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The history of the medical use of creosote or medicinal creosote began centuries centuries before creosote was identified as a specific, distillable compound in the use of different medicinal remedies in cultures around the world in which it would nonetheless have been the chief active component. Creosote, being the portion of a wood, coal, or any other type of tar that is remains heavier than water, was seen as effective as a remedy because of both the anti-septic properties of tar acids in the solution and its low solubility. During antiquity, pitches and resins of tars were commonly used as medicines, a practice that continued up through the 1830s, when the creosote distillate was first isolated by Carl Reichenbach. Encouraged by the past use of tar-derived remedies, and by the use of herbs heavy with creosotic chemicals in other parts of the world, it quickly became the subject of research and experimentation, and commonly used in many medical applications throughout the 19th century and into the mid-20th century.

Creosote derived from wood-tar — primarily beechwood — was used a styptic, expectorant, anti-septic, astringent, anaesthetic and a laxative. With anti-biotics not yet in existence, it was spun off into many different applications, in hope that its anti-septic properties could help with treatment of tuberculosis and other pulmonary diseases. The experimentation stopped when radiation therapy looked to be a more promising bactericide. Today, creosote in its wood-tar form has largely been replaced by newer, more effective medicines, although many of them, such as guaifenesin, were originally chemical derivatives of creaosotic chemicals. Older style medicines that contain beechwood creosote can still be purchased today, as well as herbal remedies.

Coal-tar creosote, which was more commonly labeled as "creosote oil", was used as an escharotic to burn malignant skin tissue and popularly used in dentistry to deaden nerves and prevent necrosis. Its no longer is used that way because of its toxic, carcinogenic properties and because better and safer treatments are now available.

Precursors (—1833)

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Indigenous remedies

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Larrea tridentata, or the so-called creosote bush, as named after its distinct creosote smell, was used by Native Americans in the Southwest as a treatment for many maladies. The Cohahuillia Indians used the plant for intestinal complaints and tuberculosis, the Pima would drink a decoction of the leaves as an emetic, and applied the boiled leaves as poultices to wounds or sores.[1] Popago Indians prepared it medicinally for stiff limbs, snake bites, and menstrual cramps.[2] Guaiacum, after which the guaiacol in creosote was named, was used by native Caribbean islanders to treat tropical diseases and later for syphilis.[3][4]

Both ancient Native American and European cultures are also known to have chewed wood-tar products, a practice that eventually evolved into modern chewing gum. Although largely recreational, ethnological record suggests it would have also been used for medicinal purposes. Mesolithic peoples in Northern to Central Europe — Ertebølle, Maglemosian, and Kongemose cultures through Scandinavia, Finland, Switzerland, and Southern Germany — would chew a gum produced from the tar of birch bark; sometimes sweetened with honey for taste. Replicative experiments show that the bark would have needed to be heated to 800°F to force the tar out. Besides simple chewing, the tar was likely also used for cleaning teeth and gums, and in medicinal treatments, such as aid with congestion, tooth-aches, sore throats, stomachaches, heartburn, ringworm, and frostbite. Native American Indians and Inuits are known to have chewed gum produced from spruce and maple resin.[5][6]

Antiquity

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Pliny, as well as Galen, discuss a variety of tar-like substances being used as medicine which would have relied on a heavy creosotic component.[7]

Cedria and pissinum

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(Main article: Cedria) One was cedria, which referred to the pitch and resin of the cedar tree — the equivalent to the oil of tar and pyrolingeous acid which are used in the first stage of distilling creosote.[8][9] Both Pliny and Galen recommend cedria to ease the pain in a tooth-ache; with Pliny describing it as having the effect of "breaking the teeth and extracting them", and so allaying the pain; saying that it would be typically be combined with vinegar and used as a mouth rinse. He also discusses its application internally for the use of quinsy and dyspepsia, as in an injection in the ear in the case of hardness of hearing, kill parasitic worms, as a treatment for phthiriasis and porrigo, as an antidote for the poison of the sea hare, as a liniment for elephantiasis, and as an ointment to treat ulcers both on the skin and in the lungs. He further talks about how it can be used for contraceptive purposes, by rubbing it on the male organs before intercourse.[7]

