Volume 1, Number 1 | Spring 2006

Clinical Report 3 (Japan)
Maoto Demonstrated as Highly Effective for the Treatment
of Influenza (B)Kazuhiro Oribe
Oribe Medical Clinic, Oita-shi

Introduction
Recently avian influenza has received a good dealof attention in the media. Currently, secondary
infection among people does not seem to occur. If sucha pathogenecity would be acquired, the disease would
be associated with considerable mortality because thehuman race does not have antibodies to use against it.
In western medicine the drug Oseltamivir (brand
name: Tamiflu) seems to be highly effective, so thatstockpiling of the drug by the individual nations has
been recommended. Yet, it must be noted that upon
indiscriminate administration, side effects cannot bedisregarded. Moreover, in order for the drug to beeffective, it needs to be administered within 48 hours
after onset and its administration has to be continued
over a period of 5 days2).
The author has 20 years of experience having
treated over 1,000 patients with influenza. This has
been done solely with Kampo medicine in his clinic
which specializes in Kampo treatment. In January lastyear, the author had a chance to use Oseltamivir,
providing the opportunity to compare it with Kampo
preparations. His experience is presented below.
One patient with influenza who was successfully
treated with Kampo is presented below.
Patient: age 32, male, employed.
Chief complaint: chills, fever, generalized arthralgia.
Family history, past history: n.p.
Description of occurrence of illness:
On January 1, 2005 the patients went to work at
9:00am, but suddenly felt chills over his back. Thiswas followed by shaking of the entire body which thepatient could not stop intentionally (shaking chills).
After a short period, he started to feel feverish,
developed a headache and joints and muscles
throughout the body started aching. At the same time
he felt drained of energy. The patient visited our clinic
at 5:00pm of that same day.
Initial Observation
Inspection: pale face and appeared generally
exhausted

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Listening: voice was rather loud.
Reasoning: clear
History: Loss of appetite, bowel movements andmicturition remained normal. Influenza seemed to beprevalent in his environment with many people being
absent from work. He claimed to have a lot of work to
do and thus needed to recover as quickly as possible.
Palpation (physical findings):
Physical build and nutritional status were good.
Examination of the pulse showed a rate of 100/min,regular floating, tense, fast. Blood pressure was 120/78
mmHg. The throat was slightly inflammed.
Auscultation of the heart and lungs did not reveal any
anomalies.
Abdominal
examination
showedintermediate abdominal tension and mild tenderness
in the right hypochondrial region (these abdominal
findings would be designated “fullness, tenderness or
discomfort of the hypochondrium). Body temperature
was 38.3°C. There was no perspiration.
Diagnosis
Western medical: quick diagnostic kit identifies type B
influenza.
Kampo medical: according to the “Shang Han Lun” thecondition is considered to be a cold injury excess
disorder of the greater yang type.
Prescribed Course
Maoto made by Tsumura (a 7.5-g portion of the
drug contains the following amount of dried crude drug
extract 1.75 g (Ephedra 5.0 g, Apricot Seed 5.0 g,
Cassia Bark 4.0 g and Licorice Root 1.5 g) was given inpackages of 2.5 g each taken with warm water atintervals of 4 hours. The patient was instructed tocover the body until the body warmed and he started
perspiring. The patient called, reporting that after
taking three packages, the body temperature
conversely had risen above 39°C, but he was still not
perspiring. Therefore I instructed the patient tocontinue the medication.
On the next morning, the patient called again,
reporting that 30 minutes after taking anotherpackage he started to sweat profusely over the entire
body, which in turn caused a fall in his temperatureand the alleviation of the joint and muscle aches. At
the time he was calling, he said he was feelingrefreshed. After that I instructed the patient todiscontinue the medication and take a day off to rest
quietly. Four days after the initial onset, he returned
to work without any recurrences.

