Quinine is an essential ingredient of a Gin & Tonic. So let’s start our treatise first with cinchona bark, quinine and malaria.
The cinchona tree
Anonymus: A description of the genus Cinchona. 1797, page 15. [26-15]
The genus Cinchona, under which the cinchona trees are grouped, includes about 25 species. Their original range is in the mountainous regions of Central America – in Costa Rica and Panama – and those in western South America – Bolivia, Colombia, Ecuador, Peru, Venezuela and Brazil. [2-14][2-15][3]
The bark of the cinchona tree helps against malaria through the alkaloid it contains, called quinine. [2-11] The quinine content of the bark differs between species, depending on genetics and environment. They form hybrids with each other, so it is difficult to tell them apart. [2-44][2-45]
The healing properties of cinchona bark
It is not known who discovered the healing properties of cinchona bark. In the Spanish records from the time of the conquest of South America, there is no description of cinchona bark. The healing properties of other plants, on the other hand, are described. The first source to report that malaria was treated with cinchona bark comes from Antonio de la Calancha, a friar of the Augustinians in Peru. In 1633 he wrote about a tree called the fever tree, “arbol de calenturas”, whose cinnamon-coloured bark, ground into powder, administered as a drink, cured fevers and cyclically recurring fevers and had produced miraculous results in Lima. [2-16] Cyclic recurrent fevers are also typical of malaria disease. [2-16] Malaria originated in Africa and only reached the South American continent together with Europeans and West African slaves and quickly established itself there in the low-lying coastal areas. [2-17][13]
It was probably not Antonio de la Calancha who discovered the effect of cinchona bark. This probably happened at least 60 years before he recorded it, i.e. around 1570 or earlier, and it is thought that this must have happened in the high-altitude area around Loja, a town in Ecuador. In two books published in 1574 and 1600, there is a reference to an unknown tree whose description is very similar to that of a cinchona tree. Cinchona trees grow around Loja, and the region was known for the excellent quality of its cinchona bark in the 18th century.[2-17]
In 1824, Sigmund Graf reported in his book on fever barks about the discovery of cinchona bark. We could not formulate it better, and therefore we will let him speak for himself: “Since the period of discovery of most remedies, especially from the area of the plant kingdom, is usually shrouded in deep darkness, nothing reliable is known about the actual discovery of fever bark. Most of what is known to us is based on legends, some of which are fabulous, and some of which, according to the convictions of later travellers to southern America, contradict the local and other conditions there. De la Condamine (Memoires de l’Academie des sciences de Paris 1738, p. 233) relates an old, least credible legend, according to which American, unmown lions (Felis concolor) are said to have been the first cause of the discovery of fever bark, in that they are said to have instinctively chewed it and been cured of fever. Geoffroy (Tractatus de materia medica T. 2. p. 78) says that some fever bark trees were blown down by the wind and fell into a swamp, giving the water such bitterness that no one could drink of it, until at last a native suffering from the most violent fever overcame his disgust and, finding no other, drank of this water. He is said to have been cured and to have introduced his confreres to the healing powers of fever bark. Hyppolit Ruiz (Quinologia, ò tratado del’ arbol de la Quina. Madrid 1792, translated into Italian under the title: Della China e delle altre sue specie nuovamente scoperte e descritte da D. Ippolito Ruiz. Roma 1792, and German: Von dem officinellen Fieberrindenbaume und den andern Arten desselben by Prof. Osiander. Göttingen. 1794. p. 16 *)) finally, who was the first botanist to undertake a botanical expedition to Peru in 1777 on the orders of the Spanish court, accompanied by Joseph Pavon and Dombey, and who was advised that the fever bark trees, as well as the study of all that related to them, was the most important object of his journey, relates the following, which he heard very often from credible persons during his stay in Peru: In the year 1636, an Indian of the province of Loxa had praised the good properties of fever bark to the Corregidor of Loxa, Don Juan Lopez de Cannizares, who was ill with a cold fever. The corregidor, longing to regain his health as soon as possible, asked this Indian to give him some of the bark, together with the method of using it. He followed the instructions given, which consisted of pouring or boiling the bark with any quantity of cold water and drinking it repeatedly, and in a few days he recovered completely from his protracted illness. When the Corregidor heard in 1638 that the Vicerine of Peru was ill with a three-day fever, he wrote to her husband Don Geronimo Fernandez de Cabrera, Bobadella y Mendoza, Count of Cinchon, and sent him some of this bark, together with an indication of its effect and the method of using it. The Viceroy had several experiments carried out with it in the hospitals of Lima, and as all of them corresponded perfectly to the report sent in, he also had his wife use it, who recovered perfectly. Convinced of the then miraculous healing powers of the bark, the Countess of Chinchon now had this bark distributed free of charge, from where this remedy first received the name Powder of the Countess (Pulvis Comitissae). Later, when she travelled to Europe with her husband, she gave the Jesuits a considerable amount of fever bark, together with the order to distribute it, which they did and from where the name Jesuit powder (Pulvis Jesuiticus aut Patrum) originated. The Jesuits also sent some of this bark to the then Cardinal de Lugo in Rome, where it was first used in the pharmacy of the Roman College for the use of poor religious people. The Cardinal himself, however, is said to have freed the Dauphin and later King Louis XIV from a fever on a journey to France, whence the name Cardinalis-Pulver (Pulvis Cardinalis). The personal physician of the Count of Chinchon, Joh. de Vega, first brought the fever bark to Spain in 1640 and sold the pound for 5 scudi. Soon afterwards, however, its price rose so much that in Rome it was considered equal to silver, and a pound of bark was paid for with a pound of silver.” [18-59][18-60][19-1][19-2][19-3][19-4]
Sigmund Graf: Die Fieberrinden in botanischer, chemischer und pharmaceutischer Beziehung. 1824, page 1-4. [19-1][19-2][19-3][19-4]
