GALEN AND PHARMACEUTICAL TECHNOLOGY

Abstract

Using certain examples we have shown, that Galen took the properties of the used components and their components into consideration, offered sensible ingredients combinations and blends, and prepared a dosage form, capable of implementing its pharmacological action. The analysis of the materials gave grounds to consider Galen not only as an outstanding doctor, but one of the first manufacturing chemist.

Full Text

On the opinion of many authors, Galen was an outstanding doctor, whose contribution into medicine is hard to overestimate. It is considered that he played its principal role in anatomy development. There are several pages in student books on this subject devoted this Roman doctor. Galen also influenced the development of physiology and pharmacology, but there is no reference to him in the books on these subjects. Apparently from the point of view of contemporary physiologists and pharmacologists his role in their fields was not as significant as medicine historians think. However the medicine field where Galen contribution is considered to be decisive is pharmacy. All pharmacy student books note a big contribution of Galen, particularly in technology of pharmacy. Why the role of Galen in pharmacy is so special? To answer this question we will analyze some expressions of the medicine and pharmacy historians. Here are some of them. I.I. Levinstein do not speak about a special contribution of Galen into pharmacy, but notes the division of drugs into “simple, which act with element properties (cold, warm, humidity, dryness), and complex, which act depending on different combinations of principal and side effects (bitter, sweet, sour etc.)”. On the author’s opinion, Galen for the first time questioned the postulates of Hippocrates school, which believed that drugs are given by nature in its final form. Galen supposed, that plants and animals have useful compounds (drugs) and harmful compounds, which need to be eliminated. On his opinion, the basic technological methods for drugs preparation were “indentation, grinding (bucking), maceration, decoction, firing etc.” [1] According to G. Gezer’s opinion Galen himself would implement simple drugs [2]. Explanation of Galen’s contribution into pharmacy by K.S. Yatsuta in “Brief Course of Pharmacy and Pharmacognosy” is interesting. On the opinion of this author, all drugs were divided by Galen in terms of their preparation: - simple, which include substances of animal and vegetable origin (herbs, leaves, rhizomes, organs, and tissues of animals); - chemical and pharmaceutical, which are prepared by chemical methods (soda, sulfur etc); - complex or galena drugs. Thus the complexity of galena drugs is in the fact that they can consist representatives of both first groups [3]. In our opinion, the point of view of such medicine historians as T. Meyer-Steineg and K. Zudgov. According to them Galen calculated three stages of drugs action. The first stage includes primarily the appearance of basic properties (warmth, cold, dryness, humidity). The second stage includes combined action of the basic properties, and the third stage comprises the realization of specific properties of separate drugs (emetic, depletory, diuretic action) The next principal for drug substances classification is the method of “acting substance (potential)”. According to Galen these substances differ by the action degree. The first group is represented by the compounds with barely pronounced action, the second group is represented by the substances with pronounced action, the third group includes strong active substances, and the forth group comprises harmful and organism destroying compounds [4]. There is a statement in the Big Medical Encyclopedia (second edition), in the article devoted to Galen (author B.D. Petrov), that he generalized the ways for drug substances processing and deflated the views if Hippo- crates followers, who considered that drugs exist in nature as a ready to use product and do not need any processing [5]. We believe that Professor I.A. Muravyov was the closest scientist to understanding of the Galen’s contribution in pharmaceutical science. He supposed that historic contribution of Galen in pharmacy is in his change of view about drugs which was in II century influenced by Hippocrates school. As it was mentioned above, Hippocrates believed that drugs in nature are ready to use in its optimal combination, and the doctor’s task is to keep their natural condition. Galen for the first time supposed that vegetable and animal origin medicines have substances which are useful, since they implement treatment activity, and useless substances which need to be eliminated. The idea about extracts from plants and animals with active substances appeared in this manner. Paying a tribute to Galen, I.A. Muravyov writes “The significance of Galen in the development of drugs technologies and pharmacy is in the principals proposed by him, theories, technical methods, and guidelines which were given in his works survived his epoch and had authority up to XVI century.” [6]. As we can see, Ivan Alekseevich Muravyov shares point of view of previous authors, but he emphasizes that Galen offered technical methods for drugs production, apart from certain theoretic bases of pharmacy stipulation. We can note that while obtaining drugs Galen processed raw materials using special methods, and made a form, capable of efficient action of its treating properties. In this study we had a purpose to prove