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Volume 1, Number 1 | Spring 2006

Discussion
This patient followed a typical course of patientstreated during the early phase of influenza with maoto.
The author has treated over 1,000 patients with
influenza, and found that during the initial phase 90% of
the patients recovered within 2-3 days following
treatment with maoto after perspiration anddefervescence. When the fever continued, even after theadministration of 9 packages without perspiration, andin the presence of feverish restlessness or dry mouth,
switching to the preparation daiseiryuto usually resulted
in the onset of perspiration, defervescence and recovery
within 24 hours.
In case of influenza, patients usually can tell rather
precisely on “what day and at what hour” the sudden
onset of chills, fever, arthralgia, general malaise, loss ofappetite or the development of cough occurred
approximately 1 or 2 days after the infection. Thiscondition had in the latter half of the second century AD
been described in the “Shang Han Lun” edited by Zhang
Zhong Jing of the later Han period in China. In thechapter on greater yang diseases it states: “During
greater yang disease, fever develops, or if it has not yet
developed chills set in, the body starts aching, there will
be vomiting and both yin and yang pulses will be tense.”
The description in this text coincides with the “ShangHan” (Shokan) pathology.
For this Shokan condition the text states maoto
governs the greater yang condition characterized byheadache, fever, body pain, low back pain, pain in thebones and joints, chills and a lack of perspiration3).
Thus, following the instructions in the text, and taking
maoto warm, the drug results in perspiration anddefervescence and is characterized in that it
simultaneously improves all the other symptoms,
eventually leading to a complete cure without any
complications or sequelae. Yet, maoto is only effective
for the early phase of influenza. This means thecondition described in the “Shang Han Lun” as thegreater yang disease phase when it is used for the
aforementioned symptoms. This resembles theprovision that Oseltamivir should be administered
within 48 hours after onset.
As described above, Oseltamivir should be
administered within 48 hours after onset and thencontinued over a period of 5 days2). Definitely the author
achieved defervescence in all 10 patients who weretreated within 48 hours after onset, but in 2 out of 5
patients who discontinued the medication after 3 days arecurrence of fever and cough was observed 2-3 days
later. The condition here had to be viewed in Kampo
medical terms as a lesser yang condition that thenrequired treatment with shosaikoto.
When maoto is administered for its indicatedsymptoms, defervescence can be achieved in mostpatients within a period of 24 to 48 hours. Whenperspiration is not observed within a period of 48 hours
and the patient develops signs of (feverish) restlessness,
the author prescribed daiseiryuto. Application of boththese preparations led in almost 100% of the patientsthe onset of perspiration and defervescence within 72
hours. Subsequently, the course was favorable andwithout recurrences.
Considering financial aspects shows that 2 capsulesof Oseltamivir per day for 5 days would amount to,according to the Japanese drug price in the National
Health Insurance scheme, 3,780 Yen (USD31.50). The
price for a 3-day dose of maoto is only 210 Yen per day(USD1.75). Conversely, since the daiseiryuto is not aready-made extract preparation, it is prepared from twoavailable extract preparations. When preparing it using
Tsumura’s extracts, the author used 7.5 g of maoto and7.5 g of eppikajutsuto per day. In this case, the price fortwo days is 340 Yen (USD2.80). Applied for suitableindications, Kampo preparations are not only highly
effective for the treatment of influenza, but also
economically superior.

Conclusion* One case was reported where the greater yang
condition described in the “Shang Han Lun” can beviewed as a cold injury and the treatment with 7.5 gof maoto made by Tsumura per day and proved to bemarkedly effective within 2 days.
* Oseltamivir is definitively effective, but Kampo
medicine, in particular maoto and daiseiryuto, whenadministered based on a suitable pattern
identification, appear to have equivalent effects.
* Considering cost factors, maoto and daiseiryuto(combination of maoto and eppikajutsuto) seem to beeconomical.

Reference
1.

Kida H: Highly pathogenic avian influenza for zoonotic
infections and vaccines; Journal of the Japan Medical
Association, Vol. 134, No. 10, 1940-1944, 2006

2.

Kashiki S: Practical Therapy of Influenza; Journal of theJapan Medical Association, Vol. 134, No. 10, 1921-1923,
January 2006

3.