– “Da gewöhnlich die Entdeckungsperiode der meisten Heilmittel, besonders aus dem Gebiethe des Pflanzenreichs in ein tiefes Dunkel gehüllt ist, so ist auch über die eigentliche Entdeckung der Fieberrinde nichts zuverlässiges bekannt. Das meiste, was uns bekannt ist, beruht auf Sagen, die zum Theil fabelhaft, zum Theil nach der Ueberzeugung späterer Reisenden nach dem südlichen Amerika mit den dortigen Local- und andern Verhältnissen im Widerspruche sind. De la Condamine (Memoires de l’Academie des sciences de Paris 1738, p. 233) erzählt eine alte, am wenigsten glaubwürdige Sage, nach welcher amerikanische, ungemähnte Löwen (Felis concolor) die erste Ursache der Entdeckung der Fieberrinde gewesen seyn sollen, indem sie fieberkrank instinktmässig von ihr gekaut und geheilt worden seyn sollen. Geoffroy (Tractatus de materia medica T. 2. p. 78) sagt, es wären einige Fieberrindenbäume vom Winde umgeworfen in einen Sumpf gefallen, und hätten dem Wasser eine solche Bitterkeit mitgetheilt, dass Niemand davon trinken konnte, bis endlich ein Eingeborner am heftigsten Fieber leidend, seinen Ekel überwunden, und da er kein anderes fand, von diesem Wasser getrunken hatte. Er soll hierauf geheilt worden seyn, und seine Mitbrüder mit den Heilkräften der Fieberrinde bekannt gemacht haben. Hyppolit Ruiz (Quinologia, ò tratado del’ arbol de la Quina. Madrid 1792., in’s italienische übersetzt unter dem Titel: Della China e delle altre sue specie nuovamente scoperte e descritte da D. Ippolito Ruiz. Roma 1792., und deutsch: Von dem officinellen Fieberrindenbaume und den andern Arten desselben von Prof. Osiander. Göttingen. 1794. S. 16 *)) endlich, der als erster Botaniker im Jahre 1777 auf Befehl des spanischen Hofes eine botanische Entdeckungsreise, begleitet von Joseph Pavon und Dombey nach Peru unternahm, und die Fieberrindenbäume, so wie die Untersuchung all dessen, was darauf Bezug hatte, ihm als der wichtigste Gegenstand seiner Reise anempfohlen wurde, erzählt Folgendes, was er während seines Aufenthaltes in Peru von glaubwürdigen Personen sehr oft gehört: Im Jahre 1636 habe ein Indianer der Provinz Loxa dem Corregidor von Loxa, Don Juan Lopez de Cannizares, der an einem kalten Fieber krank lag, die guten Eigenschaften der Fieberrinde angerühmt. Der Corregidor sich nach der baldigen Erhaltung seiner Gesundheit sehnend, liess sich von diesem Indianer etwas von der Rinde, nebst der Verfahrungsart sie zu gebrauchen, geben. Er befolgte die angegebene Vorschrift, welche darin bestand, die Rinde mit einer beliebigen Menge kalten Wassers aufzugiessen oder zu kochen, und zu wiederhohlten Mahlen davon zu trinken, und genas in wenigen Tagen vollkommen von seiner langwierigen Krankheit. Als der Corregidor hierauf im Jahre 1638 vernahm, dass die Vicekönigin von Peru an einem dreytagigen Fieber krank liege, schrieb er an ihren Gemahl Don Geronimo Fernandez de Cabrera, Bobadella y Mendoza, Grafen von Cinchon, und schickte ihm von dieser Rinde, nebst einer Anzeige ihrer Wirkung und der Verfahrensart sie zu gebrauchen. Der Vicekönig liess in den Hospitälern von Lima mehrere Versuche damit anstellen, und da alle dem eingeschickten Berichte vollkommen entsprachen, liess er auch seine Gemahlinn davon gebrauchen, welche vollkommen genas. Ueberzeugt von den damahls wunderbaren Heilkräften der Rinde, liess nun die Gräfinn von Chinchon diese Rinde unentgeltlich austheilen, woher dieses Mittel zuerst den Nahmen Pulver der Gräfinn (Pulvis Comitissae) erhielt. Als sie später mit ihrem Gemahl nach Europa reiste, gab sie den Jesuiten eine bedeutende Menge Fieberrinde, nebst dem Auftrage, sie zu vertheilen, welche es auch thaten und woher der Nahme Jesuiten-Pulver (Pulvis Jesuiticus aut Patrum) entstand. Die Jesuiten schickten auch von dieser Rinde an den damahligen Cardinal de Lugo nach Rom, woselbst sie zuerst in der Apotheke des römischen Collegiums zum Gebrauche armer Religiosen in Anwendung gebracht wurde. Der Cardinal selbst soll aber auf einer Reise nach Frankreich den Dauphin und nachherigen König Ludwig den XIV. von einem Fieber befreyt haben, woher der Nahme Cardinalis-Pulver (Pulvis Cardinalis). Der Leibarzt des Grafen von Chinchon Joh. de Vega, brachte im Jahre 1640 die Fieberrinde zuerst nach Spanien und verkaufte das Pfund um 5 Scudi. Bald darauf stieg sie aber so im Preise, dass sie in Rom dem Silber gleich gehalten wurde, und man das Pfund Rinde mit einem Pfund Silber bezahlte.”[18-59][18-60][19-1][19-2][19-3][19-4]
There are numerous variants of the latter story about the countess’s cure. The wife of the Viceroy of Peru, who was also the fourth Count of Cinchon, Doña Francisca Henríques de Ribera, was lying on her deathbed with a fever around 1630, some say 1638, when she received a dose of cinchona bark either from a Peruvian maid or official or from the Viceroy’s Jesuit priest and personal physician, Juan de Vega. Miraculously, the healing began. She then returned to Europe to give the cinchona bark to people who were suffering there. So much for the legend – but her illness is not recorded in her husband’s detailed diaries, nor can she have returned to Europe, for she died before returning to Spain. So this story does not seem to be true either. [2-20][3][5] Alexander von Humboldt aptly concludes: “The story of Countess Chinchon, Vicerine of Peru, so often rewritten, is probably even more doubtful than is commonly believed.” [18-59]
Alexander von Humboldt: Über die Chinawälder in Südamerika. 1807, page 59. [18-59]
– “Die so oft nachgeschriebene Geschichte der Gräfin Chinchon, Vicekönigin von Peru, ist wohl noch zweifelhafter als man gemeinhin glaubt.”[18-59]
Others, however, say it was the Viceroy’s first wife, Anna de Osorio, who was cured with cinchona bark. However, she died in 1625 and her husband only became Viceroy of Portugal in 1629. [6]
One can also doubt the other traditions: “After Humboldt has discussed all the hypotheses about the discovery of the efficacy of fever bark, he believes that the bark was first brought to Europe by the Countess of Chinchon, but doubts that the Corregidor of Loxa became acquainted with it through a native. For not only is there no oral tradition of this kind there, but the use of fever bark is completely unknown to the Americans, who cling to their ancestral customs and traditions with unchanging persistence. Humboldt says that in the deep and hot mountain valleys of Catamajo, Rio Calvas, and Macara, alternating fevers are very common, but the natives, to whatever caste they may belong, would rather die than use the fever bark, which they count in the class of ardent poisons. In Malacates, where many cascarilleros (peelers of cinchona bark) live, it is beginning to be used. In Loxa, on the other hand, there is an old legend that the Jesuits, according to the custom of the country, distinguished between the different species of trees by chewing the bark, and because of its bitterness, since there were always people with knowledge of medicine among the missionaries, they began to give it as an infusion in a three-day fever.”[19-13][19-14]“From 1638 to 1776 all fever bark came to Europe from Loxa, but later it was also discovered north of the equator, between Loxa, Quito and Santa Fe de Bogota …”[18-65][19-14]
