Morphine extraction

Morphine is the major alkaloid in opium, the dried latex obtained from the opium poppy, Papaver somniferum. About 25% of the mass of opium is composed of alkaloids, with morphine constituting about 12-15%. Morphine is a powerful analgesic, and remains one of the most valuable for relief of severe pain. However, most of the morphine extracted from opium is processed further to give a range of semi-synthetic drugs, with enhanced or improved properties. A means of extracting morphine from the other alkaloids in opium is thus desirable. 

Poppy cultivation and opium processing also have consequences for the environment. Waste from morphine extraction can cause environmental damage when dumped by processors. In addition to water pollution from this chemical dumping, other environmental concerns include the deforestation that may occur when clearing land for poppy cultivation, soil erosion, and dangers to wildlife in the area where these chemicals are dumped. 

Temazepam and morphine have been separated from a whole blood matrix using SC CO2. In the first instance, the extractants were CO2 and ethyl acetate at 65°C and 207 bar, and recoveries ranged from 80% to 100%. The extraction was monitored at 254 nm, with individual separation of the analytes carried out by high-performance liquid chromatography (HPLC). For morphine extraction from dried blood, methanol/triethylamine was added as a modifier to 90% CO2 at 100°C and 241 bar, and the extracts were analyzed by GC-MS. The SFE method proved to be faster and cleaner than solid-phase extraction (SPE). 

C morphine to correct for extractive losses. Morphine conjugates were hydrolyzed by B-gluc-uronidase and morphine extracted with ether. Nalorphine was used as an internal standard and... 

MORPHINE EXTRACTION FROM POPPY STRAW The production of opium is, as is evident from the description above, a method that is very labour intensive. Therefore methods have been developed to extract morphine directly... 

Analysis of a number of herbal extracts has identified chemicals later shown to have true antitussive actions in experimental animals and sometimes in humans. To conclude that the herb itself is a remedy for cough is clearly unjustifiable on fhis evidence, allhough if is a reasonable hypothesis that could be tested. To give an example, pure opioids such as morphine extracted from poppy (Papiver somniferum) are established antimssives in animals and humans, but there seems to be no evidence that nonpurified extracts of the plant, as would be used in herbal medicine, are also effective if they were, they could be working by a placebo effect. 

Papaverine usually occurs to the extent of 0.5 to 1 % in opium (1) and was isolated from the mother liquors of the morphine extraction in 1848 (2). It is found in all parts of Papaver somniferum L. (var. album), especially in... 

The last alkaloid to separate from the mother liquors of the morphine extraction, laudanosine was isolated from opium in small amounts by Hesse (4, 74) in 1871. Opium contains less than 0.1 % of this compound. 

The Opiates. The International Narcotics Control Board—Vienna, tracks the tick production of narcotic dmgs and annually estimates world requkements for the United Nations. Thek most recent pubHcation (100) points out that more than 95% of the opium for Hcit medical and scientific purposes is produced by India and, in a declining trend, only about 600 t was utilized in 1988. This trend appears to be due to the fact that the United States, the largest user of opium for alkaloid extraction, reduced the amount of opium being imported from about 440 t in 1986 to 249 t in 1987 and 224 t in 1988. The United States used about 48 t of morphine (2, R = H) in 1988, most (about 90%) being converted to codeine (2, R = CH3) and the remainder being used for oral adrninistration to the terminally ill (about 2 t) and for conversion to other materials of minor commercial import which, while clearly alkaloid-derived, are not naturally occurring. 

Evidence soon emerged that the endogenous opioids were peptides rather than simple morphine-like molecules (9). The first direct evidence for endogenous opioids in brain extracts was provided in 1975 when two pentapeptides were purified that differed only in the carboxyl terminal amino acids (10) (Table 1). These peptides were called methionine- (Met-) and leucine- (Leu-) enkephalin, from the Greek term meaning "in the head."... 