Okuda K: Shang Han Lun Lectures, Ido no Nippon Sha, 1965

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Volume 1, Number 1 | Spring 2006

Clinical Report 3 (Japan) - continued
Efficacy of Kampo Medicine for Influenza – with Particular
Focus on Maoto
Chizuno Hidaka, Hiromichi Yasui, Hideaki Yamaguchi

History records reveal that approximately 1800 years
ago there was an epidemic of a condition called “Shanghan (cold injury)” in China, that closely resembled what
we today call influenza. Descriptions of therapies for thisdisease found in the book “Shang Han Lun” are actuallyhighly effective for the treatment of influenza. In fact,
more than half of the Kampo prescriptions currently usedin Japan are derived from either this “Shang Han Lun(Treatise on cold-induced diseases)” or else the “Jin Kui
Yao Lue (Synopsis of the Golden Chamber)”. For thisreason Kampo medicines are frequently used in Japan for
the treatment of influenza. In particular, the early phase
after the onset is often an indication for the use ofprescriptions containing Ephedra like maoto ordaiseiryuto.
Clinical research
Signs considered to be indications for maoto include
chills, fever, headache, arthralgia, muscle aches, atendency towards perspiration etc.; closely resembling thesymptoms observed during the early phase of influenza.
For this reason maoto is often used for the treatment of
this condition.
Abe published detailed reports on the treatment ofinfluenza with Kampo medicine before the introduction ofantiviral agents. In these reports, he indicated that for
symptomatic treatment, Kampo medicines are superior towestern medications1). Later research comparing theantipyretic effects of amantadine and maoto revealed
almost equivalent effects.2)
In recent years, Oseltamivir has come into use, andthus many studies have been conducted examining theeffects of a combination therapy with maoto. The
combination of inhibition of the virus proliferation by
Oseltamivir, and improvement of the body defences
facilitated by maoto, is considered to provide an ideal
therapy form. Below are several clinical studies thatinvestigated these questions.
Kubo et al. treated a total if 49 patients(male:female = 24:25) with an age ranging from 5months and 13 years with influenza symptoms
including high fever of over 38°C. These were divided
into a group of 18 patients treated with Oseltamivir, agroup of 14 patients treated with a combination therapyof Oseltamivir and maoto and a group of 17 patientstreated with maoto3).

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Among these patients those over one year of age
were diagnosed using a quick diagnostic kit for
influenza and subsequently randomly assigned into (1)a Oseltamivir (brand name: Tamiflu) group treated with
4 mg/kg for 2 days and (2) a maoto made by Tsumura
0.18 g/kg for 3 days) and (3) a combination therapy ofOseltamivir and maoto. Patients under one year, notsuitable for treatment with Oseltamivir and patients inwhom the influenza quick diagnostic test was negative,
were treated only with maoto (independent therapy).
Guardians were requested to supervise the actual
application of the drug and record measurements ofbody temperature. The study then compared thedifferences between the individual groups until
defervescence (down to 37.2°C) had been achieved.
Differences in background factors like average age at
the initiation of the treatment, male-female ratio,
duration of the fever prior to treatment begin, degree ofthe fever, history of vaccinations etc. were not observed.
Regarding the time from beginning treatment until
defervescence in all three groups was in the Oseltamivir
treatment group, on the average 31.9 hours; in the
maoto – Oseltamivir combination therapy group 21.9
hours; and in the maoto group 17.7 hours. Side effects
or adverse events were observed in none of the groups.
Similar studies have also been conducted by Kuroki,
Fukutomi et al. and Kimoto et al. Kuroki investigatedthe effects of a maoto – Oseltamivir combination
therapy for the treatment of influenza over the threeseasons from 2003 to 2005 and obtained results similar
to those reported by Kubo. In the combination therapy
group, improvement in clinical symptoms wasreportedly superior4).
Fukutomi et al. divided 24 patients diagnosed with
influenza using the quick diagnostic kit from winter2003 until spring 2004 into two groups and treatedthem with a regimen similar to that described above.
The results showed that the duration of headache indays and the number of days general malaise continued
was shorter with a combination therapy of Oseltamivir
and maoto than in the group treated only with
Oseltamivir (significant difference) 5).
Kimoto et al. treated patients diagnosed with
influenza using the quick diagnostic kit during theperiod from January to March 2004 with Oseltamivir
and then compared the clinical course with patientstreated either with maoto or else ordinary western
medications. Defervescence occurred in the grouptreated with a maoto combination therapy
approximately 12 hours earlier than in the group

