TCM Principles

Dosing Guidelines for Granule Products

A Clinician’s Guide to using Granule Extracts - Practical Master Class for Clinical Success

In recent years, granules have become the most popular delivery form for Chinese herbal medicine in the West. However, while granule efficacy can be maximised by observing modern clinical trends in Asia, resources that shed light on this subject are few and far between. In an effort to bridge this knowledge gap, Eric Brand has travelled to factories, hospitals, and clinics throughout Asia to research the manufacturing and clinical trends in the world of granules. In this practical granule handbook for clinicians, Eric covers: *Effective dosing strategies *Methods of formula combining *Common clinical approaches seen in mainland China and Taiwan *Concentration ratios and their effect on dosage * Various manufacturing methods and their impact on patient care * How to set up an efficient pharmacy with attention to good compounding practices.

The following is an excerpt from Eric Brand’s book, “A Clinician’s Guide to Using Granule Extracts”, published by Blue Poppy Press, and reprinted with kind permission from Eric Brand, slightly edited for length.

In Taiwan, granules have been used extensively because they are the only herbal products that are covered by the national health insurance system. While the insurance system limits the maximum dose that a doctor can prescribe, the inclusion of granules into the national insurance system has stimulated tremendous research and experience in the use of granules. There is nowhere in the world that uses granules more frequently than Taiwan, so the Taiwanese experience is invaluable in assessing the granule field.

Granule prescriptions in Taiwan are generally created by combining multiple base formulas together. In addition to starting with whole formulas, Taiwanese doctors commonly add single medicinal extracts when customising the prescription. This practice of combining base formulas with single-herb additions is one of the most distinctive features of Chinese medicine in Taiwan.

The vast majority of Practitioners in Taiwan believe that combining whole granule formulas that were cooked together is superior to using single extracts to build a formula from scratch. In truth, this viewpoint is so pervasive that few doctors in Taiwan have tried prescribing granules any other way. While it is impossible to assess whether the Taiwanese method objectively yields superior results, the efficacy of their method has been well-demonstrated in millions of patient visits.

In Taiwan, it is common for the clinic to mix a granule prescription and dispense it in small plastic bags. The plastic bags are formed by a machine that divides the powder into specified doses, eliminating the need for the patient to measure the powder with a spoon. The prescription is recorded in the patient’s digital file, and a printout is usually included with the prescription from the pharmacy.

According to research conducted by Dr. Chang Hsien-Cheh of China Medical University in Taiwan, over 30 million patient visits with TCM were recorded annually by Taiwan’s National Health Insurance system during 2004 and 2005. During this two-year time period, over 4000 Chinese medical doctors prescribed nearly 2.7 million kilograms of granule extracts. This represents the most complete digital database of granule therapy in the world.

The national insurance system in Taiwan pays for up to six grams of granules per dose. The typical six-gram dose is usually given three times per day, for a total of 18 grams of concentrated extract powder per day. The precise extraction ratios for each product are clearly stated on the granule labels in Taiwan. However, most doctors there think less in terms of calculating extraction ratios and replicating raw herb doses by weight, and focus more on the ratio of herbs and formulas within the daily target dose of 18 g/day.

The dosage used by most doctors in Taiwan tends to fluctuate between 12–18 g/day, with 18 g being the most common for adults. Taiwan’s insurance system uses a digital chip embedded in an ID card that is linked to the patient’s chart. The computer system that hospitals and clinics use with the insurance card does not allow the dosage of granules to exceed 6.0 grams per dose, so most practitioners think about granule dosage within the context of a six gram single dose. The total dose that is entered is usually 4-6 grams, and each dose is given three times per day.

The dosage of granule prescriptions in Taiwan is generally calculated based on the relative proportions of a given medicinal or formula within the maximum six-gram dose. Many Taiwanese doctors have mastered a huge repertoire of formulas, so their prescriptions often contain classical formulas that may not be familiar to most Western Practitioners.