the data mentioned above on vivid examples, by studying open literature sources. Unfortunately, our tries to reveal understandable for contemporary readers sources of Roman doctor, devoted to the drugs production were not successful. All we could find was written in XV century in classic Latin in Gothic font. Deciphering of these papers should be done by experts. However we could find a reliable source with Galen quotes. It was a colossal work of Avicenna “The Canon of Medicine”. Galen’s name is encountered rather often there, which proves a big influence of his works on Ibn Sina. So the first book quotes Galen 35 times, in II book, they are encountered 77 quotes, in III book (vol. I and II) the scientists is mentioned 70 times, in IV book - 49 times, and in V book 27 times. Quoting Galen, Ibn Sina put a respectful epithet before his name - “well-deserved doctor”. In the second book of Canon, where the author de- scribes the properties of simple drugs there are expressions: “Galen said…”, “according to Galen…”, “following the Galen’s statement…”, “unlike Galen…”. I.e. after 9 centuries Avicenna openly quotes Galen, make remarks to him, argue with him, and make respect to him [7]. We cite several passages with comments below. In the II book Avicenna writes “Galen tells that he could by chance grind composite parts of communia (cumin seeds, aut), and it transformed into diuretic agent. Therefore it is necessary to draw the line in grinding of medicines with rare substance” [7]. This example shows that Galen in his time understood the importance of the technological index of the powder particles size after raw materials grinding. Technologies of preparation of medicinal paps with different pharmacological effects, shown in “Canon” of Ibn Sina are also interesting: 1. “Medicinal pap of Galen, which heals kidneys, bladder, and the whole body. Its plant components (leaves, roots, seeds - together 13 components), got in equal volume, are blended, mixed with honey without foam”. 2. One more medicinal pap of Galen which treats liver aches, caught, and blood vomit is prepared as following. 12 plant components, honey, wine, gum are blended together, milled, sowed and mixed with honey. 3. Galen’s pap with turmeric “helps in treatment of old diseases in liver, spleen, opens all corkings in digestive organs, eliminates winds, sends urine, treats all diseases in kidneys, bladder, and womb. It requires 21 plant component, adding it with Ceterach officinarum, then it’s milled and sowed, moisture with balsam oil and mixed with honey”. 4. Medicinal pap of Galen effective for the treatment of lungs diseases. “It starts with the preparation of a blend of honey and gum of terpentine tree. The blend is prepared in a boiler with double bottom and, when it starts getting thicker, it is added with galbanum and is boiled on up to the moment when the drop doesn’t form. After cooling of the blend it is added with the rest of mixed and milled medicinal components”. The analysis of these paps, which contained mainly plant components, gives evidence that at the beginning Galen mixed ingredients, milled and sowed them. The powder obtained he mixed with honey, which was prepared in a special way, removing foam from the surface. Thoroughness of the plant materials preparation is remarkable. It was mixed, milled, sowed, achieving the standard sizes of powder particles. If in first two recipes the blend of plant components was mixed with honey at once, in third recipe the powder obtained was moisture with oil, and then added with honey. Galen probably knew that oil implementation allowed extraction of useful components from the seeds (for example essential oils), which are imposible to isolate in any other way. Preliminary preparation of honey is also remarkable. In II century honey was boiled, cleaned from undesirable components, expanding its expiry day. The use of the boiler with double bottom is one more important detail. We think that this boiler in reality is a water bath, which would allow keeping the stable temperature while vaporization of liquid components up to the viscosity needed. Besides, we still use the method of a final product’s viscosity de- termination nowadays. Preparation of general strengthening and tonic agent - vinegar honey - by Galen is made using the following method: “fine honey is taken, put on cinders, foam is removed, added with vinegar, not sour but not weak, carefully boiled in flames for their good mixture, and vinegar would not remain raw. Then it is cooled and pre- served. Before using it is mixed with water. But there is no need to mix them, as patient would like. Those who like sour vinegar can add more agent, and those who like it sweet take more water”. The following feature of this agent preparation attracts attention. The first is the honey preparation: boiling and foam removal, and the second is vinegar-honey, mentioned above, which can be considered intrapharmacy preparation with prolonged expiry date, which can be used and prepared near the patient’s bed. Galen probably knew the preservative properties of honey. One more interesting fact is that Galen recommends using different water for his syrups with honey. In on recipe Galen advices using transparent, fresh, springwater, and in another he uses rainwater. Therefore there is no doubt Galen differentiated simple, “mineral”, and distilled, “rain” water. Complex agent of Galen, which helps treating “the diseases of a lung tube, ulcers of lungs, gleet and blood cough” has multi-component content with 