meddelad i Stockholm den 23 december 2008 KLAGANDE Intrång i tilläggsskydd för läkemedel ÖVERKLAGADE AVGÖRANDET Svea hovrätts dom den 6 november 2007 i mål T 5467-06Högsta domstolen fastställer hovrättens domslut. Pfizer Aktiebolag skall utge ersättning till STADApharm AB för rätte-gångskostnader i Högsta domstolen med tvåhundratjugosextusenfemhundra(226 500) kr, avseend
- A |
J |K |
U |V |
Mume pill v scheidMume Pill (wu mei wan
): A Clinical History
) is one of the more enigmatic prescriptions in the Chinese pharmacopoeia. We sense it may be important - after all, it is one of themain formulas for jueyin diseases in the Shanghan lun - but one look at itscomposition and indications convinces us that it is not that important, at leastnot for our patients. For how many of these present with vomiting up of wormsas their main complaint? Modern textbooks extend the use of Mume Pill to thetreatment all types of worm infestation. But biomedical drugs are more reliableand more convenient to take, especially for children who constitute the maincategory of patients for whom this use might be indicated in the West. Finally,Mume Pillʼs combination of very cold and bitter drugs (which easily injure thestomach) with very hot and acrid drugs (which easily injure yin and fluids) doesnot help to endear this formula to the average Western practitioner, who preferssupplementation over draining and avoids the use of harsh drugs.
These, at least, were my own feelings towards Mume Pill until in 1994 I met ayoung Chinese doctor from a small town in Liaoning Province. Unlike most of herpeers, she worked in a hospital where no biomedical diagnostic and treatmentfacilities were available. This meant that even in serious conditions, where mostmodern doctors tend towards the use of Western medicine, she had to rely onChinese medicine alone. Mume Pill was one of her most frequently usedformulas and my interest was aroused. Reading through the case histories offamous past and contemporary physicians I quickly discovered that far frombeing a marginal formula banished to the back of textbooks, Mume Pill was atthe forefront of many of these doctorsʼ minds in the treatment of clinicalproblems ranging from diarrhoea, vomiting and abdominal pain to loss ofconsciousness and convulsions. What follows is a brief and personal re-evaluationof Mume Pill based on a wide reading of classical and contemporarysources and usage in my own practice.1 Original Indications
Mume Pill is first mentioned in Section 338 of the Shanghan lun, the thirteenthsection of the chapter on jueyin diseases.
"Cold damage [with] weak pulse [and] inversion. [If this condition] lastsseven or eight days the skin will be cold. The patient is restless withoutany periods of ease. This is visceral/organ/zang inversion, not thread-worm inversion. In thread-worm inversion the patient should vomit upworms. Now as with this disease, the patient is quiet and then becomesirritable again, this is visceral/organ/zang cold where thread-wormsascend upwards entering the diaphragm causing irritability. At an instant[these symptoms] stop again, the patient has to eat but vomits [it up again].
When the patient becomes irritable again, [this is because] the thread-wormssmell the foodʼs odour which makes them come out. Such a patientwill frequently and spontaneously vomit up thread-worms. Thread-worminversion is mastered by Mume Pill which also masters long-term diarrhoeaFructus Pruni Mume (wū méi) 300 fruits, Herba cum Radice Asari (xì xīn) 6 liang, Rhizoma Zingiberis Officinalis (gān jiāng) 10 liang, Rhizoma Coptidis (huáng lián) 16 liang, Radix Angelicae Sinensis (dāng guī) 4 liang, Fructus Zanthoxyli Bungeani (chuān jiāo) 4 liang, Radix Lateralis Aconiti Carmichaeli Praeparata (fù zǐ) 6 liang blast-fried, Ramulus Cinnamomi Cassiae (guì zhī) 6 liang, Radix Ginseng (rén shēn) 6 liang, Cortex Phellodendri (huáng bǎi) 6 liang" 2(Note: The “liang” used as a measurement is thought to be from 3-15g and probably is the latter) Jueyin and Ministerial fire
Apart from the composition of the formula, its preparation and indication, thistext passage provides information about the basic cause of the pattern that theprescription treats. This is “cold storage” and implies that external cold hasdirectly penetrated to the jueyin level (as opposed to the penetration of heatfrom cold transformation). In order to understand the resulting pathology it isnecessary to briefly review the functions of jueyin.