Each six-gram dose tends to contain about 4-6 grams of formulas that treat the chief presenting pattern. For secondary patterns, whole formulas are commonly added in a dose range of 0.3-1.2 grams. Singles are often added at a dose of 0.1–1 gram TID (three times per day). The most common dose range seen for singles is about 0.3 g TID, or about 1 gram per day for most items.

Below are some examples, taken from the author’s observation of doctors at Chang Gung Memorial Hospital in Taiwan. All of these prescriptions come from senior Practitioners. While the case notes provided are often not sufficient to illustrate the patient’s full clinical picture, the dosage levels and complexity of the formulas illustrate the standard approach used in Taiwan

Example one:

In the gynaecology department, female patients would commonly come in for treatment for late menstruation. The doctor would typically administer a pregnancy test, and if the pregnancy test was negative, the following formula was fairly common:

Xue Fu Zhu Yu Tang (House of Blood Stasis - Expelling Decoction) 3.5 g

E Zhu (Curcumae Rhizoma) 0.3 g

Ze Lan (Lycopi Herba) 0.3 g

This formula is very small, but it is relatively straightforward. 4.1 grams are given per dose, for a total of about 12.3 grams per day. If the above formula failed to bring on menstruation within a few days, a more customised formula would typically be indicated.

Example two:

In another example, consider the following formula for a patient suffering from cough and sinus congestion:

Xin Yi San (Officinal Magnolia Flower Powder) 2.0 g

Cang Er Zi San (Xanthium Powder) 0.75 g

Xiao Qing Long Tang (Minor Black Dragon Decoction) 0.3 g

Ma Xing Gan Shi Tang (Ephedra, Apricot Kernel, Gypsum, and Licorice Decoction) 1.25 g

E Bu Shi Cao (Centipedae Herba) 0.2 g

Lu Lu Tong (Liquidambaris Fructus) 0.2 g

Zao Jiao Ci (Gleditsiae Spina) 0.2 g

Here, 4.9 grams of granules were given three times per day, for a total of about 14.7 grams per day. Note the complex use of formulas in this prescription. Four whole formulas are prescribed simultaneously. The formulas together make up 4.3 grams, or about 88% of the total dose, but no single formula is used at a dose of over 2.0 grams. Combining as many as four formulas together is not uncommon in Taiwan, but many prescriptions do use fewer formulas than this.

Example three:

The following prescription was given to a middle-aged male patient with chronic hepatitis. He exhibited pitting edema in the lower legs, and had a large, slightly red tongue with yellow coating.

Da Chai Hu Tang (Major Bupleurum Decoction) 1.5 g

Jiang Can (Bombyx Batryticatus) 0.3 g

Chan Tui (Cicadae Periostracum) 0.3 g

Lu Gen (Phragmitis Rhizoma) 0.3 g

Chi Shao (Paeoniae Radix Rubra) 0.3 g

Tao Ren (Persicae Semen) 0.3 g

Long Dan Xie Gan Tang (Gentian Liver- Draining Decoction) 2 g

Huang Lian (Coptidis Rhizoma) 0.3 g

Bai Shao (Paeoniae Radix Alba) 0.3 g

Bie Jia (Trionycis Carapax) 0.4 g

Here, the total dose was 6.0 grams, given three times per day for a total of 18 grams per day.

Example four:

The following prescription was given to 42-year-old female patient with Sjogren’s Syndrome, rheumatoid ar thritis, and urticaria. She had swelling and pain at her knuckles and had poor sleep, thick slimy tongue fur and a dark tongue with stasis and a red tip. She also suffered from recent insomnia.

Shu Jing Huo Xue Tang (Channel-Coursing Blood-Quickening Decoction) 1.5 g

Gan Lu Yin (Sweet Dew Beverage) 1.5 g

Long Dan Xie Gan Tang (Gentian Liver- Draining Decoction) 1.5 g

Mu Dan Pi (Moutan Cortex) 0.5 g

Yi Yi Ren (Coicis Semen) 0.4 g

Chi Shao (Paeoniae Radix Rubra) 0.3 g

Mu Gua (Chaenomelis Fructus) 0.3 g

This prescription was prescribed at a total dose of 6.0 grams, three times per day (18 g/day). It contains three formulas in even proportions.

