« 이전계속 »
therapeutic experience of the past based the medium dose was an Opium which really contained 16 per cent. of pure morphia, or within
say per cent. of this on either side of this number—that is, 14 to 17 per cent.
Then it follows that if the new Pharmacopeia should adopt a standardized powdered Opium, which would represent the recorded therapeutic uses and doses of the drug, it should contain 14 to 17 per cent. of morphia.
In an effort to find out what strength of Opium was applied to the markets as a medicinal agent, the writer has collected the assays. of 8 lots of moist commercial Opium, all of the crop of 1879 and 1880.. These 8 lots comprise 191 cases, and the lots were severally 10, 10, 7, 5, 10, 50,29 and 70 cases. The minimum yield was 9.0 per cent. and the maximum 11.1 per cent., and the average was 10.25 per cent., tor the 191 cases. This being all old Opium, would give a minimum loss in drying and powdering for medicinal uses. Say that it would lose the minimum of 17 per cent., then the powdered Opium from this would contain 12.35 per cent. of pure niorphia. But much, if not all of this. Opium, was below the average market grade for medicinal uses, and was sold at low prices to makers of morphia salts. None of it, or at
, least very little of it, would have brought the current prices of prime Smyrna Opium, and some was so poor-looking that it would not have been sold at all without being previously assayed. Leaving out the poorest lot of 50 cases, which contained 9.6 per cent. of morphia, the average would be 10.5 per cent., or, if dried and pow. dered, the 141 cases would average not less than 12.65 per cent. And the 50 cases of 9.6 per cent. Opium, taken alone, would yield a powdered Opium of 11.6 per cent. morphia strength.
When Opium is objected to on account of its poor appearance, either in the New York market or the Custom House, the writer occasionally serves as referee. Two lots, one of 28 cases, and the other of 7 cases, gave an average for the 35 cases of 10.3 per cent., equal to 12.8 per cent. if dried and powdered. Another lot of 3 cases, very old and dry, gave an average of 12 per cent., equal to 14 per cent. if dried and powdered. Another lot of one case gave 12.7 per cent., equal to 15 per cent. it dried and powdered.
This aggregate of 230 cases of Opium fairly represents the worst Opium that is knowingly admitted into this country under the operation of the present law, which says no Opium shall come in which has less than 9 per cent. of pure morphia, and the average of the whole 230 cases is 10.29 per cent., equal to 12.45 per cent. if dried and powdered.
It was next very desirable to know the morphia strength of the better or ordinary grades of Opium, or that which is generally supplied to dispensing pharmacists, and which thus comes more within the scope of the Pharmacopeia. First the writer, and then an unkuown messenger bought "a quarter of a pound of the best powdered opium for dispensing,” from eight of the largest wholesale drug houses of Philadelphia and New York, if not the largest in the country. These eight firms probably supply the powdered Opium for prescription use and for preparations of Opium, to 75 or 80 per cent. of the pharmacists of New York, Brooklyn, Jersey City and neighboring towns and villages, or over two millions of population, to say nothing of their distributing business all over the United States. These eight samples were carefully assayed by a process, to be given hereafter, and yielded, respectively, 15.1, 14.5, 14.4, 14.3, 14.0, 13.9, 12.5 and 9.5 per cent. of pure morphia. The last sample, the 9.5 per cent., was badly adulterated with dextrine or some form of gum. And the next to the last, or the 12.5 per cent., bore the label and seal of Merck, of Darmstadt This sample also seemed to have some gummy admixture which rendered the assay process difficult and tedious; but the proportion was not larger than would be necessary to standardize a richer Opium, and it is presumed from the high character of this manufacturer that he sells a standardized powdered Opium of uniform strength. The last, 9.5 per cent, sample, had much the same appearance as that of Merck, and differed from all the others, so that it is not improbable that it was imported in powder.
As the firms who dispensed these last two samples do a much smaller business than any of the others, and as the samples are exceptional, they might be left out. But as the original design was to take the whole eight houses, they are retained in the average. This average is 13.52 per cent. of pure morphia. The writer himself supplies a considerable quantity of powdered Opium, which, if added, would not reduce the average, but which is excluded from consideration in this paper. It may be, therefore, pretty fairly represented that the powdered Opium of this market is uniformly of the same grade or kind, and that that grade does not vary more than 1 per cent. between the extremes of morphia strength, and that that strength is not far from 14 per cent. Calculating this 14 per cent. powder back to the moist condition, it indicates for the moist commercial drug, as imported, a morphia strength of 11.2 per cent. for this grade of Opium, or about :9 per cent. higher than the average
of the 230 cases of lower grade as given above, and all are well within the 9 per cent. minimum limit set by law, and the whole result is an excellent illustration of the advantages of the law, and also of the inutility of the Pharmacopæia setting a standard which is below the law, as it did both in 1860 and 1870, but which it should never again do. If the Pharmacopæia should still adhere to its low minimum, and if the law now before Congress should pass, making the Pharmacopeia its standard, this will repeal the present law, which has served so well, and will reduce the minimum to 8 per cent. instead of 9 per cent., and will place the Pharmacopeia in the undesirable position of leading downward instead of upward. Should the Pharmacopeia for 1880 adhere to the present minimum of 8 per cent.