Pliny and other authors also discuss cedar distillates related to cedria as used by Egyptians as an embalming agent for preparing mummies. He refers to both cedrium, or "cedar material", and cedri succus, or "cedar juice". Five centuries earlier, Herodotus referred to two different cedar-based oils, one produced from the tree and from a product from the cedar tree, that would be injected using a syringe.[10] Diodorus also referred to the anointing of the body with a "cedar oil", or cedrelæum, that would be be swim above pitch or resin when boiled, and would be collected with wool.[11][8] There was initially some doubt whether the authors were identifying the tree now commonly known as cedar, or of the juniper tree, and whether cedria and cedrium referred to the same material. The wood of juniper trees had been commonly called "cedar" since ancient times, the oil of the juniper as "cedar oil", and from that, substances from the oils and tars were known as cedrol and cedrene, which caused some confusion.[12][13][14] A analysis of embalming material in 2003 confirmed the accuracy of the common translations, and established .[12] Further studies showed the source to be the African cedar (Cedrus atlantica).

Another tar derivative was pissinum — meaning "pitch material" — and alternatively referred to by Pliny as pisselæon — "pitch oil" — was a tar-water that was made by boiling cedria, or similar pitches made from pines and firs, and spreading wool fleeces over the vessels to catch the steam, and then wringing it out.[15][16]

Mastic

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(Main article: Mastic) Pliny also discusses a product similar to earlier wood-tar gums, referred to as mastic or mastich, likely the root for the word mastication. The resin used would come from numerous plants with different levels of quality: the most desirable was a white mastich from the lentisk or mastic tree, then from a prickly shrub known as lama or laina and from the terebinth, and the least desirable came from the cypress, which was considered too acrid. Mastich was used as a cream to smooth the skin and soothe abrasions, and was believed to cure chronic cough and the spitting of blood.[5]

Mumia

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(Main article: Mumia) A tar derived from mineral pitch is also believed to be used in embalming mummies, named as momia or mumia by Dioscorides, a first century Greek physician, and described as a native oil of tar or petroleum. Mumia also discussed by Pliny, who says its useful in treating itches and mammary excoriations.[17]

Modern Europe

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Materia medica and herbals published up until the creosote was isolated show a continuation of the traditions of antiquity, often quoting Pliny, Galen, and other ancient sources for wisdom.[18][19] More particular variations on the same remedies were also developed; wood-soot was listed as a remedy in many Materia medica, with details for different preparations, and different types of empyreumatic oils were produced and sold, many as patent medicines, with the chief ingredient being pyroligneous acid. There was particular scientific interest in researching tar-derivatives in the mid-18th century, largely because of the promotion of tar-water by Bishop Berkeley.

Tar-water

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(Main article: Tar-water) Tar-water had been used as a folk remedy since the Middle Ages to treat affections like dyspepsia, although its use within time had declined and wasn't widely known in Europe by the 1700s. It came to Berkeley's attention during his stay in America in the 1720s and 1730s, when he found that tar-water had been used there successfully as medicine, and soon after researched the subject and found confirmation it had been used elsewhere around the world. He thereafter decided to recommend it as a cure for the sick in his diocese, and wrote a philosophical work centered the substance in 1744 titled Siris: a Chain of Philosophical Reflexions and Inquiries Concerning the Virtues of Tar Water, and Divers Other Subjects Connected Together and Arising One from Another. In his book, he discussed the various cases in which tar-water worked well, explained its mode of preparation, and gave details about the best dosages and preparations for various types of illnesses, and then moved to a metaphysical discussion in order to explain why it had its curative properties. He concluded, based on the role of sunlight in plant physiology, that tar was simply "condensed light" and and that light was — as was the sun — empowered because it was close substantively in the great chain of being to God, and went so far as to suggest that he had discovered the universal panacea that had been sought after for long by alchemists. The book was enormously popular, with six-editions selling out within a few months.[20]

