, leaves, flowers, and fruits have specific harvest times. These resources, if grown in the wrong areas or harvested at the wrong times, will cause their flavors and attributes to diminish.?A folk proverb also said, ÒJanuary is the best time of harvest for Artemisia capillaries while February is the best time of harvest for Artemisia argyi; however, by March, Artemisia capillaries are treated like fire wood (without medicinal value).?
The appropriate harvest time of medicinal herbs also vary depending on the plants and the applicable parts desired. For instance, Fructus Lycii and Fructus Corni are harvested when the fruits ripen and appear red in color. Fructus Aurantii and Fructus Citri sarcodactylis on the other hand, are harvested when the fruits turn greenish yellow or yellow. ÒWhole-herb?type medicinal herbs use flowering or budding of the plant as an indication that the herbs are ready to be harvested. On the contrary, other herbs such as Herba Artemisiae capillaris and Radix Pulsatillae are harvested at the young, sprouting stage. The harvest yield and amount of active constituents for each medicinal plant varies throughout its entire growth processes. However, there is a period of time for every medicinal plant in which it reaches a peak where the amount of active constituents or harvest yield is highest. For instance, the herb Flos Lonicerae has the highest yield and content of chlorogenic acid when it is budding, whereas Flos Sophorae has a 10% or higher amount of rutin when it is budding, but a higher yield when it is flowering. Root and tuber-type medicinal herbs are harvested after the plants are fully-grown and have entered their hibernation stages. During this period of time, the root and tuber-type herbs are at its best condition and have the highest deposit of active constituents. It is also during this period of time, the yield rate from the drying process are at its highest. For instance, when Radix Salviae miltiorrhizae, a root/tuber type herb, is harvested pre-maturely around September, the amount of the active constituent tanshinoneII-A accounts for only 0.04%, whereas when harvested after hibernation, the amount of tanshinoneII-A increases to 0.11%.
The total yield and amount of active constituents for leaf-type medicinal herbs varies along its entire course of growth and is affected by various factors including climate, environment, sunlight, and season. Thus, it is not uncommon for some leaf-type herbs to have significant differences in its properties throughout the course of one day. For instance, the essential oil derived from the leaf-type herb Herba Menthae is highest when the plant experiences a full week of fine weather and is harvested after the morning dew is dried and before two oÕclock in the afternoon. In contrary, when harvested after 2?3 days of continuous raining, the essential oil content will be reduced by 3/4. Also, within a single day, the harvesting of Herba Menthae yields the highest essential oil content between ten in the morning and four in the afternoon and is lowest at night.
The harvest times for medicinal herbs can be divided into four different categories; 1-year type, 2-year type, multi-year-type, and annually. 1-year type herbs are usually harvested annually with few 1-year type herbs harvested from perennial plants or shrubs such as ginger, Radix Curcumae, and Rhizoma Curcumae longae. 2-year type herbs are usually harvested biennially with few derived from perennial plants such as Bulbus Fritillariae thunbergii, Rhizoma Corydalis, Rhizoma Chuanxiong, Radix Aconiti Lateralis, Rhizoma Atractylodis macrocephalae, Radix Codonopsis, Radix Angelicae sinensis, and Rhizoma Dioscoreae. Multi-year type herbs are harvested from perennial plants or trees and may take up to 30 or even 100 years before they can be harvested. Examples include herbs such as Cortex Magnoliae officinalis, Cortex Eucommiae, and Cortex Phellodendri. Annually harvested medicinal herbs consist mainly of fruits, seeds, flowers, and/or leaves from perennial plants and trees such as Fructus Citri sarcodactylis, Fructus Corni, Flos Lonicerae, and Cacumen Platycladi.
There are several advantages for the on-site processing of medicinal herbs. The identification of the authenticity of harvested herbs and the processes of removing the coarse parts while retaining the applicable portions are conducted at this time. On-site processing also allows the preservation of the active constituents within the herbs and ensures the quality. It is also convenient for packaging, storage, and shipping procedures (Fig. 12). There are even some herbs which require processing in order to remove toxins such as Radix Aconiti Lateralis and Rhizoma Pinelliae.
Cortex Magnoliae officinalis is an herb known to originate from the Jiang Xi province. The herb is derived from the trunk bark of the trees 20 years or older and is processed by baking and sun drying methods. After processing, the inner surface of the bark appears purplish brown and oily, which are signs of excellent quality. The primary place of origin for Cortex Moutan is An Hui province. Feng Dan Moutan Cortex, which is a renowned type of Cortex Moutan, is extremely popular and widely accepted both domestically and abroad. This herb is cut into thin slices and sun dried after a brief immersion process which moistens and softens the herb. According to recent studies concerning Cortex Moutan, this processing method is best compared to other methods because it yields the highest content of paeonol, which is the main active constituent of the herb. This explains the practice of Òless immersion, more moistening?encouraged by our ancestors holds scientific reasoning. In general, the processing of medicinal herbs is aimed at (1) lowering side effects, (2) altering the original characteristics, (3) improving pulverization character, (4) eliminating impurities and non-therapeutic parts, (5) promoting solubility, (6) enhancing effects, (7) increasing shelf-life, (8) increasing purity, (9) and preserving flavoring and coloring effects.
4. Quality Control
GMP certified pharmaceutical plants are required to have a complete set of protocols for the inspection and the receiving of all medicinal materials used. The following are included:
1. Source identification: To identify the source of every herbal material used with reference to the scientific name of its host/source plant to avoid any misuses and/or confusion (Fig. 13).
