Opium extracts, preparation

The first series of compounds assayed directly by CD detection were the morphine alkaloids. They were supported in aqueous solutions, in a chiral cholesteric liquid crystal solvent, and mixed in pellet form with solid KBr. ° Contrary to expectations, the homogeneous aqueous solution medium gave the best selectivity among 10 related opiates and the most quantitative results. The pH-dependence of phenol substituted analogs, which in some instances caused the sign of the CD signal to invert, enhanced the selectivity. Heroin was assayed both directly and as the morphine hydroly-sate.f Direct multicomponent analyses were made for prepared mixtures of morphine, codeine, thebaine, noscapine, and opium extracts. ... 

Codeine may be isolated from opium by the Gregory process [9], in which the concentrated aqueous opium extract is treated with a concentrated solution of calcium chloride, when calcium meconate, lactate, and sulphate are precipitated and removed, when the filtrate on concentration deposits the Gregory salt , a mixture of the hydrochlorides of morphine and codeine. This is purified, dissolved in water, and the morphine precipitated by ammonia, when the codeine remains in solution from which it is extracted by benzene, or the solution concentrated to the point at which a mixture of codeine hydrochloride and ammonium chloride separates. Other procedures for the isolation of codeine are available [7, 8, 10-22 inc.], critical summaries of which are given by Kanewskaja [23] and Barbier [24], Codeine may be separated from neopine (see Chap. VII) through the sulphate [25] and from morphine by chromatography [26-29]. Most of the codeine used commercially is prepared by the methylation of morphine (see below). 

Preparation of Opium Extracts. 200mg of finally powdered opium is triturated to a paste in a glass mortar and pestled with 0.5 ml methanol and 0.5 ml concentrated ammonium hydroxide solution. Then 3g of aluminum oxide is added and the trituration continued until a homogeneous free-flowing powder is obtained. The triturate is then transferred quantitatively to a chromatographic column (30 x 1cm). The alkaloids are eluted with 80 ml of a mixture of chloroform-isopropyl alcohol (3 1). The rate of flow is adjusted to about one drop per second. The eluate is finally concentrated almost to dryness under vacuum and then transferred to a small vial to evaporate to dryness in a stream of nitrogen to obtain the opium extract. 

The processes used in the manufacture of morphine are believed to be still based on that described by the Scottish chemist Gregory,in 1833, with improvements devised by Anderson. A description has been published by Schwyzer, who also deals with the manufactme of codeine, narcotine, cotarnine, and the commercially important morphine derivatives, diamorphine (diacetylmorphine), and ethylmorphine (morphine ethyl ether). More recently Barbier has given an account of processes, based on long experience in the preparation of alkaloids from opium. Kanewskaja has described a process for morphine, narcotine, codeine, thebaine and papaverine, and the same bases are dealt with by Chemnitius, with the addition of narceine, by Busse and Busse, and by Dott. It is of interest to note that a number of processes for the extraction and separation of opium alkaloids have been protected by patent in Soviet Russia. ... 

While morphine as a component of opium has been in use for centuries and the first synthetic opioid, pethidin, was prepared as early as 1939, opioid peptides, the endogenous pentapeptides Met- and Leu-enkephalin (YGGFM and YGGFL), were identified in brain extracts only in 1975 by Kosterlitz and Waterfield (Hughes et al., 1975 also see Cox et al., 1975 Hughes, 1975 Lord et al., 1977). 

Preparation Codeine is extracted from opium (present in... 

Preparation By extraction of poppy capsules or opium (opium contains 9-14 % morphine depending on the source) with water, precipitation with aqueous Na2C03 solution, washing of the precipitate with ethanol and dissolution in dilute acetic acid (Horner et al. (Knoll), 1977, Trauner et al.,1983, Hudlicky et al.,1996). 

Codeine is the methylic ether of morphine (3-methylmorphine) and can be isolated from opium during the extraction of morphine, but is usually prepared by the methylation of morphine. Codeine is used in medicine as an antitussive drug and furthermore it has analgesic properties. It may cause addiction, but less than morphine. 