Replacing one carbon atom of naphthalene with an a2omethene linkage creates the isomeric heterocycles 1- and 2-a2anaphthalene. Better known by their trivial names quinoline [91-22-5] (1) and isoquinoline [119-65-3] (2), these compounds have been the subject of extensive investigation since their extraction from coal tar in the nineteenth century. The variety of studies cover fields as diverse as molecular orbital theory and corrosion prevention. There is also a vast patent Hterature. The best assurance of continuing interest is the frequency with which quinoline and isoquinoline stmctures occur in alkaloids (qv) and pharmaceuticals (qv), for example, quinine [130-95-0] and morphine [57-27-2] (see Alkaloids). 

More interesting, as regards future developments, are the eiforts now being made to dispense with opium as an intermediate in the production of morphine. The early history of experiments in the direct extraction of the alkaloid from poppy capsules and poppy straw has been recounted by Goris and by Wiiest and Frey. ... 

Estimation of Morphine in Opium. The problem of determining with reasonable accuracy the percentage of morphine in opium is of importance for the standardisation of medicinal opium, as a means of fixing the price of crude opium, and of controlling factory operations in the extraction of... 

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. ... 

Papaverine, C20H21O4N. This alkaloid, first obtained by Merck, occurs in the mixture precipitated by ammonia from the mother liquors of opium extract from which morphine and codeine have been separated in Gregory s process, and methods for its isolation from this mixture have been published by Hesse and others. The alkaloid may be purified by conversion into the acid oxalate, B. H2C2O4, m.p. 196° or 201-5-202°, which is nearly insoluble in alcohol. 

Alkaloids such as caffeine, coniine, and morphine (Figure A) are amines that are extracted from plants. 

Caffeine occurs in tea leaves, coffee beans, and cola nuts. Morphine is obtained from unripe opium poppy seed pods. Coniine, extracted from hemlock, is the alkaloid that killed Socrates. Fie was sentenced to death because of unconventional teaching methods teacher evaluations had teeth in them in ancient Greece. 

Erythromycin is extracted by an organic solvent such as pentyl acetate. Similarly, steroids, vitamin B12, morphine and codeine are extracted with organic solvents. 

Opium is an extract of the juice of the poppy Papaver somnifemm, which contains more than 20 distinct alkaloids, including morphine, codeine and papaverine. 

Morphine, when extracted from raw opium and treated chemically, yields the semisynthetic narcotics hydromorphone, oxymorphone, oxycodone, and heroin. Heroin is an illegal narcotic in the United States and is not used in medicine. Synthetic narcotics are those man-made analgesics with properties and actions similar to the natural opioids. Examples of synthetic narcotic analgesics are methadone, levorphanol, remifen-tanil, and meperidine Additional narcotics are listed in the Summary Drug Table Narcotic Analgesics. 

The profound physiological effects of alkaloids have been known for centuries. For example, Socrates was put to death with an extract of hemlock, which contains a poisonous alkaloid, coniine. Other alkaloids have long been valued for their beneficial medical effects. Examples include morphine (a painkiller), quinine (used to treat malaria), and atropine (used to treat Parkinson s disease and in eye drops that dilate the pupils). 

Because of their basic properties, aikaioids were among the first naturai substances that eariy chemists extracted and purified. Morphine was isoiated from poppies in 1805 and was the first aikaioid to be characterized. When treated with aqueous strong acid, aikaioids accept protons to produce water-soiubie cations. The protonated aikaioids dissoive, ieaving the rest of the piant materiais behind. Adding strong base to the aqueous extract reverses the proton-transfer reaction, converts the aikaioid back to its neutrai base form, and causes pure aikaioid to precipitate from the soiution ... 

The oxidation of morphine by whole-cell suspensions and cell extracts of Cylindrocarpon didymum gave rise to the formation of 2,2 -bimorphine (for structure, see Fig. 6). The identity of 2,2 -bimorphine was confirmed by clas-... 

Fig. 3.4 Permeability profiles for (a) warfarin (acid), (b) propranolol (base) and (c) morphine (ampholyte) based on a BBB PAMPA model (plON) composed of animal brain extract of lipids. The data (unpublished) were analyzed with the pCEL-X program (plON), with the refined parameters indicated in the three frames. In all three cases, there was evidence for the permeation of charged...

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