Sigmund Graf: Die Fieberrinden in botanischer, chemischer und pharmaceutischer Beziehung. 1824, page 13-14. [19-13][19-14]
– “Nachdem Humboldt alle Hypothesen über die Entdeckung der Wirksamkeit der Fieberrinde abhandelt, so glaubt er zwar, dass die Rinde durch die Gräfinn v. Chinchon zuerst nach Europa gebracht wurde, zweifelt aber dass der Corregidor von Loxa solche durch einen Eingebornen kennen lernte. Denn es herrscht daselbst nicht nur keine mündliche Überlieferung dieser Art, sondern den Amerikanern, die mit unabänderlicher Beharrlichkeit an ihren hergestammten Sitten und Gebräuchen hängen, ist der Gebrauch der Fieberrinde gänzlich unbekannt. Humboldt sagt, in den tiefen und heissen Gebirgsthälern von Catamajo, Rio Calvas, und Macara sind Wechselfieber sehr gemein, aber die Eingebornen, zu welcher Kaste sie gehören mögen, sterben lieber als dass sie die Fieberrinde gebrauchen sollten, die sie zur Classe der Branderregenden Gifte zählen. In Malacates, wo viele Cascarilleros (Chinarinden-Schäler) wohnen, fängt sie an in Aufnahme zu kommen. Dagegen herrscht aber in Loxa die alte Sage, dass die Jesuiten nach Landessitte beym Holzfällen durch Kauen der Rinde die verschiedenen Baumarten unterschieden haben, und so wegen ihrer Bitterkeit, da unter den Missionären stets sich Arzeneykundige befanden, sie anfingen im dreytagigen Fieber als Aufguss zu geben.“[19-13][19-14]„Von 1638 bis 1776 kam alle Fieberrinde von Loxa aus nach Europa, später wurde sie aber auch nördlich vom Äquator entdeckt, und zwar zwischen Loxa, Quito und Santa Fe de Bogota … ” [18-65][19-14]
The naming
The story of the Vicerine, whichever one it was, was popular in any case, and so Carl von Linné, in his book “Genera Plantarum” published in 1742, honoured the wife of the Peruvian Viceroy, who had become the Countess of Chinchón by marriage, by naming the genus after her. However, he unfortunately misspelled her name. He forgot an “h”, and so the genus is still called Cinchona instead of Chinchona. [2-20][3][4-527][19-9]
The German name Chinarindenbaum (“China bark tree”) has nothing to do with China. The origin of the word probably lies in the Quechua word kina-kina, also written quina-quina, which means “bark of the barks”, referring to the bark of the red cinchona tree used as a remedy. [3]
However, cinchona bark was also sold under many other names, including fever tree, quina, calisaya, Peruvian bark or jesuit’s bark. It was sometimes classified on the basis of its colour, and the best was said to be red in colour, the worse yellow and grey. The bark was also often confused with that of another medicinal tree, the balsam tree Myroxylon balsamum. [2-21][7]
Use as medicine in Europe
Around 1640, the bark began to be exported to Europe, [2-20] according to Kim Walker and Mark Nesbitt. But they must be mistaken. The Frenchman Michel de Montaigne wrote in his Second Book of Essais, i.e. in the 1580s, already: “We do not appreciate, a very eminent physician has said, a method of treatment which is intelligible to us, as well as the herbs which we gather ourselves. If there should be physicians among the peoples from whom we obtain guaiac resin, smilax and cinchona bark, one can imagine the enormous value that will be placed there on our cabbage and parsley as a result of the same idolatry of the strange, the rare and the costly! Who would dare to despise things which are brought from such distant lands and which have undergone such a long and dangerous passage?” [14-383]
– “Wir schätzen ja, hat ein sehr bedeutender Arzt gesagt, eine uns verständliche Behandlungsmethode ebensowenig wie die Kräuter, die wir selber sammeln. Falls es bei den Völkern, von denen wir das Guajakharz, die Stechwinde und die Chinarinde beziehn, Ärzte geben sollte, kann man sich denken, welch ungeheuren Wert man dort infolge der gleichen Vergötterung des Fremdartigen, Seltnen und Kostspieligen auf unsern Kohl und unsre Petersilie legen wird! Wer würde es schon wagen, Dinge zu verachten, die man aus derart fernen Ländern holt und die eine derart lange und gefährliche Überfahrt hinter sich haben?” [14-383]
Not everywhere, however, people liked to accept and use the medicine. In Britain, for example, a true Protestant initially wanted nothing to do with a Catholic medicine. Jean-Jaques Chifflet wrote about cinchona bark as a “papal fraud”. [2-21] Notwithstanding these adversities, cinchona bark was eventually accepted as a standard medicine in Europe because of its efficacy. For example, as early as 1677, the Pharmacopoeia Londinensis reported that cinchona bark helped against all kinds of fevers [2-22] and by the mid-18th century, cinchona bark was widely regarded as a remedy for intermittent fevers. [2-32]
Interestingly, there are indications that in Britain they treated alternating fevers with wormwood, for example with Artemisia vulgaris or Artemisia abrotanum. In China, too, wormwood was described 2000 years ago as a remedy for such fevers. Even today, extracts of Artemisia annua are used as a modern remedy against malaria. [2-23]Robert Talbor’s remedy, which was called “English Remedy”, also achieved some fame. He lived from 1642 to 1681, went through an apothecary apprenticeship, moved to university, and there developed an interest in treating fevers. In 1668 he moved to Essex, experimented with cures and developed his own medicine, which he said was safer to use than pure cinchona bark. He kept his recipe secret. Among those cured by him was a French officer who spoke about it to King Charles II. So it happened that Richard Talbor was invited to his court. After he had also cured the king, he was knighted in 1678 and sent to France. There, King Louis XIV became aware of him and wanted to obtain the prescription for the cure. He received it on condition that it not be published until after Robert’s death. Robert Talbor returned to Cambridge University in 1681 and died in the same year. The following year, 1682, the recipe for his English Remedy was published. [2-22] It became so well known that his remedy not only contained cinchona bark and was made on the basis of a wine, but also contained pain-relieving opium in addition to parsley and aniseed. [2-23][16][19-5] The production of a quinine wine thus dates back at least to this time.