Berkeley's work brought opposition from many established pharmacists, who characterized his prescriptions as quackery and an affront to medical science. Thomas Reeve was one of the first to reply, claiming that Siris was full of errors because of ignorance of chemistry, and mocked the idea that it should be used because of its inexpensiveness. Several authors replied to Reeve in Berkeley's defense. Many anonymous pamphlets were published, including one titled Anti-Siris was published, mocking it as a fad, with the author suggesting that when he first arrived in London, the medical fad was sugar, only to later be replaced by water, followed by Joshua Ward's 'Pill and Drop' and later the ' Nostrum of Tar Water '. Another pamphlet, titled Siris in the Shades, was a work of fiction taking place in Hades, where Pluto, after reading Siris orders Samuel Garth to prepare tar-water and feed it to Tantalus, who thereafter got sick from it, only to beg for more, to cure his new sickness.[21] In defense of Berkeley's prescription, a poem was written by Charles Hanbury Williams titled Tar-Water, a Ballad.[22] Berkeley wrote a poem of his own, titled On Tar, which appeared in later editions of Siris.

By Berkeley and others, tar-water was said to act as a stimulant, so as to successfully treat cutaneous eruptions and ulcers, ulceration of the bowels, distemper, and coughs due to the ulceration of the lungs, and as a diuretic, to cure indigestion, and to restore appetite.[23][24]

Sir Alexander Crichton published a pamphlet in 1817 discussing the beneficial effects of tar water in the treatment of pulmonary tuberculosis.

Wood-soot

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(Main article: Wood-soot) Wood-soot also became popularly used for treatments since at least the 17th century, prepared by burning wood under a small flue, and collecting the soot which deposited in the chimney. This would correspond to what would be referred to in modern terms as the "creosote" as produced in the process of smoking meat, when wood is used as the fuel source. Referred to by the Latin fuligo ligni, it would also be used in many different preparations. This included decoctum fuliginis or lotio fuliginus, a decoction or lotion of wood-soot, depending on how it was applied, and made by mixing wood-soot with boiling water -- tinctura fuliginis or tincture of wood-soot -- wood soot mixed with a proof spirit -- spiritus fuliginis, spirit of soot -- made with one part wood soot, five parts proof spirit, and fifteen parts water, distilled into four parts -- unguentum fuliginis or ointment of wood-soot --- made with wood soot and lard, sometimes with salt added -- oleum fuliginis or oil of wood-soot, which was officinal in the London Pharmacopœia -- and sal fuliginis or salt of wood-soot, which was prepared through dry distillation similar to salt of hartshorn.[25][26]

Preparations of wood-soot were generally suggested to be used as anti-spasmodics and in the treatment of various nervous diseases, including epilepsy. It was also prescribed in the later stages of whooping cough.[26] In the 1830s, P. Blaud de Beaucaire, the French physician who first developed iron pills, reported success in the use of wood-soot for the treatment of ulcers and a variety of skin diseases, mixed with olive oil as an ointment for ulcer and with axonge (pork lard) as an ointment for skin diseases.[25]

By the early 19th century, several pioneers of the field of dermatology suggested ointments and pills made from tar or pitch to treat skin diseases. Pierre Francois O. Rayer, the founder of the first French dermatological journal, recommended an ointment of one part tar to four parts pig lard, while Thomas Bateman, a British physician, said that pitch in pill-form was the most effective treatment for ichthyosis, saying that it helped with controlling the languid circulation and the arid condition of the skin.[27]

Empyreumatic oils

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(Main article: Empyreumatic oils) A number of oils known as empyreumatic oils began to be produced, which were different distillates of different organic products, mainly based on the efficacy of the pyroligneous acids, similar to cedria.[28] This included hartshorn oil, a by-product from the distillation of the bone and horns of deer, beech-oil, oil of galbanum, oil of guaiajac, oil of amber, oil of wax, and cedar-oil. The Pharmacopeé of Lyons, published in 1786, says that cedar tree oil can induce vomiting, and suggests it help with urination, induce the menstrual cycle, and be used to medicate tumors and ulcers.[27][29]