The physiological functions of jueyin can be summarized as constituting thataspect of space-time, in which the powers of yin attenuate and transform intoyang.3 Jueyin as the point of transformation from yin into yang is thereforesometimes compared to the leaf of a door (he). Yin must pass through this doorin order to become yang. The concrete transformation of yin into yangaccomplished by jueyin in the human body must be placed in the context of thephysiology of ministerial fire (xiang huo) and the circulation of basal qi (yuan qi).
According to contemporary Chinese textbooks ministerial fire is another name forthe fire of the “Gate of Life” (mìng mén), which is also sometimes equated withkidney yang.4 It embodies the power or “fire” of mìng mén and in itssubsequent circulation throughout the body functions as the foundation for aswell as the expression of all physiological activity. Zhu Danxi, an influentialwriter on ministerial fire, has cogently described this dual aspect of basal qi in relation to both its macrocosmic and microcosmic manifestations: “Fire is yin inside and yang outside, [and] it unfolds in activity. Therefore,all activities pertain to fire.… Heaven unfolds in the generation of things,hence they are constantly active. As people also partake in this generationthey also are constantly active. This constant activity is due to the ministerfire.”5 Basal qi thus generated within the kidneys issues forth at the bladder. Fromthere it begins its upward circulation throughout the body by way of theshaoyang. The power that drives this circulation, however, emanates fromjueyin. Chen Jin'ao, a Qing dynasty physician, expressed this when he noted that"…all generated yang qi arises in the jueyin and there is nowhere in theentire body, high or low, which does not avail itself of this qi." 6 Without going into detail, we can briefly note that within jueyin liver can beconsidered as the power or motivating force that takes yang (ministerial fire, basalqi) out of the yin (kidneys, lower burner, Gate of Life) and distributes it all overthe body. This corresponds to the physiological movement of liver qi from belowto above. Pericardium, on the other hand, can be imagined as the moment oftransition of the latent powers of yin into actual transformative activity. It isthat aspect of space-time in which undifferentiated basal qi unfolds intoconcrete physiological function such as digestion or emotional self-expression.
This corresponds to the physiological movement of pericardium blood fromabove to below.
The other important but difficult to grasp point is that function and structureare the same thing in Chinese medicine. Ministerial fire or basal qi is both thefoundation for and the expression of physiological activity within the organism.
Ministerial fire is yang qi, yet it also what yang qi does. Jueyin, likewise, is thephysiological function that enables the transformation of undifferentiated basalqi into concrete and specific functions, yet liver and pericardium yangsimultaneously are themselves manifestations of ministerial fire in the body.
The Mume Pill Pattern: Jueyin qi Aspect Cold Stasis
The Shanghan passage above indicates that Mume Pill is indicated for situationswhere external cold has penetrated directly into jueyin causing the movement ofworms upward from the bowels into the area above the diaphragm in search ofwarmth and food. The more general symptomatology of such jueyin cold damageis described in Shanghan section 326: “Jueyin illness [is characterised by] wasting thirst, qi rushing upwards,pain and heat in the heart, hunger but no desire to eat. In severe casesthere is a spontaneous vomiting up of thread-worms and unstoppablediarrhoea.”7 This pattern is often referred to as “cold below, heat above” (xia han shang re).
The Mume Pill pattern has two additional important symptoms. The first is jueor cold extremities indicating that yang qi is unable to penetrate to theextremities. The second is vomiting of thread-worms indicating a pre-existinginfestation. Many physicians in the history of Chinese medicine associateparasite infestation with the presence of damp, specifically damp heat. We canthus interpret the infestation as an indication that there is a pre-existingweakness or disturbance of orthopathic qi in the middle burner aggravated byjueyin cold damage.
Most commentators identify a cold pathogen having penetrated into the lowerjiao, where the liver is located, as responsible for the symptoms of cold below.
The cold prevents ministerial fire from being transported to the extremities andmiddle, hence the symptoms of incessant diarrhoea and cold extremities.