It was nothing unusual to mix the bitter cinchona bark with other things. It was ground and then taken as a pill or drunk dissolved in port wine. The bitterness was masked with herbs and cinnamon, cloves or orange peel, and sugar or honey was also added. [2-23]
Cultivation of cinchona trees
Initially, cinchona bark was harvested in the forests of the Andes. But the political situation in South America became unstable in the early 19th century, when people there wanted to be independent from Spain. [2-41] Therefore, trees rich in quinine were selected and tried to be cultivated in other colonies. As early as 1813, it was proposed to plant cinchona trees in India, [2-45] because the demand for quinine and cinchona bark was enormous. In the 1840s, British citizens and soldiers in India consumed 700 tons of cinchona bark annually. [24] In 1859, the Indian government spent a lot of money on imported cinchona bark, [2-48] and it was considered urgent to cultivate it. In 1860 plants and seeds were stolen from Peru and Ecuador and sent to India via Kew, a district of London. [2-49] Cinchona trees were also cultivated on Dutch-controlled Java. [2-52] However, it took another 15 years before the first harvest in the colonies. [2-52] But by 1883, cinchona bark from South and Southeast Asia dominated the market. [2-53]
Soon, around 1890, however, malaria parasites became resistant to quinine in some areas. [2-57]
Quinine
In 1820, Joseph Bienaimé Caventou and Pierre-Joseph Pelletier succeeded in extracting the first two of the four alkaloids contained in cinchona bark from the bark using alcohol. They named them cinchonine and quinine. With the extracted active substance, it was possible to dose the amount more precisely. [2-11][2-45][8][19-49][19-50] It was first extracted from the bark of Cinchona species on an industrial scale in 1823 by the pharmacist Friedrich Koch in Oppenheim. [8]
Quinine dissolves particularly well in alcohol and less well in water. The Encyclopaedia Britannica states in 1911 that the quinine sulphate commonly used in commerce is soluble in about 780 parts of cold water, or in 30 parts of boiling water, or in 60 parts of rectified alcohol with a relative density of 0.83. Its solubility is reduced by sodium or magnesium sulphate, but increased by potassium nitrate, ammonium chloride and most acids. [20][21][22-22][22-23][23] This poor solubility explains why there is always an acid present in tonic water.
The Asiatic Journal and Monthly Register for British India and its Dependencies. Vol. XXX, July 1825, page 76. [17-76]
The advantage of quinine application compared to bark is described in 1825 by the Asiatic Journal: “Before the meeting broke up, some important observations were made by a member, regarding the employment of the new medicine, Quinine, in the fevers of the country. The preparation particularly alluded to was the sulphate of Quinine, a small supply of which had been received a few months before in Calcutta. It is represented to be a most powerful tonic, in the common acceptation of the term, as curing obstinate intermittents, and even remittents, partaking of the type of the former, in an incredibly short space of time. The dose is so small (from three to five grains) that it may be swallowed in the form of a pill, and a few such are found more efficient than ounces of bark in removing the fever, and afterwards guarding the patient against the danger of a relapse.”[17-76]
At this point, unfortunately, it is necessary to turn to the grain, because we will find this indication of quantity even more frequently in the following. In English it is called “grain” and is abbreviated to “gr”; this should not be understood to mean “gram”. However, the meaning of a grain varies, because it depends on the system used. An English grain is an obsolete unit of measurement and corresponds to exactly 64.79891 milligrams in the troy, avoirdupois and apothecary systems. A grain in the troy system is equal to 1/5760 troy pounds; in the avoirdupois system, 1/7000 pounds; in the apothecary system, 1/5760 apothecary pounds. The French grain, on the other hand, was equal to 1/9216 of the old French pound, about 53.115 mg. In the Nuremberg apothecary weights, a grain was equivalent to about 62 mg. [9][10][11]
The three to five grains mentioned here were probably between about 194 mg and 324 mg.
Today, malaria treatment is carried out over one and a half to two weeks by oral administration of quinine salts in doses corresponding to at least 0.8 g to 1 g free quinine base per day, for example in the form of 1.95 g quinine sulphate dihydrite. [16] This would therefore correspond to 41 to 51 parts quinine base to 100 parts quinine sulphate dihydrite.
Has anything other than quinine sulphate dihydrite been used in the past? It seems so, because in the “Encyclopädie der medicinischen Wissenschaften” (Encyclopaedia of Medicinal Sciences) the following conversion factors were given in 1830: “Nowadays, the quinine alkaloids are almost generally used pure or in salt form. The most common salts are: the sulphuric acid quinine or cinchonine; the neutral and effloresced sulphuric acid quinine is usually preferred, because its composition is invariable and always offers 86 base to 100 parts; while that which is not effloresced, depending on whether it is in a more or less humid place, can contain 76 to 86 parts of quinine. The sulphuric acid cinchonine is used under the same circumstances as the sulphuric acid quinine, although it is less effective. Acetic quinine is not used because it is almost insoluble, especially in the cold.” [15-133]
Friedrich Ludwig Meissner: Encyclopädie der medicinischen Wissenschaften. Dritter Band, 1830, page 133. [15-133]
– “Man wendet jetzt fast allgemein die Chinaalkaloide rein, oder in Salzform an. Die gebräuchlichsten Salze sind: das schwefelsaure Chinin oder Cinchonin; man zieht am gewöhnlichsten das neutrale und eftlorescirte schwefelsaure Chinin vor, weil seine Zusammensetzung unveränderlich ist und jederzeit 86 Base auf 100 Theile darbietet; während jenes, welches nicht eftlorescirt ist, je nachdem es an einem mehr oder weniger feuchten Orte sich befindet, 76 bis 86 Theile Chinin enthalten kann. Das schwefelsaure Cinchonin wird unter den nämlichen Umständen, wie das schwefelsaure Chinin, angewendet, obschon es weniger wirksam ist. Das essigsaure Chinin wird nicht gebraucht, weil es, vorzüglich in der Kälte, fast unlöslich ist.” [15-133]
In Germany, a maximum of 85 mg/kg quinine(base) is allowed in soft drinks, and 300 mg/kg in spirits. [2-92][12][16] This means that one would have to drink about 10 litres of tonic water to consume the amount of quinine necessary for malaria treatment. Camper English even writes that one would have to drink over 20 litres of tonic water, as he sets the daily dose of quinine higher; in the USA, comparable to Germany, a maximum of 83 mg of quinine per litre is allowed in drinks. [1-72]
Quinine must be dosed carefully. An overdose leads to dizziness, headache, tinnitus, deafness, temporary blindness or even cardiac and respiratory paralysis. The lethal dose for an adult human is about five to ten grams of quinine. [16]
After this general description of the cinchona tree and quinine, we turn to the medicinal uses of quinine in the next part of this series. There we report on malaria, fever and alternating fever and its treatment with quinine wine.