Hartshorn oil later became refined in Dippel's oil, in combination with blood and various other animal matters. This was also sold more generally as animal oil, and believed by Reichenbach to base its efficacy on creosote. Pyrothonide or liquor pyro-leosus e linteo paratus referred to a product made from burning the tar of linen, hemp, or cotton cloth, when it was known as rag oil, [30] or burning the tar of paper, when it was known as paper oil.[31][32] Hugues-Félix Ranque, the chief physician at the Hôtel-Dieu in Orléans, introduced the treatment in the 1820s. It was listed as a styptic, caustic, and astringent. Ranque prescribed for ophthalmia, as an injection in uterine hemorrhage, in corrhea gonorrhea, and amygdalitis. For amygdalitis, along with some other home care instructions, he suggested to mix with cold barley-water and honey, to be taken through ten or twelve gargles a day.

Another popular solution was aqua Binelli,[27] named after Fidele Binelli, the Piedmontese physician who developed it in 1797, and also sold as aqua balsamica arteriale, for its reputed property of arresting both internal and external hemorrhages, and used as a styptic.[33] [34] Binelli also created a preparation known as aqua brocchieri, made through the distillation of pine wood, that was designed as a treatment for ailments of the respiratory tract. Aqua Binelli continued to be used in Italian hospitals even towards the end of the 19th century.[35] A solution sold in Germany known as aqua empyreumatica, or "empyreumatic water", was developed by Friedlieb F. Runge and J. W. Hancke, and was often used to treat diseases of the nervous system. It was also said to have the same efficacy as aqua Binelli in the treatment of hemorrhaging. Empyreumatic water was produced by saturating pyroligneous acid with chalk.[34]

Naphtha

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(Main article: Naphtha) Naphtha, a product in coal-tar-creosote, was recommended to treat dental caries, recommended as early as the late 17th century to help toothaches.[7]

Older remedies

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Remedies designed from the mineral tar pitch described by Dioscorides continued to be popular through the Middle Ages. Substances sold as mumia, mummia or simply "mummy" would either be an embalming fluid imitative of the ancient momia, or would be a powder made from ground mummies.[17]

Research and development (1833–1910)

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Given this history, and the anti-septic properties known to creosote, it became popular among physicians in the 19th century. A dilution of creosote in water was sold in pharmacies as aqua creosoti, along the same lines as earlier dilutions of empyreumatic oils. It was prescribed to quell the irritability of the stomach and bowels and detoxify, treat ulcers and abscesses, neutralize bad odors, and stimulate the mucous tissues of the mouth and throat.[36][37] Creosote in general was listed as an irritant, styptic, anti-septic, narcotic, and diuretic, and in small doses when taken internally as a sedative and anaesthetic. It was used to treat ulcers, and as a way to sterilize the tooth and deaden the pain in case of a tooth-ache.[36]

Creosote was suggested as a treatment for tuberculosis by Reichenbach as soon as 1833. Following Reichenbach, it was argued for the same purposes by John Elliotson in 1934 and Sir John Rose Cormack in 1936.[36] Elliotson argued for treatment by inhalation, inspired by the use of creosote to arrest vomiting during an outbreak of cholera. He did not propose it as a remedy for the disease, but that it could have a beneficial effect in treating it if it wasn't severe. He also suggested it for epilepsy, neuralgia, diabetes and chronic glanders.[38] Because of its causticity and irritating effect on the stomach, it gradually fell into disuse. The idea of using it for tuberculosis also failed to take hold, and use of this purpose was dropped, until it was revived later in 1876 by the British doctor G. Anderson Imlay, who suggested it be applied locally in spray to the bronchial mucous membrane.[36][39][40] This was followed up in 1877 when it was argued for in a clinical paper by Charles Bouchard and Henri Gimbert.[41] Germ theory had been established by Pasteur in 1860, and Bouchard, arguing that a bacillus was responsible for the disease, sought to rehabilitate creosote for its use as an anti-septic to treat it. He began a series of trials with Gimbert to convince the scientific community, and claimed a promising cure rate.[42] A number of publications in Germany confirmed his results in the following years.[41] Guaiacol, instead of a full creosote solution, was suggested by Hermann Sahli in 1887; he argued it had the active chemical of creosote and had the advantage of being of definite composition, and with less of a less unpleasant taste and odor.[43]

Following that was a period of experimentation of different techniques and chemicals using creosote in tuberculosis, which lasted until about 1910, when radiation therapy looked to be a more promising treatment.