Commentators differ in their explanations of the heat above. Some argue itshould be seen as extreme yin turning into yang or as the separation of yin andyang. Others see it as shaoyang qi stagnation engendering heat. Yet others see itas a kind of empty heat.
My personal opinion is to define Mume Pill Pattern as jueyin qi aspect cold stasis that leads to damp heat accumulation. Jueyin cold stasis is not depletion but a condition of constraint. Unlike the better-known condition of liver qi constraint, what is constraint here is liver yang or ministerial fire. This manifests in the simultaneous presence of cold yin-type symptoms and signs caused by a failure of ministerial fire to carry out is transformative functions, and hot yang-type symptoms indicating the presence of local heat accumulation. Because the spleen is dependent on ministerial fire for carrying out its functions of transportation and transformation, jueyin cold stasis is will ultimately be reflected in symptoms of spleen transportation and transformation failure like diarrhoea and cold extremities. The simultaneous presence of damp-heat is due to food not being rottened and ripened properly in the stomach. Because food is not transformed into essence, there will be hunger, but because spleen assimilation is impaired there is no desire for food. The symptom of “pain and heat in the heart” is an ancient way of referring to burning pain in the epigastric region and thus confirms this analysis. Inversion of qi, finally, is a manifestation of liver being unable to control the smooth ascending of qi from below to above.
Mume Pill: Analyses of its Composition and Later Usage
The composition of Mume Pill clearly addresses the symptomatology of “heatabove, cold below” as a qi aspect cold stasis pattern. On the most simplistic levelof analysis, the formula is made up of four groups of drugs.
• The first group of drugs (consisting of Herba cum Radice Asari (xì xīn),Rhizoma Zingiberis Officinalis (gān jiāng), Fructus Zanthoxyli Bungeani (chuān jiāo),Ramulus Cinnamomi Cassiae (guì zhī) and Radix Lateralis Aconiti CarmichaeliPraeparata (fù zǐ)) warms and moves liver yang and ministerial fire. Thenumerical preponderance of these drugs marks cold stasis as the primarycausative factor. Taken together these drugs mobilise and move all aspectsof the distribution of ministerial fire by liver yang, propelling it from thelower to the middle and upper jiao and from the inside to the outside.
• The second group of drugs (consisting of Rhizoma Coptidis (huáng lián) andCortex Phellodendri (huáng bǎi)) clears and drains qi aspect damp-heat. As theaccumulated stasis heat is of an excess type, cold bitter heat drainingdrugs are employed. Rhizoma Coptidis (huáng lián) drains heat from thestomach and pericardium, the upper and middle burners, while CortexPhellodendri (huáng bǎi) clears heat that may accumulate as a result of stasisin the lower burner.
• The third group of drugs (consisting of Radix Angelicae Sinensis (dāng guī)and Radix Ginseng (rén shēn)) supplements and harmonises qi and blood toreplenish the qi lost in the course of the illness and its treatment. Some commentators include Angelicae Sinensis (dāng guī) in the drugs of the first group and argue that, essentially, it warms and mobilizes liver blood.
• Fructus Pruni Mume (wū méi), as the main drug, effectively treats threadworminfestation. It is also sour, the taste associated with wood-liver,which is said to guide the entire formula into the jueyin aspect. This sourness guarantees that once yang constraint is resolved ministerial fire is released in a controlled manner and does not transform into uncontrolled liver yang or liver fire.
There exist many other analyses of the formulaʼs composition. Some doctors, forinstance, interpret Mume Pill as a variation of Bàn xià xiè xīn tāng, while otherssee it as a combination of Dāng guǐ sì ní tāng and Sì ní sàn. There is insufficient space to discuss all these in detail. By examining the basic mode of action we can,however, gain an understanding of how later Chinese physicians extended theusage of the formula.
First, we should interpret the use of the acrid warm drugs in the formula not asprimarily dispelling cold but as boosting liverʼs yang function of moving ministerfire and thereby as moving liver yang itself. Second, the cold bitter heat drainingdrugs can be seen to assist the warm acrid drugs in opening up normal qicirculation by draining repletion heat from all three burners and specificallyfrom jueyin and yangming. The use of the sour drug Fructus Pruni Mume (wū méi)ensures, on the one hand, that stimulation of liver yang is checked and alluncontrolled qi redirected into the physiological qi mechanism. On the otherhand, it conserves yangming yin and ensures that fluids are not excessivelydamaged in spite of moving and draining. This combined use of sour, acrid andbitter drugs is defined by many physicians as the basic treatment strategy forthe movement and harmonization of liver qi and yang.