Sources
Camper English: Tonic Water AKA G&T WTF. Second Printing, Rutte Distillery Edition, 2016
Kim Walker & Mark Nesbitt: Just the Tonic. A natural history of Tonic Water. ISBN 978 1 84246 689 6. Kew 2019.
Michel de Montaigne: Essais. Erste moderne Gesamtübersetzung von Hans Stilett. Die Andere Bibliothek. ISBN 3-8218-4472-8. Eichborn Verlag, Frankfurt am Main, 1998. – Zweites Buch. Über die Ähnlichkeit der Kinder mit ihren Vätern.
https://archive.org/details/b28038514/page/n31/mode/2up Anonymus: A description of the genus Cinchona, comprehending the various species of vegetables from which the Peruvian and other barks of a similar quality are taken. Illustrated by figures of all the species hitherto discovered. To which is prefixed Professor Vahl’s dissertation on this genus, read before the Society of natural history at Copenhagen. Also a description, accompanied by figures, of a new genus named Hyænanche: or hyæna poison. London, 1797.
The cinchona tree
The genus Cinchona, under which the cinchona trees are grouped, includes about 25 species. Their original range is in the mountainous regions of Central America – in Costa Rica and Panama – and those in western South America – Bolivia, Colombia, Ecuador, Peru, Venezuela and Brazil. [2-14] [2-15] [3]
The bark of the cinchona tree helps against malaria through the alkaloid it contains, called quinine. [2-11] The quinine content of the bark differs between species, depending on genetics and environment. They form hybrids with each other, so it is difficult to tell them apart. [2-44] [2-45]
The healing properties of cinchona bark
It is not known who discovered the healing properties of cinchona bark. In the Spanish records from the time of the conquest of South America, there is no description of cinchona bark. The healing properties of other plants, on the other hand, are described. The first source to report that malaria was treated with cinchona bark comes from Antonio de la Calancha, a friar of the Augustinians in Peru. In 1633 he wrote about a tree called the fever tree, “arbol de calenturas”, whose cinnamon-coloured bark, ground into powder, administered as a drink, cured fevers and cyclically recurring fevers and had produced miraculous results in Lima. [2-16] Cyclic recurrent fevers are also typical of malaria disease. [2-16] Malaria originated in Africa and only reached the South American continent together with Europeans and West African slaves and quickly established itself there in the low-lying coastal areas. [2-17] [13]
It was probably not Antonio de la Calancha who discovered the effect of cinchona bark. This probably happened at least 60 years before he recorded it, i.e. around 1570 or earlier, and it is thought that this must have happened in the high-altitude area around Loja, a town in Ecuador. In two books published in 1574 and 1600, there is a reference to an unknown tree whose description is very similar to that of a cinchona tree. Cinchona trees grow around Loja, and the region was known for the excellent quality of its cinchona bark in the 18th century.[2-17]
In 1824, Sigmund Graf reported in his book on fever barks about the discovery of cinchona bark. We could not formulate it better, and therefore we will let him speak for himself: “Since the period of discovery of most remedies, especially from the area of the plant kingdom, is usually shrouded in deep darkness, nothing reliable is known about the actual discovery of fever bark. Most of what is known to us is based on legends, some of which are fabulous, and some of which, according to the convictions of later travellers to southern America, contradict the local and other conditions there. De la Condamine (Memoires de l’Academie des sciences de Paris 1738, p. 233) relates an old, least credible legend, according to which American, unmown lions (Felis concolor) are said to have been the first cause of the discovery of fever bark, in that they are said to have instinctively chewed it and been cured of fever. Geoffroy (Tractatus de materia medica T. 2. p. 78) says that some fever bark trees were blown down by the wind and fell into a swamp, giving the water such bitterness that no one could drink of it, until at last a native suffering from the most violent fever overcame his disgust and, finding no other, drank of this water. He is said to have been cured and to have introduced his confreres to the healing powers of fever bark. Hyppolit Ruiz (Quinologia, ò tratado del’ arbol de la Quina. Madrid 1792, translated into Italian under the title: Della China e delle altre sue specie nuovamente scoperte e descritte da D. Ippolito Ruiz. Roma 1792, and German: Von dem officinellen Fieberrindenbaume und den andern Arten desselben by Prof. Osiander. Göttingen. 1794. p. 16 *)) finally, who was the first botanist to undertake a botanical expedition to Peru in 1777 on the orders of the Spanish court, accompanied by Joseph Pavon and Dombey, and who was advised that the fever bark trees, as well as the study of all that related to them, was the most important object of his journey, relates the following, which he heard very often from credible persons during his stay in Peru: In the year 1636, an Indian of the province of Loxa had praised the good properties of fever bark to the Corregidor of Loxa, Don Juan Lopez de Cannizares, who was ill with a cold fever. The corregidor, longing to regain his health as soon as possible, asked this Indian to give him some of the bark, together with the method of using it. He followed the instructions given, which consisted of pouring or boiling the bark with any quantity of cold water and drinking it repeatedly, and in a few days he recovered completely from his protracted illness. When the Corregidor heard in 1638 that the Vicerine of Peru was ill with a three-day fever, he wrote to her husband Don Geronimo Fernandez de Cabrera, Bobadella y Mendoza, Count of Cinchon, and sent him some of this bark, together with an indication of its effect and the method of using it. The Viceroy had several experiments carried out with it in the hospitals of Lima, and as all of them corresponded perfectly to the report sent in, he also had his wife use it, who recovered perfectly. Convinced of the then miraculous healing powers of the bark, the Countess of Chinchon now had this bark distributed free of charge, from where this remedy first received the name Powder of the Countess (Pulvis Comitissae). Later, when she travelled to Europe with her husband, she gave the Jesuits a considerable amount of fever bark, together with the order to distribute it, which they did and from where the name Jesuit powder (Pulvis Jesuiticus aut Patrum) originated. The Jesuits also sent some of this bark to the then Cardinal de Lugo in Rome, where it was first used in the pharmacy of the Roman College for the use of poor religious people. The Cardinal himself, however, is said to have freed the Dauphin and later King Louis XIV from a fever on a journey to France, whence the name Cardinalis-Pulver (Pulvis Cardinalis). The personal physician of the Count of Chinchon, Joh. de Vega, first brought the fever bark to Spain in 1640 and sold the pound for 5 scudi. Soon afterwards, however, its price rose so much that in Rome it was considered equal to silver, and a pound of bark was paid for with a pound of silver.” [18-59] [18-60] [19-1] [19-2] [19-3] [19-4]