Example five:

The following prescription was given to a 35 year-old female patient with lupus (SLE), presenting with a rash from her feet up to her calves. She had a thin red tongue with a thin coat that was peeled at the edges. She reported no current pain or itching, and had a thin rough pulse. She experiences dry lips and dry throat.

Gan Lu Yin (Sweet Dew Beverage) 1.5 g

Long Dan Xie Gan Tang (Gentian Liver- Draining Decoction) 1.5 g

Yin Qiao San (Lonicera and Forsythia Powder) 1.5 g

Mu Dan Pi (Moutan Cortex) 0.3 g

Bai Shao (Paeoniae Radix Alba) 0.3 g

Yi Yi Ren (Coicis Semen) 0.3 g

Sang Bai Pi (Mori Cortex) 0.3 g

Here, 5.9 grams of granules were prescribed three times per day, for a total of 17.7 grams per day.

Example six:

The following prescription was given to a 53 year-old female with tinnitus, dizziness, and poor sleep. She had a dry mouth with a bitter taste, anxiety, and a history of pain and swelling in her knee, along with frequent crying.

Mu Gua (Chaenomelis Fructus) 0.4 g

Zhi Bai Di Huang Wan (Anemarrhena, Phellodendron, and Rehmannia Pill) 1.4 g

Suan Zao Ren Tang (Spiny Jujube Decoction) 1.2 g

San Qi (Notoginseng Radix) 0.4 g

Tian Ma Gou Teng Yin (Gastrodia and Uncaria Beverage) 1.4 g

Dang Gui (Angelicae Sinensis Radix) 0.4 g

Bai Shao (Paeoniae Radix Alba) 0.4 g

Tian Men Dong (Asparagi Radix) 0.4 g

This patient was prescribed 6.0 grams of granules three times per day, for a total of 18 grams per day.

Example seven:

The following prescription was given to a patient that presented with infertility and endometriosis. She had just received a hormonal check and all the results came back within normal limits. She had a pale tongue with cold hands, and her pattern presented with signs of kidney yang vacuity and liver depression.

Jia Wei Xiao Yao San (Supplemented Free Wanderer Powder) 3.0g

You Gui Wan (Right-Restoring Pill) 2.5 g

Yin Yang Huo (Epimedii Herba) 0.5 g

Here, 6.0 grams were given three times per day, for a total of 18 grams per day. Note the use of two compound formulas with only a single addition.

Example eight:

The patient was an 11 year old male with allergic rhinitis. He had experienced sneezing, clear nasal discharge, and sinus congestion for several years. These symptoms were particularly prevalent upon awakening. Postnasal drip and cough were occasionally noted, along with frequent throat clearing. He had no history of food allergies or asthma, although blood tests indicated an allergic response to eggs, shrimp, and mites. He was diagnosed with lung and spleen qi vacuity.

Xiao Qing Long Tang (Minor Green-Blue Dragon Decoction) 0.4 g

Xin Yi San (Officinal Magnolia Flower Powder) 2.8 g

Xiang Sha Liu Jun Zi Tang (Costusroot and Amomum Six Gentlemen Decoction) 0.4 g

Here, we see the use of granules at a dose of 3.6 grams, given three times per day (13.2 grams total). This dose range is somewhat lower than the typical adult dose, but it is consistent for a child of 11 years of age. This formula relies on Xin Yi San to open the nose, complemented by a small amount of Xiao Qing Long Tang to warm cold-rheum and eliminate wind-cold. Xiang Sha Liu Jun Zi Tang is used to support the spleen to treat the root problem of phlegm.

Overall, Taiwan uses a very distinctive and innovative approach to granules. Doctors in Taiwan have a tremendous degree of experience with granules, but their approach has not been adequately studied and implemented outside of Taiwan.

Even within Taiwan, there are not any books or training courses that truly provide comprehensive training in the local granule approach. Doctors tend to imitate their teachers, and forty years of granule use in Taiwan has slowly caused a distinctive style to emerge. Taiwan has a number of excellent granule suppliers and hundreds of clinical experts, so the global impact of Taiwan on the granule field cannot be underestimated.