Radix Ginseng (rén shēn) and Radix Angelicae Sinensis (dāng guī) further supplement qi and fluids, ying and wei. They strengthen middle jiao yin and yang and order the chong mai, thus backing up the main treatment strategy but attending to the background connections (physiologically, anatomically) between the varioussubstances, organs and channels involved in the disorder.
We can therefore define the basic pattern treated by Mume Pill as one of jueyinqi aspect stasis and accumulation of heat and disordering of the qi mechanismwithin both jueyin and yangming. Cold damage is one possible proximal cause ofthis pattern. In this case the ascending leg of jueyin qi circulation is primarilyblocked. Primary blockage in the descending leg due to liver qi repletion ordisordered unfoldment of liver yang, both of which disturb normal circulation of qi within jueyin and yangming and even depletion or heat in the jueyin blood aspect are other possibilities.
At first sight, the use of acrid warming drugs in such cases appears inappropriate. If there is already an excess of liver qi, will not the use of such drugs further aggravate its unordered circulation? If we think of qi circulation as what it is, a circulation, then this strategy begins to appear as no less unreasonable, however, than the clearing of heat in the case of cold stasis. In the latter case one has to clear heat produced by qi stasis. In the former case, acrid drugs help to move and order liver qi after one has cleared its excess with bitter heat draining drugs and ordered it with sour drugs. One would, however, adjust the composition of the formula to allow for this change of causation by reducing the number and dosage of acrid warming drugs, and increasing that of bitter cold drugs, or by adding additional sour, sweet or yin supplementing drugs such as Radix Paeoniae Lactiflorae (bái sháo), Herba Dendrobii (shí hú), Radix Rehmanniae Glutinosae (shēng dì huáng).
Based on an overview of the literature the key symptoms for the extended useof Mume Pill thus are: • Diarrhoea, soft stools or constipation indication blocked passage of qi inthe yangming due to liver qi stagnation • Cold extremities or cold feet and hot hands also indicating liver qistagnation with ministerial fire unable to penetrate to the periphery • Vomiting or other signs of inversion of qi in yangming or pericardiumsuch as chest pain, dry retching, throat obstruction, inability to eat in spiteof hunger • A tongue with a yellow, greasy and dry coating in the centre and withlittle or white coating at the sides. If treatment is successful the yellowcoat should disappear first as a sign that the stagnation is being removed.
• A wiry, replete and perhaps deep pulse.
The pattern must be differentiated from other middle jiao repletion patterns notinvolving jueyin such as Xiè xīn tāng patterns. This can be done by ascertainingthat there are no pointers to any kind of liver involvement such as association ofsymptoms with irritability, planning and decision making, green facial complexion and so on. It must also be differentiated from shaoyang qi aspect depression patterns treated by Chái hú tāng formulas and from liver depletion patterns causing stagnation treated by formulas such as Xiāo yáo sǎn. It must also be differentiated further from qi stagnation patterns where the primary emphasis is on the treatment of qi rather than on a particular organʼs transformation of qi, even if such qi stasis reflects onto the function of specific organs. Jué yù wán or Sì mō wán are typical formulas to treat such patterns. Following the guiding symptoms outlined above such differentiation should not be too difficult.
Once the basic pathomechanism and treatment principle has been firmly grasped, all kinds of further variations of the formula are possible. Most of these are based on its use as a decoction rather than as a pill. The contemporary physician Su Baoying, for instance, uses the standard formula to treat complicated hot cold patterns and makes the following additions and subtractions according to presentation.
