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Albendazole also kills neurocystcerci when given daily for one month; a cortcosteroid or an anthistamine is also given to reduce any infammatory reacton effective deltasone 5mg allergy forecast waukesha wi. Intestnal Nematode Infectons: Intestnal nematode infectons include ascariasis cheap deltasone 40mg line allergy like symptoms, capillariasis purchase 10mg deltasone with visa allergy omega 3 symptoms, enterobiasis cheap deltasone 40 mg without prescription allergy medicine kellymom, hookworm infecton, strongyloidiasis, trichos- trongyliasis and trichuriasis. Ascariasis: Ascariasis is an infecton, usually of the small intestne, caused by Ascaris lumbricoides (roundworm). Single doses of levami- sole or pyrantel are efectve; the broad-spectrum anthelmin- thics, albendazole or mebendazole are also efectve. Capillariasis: Capillariasis is caused by infecton of the intestne with Capil- laria philippinensis. Prolonged treatment with mebendazole or albendazole ofers the only prospect of cure. Enterobiasis: Enterobiasis is an infecton of the large intestne caused by Enterobius vermicularis (pinworm, threadworm). All household members should be treated concurrently with a single dose of mebendazole, albendazole or pyrantel. Since reinfecton readily occurs, at least one further dose should be given 2-4 weeks later. Piperazine is also efectve but must be taken regularly for at least 7 consecutve days. Hookworm Infectons: Hookworm infectons are caused by Ancylostoma duodenale (ancylostomiasis) and Necator americanus (necatoriasis); they are a major cause of iron-defciency anaemia in the tropics and sub-tropics. In hookworm, broad-spectrum anthelminthics are preferred wherever other nematode infectons are endemic. There is some evidence to suggest that the use of mebendazole in pregnancy is not associated with an increased incidence of adverse efects on the fetus. However, neither mebendazole nor albendazole should be used during the frst trimester of pregnancy to treat nema- tode infectons. Both drugs are contraindicated for the treat- ment of cestode infectons in pregnancy. Levamisole is efectve in the treatment of mixed Ascaris and hookworm infectons and pyrantel has been highly efectve in some community-based control programmes, although several doses are ofen needed to eliminate Necator ameri- canus infecton. Patents with iron-defciency anaemia caused by hookworm infecton require supplementary iron salts and should receive ferrous sulphate (200 mg daily for adults) for at least 3 months afer the haemoglobin concentraton of 12g/100 ml is obtained. Strongyloidiasis: Strongyloidiasis is an infecton of the small intestne caused by Strongyloides stercoralis. Ivermectn in a single dose of 200 µg/kg or 200 µg/ kg/day on two consecutve days is the treatment of choice for chronic strongyloidiasis but it may not be available in all coun- tries. Albendazole 400 mg once or twice daily for 3 days is well tolerated by both adults and children aged over 2 years and it may eradicate up to 80% of infectons. Mebendazole has also been used but, to be efectve, it must be administered for longer periods as it has a limited efect on larvae and hence the preventon of autoinfecton. Trichostrongyliasis: Trichostrongyliasis is an infecton of the small intestne caused by Trichostrongylus spp. In symptomatc trichostrongyliasis, a single dose of pyrantel (10 mg/kg) or albendazole (400 mg) is efectve. Trichuriasis: Trichuriasis is an infecton of the large intestne caused by Trichuris trichiura (whipworm). Chemotherapy is required whenever symptoms develop or when faecal samples are found to be heavily contaminated (up to 10,000 eggs per gram). Tissue Nematode Infectons: Tissue nematode infectons include angiostrongyliasis, anisaki- asis, cutaneous larva migrans, dracunculiasis, trichinellosis and visceral larva migrans. Angiostrongyliasis: Angiostrongyliasis is caused by infecton with the larvae of the rat lungworm, Parastrongylus cantonensis (Angiostrongylus cantonensis). Anisakiasis: Anisakiasis is caused by infecton with seafood containing larvae of Anisakis, Contracaecum or Pseudoterranova