In the process of preparing a tincture, some pharmacologically active constituents of the plant are extracted by the alcohol. Although not all substances are soluble in alcohol, those that are include the alkaloids. In the case of a tincture of raw opium, the soluble alkaloids include morphine, codeine, noscapine, and papavarine. Such tinctures of opium were the infamous laudanum preparations of the late 1800s (see Appendix). 

Paracelsus abandoned all this witchcraft and superstition. He started the search for the potent drugs which the alchemist was to prepare or purify. Even the many herbs and extracts in common medical use were placed secondary to the value of these chemicals. There were many who gave ear to his instructions They went back to their laboratories, threw away the crucibles filled with the strange concoctions that would not change to gold, and sought medicines to relieve human suffering. Paracelsus himself showed the way. He experimented in his laboratory, and introduced into medicine salves made from the salts of mercury. He was the first to use tincture of opium, named by him laudanum, in the treatment of disease. The present pharmacopoeia includes much that Paracelsus employed —lead compounds, iron and zinc salts, arsenic preparations for skin diseases, milk of sulfur, blue vitriol, and other chemicals. 

In order to extract the morphine, the opium resin must first be prepared. This is achieved by adding the raw opium to boiling water, in which the alkaloids dissolve, while the insoluble material can be removed while it floats, or is filtered from the solution. To extract the morphine from the processed opium, the latter is placed in a large volume of boiling water and calcium hydroxide added. The water is cooled and the unwanted alkaloids precipitate, while the morphine and some codeine remain in solution. The solution is then re-heated and ammonium chloride (and sometimes ethanol and diethyl ether) added. When the pH reaches 8-9, the... 

A similar solvent system was also used by Rasmussen et al.51 for the analysis of morphine in organic poppy extracts (Fig. 7.13). The extracts could be analyzed without any purification prior to HPLC analysis. Gimet and Filloux performed analyses on alkaloids -including opium alkaloids - in pharmaceutical preparations, and used a microparticulate silica gel column and diethyl ether or diethyl ether saturated with water as mobile phase. In both cases 0.4% diethylamine was added to the mobile phase (Fig. 7.14). An increase... 

The first controversy is to know who discovered morphine. Jean-Francois Derosne, in Paris, prepared a crude extract of opium (with alcohol and water), and obtained, after potassium carbonate precipitation, what he called sel... 

Crude opium is used as the starting material for the extraction of morphine (of which 80% is methylated to codeine), codeine and noscapine. Opium, according to the pharmacopoeia, is used for the preparation of opium tincture, which is an excellent remedy for the treatment of tropical diarrhoea. 

Codeine is nsed in medicine for its narcotic analgesic action. It is used as a sedative in cough mixtures. Codeine occurs in opium from 0.7% to 2.5%. It is prepared from morphine by methylating the phenolic —OH group of the morphine. It is also obtained by extraction of opinm. 

The commercial preparation of morphine takes place from opium and from poppy straw at approximately equal proportions. [72] Since 1960, the production of thebeine has gained growing significance, due to an increased demand for semi-synthetic opiates. This is generated from opium like morphine, codeine and papaverine. The key step is removal of the crude morphine with tartaric acid. The various alkaloids are subsequently separated by fractional crystallisation and extraction (Fig. 5.53). 

In 1834, codeine was isolated from opium by Pierre Jean Robiquet (1780-1840). One year later, Pierre-Joseph Pelletier (1788-1842) and M. Thiboumery discovered thebaine (named after the ancient Egyptian city of Thebes). In 1848, at the University of Giessen, papaverine was extracted from poppy waste by Georg Merck (1825-1873), the son of Heinrich Emanuel Merck. In 1870, Augustus Matthiessen (1831-1870) and Charles R. A. Wright (1844-1894) recognised that codeine is the monomethyl ether of morphine. After the selective methylation of morphine for the preparation of codeine had failed, Felix Hoffmann (1868-1946) tried out in 1897 a selective acetylation, in analogy to the synthesis of aspirin from salicylic acid. [91]... 

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