• If stasis leads to constipation rather than diarrhoea replace Cortex Phellodendri (huáng bǎi) with Rhei Radix et Rhizoma (dà huáng) • In case of fever (i.e. shaoyang stagnation) add Radix Bupleuri (chái hú) and Radix Scutellariae Baicalensis (huáng qín) • If the tongue has not white coating at the side replace Radix LateralisAconiti Carmichaeli Praeparata (fù zǐ), Cortex Cinnamomi Cassiae (ròu guǐ) andHerba cum Radice Asari (xì xīn) with Herba Artemisiae yinchenhao (yīn chén hāo)and Fructus Gardeniae Jasminoidis (zhī zǐ) • If the white coating is very thick or extended replace Cortex Phellodendri(huáng bǎi) with Fructus Evodiae Rutaecarpae (wú zhū yú) and increase thedosage of Radix Lateralis Aconiti Carmichaeli Praeparata (fù zǐ) and RhizomaZingiberis Officinalis (gān jiāng) The Qing Dynasty physician Ye Tianshi used Mume Pill in an extremely flexiblemanner drawing on its main treatment mechanism rather than the formulaitself. The following are some examples: • In a case of liver repletion attacking the stomach with diarrhoea, throatobstruction and vomiting and a wiry pulse he replaced Cortex Phellodendri(huáng bǎi), Ramulus Cinnamomi Cassiae (guì zhī), Radix Lateralis Aconiti CarmichaeliPraeparata (fù zǐ), Herba cum Radice Asari (xì xīn) and Radix Ginseng (rén shēn) withFructus Meliae Toosendan (chuān liàn zǐ) and Radix Paeoniae Lactiflorae (bái sháo).
• In a case of stomach yang depletion with liver qi invading yangming characterised by vomiting of frothy sputum or clear fluid, superficial oedema, borborygmus and abdominal pain and threatened loss of consciousness he used a variation composed of Radix Ginseng (rén shēn), Sclerotium Poriae Cocos (fú líng), Fructus Zanthoxyli Bungeani (chuān jiāo), Rhizoma Zingiberis Officinalis (gān jiāng), Pericarpium Citri Reticulatae (chén pí), Fructus Pruni Mume (wū méi) and Radix Paeoniae Lactiflorae (bái sháo).
• In a case of wasting thirst with dry retching, inversion of stomach qi, restlessness, diarrhoea, heat and cold and a bright red tongue he used a variation composed of Fructus Pruni Mume (wū méi), Radix Ginseng (rén shēn), Rhizoma Coptidis (huáng lián), Tuber Ophiopogonis Japonici (mài mén dōng), Gelatinum Corii Asini (ē jiāo) and Radix Rehmanniae Glutinosae (shēng dì huáng).
I have successfully used Mume Pill in my own practice following the above guidelines. The following is a typical case.
The patient was a woman in her mid-thirties complaining of continuousbelching, occasional vomiting, a bitter taste and diarrhoea with foul-smellingstools for over a year. She had a history of bulimia and was an unreformedworkaholic, running a private printing business on top of looking after twochildren, being responsible for a big house and involvement in her husband'sbusiness. This required her to work late into the night with little sleep. She felttired and exhausted most of the time but never failed to do everything she setout to achieve. When asked why she worked so much she said that it wasdifficult for her to know what she really wanted, that she could never say no ifsomeone asked her a favour, and that she was never really happy because shenever really did what she wanted to do herself. In spite of her personal historyand the current demands on her energy, she looked very young. Her pulse wasstrong and wiry, slippery on the right guan position and her tongue was redwith a thin greasy yellow fur in the middle. She also indicated that she sufferedfrom frequent sinus infections and that she was prone to migraines with one ortwo attacks per week. Upon questioning she said her feet very always cold, butthat her face easily flushed up.
My diagnosis was one of Mume Pattern. Tongue, pulse and her relative vitalityall marked this as a repletion pattern. Taken together the symptoms and signsindicate jueyin qi aspect repletion stasis with yangming heat and phlegmaccumulation. Heat is predominant and cold is secondary. The inability to say noin conjunction with the cold legs also indicate, however, insufficient spreading ofministerial fire by liver yang. Based on this analysis I gave her a variation ofMume Pill in which Radix Lateralis Aconiti Carmichaeli Praeparata (fù zǐ), RamulusCinnamomi Cassiae (guì zhī) and Herba cum Radice Asari (xì xīn) were replaced with Fructus Meliae Toosendan (chuān liàn zǐ), Rhizoma Corydalis Yanhusuo (yán hú suǒ), Radix Paeoniae Lactiflorae (bái sháo) and Fructus Trichosanthis (guā lóu).