=10 per cent. for dried Opium, and should the bill to prevent adulterations, now before Congress, become a law, and thus repeal the present 9 per cent. law; and should the new Pharmacopæia adopt a standardized Opium with a standard so low as 10 per cent. , it would not only materially disturb, but would revolutionize, the preparations of Opium. The medium dose of the tincture and deodorized tincture equal to a grain of Opium is 13 minims or 25 drops; but should these preparations be made from powdered Opium of 10 per cent., this dose will be equivalent to only '11 grain of morphia, when, as above shown, the stated medium dose for the morphia in morphia salts is 16 grain, or nearly 50 per cent, more. But when these tinctures are made from the average of powdered Opiums now being supplied in the market-namely, 13.5 per cent. —their medium dose becomes •14 grain of morphia, or much more nearly equal to the authoritative dose of the morphia salts. If a powdered Opium of 14 to 14.5 per cent. be taken for these preparations, then the authoritative doses of the tinctures and of the salts of morphia approach still closer to their proper equivalency, though the morphia in the dose of tincture is still only •141 against •16. But as the other sedative alkaloids of the tinctures must be taken into account, the total sedative and anodyne effect may be estimated as high as '15 against :16. It seems plainly deducible from those considerations that the strength of powered Opium upon which the doses. of the preparations are based and adjusted is about 15 per cent., and such Opium can always be had in the general market. And not only that, but such powdered Opium is now very generally supplied, so that these tinctures containing '15 grain of morphia to the medium dose are now in very general use, and the current therapeutic practice and experience must be largely based upon this strength. A
powdered Opium of 10 per cent., if thoroughly exhausted, gives tinctures containing 3.75 grains of morphia in each fluidounce. An Opium 14.5 to 15 per cent. gives tinctures of 5.5 grains in the fluid
But in the officinal processes for these tinctures, the Opium is never quite exhausted. There is a tradition, without much authority, that laudanum should contain 4 grains of pure morphia in each fluidounce, and that is probably a good standard for laudanum that is sold for popular uses, as contradistinguished from the officinal tinctures dispensed in prescription use, yet there are great objections to having two strengths for synonymous names. In trying to solve this problem of the proper morphia strength for preparations of Opium, some twenty-two years ago, when the Pharmacopeia was silent on the subject, therapeutic experience in the equivalent doses led the writer to adopt the traditional strength of 15 to 17 per cent. for powdered Opium and 4 grains of pure morphia to the fluidounce for the liquid preparations made by him, and these latter preparations have always been made by assay, and were, therefore, always independent of the strength of Opium from which they were made. But it appears now, from more recent and more accurate knowledge on the subject, that they should be much stronger.
From these and other inferior considerations, this writer would recommend for the new Pharmacopoeia, that Opium, in its moist commercial condition, be limited to contain not less than 9 per cent., nor more than 15 per cent. of morphia by the officinal process of assay. Prof. Flückiger is of the opinion that the German Pharmacopæia should demand 10 per cent., and quotes the assays of G. della Sudda in support of his judgment.
This, in its minimum limit, would conform to and continue the present Drug Law, which has answered so well and has become so well established that it has left the lower limitations of past revisions of the Pharmacopæia without force and inoperative. For even the implied invitation to reduce the strength of imported Opiums to the officinal minimum has had no general effect.
Next, he would recommend the introduction of a new heading, and to the Pharmacopeia a new article, namely, Powdered Opium, and limit this to contain not less than 14, nor more than 18 per cent, of pure morphia by the officinal process of assay.
Few, if any, pharmacists powder their own Opium, but nearly all buy it in powder, and all know where to get good powdered Opium or poor, in accordance with their conscientiousness in their business. And while pharmacists should powder many, if not most, of their important medicinal drugs, Opium is an exception, because they would buy only a lump or two at a time, and these lumps vary so much in morphia strength that they could rarely get uniform results. Good powdered Opium can only be made by powdering an entire case or more at once. Then, if the pharmacist be authorized to buy his powdered Opium, and be supplied with a limit of strength within which to buy it, the assaying process will be put upon the wholesale dealer, who will assay a sample of each case as powdered, and from good houses the assay would soon appear upon the label of each bottle. Naturally, and in accordance with present established practice with good houses, as above shown, the morphia strength of the powders sold would be about 14 per cent., and would not exceed 15, and either of these strengths would be entirely proper for all the preparations of the Pharmacopæia. These preparations should also be limited in strength, so that when a stronger Opium was obtained less of it should be taken. The stronger Opiums are always cheaper than the weaker ones, and thus an inducement would be offered in this direction. In buying the samples of powdered Opium for the assays of this paper, the prices varied between $5.50 and $8 per pound. Taking the average percentage of morphia yielded by them, namely, 13.5 per cent., and dividing it into the average price paid, namely, $6.44 per pound, the cost of each per cent. of morphia is 47.7 cents – say 48 cents. Now, if a powdered Opium of 13.5 per cent. costs $6.44 per lb., a 15 per cent. Opium would be cheaper at any price less than (6.44+72=) $7.16, while a 17 per cent powdered Opium would, upon the same basis, be worth $8.12. The higher grades of moist Opium which are imported into this market, such as Boghaditch, Yerli, Salonica, etc., are usually sold at perhaps 50 cents to $1 more per pound than the ordinary grades of prime Smyrna Opium. Yet they yield a powder which rarely falls below 16.5 per cent. and occasionally reaches 18 per cent.
Hence the wholesale dealers who should buy these grades for powdering, and sell their powder by assay, would more than double their profits at relative morphia cost prices. If the Pharmacopoeia should lead in such a direction, these considerations would soon come into practical effect.
The chief objections to an arbitrary standardized Opium, apart from the great difficulty of deciding upon an arbitrary standard, is first to know who is to standardize it. To be done effectively the wholesale dealer would have to do it, or the manufacturer of pharmaceutical preparations. And unless there was a good profit in it they would not be likely to do it, but would much prefer to