The Taiwanese method of formula combining is truly a new development in Chinese medicine, and Taiwan’s digital system is unique in its ability to gather statistical data and evidence-based results derived from the local granule approach. As time goes on, hopefully our community will see more and more literature on Taiwan’s approach to granules and formula combining.

Dosing formulas made from singles

In general, the total granule dosage should be between 10 - 18 grams per day. For children, the dosage often ranges from 3 - 10 grams per day, while severe and acute conditions can be treated with 15 - 25 grams per day. For the sake of simplicity let us use an example based on an average patient that is being prescribed 10 - 18 grams per day.

First, consider the total amount that is going to be prescribed per day. If prescribing a formula with 15 - 18 ingredients, the total dose should be closer to 18 grams per day. If only 5 - 12 ingredients are used, a dosage of 10 - 18 grams is probably sufficient. If the case is mild or the patient is weak, the dosage should be on the low side. If the case is severe or the patient is large and robust, the dosage should be on the high side. As a rule of thumb, multiplying the number of ingredients by 1.5 should give a reasonable total daily dose.

Next, consider how many medicinals are in the prescription. If 18 grams will be prescribed and 12 ingredients are used, the average dose of each medicinal will be about 1.5 grams.

In any given formula, some items will be used at higher doses than others. Medicinals that are potent by weight or extreme in nature should be given at low doses, generally 0.3 - 1.5 grams per day. Examples include items such as Rou Gui (Cinnamomi Cortex), Ren Shen (Ginseng Radix), Fu Zi (Aconiti Radix Lateralis Praeparata), Sha Ren (Amomi Fructus), Chai Hu (Bupleuri Radix) and Wu Zhu Yu (Evodiae Fructus).

By contrast, medicinals that have a balanced nature and a relatively high standard dose in raw decoctions should be used at higher doses, typically 1 - 3 grams per day. Examples include items like Shu Di Huang (Rehmanniae Radix Praeparata), Shan Yao (Dioscoreae Rhizoma), Yi Yi Ren (Coicis Semen), Mu Li (Ostreae Concha), and Yu Zhu (Polygonati Odorati Rhizoma).

Items that have a moderate, mid-range dosage in decoctions are often used at a dose of 1 - 2 grams per day. Such items include Dang Gui (Angelicae Sinensis Radix), Bai Zhu (Atractylodis Macrocephalae Rhizoma), Bai Shao (Paeoniae Radix Alba), Ba Ji Tian (Morindae Officinalis Radix), etc.

Some items are used at different dosages for different purposes. For example, Chai Hu (Bupleuri Radix) is often used in low doses to raise yang in formulas such as Bu Zhong Yi Qi Tang (Centre-Supplementing Qi- Boosting Decoction). In such applications, 0.3 - 0.8 grams of granule Chai Hu is generally sufficient. If Chai Hu is instead used to course the liver qi, slightly larger granule doses are typical, such as 0.5 - 1.5 grams. For treating lesser yang disease, even higher quantities would be called for, such as 1.5 - 3.0 grams. Similarly, Gan Cao (Glycyrrhizae Radix) is generally used at a low dose as a courier to harmonise a formula (0.5 - 1.0 grams), but it can be used in high doses (2 - 3 grams) as a sovereign medicinal in a formula such as Zhi Gan Cao Tang (Honey-Fried Licorice Decoction).

Consider the following examples. In the first example, a small formula with only eight ingredients is used. In this example, the daily target dose will be around 12 grams.

In this first example, the formula is relatively small. Consider the example below, with a larger formula of 12 ingredients. Here, the total daily target dose will be about 18 grams.

In a larger formula such as this one, there are many factors to pay attention to. The medicinals should always be in proportion to the patient’s presentation. For example, if blood vacuity is prominent, the relative doses of medicinals such as Shu Di Huang, Bai Shao, and Dang Gui should be relatively high. Within those three, Shu Di Huang will tend to be the highest because its raw dose standard is the highest. Bai Shao and Dang Gui can be used at similar dose ranges, but Dang Gui is somewhat prone to producing side-effects such as diarrhoea if its dosage is too high.