After one week the patient returned and indicated that all major symptoms hadimproved. The phlegm was visibly reduced and she had had no headaches. Mostamazing to her was the fact that she had been able to say no to one of herfriends. She took two more weeks supply of a slightly altered formula and hasbeen well since.
This short clinical history has merely touched the surface of the large literatureon Mume Pill available in original Chinese texts. My intention was to show thatengagement with that literature can lead to a deepened understanding of both pathophysiology and the pharmacopoeia, resulting in improved clinical results.
1Given the nature of this article these sources will not all be cited in this article, which is conceived as a personal account rather than a scholarly monograph.
2 Shanghan lun (Tang Dynasty Edition by Cheng Wuji). Reprinted in Qian Shaojin, “Shanghan lun wenzai tongkao”, Xueyuan chubanshe, Beijing, 1993, pp. 332-3.
3 The divergences and overlaps between “six channel” (liù jīng) and “visceral system” (zàngfû) theories in Chinese medicine is too complex to discuss at this point. For an overview of relevant discussions see Li Peisheng & Liu Duzhou (1987), 7-8.
4 Although this simplifies a much more complex set of relations, we can nevertheless use it - for the moment at least- as an adequate basis for understanding liver yangʼs physiological function. The famous Ming scholar-physician Zhang Jiebin, whose theories had a major impact on the content of the curricula of contemporary Chinese medical colleges, for instance, stated explicitly that: “There are two kidneys, which are not both kidney. The left is the kidney, the right is mìng mén.” He also argued that mìng mén constitutes the “sea of qi and blood”, the “foundation of the five zàng and the six fû” and the “root of the yuán qì” - views that make mìng mén a structure/function prior to the zàng and not an aspect of them Zhang Jiebin. Jingyue quanshu (Collected Treatises of [Zhang] Jingyue). Xiao Lixun (chief ed). Beijing: Renmin weisheng chubanshe, 1991 [1637 ].
Part of the problem for Chinese physicians is the fact that starting with the Neijing, the canonical literature lists various types of fire which occur within the body or affect it from the outside. Besides minister and mìng mén fire, we thus find a “lesser fire” (shǎo huǒ), a “vigorous fire” (zhuàng huǒ), heat (rè), (summer-)heat (shû), as well as various types of zàngfû fire, vacuity and repletion fire, etc. The precise nature of the various types of fire and their relation to each other are nowhere clearly defined and have been a hotly debated topic in the history of Chinese medicine. The Er huǒ biàn wàn (“The Absurd Differentiation Between the Two Fires”) is a classical contribution to this debate which contains extensive citations from and discussions of classical sources.
5 Zhu Danxi. Gé zhì yú lùn (Inquiry into the Propensities of Things).” In Dānxī yī jí ([Zhu] Danxi's Collected Medical Works). Ed. Zhezhiang Province Academy of Chinese Medicine Literature Research Institute. Beijing: Renminweisheng chubanshe, 1993 . 3-44, lùn 17, 38.
6 Chen Jin'ao. Zá bìng yuán liû xí zhú (Wonderous Lantern for Peering into the Origins of Miscellaneous Disorders). Beijing: Zhongguo zhongyiyao chubanshe, 1994 . juan 10, 153.
7 Shanghan lun (Tang Dynasty Edition by Cheng Wuji). Reprinted in Qian Shaojin, “Shanghan lun wenzai tongkao”, Xueyuan chubanshe, Beijing, 1993, pp. 328.
F A C H I N F O R M A T I O N (Zusammenfassung der Produkteigenschaften) 1. Bezeichnung 2. Zusammensetzung (arzneilich wirksame Bestandteile nach Art und Menge) 1 g Augensalbe enthält: 10 mg Chloramphenicol 3. Darreichungsform 4. KLINISCHE ANGABEN 4.1 Anwendungsgebiete Bakterielle Infektionen am Auge wie akute Konjunktivitis, Blepharitis, Blennorrhoe,Hordeolosis, Chalaziosis, Tr