– “Da gewöhnlich die Entdeckungsperiode der meisten Heilmittel, besonders aus dem Gebiethe des Pflanzenreichs in ein tiefes Dunkel gehüllt ist, so ist auch über die eigentliche Entdeckung der Fieberrinde nichts zuverlässiges bekannt. Das meiste, was uns bekannt ist, beruht auf Sagen, die zum Theil fabelhaft, zum Theil nach der Ueberzeugung späterer Reisenden nach dem südlichen Amerika mit den dortigen Local- und andern Verhältnissen im Widerspruche sind. De la Condamine (Memoires de l’Academie des sciences de Paris 1738, p. 233) erzählt eine alte, am wenigsten glaubwürdige Sage, nach welcher amerikanische, ungemähnte Löwen (Felis concolor) die erste Ursache der Entdeckung der Fieberrinde gewesen seyn sollen, indem sie fieberkrank instinktmässig von ihr gekaut und geheilt worden seyn sollen. Geoffroy (Tractatus de materia medica T. 2. p. 78) sagt, es wären einige Fieberrindenbäume vom Winde umgeworfen in einen Sumpf gefallen, und hätten dem Wasser eine solche Bitterkeit mitgetheilt, dass Niemand davon trinken konnte, bis endlich ein Eingeborner am heftigsten Fieber leidend, seinen Ekel überwunden, und da er kein anderes fand, von diesem Wasser getrunken hatte. Er soll hierauf geheilt worden seyn, und seine Mitbrüder mit den Heilkräften der Fieberrinde bekannt gemacht haben. Hyppolit Ruiz (Quinologia, ò tratado del’ arbol de la Quina. Madrid 1792., in’s italienische übersetzt unter dem Titel: Della China e delle altre sue specie nuovamente scoperte e descritte da D. Ippolito Ruiz. Roma 1792., und deutsch: Von dem officinellen Fieberrindenbaume und den andern Arten desselben von Prof. Osiander. Göttingen. 1794. S. 16 *)) endlich, der als erster Botaniker im Jahre 1777 auf Befehl des spanischen Hofes eine botanische Entdeckungsreise, begleitet von Joseph Pavon und Dombey nach Peru unternahm, und die Fieberrindenbäume, so wie die Untersuchung all dessen, was darauf Bezug hatte, ihm als der wichtigste Gegenstand seiner Reise anempfohlen wurde, erzählt Folgendes, was er während seines Aufenthaltes in Peru von glaubwürdigen Personen sehr oft gehört: Im Jahre 1636 habe ein Indianer der Provinz Loxa dem Corregidor von Loxa, Don Juan Lopez de Cannizares, der an einem kalten Fieber krank lag, die guten Eigenschaften der Fieberrinde angerühmt. Der Corregidor sich nach der baldigen Erhaltung seiner Gesundheit sehnend, liess sich von diesem Indianer etwas von der Rinde, nebst der Verfahrungsart sie zu gebrauchen, geben. Er befolgte die angegebene Vorschrift, welche darin bestand, die Rinde mit einer beliebigen Menge kalten Wassers aufzugiessen oder zu kochen, und zu wiederhohlten Mahlen davon zu trinken, und genas in wenigen Tagen vollkommen von seiner langwierigen Krankheit. Als der Corregidor hierauf im Jahre 1638 vernahm, dass die Vicekönigin von Peru an einem dreytagigen Fieber krank liege, schrieb er an ihren Gemahl Don Geronimo Fernandez de Cabrera, Bobadella y Mendoza, Grafen von Cinchon, und schickte ihm von dieser Rinde, nebst einer Anzeige ihrer Wirkung und der Verfahrensart sie zu gebrauchen. Der Vicekönig liess in den Hospitälern von Lima mehrere Versuche damit anstellen, und da alle dem eingeschickten Berichte vollkommen entsprachen, liess er auch seine Gemahlinn davon gebrauchen, welche vollkommen genas. Ueberzeugt von den damahls wunderbaren Heilkräften der Rinde, liess nun die Gräfinn von Chinchon diese Rinde unentgeltlich austheilen, woher dieses Mittel zuerst den Nahmen Pulver der Gräfinn (Pulvis Comitissae) erhielt. Als sie später mit ihrem Gemahl nach Europa reiste, gab sie den Jesuiten eine bedeutende Menge Fieberrinde, nebst dem Auftrage, sie zu vertheilen, welche es auch thaten und woher der Nahme Jesuiten-Pulver (Pulvis Jesuiticus aut Patrum) entstand. Die Jesuiten schickten auch von dieser Rinde an den damahligen Cardinal de Lugo nach Rom, woselbst sie zuerst in der Apotheke des römischen Collegiums zum Gebrauche armer Religiosen in Anwendung gebracht wurde. Der Cardinal selbst soll aber auf einer Reise nach Frankreich den Dauphin und nachherigen König Ludwig den XIV. von einem Fieber befreyt haben, woher der Nahme Cardinalis-Pulver (Pulvis Cardinalis). Der Leibarzt des Grafen von Chinchon Joh. de Vega, brachte im Jahre 1640 die Fieberrinde zuerst nach Spanien und verkaufte das Pfund um 5 Scudi. Bald darauf stieg sie aber so im Preise, dass sie in Rom dem Silber gleich gehalten wurde, und man das Pfund Rinde mit einem Pfund Silber bezahlte.” [18-59] [18-60] [19-1] [19-2] [19-3] [19-4]
There are numerous variants of the latter story about the countess’s cure. The wife of the Viceroy of Peru, who was also the fourth Count of Cinchon, Doña Francisca Henríques de Ribera, was lying on her deathbed with a fever around 1630, some say 1638, when she received a dose of cinchona bark either from a Peruvian maid or official or from the Viceroy’s Jesuit priest and personal physician, Juan de Vega. Miraculously, the healing began. She then returned to Europe to give the cinchona bark to people who were suffering there. So much for the legend – but her illness is not recorded in her husband’s detailed diaries, nor can she have returned to Europe, for she died before returning to Spain. So this story does not seem to be true either. [2-20] [3] [5] Alexander von Humboldt aptly concludes: “The story of Countess Chinchon, Vicerine of Peru, so often rewritten, is probably even more doubtful than is commonly believed.” [18-59]
– “Die so oft nachgeschriebene Geschichte der Gräfin Chinchon, Vicekönigin von Peru, ist wohl noch zweifelhafter als man gemeinhin glaubt.” [18-59]
Others, however, say it was the Viceroy’s first wife, Anna de Osorio, who was cured with cinchona bark. However, she died in 1625 and her husband only became Viceroy of Portugal in 1629. [6]