Creosote and guaiacol preparations

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Common creosote and guaiacol preparations
Trade name Compound Developer Manufacturer
benzosol guaiacol benzoate
C6H5CO.O(C6H4.OCH3)
J. Bongartz, 1890 Meister, Lucius & Brüning, Hoescht
creosote benzoate
styracol guaiacol cinnamate
C6H5.CH:CH.COO(C6H4.0CH3)=C6H14O3
Knoll & Co., Ludwigshafen a.Rhn.
creosal, tanosal creosote tannate H. Dubois, 1890 Feigel, Mühlhausen
guaiaform guaiacol-formaldehyde condensate
CH2(C6H3(OH)OCH3)2
J. Brissonnet, 1890 Lambiotte Frerès, Prémery (Nièvre)
creosoform creosote-formaldehyde condensate J. Brissonnet, 1890 Lambiotte Frerès, Prémery (Nièvre)
duotal guaiacol carbonate
(C6H4(OCH3)O2).CO
R. Seifert & F. Hoelscher, 1891 Von Heyden AG, Munich; Bayer & Co., Leverkusen
creosotal creosote carbonate E. Chaumier, 1892 Von Heyden AG, Munich; Bayer & Co., Leverkusen
oleoguaiacol guaiacol oleate
CH3O.O6H4.O.cO.C17.H33
1893
oleocreosote creosote oleate
1893
bioguaiacol guaiacol phosphate
(C6H4.OCH3.O)3PO
H. Dubois, 1894 Baudon, Paris
phosote creosote phosphate J. Brissonnet, 1894 Lambiotte Frerès, Prémery (Nièvre)
taphosote creosote tannophosphate J. Brissonnet, 1894 Lambiotte Frerès, Prémery (Nièvre)
guaiacol succinate
C4H4(C6H4OCH3)2
H. Dubois, 1894
guaiacophosphal guaiacol phosphite
(C6H4.OCH3.O)3P
P. Ballard, 1894 Clin & Co., Paris
phosphotal creosote phosphite P. Ballard, 1894 Clin & Co., Paris
guaiacetin guiacol phenoxyacetate of sodium
C5H4(OH).OCH2.COONa.
1896
guaiacamphol guaiacol camphorate
C8H14(COOC6H4OCH3)3
G. Coronedi, 1897
cresocamphor creosote camphorate G. Coronedi, 1897
guaiaperol, guaiaperon guiacol piperdine
C6H11NH.C6H4(OH)OCH3
1897 Merck, Darmstadt
geosote guaiacol valerate
C6H4.OCH3OCOC4H9
G. Wendt, 1898 Berliner Capsules-Fabrik, Berlin
eosote creosote valerate G. Wendt, 1898 Berliner Capsules-Fabrik, Berlin
guaiamar guaiacol glycerylether
CH3O.C6H4.O(CH2OH.CHOH.CH2)
Mallinckrodt Chemical Works, St. Louis
guaiacol-salol guaiacol salicylate
C6H4.OH.CO.O.(C6H4OCH3)
salocreol creosote salicylate
monotal guaiacol methyl glycolate
CH2(O.CH3).COO.(C6H4.OCH3)
Bayer & Co., Leverkusen
thiocol potassium guaiacol sulphonate
C6H3(OH)(OCH3)(KSO3)
sirolin thiocol in syrup of orange F. Hoffmann-La Roche & Cie AG, Basel
sulfosote potassium creosote sulphonate
guaiacyl calcium guaiacolmonosulphonate
Ca(C6H3OH.OCH3SO3)2
brenzcain, pyrocain guaiacolbenzyl-ester
C6H4(OCH3).OCH2.C6H5
1897 Merck, Darmstadt
guaiacol iodide
cresotide creosote iodide
guaiasanol diethylgycoll-guaiacol hydrochloride
C13H19NO3HCl
CH3O.C6H4.O.CO.CH2.N(C2H5)2HCl
A. Einhorn & H. Hütz, 1900 Meister, Lucius & Brüning, Hoescht a.M.
eucol guiacol acetate
C6H4.OCH3.CO
G. Biscaro
guaiacacodyl, cacodyliacol guiacol cacodylate
As(OH3)2O2C6H4OCH3
(CH3)2AsO.O.C6H4(OCH3)9H2O
F. Barbary & M. Rebec, 1899
guaiachinol, guaiaquinol dibromo-guaiacol of quinine
C6U2Br2(OCH3)OH.C20.H24.N2O2
J. Castel, 1900
proposote creosote phenylpropionate
1911 Parke, Davis & Co., Detroit
hexamecol guaiacol hexamethylenetetramine
1911 F. Hoffmann-La Roche & Cie AG, Basel
guaifenesin glycerol guaiacolate
E.M. Boyd & G.L. Pearson, 1946
guacetisal guaiacol acetylsalicylate
guaimesal
guaiapate

