A study on the Compatibility of Crude Drugs Comprising Kampo Medicines

Typically, an herbal formulation consists of multiple crude drugs of natural origins (denoted here simply as “crude drugs”), and these medicines are efficacious because of the specific combinations of those crude drugs. Formulations consisting of crude drugs were developed over a long period of time based on the compatibility of crude drugs. Even if a person in a certain era devised a new formulation consisting of crude drugs and named it, that herbal medicine’s efficacy was subsequently determined over a long period of time. If it was inefficacious, it disappeared through natural selection. Only those Herbal formulations that many people feel are efficacious have been passed down to the present day. Currently, approximately 150 types of Kampo medicines are used in traditional Japanese medicine in Japan, while about 300 types are stringently selected and used in Chinese medicine in modern China, including those with the same constituents as Kampo medicines. In Japan, 148 types of Kampo formulations are currently covered by health insurance. In addition, approximately 100 types of crude drugs are covered by health insurance. In Japan, many Kampo formulations from several companies are used in daily practice. packaged as an instant extract, these formulations are boiled or provided in the form of a dry powder in advance. As example, aconite [1,2] (an extract with action “to warm and relieve pain”) and red ginseng [3] (an extract with action to “supplement ‘qi’ and relieve fatigue and malaise”) are available as extracts of a single crude drug from Tsumura. 

Typically, a single crude drug has several types of action, so the action of a herbal formulation as a whole often differs from the additive actions of the individual crude drugs that comprise it. When different formulations are taken simultaneously, the crude drugs that comprise them mix in the stomach.

The compatibility of pairs of the crude drug in herbal medicines has not been elucidated. Accordingly, when taking several different types of herbal formulations on the same day, the formulations may need to be taken after a certain interval to prevent them from mixing in the stomach. If incompatible crude drugs mix, the efficacy of each formulation may presumably decrease compared to when each formulation is taken alone. Taking the compatibility of crude drugs into account may allow added crude drugs to have an effect without decreasing overall efficacy. When considering whether to add powdered aconite extract or powdered red ginseng extract or when contemplating taking different Kampo extracts at the same time, the appropriateness of the types of formulations to add is a concern. If pairs of incompatible crude drugs can be identified by the current study, then the effects of adding certain crude drugs or combining formulations may be determined in routine practice.

This study examined the compatibility of crude drugs comprising herbal formulations, with a focus on the TOP 40 crude drugs most often contained in Kampo extracts. A total of 324 formulations were studied, including 150 formulations often used in Japan and 174 formulations that are often used in modern China as listed in a textbook from a university of traditional Chinese medicine (Table 1). 

Table 1: The formulations studied (150 Kampo formulations + 174 Chinese herbal formulations).

To identify pairs of crude drugs that do not coexist in any of the formulations studied, the following procedures (1) and (2) were performed in sequence. Procedure (1): Crude drugs comprising all of the formulations studied were entered in Excel. Formulations were sorted in descending order by the crude drugs they consisted of. Formulations containing crude drug A were selected, and those not containing crude drug B were identified. Procedure (2): Formulations containing crude drug B were selected, and they were checked to see whether or not they contained crude drug A. 

Through procedures (1) and (2), pairs of crude drugs (AB) were identified, i.e., “crude drug B is not present in formulations containing crude drug A, and crude drug A is not present in formulations containing crude drug B.” When the conditions above were satisfied, pairs of crude drugs (AB) that did not coexist were identified and designated “non-coexisting pairs” of crude drugs. Non-coexisting pairs of crude drugs are likely to be incompatible. 

This study was approved by the ethics review board of this facility.

Non-coexisting pairs are shown in table 2. Based on the current results, there were no crude drugs that were incompatible with licorice [4] or ginger. bellflower [5], pinellia tuber, and bupleurum root [6,7] were identified as crude drugs that may be incompatible with aconite. Schizonepeta spike was identified as a crude drug that is potentially incompatible with ginseng. Polyporus and perilla herb were identified as crude drugs that are potentially incompatible with peony [8]. The following pairs of crude drugs may be incompatible. Peach kernel [9] and coptis chinensis [10,11], rhubarb [12,13] and astragalus membranaceus [14], angelica acutiloba [15] and japanese yam, ephedra herb [16] and coptis chinensis, anemarrhena [17] and dried ginger [18], magnolia officinalis [19] and plaster, poria [20] and sodium sulfate, and pinellia tuber and rehmannia root [21]. In regard to non-coexisting pairs AB which are shown in table 2, number of formulations included crude drug A or B is respectively shown in table 3. The higher number of formulations included A×number of formulations included B is, the higher a possibility of existence of non-coexisting pair AB. Accordingly, most incompatible pair is thought to be pinellia tuber - rehmannia root. 

Table 2: The non-coexisting pairs in the formulations studied. 

Table 3: Number of formulations included crude drug A or B in regard to non-coexisting pairs AB which are shown in table 2. 

Pairs of crude drugs that are incompatible are presumed to have been eliminated from formulations through natural selection over a long period of time. As a result, the combinations of crude drugs in the 324 formulations studied have stood the test of time.

The non-coexisting pairs shown in table 2 were systematically organized, yielding the following findings. When one wishes to mix one formulation with the other or when one wishes to add a crude drug to a formulation, “right or wrong” should be taken into consideration based on the current results to avoid mixing of incompatible crude drug in the stomach. 

The crude drugs comprising Kampo formulations tended to contain jujube [22], ginger, and licorice in comparison to traditional Chinese medicine formulations. Licorice has action to “harmonize various drugs,” ginger has action to “promote digestion”. there were no crude drugs that were incompatible with licorice or ginger. In case of taking the formulation that include jujube, it should probably not be taken at the same time the formulation which include the crude drugs like gardenia fruit, moutan bark, anemarrhena, Ophiopogon japonicus, and bellflower. 

White atractylodes (Baizhu) is often used in traditional Chinese medicine formulations (white atractylodes: atractylodes rhizome = 27: 5), while atractylodes rhizome is often used in Kampo formulations (white atractylodes: atractylodes rhizome = 14: 35). Both atractylodes and white atractylodes are often found to be incompatible with almond kernel [23]. In case of taking the formulation that include atractylodes or white atractylodes, it should probably not be taken at the same time the formulation which include almond kernel. 

When one wishes to add powdered aconite extract to a formulation for its “warming and analgesic action,” it should probably not be taken at the same time the formulation which include bellflower, pinellia tuber, or bupleurum root. When one wishes to add powdered red ginseng extract to a formulation for its “action to promote digestive function” and “supplement ‘qi’,” it should probably not be taken at the same time the formulation which include schizonepeta spike. 

Shakuyaku-kanzo-to consists of licorice and peony. peony has “antispasmodic and analgesic action.” When one wishes to add powdered Shakuyaku-kanzo-to to another formulation for its “antispasmodic and analgesic action.” it should probably not be taken at the same time the formulation which include Polyporus or perilla herb. Kikyo-to consists of licorice and bellflower. Bellflower has “detoxifying and pus-draining action.” When one wishes to add powdered Kikyo-to to another formulation for its “antispasmodic and analgesic action.” it should probably not be taken at the same time the formulation which include dry ginger or aconite. 

Considering above, when several different formulations are taken, it may be safe to leave a time interval required for digestion to take medicine.

The current results may provide a basis for considering the appropriateness of mixing different formulations like Kampo extract or adding a crude drug to a formulation.

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