One can also doubt the other traditions: “After Humboldt has discussed all the hypotheses about the discovery of the efficacy of fever bark, he believes that the bark was first brought to Europe by the Countess of Chinchon, but doubts that the Corregidor of Loxa became acquainted with it through a native. For not only is there no oral tradition of this kind there, but the use of fever bark is completely unknown to the Americans, who cling to their ancestral customs and traditions with unchanging persistence. Humboldt says that in the deep and hot mountain valleys of Catamajo, Rio Calvas, and Macara, alternating fevers are very common, but the natives, to whatever caste they may belong, would rather die than use the fever bark, which they count in the class of ardent poisons. In Malacates, where many cascarilleros (peelers of cinchona bark) live, it is beginning to be used. In Loxa, on the other hand, there is an old legend that the Jesuits, according to the custom of the country, distinguished between the different species of trees by chewing the bark, and because of its bitterness, since there were always people with knowledge of medicine among the missionaries, they began to give it as an infusion in a three-day fever.” [19-13] [19-14] “From 1638 to 1776 all fever bark came to Europe from Loxa, but later it was also discovered north of the equator, between Loxa, Quito and Santa Fe de Bogota …” [18-65][19-14]
– “Nachdem Humboldt alle Hypothesen über die Entdeckung der Wirksamkeit der Fieberrinde abhandelt, so glaubt er zwar, dass die Rinde durch die Gräfinn v. Chinchon zuerst nach Europa gebracht wurde, zweifelt aber dass der Corregidor von Loxa solche durch einen Eingebornen kennen lernte. Denn es herrscht daselbst nicht nur keine mündliche Überlieferung dieser Art, sondern den Amerikanern, die mit unabänderlicher Beharrlichkeit an ihren hergestammten Sitten und Gebräuchen hängen, ist der Gebrauch der Fieberrinde gänzlich unbekannt. Humboldt sagt, in den tiefen und heissen Gebirgsthälern von Catamajo, Rio Calvas, und Macara sind Wechselfieber sehr gemein, aber die Eingebornen, zu welcher Kaste sie gehören mögen, sterben lieber als dass sie die Fieberrinde gebrauchen sollten, die sie zur Classe der Branderregenden Gifte zählen. In Malacates, wo viele Cascarilleros (Chinarinden-Schäler) wohnen, fängt sie an in Aufnahme zu kommen. Dagegen herrscht aber in Loxa die alte Sage, dass die Jesuiten nach Landessitte beym Holzfällen durch Kauen der Rinde die verschiedenen Baumarten unterschieden haben, und so wegen ihrer Bitterkeit, da unter den Missionären stets sich Arzeneykundige befanden, sie anfingen im dreytagigen Fieber als Aufguss zu geben.“ [19-13] [19-14] „Von 1638 bis 1776 kam alle Fieberrinde von Loxa aus nach Europa, später wurde sie aber auch nördlich vom Äquator entdeckt, und zwar zwischen Loxa, Quito und Santa Fe de Bogota … ” [18-65] [19-14]
The naming
The story of the Vicerine, whichever one it was, was popular in any case, and so Carl von Linné, in his book “Genera Plantarum” published in 1742, honoured the wife of the Peruvian Viceroy, who had become the Countess of Chinchón by marriage, by naming the genus after her. However, he unfortunately misspelled her name. He forgot an “h”, and so the genus is still called Cinchona instead of Chinchona. [2-20] [3] [4-527] [19-9]
The German name Chinarindenbaum (“China bark tree”) has nothing to do with China. The origin of the word probably lies in the Quechua word kina-kina, also written quina-quina, which means “bark of the barks”, referring to the bark of the red cinchona tree used as a remedy. [3]
However, cinchona bark was also sold under many other names, including fever tree, quina, calisaya, Peruvian bark or jesuit’s bark. It was sometimes classified on the basis of its colour, and the best was said to be red in colour, the worse yellow and grey. The bark was also often confused with that of another medicinal tree, the balsam tree Myroxylon balsamum. [2-21] [7]
Use as medicine in Europe
Around 1640, the bark began to be exported to Europe, [2-20] according to Kim Walker and Mark Nesbitt. But they must be mistaken. The Frenchman Michel de Montaigne wrote in his Second Book of Essais, i.e. in the 1580s, already: “We do not appreciate, a very eminent physician has said, a method of treatment which is intelligible to us, as well as the herbs which we gather ourselves. If there should be physicians among the peoples from whom we obtain guaiac resin, smilax and cinchona bark, one can imagine the enormous value that will be placed there on our cabbage and parsley as a result of the same idolatry of the strange, the rare and the costly! Who would dare to despise things which are brought from such distant lands and which have undergone such a long and dangerous passage?” [14-383]
– “Wir schätzen ja, hat ein sehr bedeutender Arzt gesagt, eine uns verständliche Behandlungsmethode ebensowenig wie die Kräuter, die wir selber sammeln. Falls es bei den Völkern, von denen wir das Guajakharz, die Stechwinde und die Chinarinde beziehn, Ärzte geben sollte, kann man sich denken, welch ungeheuren Wert man dort infolge der gleichen Vergötterung des Fremdartigen, Seltnen und Kostspieligen auf unsern Kohl und unsre Petersilie legen wird! Wer würde es schon wagen, Dinge zu verachten, die man aus derart fernen Ländern holt und die eine derart lange und gefährliche Überfahrt hinter sich haben?” [14-383]
Not everywhere, however, people liked to accept and use the medicine. In Britain, for example, a true Protestant initially wanted nothing to do with a Catholic medicine. Jean-Jaques Chifflet wrote about cinchona bark as a “papal fraud”. [2-21] Notwithstanding these adversities, cinchona bark was eventually accepted as a standard medicine in Europe because of its efficacy. For example, as early as 1677, the Pharmacopoeia Londinensis reported that cinchona bark helped against all kinds of fevers [2-22] and by the mid-18th century, cinchona bark was widely regarded as a remedy for intermittent fevers. [2-32]
Interestingly, there are indications that in Britain they treated alternating fevers with wormwood, for example with Artemisia vulgaris or Artemisia abrotanum. In China, too, wormwood was described 2000 years ago as a remedy for such fevers. Even today, extracts of Artemisia annua are used as a modern remedy against malaria. [2-23]Robert Talbor’s remedy, which was called “English Remedy”, also achieved some fame. He lived from 1642 to 1681, went through an apothecary apprenticeship, moved to university, and there developed an interest in treating fevers. In 1668 he moved to Essex, experimented with cures and developed his own medicine, which he said was safer to use than pure cinchona bark. He kept his recipe secret. Among those cured by him was a French officer who spoke about it to King Charles II. So it happened that Richard Talbor was invited to his court. After he had also cured the king, he was knighted in 1678 and sent to France. There, King Louis XIV became aware of him and wanted to obtain the prescription for the cure. He received it on condition that it not be published until after Robert’s death. Robert Talbor returned to Cambridge University in 1681 and died in the same year. The following year, 1682, the recipe for his English Remedy was published. [2-22] It became so well known that his remedy not only contained cinchona bark and was made on the basis of a wine, but also contained pain-relieving opium in addition to parsley and aniseed. [2-23] [16] [19-5] The production of a quinine wine thus dates back at least to this time.