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 1, Number 1 | Spring 2006

treated with a combination therapy with western drugs.
They also reported a tendency toward an early recovery
from fatigue, dizziness and loss of appetite. In the grouptreated with combination therapy with western drugs arise in CRP was observed in 3 patients, but in the grouptreated with a maoto combination therapy this was notobserved6).
Similar to the case reports published by Oribe,
symptoms were often relieved early in many patientstreated with maoto only. Therefore specialists of Kampo
medicine hold the view that Oseltamivir may notnecessarily be required. In Japan, generally the
diagnosis of influenza is confirmed with the quick
diagnostic kit first and patients are then treated with
Oseltamivir. For this purpose, case-control studies aremainly reports of combination therapies with maoto.
Yet, the accuracy of the quick diagnostic kit inestablishing a definite diagnosis is not 100%.
Immediately after onset in many cases positive results
are not obtained.
The Kampo preparation used predominantly during
the early phase is maoto followed by daiseiryuto. It
would be easy, if daiseiryuto were a decoction, but since
there are no extract preparations, this formula needs tobe prepared by combining two available extract
preparations. Mitani reported obtaining good results intreating patients with influenza associated with highfever by using combinations of either keishito +makyokansekito or else maoto + eppikajutsuto7). These
combinations contain in the first case, an excessive
amount of Paeonia and in the second case Atractylodes
rhizome, but reportedly were clinically effective. In thelatter case, the increase in the amount of Ephedra
needs to be carefully considered.
Other preparations beside maoto or daiseiryuto arealso used for the treatment of this disease. Patients do
not necessarily visit clinics during the early phasefollowing onset, or else because of factors like age or due
to a preexisting disposition. Maoto may not always besuitable. In these cases, a wide variety of otherpreparations are used. Kimoto et al. are conducting
research on this topic.
Kimoto et al. divided 155 patients diagnosed with
influenza, using the quick diagnostic kit, into an
Oseltamivir or amantadine treatment group, a Kampo
medicine treatment group, and a third group treatedwith a combination therapy. The results showed thatthe number of days the drugs were administered werefewer in the combination therapy group. The total of 11
drugs used here included for adults kakkonto, maoto,keishimaokakuhanto, shosaikoto and others, while forchildren four prescriptions including maoto were used8).
Costs versus effects
Oribe pointed out that regardless of whether it ismaoto or daiseiryuto, these drugs when compared toOseltamivir are inexpensive. Regarding the cost-effectratio, these drugs cannot compare with Oseltamivir. In
Japan, seven pharmaceutical companies produce andsell maoto. The drug price in the NHI scheme for each ofthese products is around 70 Yen/day. The drug price for
Oseltamivir is 756 Yen/day. That results in a pricedifference between the two drugs of more than 10-fold.
Since the research conducted so far appears toreveal that these two drugs (maoto and Oseltamivir)
have approximately equivalent effects, the cheaper
Kampo preparations should be made the drug of first
choice. Yet, for this decision, more research is called for.
Basic research
There is basic research about the most important
effective ingredient in the preparation used for thetreatment of influenza, namely Ephedra.
Mantani et al. noticed that for the growth of
influenza viri, an acid milieu is required within thevacuoles during the threshing process and thus
performed the following experiments. They used MEM
containing medium to cultivate Madin-Darby canine
kidney (MDCK) cells and then infected those with the
influenza strain A/PR/8/34 (H1N1 subtype) toinvestigate the inhibitory action of Ephedra on the
proliferation of the viri. The results showed that an
extract of Ephedra in dose-dependent manner, inhibitedthe acidification of the vacuolar fluid. Moreover,regarding the viral growth, Ephedra induced
immediately after the infection during a loading periodof 10 minutes a less than 50% inhibition. This suggeststhat Ephedra inhibits the growth of influenza viri
during the early phase9).
Ochiai conducted several other studies differingfrom the study of Mantani et al. described above andverified the inhibitory action of Ephedra on the growthof influenza viri10).
Avian influenza and new influenza types
In Japan so far, no people have been infected by, ordeveloped, avian influenza. Accordingly, we haven’t had
the opportunity to treat this disease and thus cannot
give definitive comments. However, China had theopportunity to treat patients with this disease and thegovernmental Department of Hygiene has classified the