The fundamental nature of each medicinal should always be taken into account. Shu Di Huang is rich and potentially stagnating, so its dosage should not be excessive in patients that are prone to dampness and diarrhoea. Chuan Xiong and Chai Hu are relatively dry medicinals, so their dosage should not be too high for most cases. Fu Ling and Ye Jiao Teng are relatively weak medicinals by weight, so their dosage should be relatively high. Zhi Gan Cao is used to harmonise here, so its dosage should be low. Medicinals such as Xiang Fu, Bai Shao, and Bai Zhu are here being used at a moderate dosage, not too high and not too low.

Dosage when combining formulas

If one is starting with base formulas, the dosing strategy changes slightly. Again, the total daily target dose will tend to be about 12 - 18 grams for the final prescription, but the quantities of each item within the formula will tend to be higher since whole formulas are used instead of single extracts.

When combining several formulas together that have similar principles, the dosage of both formulas can be reduced. For example, if Liu Jun Zi Tang (Six Gentlemen Decoction) and Bu Zhong Yi Qi Tang (Centre- Supplementing Qi-Boosting Decoction) were used together, the dosage of each one could be reduced.

If one formula treats the main pattern and it is combined with a second formula that addresses a specific symptom or an auxiliary pattern, the main formula should be used at a dose of 8 - 12 grams and the auxiliary formula for the secondary pattern or symptom should be used at a dose of 1 - 6 grams. For example, to treat constipation due to liver depression, 12 grams of Xiao Yao San (Free Wanderer Powder) could be used with 4 - 6 grams of Ma Zi Ren Wan (Cannabis Seed Pill). In this instance, Xiao Yao San would be used to treat the root pattern of liver depression, while Ma Zi Ren Wan would be added to provide symptomatic relief for the constipation.

If two formulas are used with equal emphasis, they should have roughly similar doses, especially if they have a comparable number of ingredients. For example, the formula Si Ni San (Counterflow Cold Powder) is commonly combined with the formula Tong Xie Yao Fang (Painful Diarrhoea Formula) to treat diarrhoea and pain due to a wood-earth disharmony. Both of these formulas have the same number of ingredients and both may be equally important for the condition, so the dose of each one could be 6 - 8 grams.

If three or more formulas are used together, the dosage of each formula tends to be lower than it would be if only one base formula was used. If three or more formulas are combined, the dosage of each formula is often only 2 - 6 grams.

When using a whole formula as though it were a single medicinal addition, the dosage can be quite low. A single medicinal addition is usually added at a dose of 0.5 - 3.0 grams per day, and this same dose range could be used for a whole formula. For example, if one added Huang Lian Jie Du Tang (Coptis Toxin-Resolving Decoction) to a formula instead of adding a single medicinal such as Huang Lian (Coptidis Rhizoma), the whole formula could be added at a low dose such as 0.5 grams.

Example:

A patient presents with constipation prior to menstruation. She experiences mood swings, irritability, painful menstruation, delayed menstruation, and breast distension. She is diagnosed with liver depression and mild blood stasis. She is prescribed the following formula:

Jia Wei Xiao Yao San (Supplemented Free Wanderer Powder) 8 grams

Tao He Cheng Qi Tang (Peach Kernel Qi4- Infusing Decoction) 2 grams

Qing Pi 0.8 grams

Yu Jin 1.0 grams

Xiang Fu 1.2 grams

Here, the patient is given a combination of two formulas with three single additions. The principle formula, Jia Wei Xiao Yao San, addresses the liver depression and irritability that is central to her diagnosis. The secondary formula, Tao He Cheng Qi Tang, frees the stool and quickens the blood. Although Tao He Cheng Qi Tang contains Gui Zhi (Cinnamomi Ramulus) and is slightly warm, it is used at a relatively low dose here and its warm temperature is offset by the cool nature of Jia Wei Xiao Yao San. Qing Pi, Xiang Fu, and Yu Jin together strengthen the qi-moving nature of the formula and help to relieve the breast distension.

*Reproduced with kind permission from Health World Limited - Australia and New Zealand