It was nothing unusual to mix the bitter cinchona bark with other things. It was ground and then taken as a pill or drunk dissolved in port wine. The bitterness was masked with herbs and cinnamon, cloves or orange peel, and sugar or honey was also added. [2-23]
Cultivation of cinchona trees
Initially, cinchona bark was harvested in the forests of the Andes. But the political situation in South America became unstable in the early 19th century, when people there wanted to be independent from Spain. [2-41] Therefore, trees rich in quinine were selected and tried to be cultivated in other colonies. As early as 1813, it was proposed to plant cinchona trees in India, [2-45] because the demand for quinine and cinchona bark was enormous. In the 1840s, British citizens and soldiers in India consumed 700 tons of cinchona bark annually. [24] In 1859, the Indian government spent a lot of money on imported cinchona bark, [2-48] and it was considered urgent to cultivate it. In 1860 plants and seeds were stolen from Peru and Ecuador and sent to India via Kew, a district of London. [2-49] Cinchona trees were also cultivated on Dutch-controlled Java. [2-52] However, it took another 15 years before the first harvest in the colonies. [2-52] But by 1883, cinchona bark from South and Southeast Asia dominated the market. [2-53]
Soon, around 1890, however, malaria parasites became resistant to quinine in some areas. [2-57]
Quinine
In 1820, Joseph Bienaimé Caventou and Pierre-Joseph Pelletier succeeded in extracting the first two of the four alkaloids contained in cinchona bark from the bark using alcohol. They named them cinchonine and quinine. With the extracted active substance, it was possible to dose the amount more precisely. [2-11] [2-45] [8] [19-49] [19-50] It was first extracted from the bark of Cinchona species on an industrial scale in 1823 by the pharmacist Friedrich Koch in Oppenheim. [8]
Quinine dissolves particularly well in alcohol and less well in water. The Encyclopaedia Britannica states in 1911 that the quinine sulphate commonly used in commerce is soluble in about 780 parts of cold water, or in 30 parts of boiling water, or in 60 parts of rectified alcohol with a relative density of 0.83. Its solubility is reduced by sodium or magnesium sulphate, but increased by potassium nitrate, ammonium chloride and most acids. [20] [21] [22-22] [22-23] [23] This poor solubility explains why there is always an acid present in tonic water.
The advantage of quinine application compared to bark is described in 1825 by the Asiatic Journal: “Before the meeting broke up, some important observations were made by a member, regarding the employment of the new medicine, Quinine, in the fevers of the country. The preparation particularly alluded to was the sulphate of Quinine, a small supply of which had been received a few months before in Calcutta. It is represented to be a most powerful tonic, in the common acceptation of the term, as curing obstinate intermittents, and even remittents, partaking of the type of the former, in an incredibly short space of time. The dose is so small (from three to five grains) that it may be swallowed in the form of a pill, and a few such are found more efficient than ounces of bark in removing the fever, and afterwards guarding the patient against the danger of a relapse.” [17-76]
At this point, unfortunately, it is necessary to turn to the grain, because we will find this indication of quantity even more frequently in the following. In English it is called “grain” and is abbreviated to “gr”; this should not be understood to mean “gram”. However, the meaning of a grain varies, because it depends on the system used. An English grain is an obsolete unit of measurement and corresponds to exactly 64.79891 milligrams in the troy, avoirdupois and apothecary systems. A grain in the troy system is equal to 1/5760 troy pounds; in the avoirdupois system, 1/7000 pounds; in the apothecary system, 1/5760 apothecary pounds. The French grain, on the other hand, was equal to 1/9216 of the old French pound, about 53.115 mg. In the Nuremberg apothecary weights, a grain was equivalent to about 62 mg. [9] [10] [11]
The three to five grains mentioned here were probably between about 194 mg and 324 mg.
Today, malaria treatment is carried out over one and a half to two weeks by oral administration of quinine salts in doses corresponding to at least 0.8 g to 1 g free quinine base per day, for example in the form of 1.95 g quinine sulphate dihydrite. [16] This would therefore correspond to 41 to 51 parts quinine base to 100 parts quinine sulphate dihydrite.
Has anything other than quinine sulphate dihydrite been used in the past? It seems so, because in the “Encyclopädie der medicinischen Wissenschaften” (Encyclopaedia of Medicinal Sciences) the following conversion factors were given in 1830: “Nowadays, the quinine alkaloids are almost generally used pure or in salt form. The most common salts are: the sulphuric acid quinine or cinchonine; the neutral and effloresced sulphuric acid quinine is usually preferred, because its composition is invariable and always offers 86 base to 100 parts; while that which is not effloresced, depending on whether it is in a more or less humid place, can contain 76 to 86 parts of quinine. The sulphuric acid cinchonine is used under the same circumstances as the sulphuric acid quinine, although it is less effective. Acetic quinine is not used because it is almost insoluble, especially in the cold.” [15-133]
– “Man wendet jetzt fast allgemein die Chinaalkaloide rein, oder in Salzform an. Die gebräuchlichsten Salze sind: das schwefelsaure Chinin oder Cinchonin; man zieht am gewöhnlichsten das neutrale und eftlorescirte schwefelsaure Chinin vor, weil seine Zusammensetzung unveränderlich ist und jederzeit 86 Base auf 100 Theile darbietet; während jenes, welches nicht eftlorescirt ist, je nachdem es an einem mehr oder weniger feuchten Orte sich befindet, 76 bis 86 Theile Chinin enthalten kann. Das schwefelsaure Cinchonin wird unter den nämlichen Umständen, wie das schwefelsaure Chinin, angewendet, obschon es weniger wirksam ist. Das essigsaure Chinin wird nicht gebraucht, weil es, vorzüglich in der Kälte, fast unlöslich ist.” [15-133]
In Germany, a maximum of 85 mg/kg quinine(base) is allowed in soft drinks, and 300 mg/kg in spirits. [2-92] [12] [16] This means that one would have to drink about 10 litres of tonic water to consume the amount of quinine necessary for malaria treatment. Camper English even writes that one would have to drink over 20 litres of tonic water, as he sets the daily dose of quinine higher; in the USA, comparable to Germany, a maximum of 83 mg of quinine per litre is allowed in drinks. [1-72]
Quinine must be dosed carefully. An overdose leads to dizziness, headache, tinnitus, deafness, temporary blindness or even cardiac and respiratory paralysis. The lethal dose for an adult human is about five to ten grams of quinine. [16]
After this general description of the cinchona tree and quinine, we turn to the medicinal uses of quinine in the next part of this series. There we report on malaria, fever and alternating fever and its treatment with quinine wine.
Sources
explicit capitulum
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