2. Organoleptic examination: Including general features, size, texture, surface characters, color, fracture features, flavor, and taste.
3. Loss on drying: To examine the water content of the herbal material in order to determine the extent of dryness.
4. Water-soluble extractives: To examine the contents of water-soluble constituents.
5. Diluted alcohol-soluble extractives: To examine the contents of alcohol-soluble constituents.
6. Essential oils: Testing whether the main constituents of the herbal material are evaporative essential oils.
7. Total ash: To examine the impurities and soil content in the herbal material.
8. Acid-insoluble ash: To examine the amount/level of inorganic elements within the herbal material.
9. Thin-Layer chromatography (TLC): To examine whether the herbal material contains active constituents (qualitative test).
10. High-performance liquid chromatography (HPLC): To examine the amount/level of active constituents (quantitative test), (Fig. 16).
11. Atomic absorption spectrometry (AA) or Inductively-coupled Plasma-MS (ICP-MS): To examine whether heavy metals within the herbal material exceeds specified limits. ICP-MS is capable of measuring the individual amounts of individual heavy metal content.
12. Microbial test: To examine whether the pathological microbes within the herbal material exceeds specified limits.
Once the herbal materials have passed the above tests and comply with company specifications, they can be imported. Once imported, these herbal materials must be sampled and examined again to confirm their quality and to verify that they indeed meet the specifications before they can be used in the production processes. Furthermore, the processed herbal materials have an individual set of specifications and are subjected to another series of examination. The qualified herbal materials are then used to produce scientific concentrated TCM herbal extracts under GMP conditions in order to guarantee the quality of the products.
5. Storage and Shipping
Chinese medicinal herbs are derived from animal and plant sources that contain high amounts of nutrients and second metabolites which are necessary for the proliferation of life. However, these resources are easily affected by the outside environment during shipping or storage which can cause deterioration; thus, affecting the efficacy or even the safety of these medicinal herbs. Commonly encountered deterioration conditions include: worm decay, mold growth, oil exudation, discoloration, and the change of taste and flavor.
5.1 Worm Decay
Worm decay refers to the destruction of the herbal materials caused by worms or other pests. Radix ginseng, Radix Astragali, Radix Angelicae sinensis, and Rhizoma Alismatis are amongst a vast group of medicinal herbs which contain nutritive substances such as saccharides, proteins, and fats which provide a nourishing and suitable environment for worm growth. Best condition for worm growth would be (1) a temperature range between 15 and 35 degrees Celsius, (2) with relative humidity above 60 percent, (3) and water content of medicinal herbs over 11 percent. Given these conditions, pests will propagate swiftly and destroy the herbal materials in no time. Thus, as long as GMP certified manufacturers control the warehouse temperatures, humidity levels, and water content of the medicinal herbs, they can prevent worm decay and maintain the herbs quality.
5.2 Mold Growth
Mold growth refers to the condition of mold growth on or within the herbal materials caused by excess humidity in the environment. This phenomenon is caused by the high amount of fungal spores found in the air, which gets in contact with the surface of the herbal materials. Given the correct conditions these spores will develop into mycelia and penetrate the tissues of the herbal materials to secrete enzymes that destruct the herbs, causing them to lose efficacy and medicinal value. General prevention of mold growth includes storing herbal materials in dry, dark, cool environments with good ventilation, maintaining humidity levels under 70 percent and controlling water content under 15 percent. Another method is to replace the surrounding air with nitrogen to ward off oxygen, which will also prevent mold growth.
5.3 Oil Exudation
Oil exudation refers to the condition in which the oil content within the herbal materials begins to seep out. When saccharides or mucilage within the herbal materials seeps out and forms an oily texture on the surface, it is considered as oil exudation. Reasons that can cause oil exudation include the following: natural high content of oil in the herbal materials (i.e. Semen Armeniacae amarum, Semen Persicae, Semen Platycladi, Fructus Lycii, Radix Asparagi, Radix Ophiopogonis), high temperature and humidity levels, abnormal compressing, and prolonged storage. The exuded oil will give off rancid odors resembling aldehydes and ketones due to oxidation and decomposition. Storing these herbs between 5?8 degrees Celsius will prevent oil exudation and maintain the stability of the herbal materials.
5.4 Discoloration and the Change of Taste/Flavor
Discoloration refers to when the herbal materials in storage changes color due to the effects of oxidation, enzymes, sunlight, and the temperature and humidity levels. Herbal materials that contain flavonoids, anthraquinones, and tannins undergo discoloration easily under the effects of enzymes, which form macromolecular compounds within the herb. To prevent discoloration, consider storing under low temperature and humidity conditions and avoid direct light. Commercial packages can be filled with nitrogen instead of oxygen to prevent oxidation factors which also causes discoloration. The change of taste and flavor is largely due to inappropriate storage conditions of herbal materials which contain essential substances that evaporate easily. For instance, zingiberaceaous, rutaceous, umbelliferous, and magnoliaceous are herbs with strong aromas abound in volatile oils which evaporate easily. The evaporation of these essential oils directly affects the efficacy of the medicinal herbs. These types of herbs should be used when fresh and should avoid prolonged storage to maintain its medicinal values. Storage conditions must avoid high temperatures and direct sunlight.
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