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Volume 1, Number 1 | Spring 2006

disease into four types (four stages), suggesting
therapies for these respective stages (including
prescriptions). According to that information, avian
influenza falls under the classification of “Wen Bing(warm diseases)” and not the “Shang han (coldinjuries)”11).
Conversely, for types of avian influenza with apotential man-to-man infectivity, meaning new
influenza types, it remains obscure as to what type ofclinical picture will be presented. In the past, influenza
usually was classified as “cold injury”, but that may notnecessarily hold true for the future.
The great pandemic that occurred in 1918, andclaimed many victims during the Spanish flu epidemic,
has been classified based on the experience of thephysician specializing in Kampo medicine (Dr. Mori)into three types. The type marked mainly by pathologicchanges of the gastrointestinal tract was treated withkososan with added Indian Bread Exodermis,
Atractylodes Rhizome and Pinellia Tuber; the type withpredominantly pulmonary lesions with shoseiryuto plus
added Apricot Seed and Gypsum; while the typeassociated with encephalopathies was treated withshomakakkonto with added Angelica Dahurica Root,
Cnidium Rhizoma and Asiasarum Root. These
therapies produced excellent results12).
If new types of viri should evolve in this century, we
would like to prepare as many means as possible tokeep casualties among a human race without
immunologic protection at a minimum. The
development of vaccines against new strains will
require at least 6 months, so that the number ofeffective antiviral drugs during that period is unknown.
Under these circumstances, the experiences of Morimight prove helpful for the treatment of new forms ofinfluenza.

5. Mitani K: Case reports pertaining to the treatment ofpatients with high fever with extract preparations, Phil
Kampo No. 4: 15-16, 2003

6. Fukutomi O, et al.: Experiences with maoto for the
alleviation of influenza symptoms, Kampo Medicine 29 (5):28-30, 2005

7. Kimoto H, Kuroki H: Effects of a combination therapy ofmaoto and Oseltamivir for the treatment of influenza,
Kampo Medicine 29 (4): 16-19, 2005

8. Kimoto H, Kuroki H: Significance of Kampo medicine forthe treatment of epidemic influenza, 20th Conference on
Medical and Pharmaceutical Society for WAKAN-YAKU),
Abstract collection, p.146, 2003
9. Mantani N, Imanishi N, Sakai S, et al.: Inhibitory effects of
maoto on vacuolar acidity and inhibitory action on A/PR/8
influenza strains; 17th Conference on Medical andPharmaceutical Society for WAKAN-YAKU), Abstract
collection, 2002
10. Ochiai H: Anti-influenza treatment with Japanese andChinese medicines (Wakan Yaku) directed at vital
reactions of intracellular organelles; First Conference of
the Japan Society for Oriental Medicine, joint symposiumwith the Medical and Pharmaceutical Society for
WAKAN-YAKU), Lecture recordings 8-12, 2002
11. Notification from the Department of Hygiene of thePeople’s Republic of China “treatment of highly
pathogenic avian influenza” (2005 revised edition),
2005/11/23
http://www.3552808.com/Article_Show.asp?ArticleID=5005

12. Yakazu K: Kampo Ikkan Do Medicine, p.195, 1964

Author and affiliation
Hidaka C: Japan Medical University; Laboratory of
microbiologic immunology
Yasui H: Japan Institute of TCM Research
Yamaguchi H: Tosei Hospital, Department of Pediatrics

Reference
1. Abe K: Influenza. Enlarged edition. Infection in theoutpatient clinic and Kampo, 52, Ishiyaku Publishing, 2000
2. Abe K: Comparison of western medications and Kampo forthe treatment of cold syndrome (summer illness,
influenza); Journal of the Japan Pediatric Society for
Oriental Medicine, 19: 46-52, 2003

3. Kubo T, Nakata H: Effects of maoto on pediatric influenza
infections, 56th Conference of the Japan Society for
Oriental Medicine, Abstract collection, p 204, 2005

4. Kuroki H: Practical experiences with maoto for thetreatment of influenza, 6th Japan Pediatric Kampo Social
Gathering for Discussions, 2005
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