A number of new salts and esters of creosote and guaiacol appeared on the market, developed to counter the disadvantages of the base solutions and enhance their beneficial effects. A cinnamate of guaiacol, styracol, and a benzoate of guaiacol, benzosol, were developed early on to counter the causticity, but the percentage of creosote in those solutions ended up being too small for them to be effective. Carbonates of creosote and guaiacol, creosotal and duotal were then developed, and became enormously popular among physicians as they contained the active substances in larger amounts while still showing no strong taste, caustic action, or irritation. Eosot and geosot, valerates, were later created, and were said to have likewise remedied the unpleasant effects and further noted to act on the nervous system, as were the camphorates cresocamphor and guaiacamphol.[44][45][46]

These compounds found their way into common medicines prescribed for coughs and colds, but still proved to be of limited use in treating tuberculosis. Further research for tuberculosis use developed under the framework of soil theory of disease; the aim being to replenish chemicals in the bodily organs that grew deficient due to the presence of the disease and to further create an environment — a "soil" — that would make difficult any development and growth of the bacteria. Two tannates, creosal and tanosal were so noted as useful in tuberculosis because of their drying effect on the bronchial tubes.[47][48] Creosoform and guaiaform were developed as condensation products of creosote and guaiacol with formaldehyde, and the tannates were also used with formaldehyde to to produce tannocreosoform and tannoguaiaform.[49][50]

Eventually, research moved towards using phosphates, since absorption of phosphates were believed to be key to restoring the equilibrium of the soil in the body. Chemically, the soil associated with tuberculosis was seen as inverse to the soil associated with arthritic diathesis: the tuberculous soil was deficient in mineral elements, chlorides, phosphates, and acids, while the arthritic soil was superabundant in all of these elements; and tuberculosis was also noted as rare among arthritic patients, when appearing, manifesting itself more benignly. With that in mind, the aim was to convert the tuberculous soil into an arthritic soil.[47][51][52] A phosphate and tannophosphate, phosot and taphosot which had been developed by Brissonnett earlier, were found to have extremely active effects in the body. However, they also could be deleterious; the phosphates after a while started to accumulate in the system, and continuously large doses would commonly lead to insomnia, loss of flesh, weakness in the lower limbs, and paralysis. As a result, it became necessary to interrupt the administration at frequent intervals. Phosphites, phosphotal and guaicophosphal were noted — unlike phosphates — for an ability to be readily accepted and assimilated by the body. Because of that fact, they soon became seen as the better preparation for treatment.[48][53][54]

Other compounds that were developed include monotal, a methyl glycolate of guaiacol, salocreol, a salicylate of creosote, guaiacol-salol, a salicylate of guaiacol, eucol, an acetate of guaiacol, guaiachinol, a quinine dibroguaiacolate, thiocol, a guaiacol sulphonate of potassium, sulfosot, a creosote sulphate of potassium, guaiasanol, a diethylglycocoll-guaicol hydrochlorate, ichthosot, a preparation of ichtyolammonium and creosote carbonate, guaicyl, a calcium orthoguaiacol sulphonate,

Cresol, naphtha, and carbolic acid preparations

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Treatments

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Creosote-derived compounds were found in both capsules and emulsions, and administered in a variety of ways; orally, rectally, through vaporizers, inhalers and compressed air treatments, and through hypodermic and subcutaneous injections.