16 different ingredients. “For its preparation honey and terpentine tree gum are boiled in a double vessel. When the blend gets thicker, it is added with galbanum and boiled to the moment when drops are not separated. Then the mixture is cooled and added with the rest milled components”. Again we see the application of a water bath. This recipe is interesting because of the separate procession of dry and easily melted components. Galen also described a medicine for the treatment of colonopathy (corpostasia). “Saffron, sambul, myrrh, bush, white pepper, long pepper, and galbanum, balsam oil, Chinese and Ceylonese cinnamon, bark of mandrake root, mandrake juice, devil’s-plague seeds, sagapen. Plant components are milled in a mixture of balsam oil and mandrake juice, and then mixed with honey.” In this case, as we can see, aromatic herbs and seeds are preliminary milled in oil and only then mixed with honey. Galen recommends treating sick kidneys with pastilles of the following composition: “shelled hazelnut, shelled almond, shelled seeds of garden kissa, shelled seeds of thyme, caraway, poison parsley seeds, saffron, cucumber seeds, opium, henbane seeds, and celery seeds. All is mixed with honey to form pastilles, and to drink it with warm clear water.” In this recipe honey is used to form pastilles with milled nuts and plant seeds as main components. Ointment for eyes, called by Galen “a simple ointment”, consists of 13 components, which include burned copper, opium, saffron, castor, myrrh, stannic ceruse, and gum. All this mixed with water and egg white. It is remarkable that the ointment composition has antiseptic, anesthetic, and anti-inflammatory ingredients. And to give an ointment necessary physical and chemical properties, the scientists mix it with egg white, probably with a knowledge about its emulsifying properties. Here are two prescriptions of clysters which Galen used. One of them is clyster of Anthony, which corresponds to ancient recipes. It includes “dried out grape juice, Yemen alum, calcium oxide, copper ash, orpiment, and burnt papyrus paper. All this is mixed with myrtle berries syrup, and then formed into pastilles, which are dissolved in wine or rainwater before the application.” The next clyster recipe Galen recommend for critical conditions, “when a patient simultaneously vomits and defecates. Hen- bane seeds, white pepper seeds, opium, saffron, aromatic sambul, ptyalologue are taken. All these are milled and mixed with boiled honey.” As we can see from the recipes, the doctor preliminary prepares medicines in pastilles, which are finally prepared right before the patient’s bed. Moreover, these pastilles could be left for the patient’s relatives for independent use. There are also some data about Galen to be the first doctor to prepare medicines by a written request and to send them with a courier to other cities and countries [8]. Plaster made of kalkadis (red copperas) which Galen called “Funiki” is the next recipe. This plaster helps to treat “plague, heals heavy wounds and ulcers, help in treatment of fractures, injuries, and tumors. Kalkadis, old fat, old olive oil, and lead oxid are taken. Fat is melted, kalkradis is milled with a part of olive oil. Lead oxide is milled separately in mortar with the rest of olive oil, and then all components are mixed in the mortar. Then, after thorough blending, everything is put on the frying pan and mixed with a palm branch until smooth.” Studying the consequence of action to prepare this plaster, we can see that Galen mills kalkadis and lead oxide in parts of olive oil a lot, and only then everything is finally mixed in a melted fat in the frying pan [Abu Ali ibn Sina, vol.5]. And the last. L. Meunier (1926) believes, that Galen’s duties included the preparation of imperial theriac [Meunier L., 1926]. Theriac is a medicine, andidote, which includes more than 60 components from different pharmacological groups. Its preparation is long, difficult, and multi stage process. Avicenna believes that “theriac has five readiness degrees - infancy, adolescence, youth, anility, and death. It becomes a baby in 6 months or one year. Than it starts growing, improving its properties, and becomes the best in 10 years in warm countries and in 20 years in cold countries. In 20 or 40 years it becomes weaker, and in 30 or 60 years theriac loses its properties, and it becomes a pap, without any antidote effect”. Galen tried to shorten, and to increase a number of components, but in the end, the first recipe offered by Andromache remained the best recipe of this medicine. Galen offered the determination method of its quality determination. He writes: “Wild cock is needed, for he is dryer than domestic cock. Let a venomous insect bit it, and after that it is given with theriac; if the cock survives, theriac is good” [Abu Ali ibn Sina, vol. 5]. As a gratitude for a theriac prepared by Galen, Emperor Anthony decorated him ceremoniously with a gold chain with a medal which read “Anthony, Emperor of Romans - for Galen, Emperor of doctors” [9]. We consider this fact to be a high recognition of Galen by its contemporaries not only as a doctor, but also as a manufacturing chemist. Thus, using examples we showed the knowledge and experience of Galen in pharmaceutical technology. All this gives us grounds to consider Galen one of the first manufacturing chemists, who took into consideration properties of substances, their doses, and reasonable combinations in blend, as well as dosage form and ways of its manufacturing.