Because of the unpleasant taste and odor and the irritating effects on the alimentary canal, a common suggestion for oral administration would be to mix it with combinations of milk and cod liver oil or malt. Creosote would emulsify in milk, reducing its caustic effect on the mucous membrane, and the cod liver oil and malt would mask its taste and odor.[55] [48]

Commercialization (1890–1955)

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Modern derivatives (1955—)

[edit]

Notes

[edit]
  1. ^ United States Herbarium 1890, p. 521
  2. ^ Wignall 1993, p. 104
  3. ^ Foster & Johnson 2006, p. 190
  4. ^ Bostock & Alison 1832, p. 553
  5. ^ a b Mathews 2009, p. 37-38
  6. ^ Crozier 2012, p. 44
  7. ^ a b c Cormack 1836, p. 58
  8. ^ a b Parr 1809, p. 383
  9. ^ Pliny 1856, p. 8
  10. ^ Herodotus 1862, p. 119-123
  11. ^ Lucas 1931, p. 13
  12. ^ a b Radford 2003
  13. ^ Schouw 1848, p. 140-141
  14. ^ Wharton 1855, p. 522
  15. ^ Berkeley 1744, p. 9
  16. ^ Pliny 1855, p. 290
  17. ^ a b Cormack 1836, p. 52
  18. ^ Durante 1585, p. 101-104
  19. ^ Mattioli 1645, p. 101-104
  20. ^ Bradatan 2006, p. 87-92
  21. ^ Rousseau 1991, p. 145-175
  22. ^ Williams 1786, p. 54-56
  23. ^ Chemist and Druggist 1889, p. 300
  24. ^ Croker, Williams & Clarke 1766, p. 125
  25. ^ a b Cormack 1836, p. 61
  26. ^ a b Neligan 1844, p. 50-51
  27. ^ a b c Cormack 1836, p. 59
  28. ^ Christison 1832, p. 805-807
  29. ^ Vitet 1778, p. 427
  30. ^ Percy & Timbs 1829, p. 200
  31. ^ Cormack 1836, p. 64
  32. ^ Pereira 1839, p. 229
  33. ^ Davy 1839, p. 344-354
  34. ^ a b Reichenbach 1834, p. 68-69
  35. ^ Dunglison 1887, p. 207
  36. ^ a b c d King, Felter & Llyod 1905, p. 617
  37. ^ Taylor 1902, p. 207
  38. ^ Whittaker 1893, p. 77
  39. ^ Imlay 1876, p. 514
  40. ^ Dobbell 1878, p. 315
  41. ^ a b Kinnicutt 1892, p. 514
  42. ^ Contrepois 2002, p. 211
  43. ^ Kinnicutt 1892, p. 515
  44. ^ Taylor 1897, p. 364
  45. ^ Squibb 1898, p. 532
  46. ^ Coblentz 1908
  47. ^ a b Gould & Lloyd 1901, p. 305
  48. ^ a b c Turner 1900, p. 284
  49. ^ Merck & Co. 1900, p. 65
  50. ^ Bernheim 1901, p. 263 harvnb error: multiple targets (2×): CITEREFBernheim1901 (help)
  51. ^ Brown 1901, p. 504
  52. ^ The New York Lancet 1901, p. 248
  53. ^ The British Medical Journal 1907, p. 1253
  54. ^ Barbier 1908, p. 205-206
  55. ^ Merck & Co. 1900, p. 510

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Cite error: A list-defined reference named "oertel209" is not used in the content (see the help page).

References

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