spp. Preventon is dependent upon informing communites of the hazards of eatng raw or inadequately prepared salt-water fsh; and early evisceraton of fsh afer capture and freezing of seafood at -20⁰C for at least 60 h before sale. Cutaneous Larva Migrans: Cutaneous larva migrans (creeping erupton) is caused by infecton with larvae of animal hookworms, usually Ancylos- toma braziliense and A. Dracunculiasis: Dracunculiasis (dracontasis, guinea-worm infecton) is caused by infecton with Dracunculus medinensis, acquired through drinking water containing larvae that develop in small fresh- water crustaceans. It also weakens the anchorage of the worms in the subcutaneous tssues and they can then be removed by tracton. However, since it has no efect on the larvae of pre-emergent worms, it does not immediately prevent trans- mission. Trichinellosis: Trichinellosis (trichinosis) is caused by infecton with the larvae of Trichinella spiralis. Each case of confrmed or even suspected trichinellosis infecton should be treated in order to prevent the contnued producton of larvae. In both adults and children, mebendazole (200 mg daily for 5 days), albenda- zole (400 mg daily for 3 days) and pyrantel (10 mg/kg daily for 5 days) are all efectve. Prednisolone (40-60 mg daily) may be needed to alleviate the allergic and infammatory symptoms. Visceral Larva Migrans: Visceral larva migrans (toxocariasis) is caused by infecton with the larval forms of Toxocara canis and less commonly, T. A 3 week oral course of diethyl- carbamazine kills the larvae and arrests the disease, but established lesions are irreversible. To reduce the intensity of allergic reactons induced by dying larvae, dosage is commonly commenced at 1 mg/kg twice daily and raised progressively to 3 mg/kg twice daily (adults and children). Ocular larva migrans occurs when larvae invade the eye, causing a granuloma which may result in blindness. In order to suppress allergic infammatory responses in patents with ophthalmic lesions, prednisolone should be administered concurrently, either topically or systemically. Albendazole* Pregnancy Category-C Schedule H Indicatons Echinococcus multlocularis and E. Hydatd disease: 400 mg twice daily with meals for 28 days (therapy may be repeated afer 14 days in three cycles). Contraindicatons Pregnancy, adequate measures must be taken for non-hormonal contraceptve during and one month afer therapy; hypersensitvity. Precautons Pregnancy (see notes above and Appendix 7c); liver impairment, increased intracranial pressure; seizures; monitor blood count and liver functon. Mebendazole Pregnancy Category-C Schedule H Indicatons Echinococcus granulosus and E. Precautons Pregnancy (Appendix 7c; see also notes above); lactaton; interactons (Appendix 6c, 6d); expulsion of ascaris from mouth or nose; monitor blood count or hepatc functon. Adverse Efects Gastrointestnal disturbances; headache and dizziness; adverse efects associated with use in cestode infectons; abdominal pain, diarrhoea; rashes, urtcaria, angioedema. Precautons Chronic constpaton (restore regular bowel movement before treatment); give antemetc before treatment; not efectve against larval worms; pregnancy (Appendix 7c). Adverse Efects Nausea; retching; abdominal pain; lightheadedness; pruritus; anorexia, emesis, perianal itching. Pyrantel Pamoate Pregnancy Category-C Schedule H Indicatons Ascariasis; hookworm infectons; enterobiasis; trichostrongyliasis; tssue nematode infecton. Dose Oral 11 mg/kg (max 1g) in a single dose (given for 2 consecutve days in case of heavy hookworm infestaton). Precautons Pregnancy (Appendix 7c; lactaton; liver disease (reduce dose); severe malnutriton, anaemia, concurrent administraton with piperazine. Adverse Efects Mild gastrointestnal disturbances; headache; dizziness; drowsiness; insomnia; rash and elevated liver enzymes.
The similarity valid cheap 20 mg deltasone allergy symptoms to ky jelly, the assumed change must continue to apply through of the estimated curves among the batches tested should the estimated expiration dating period cheap 10mg deltasone with mastercard allergy medicine otc. Thus order 5mg deltasone allergy medicine and decongestant, an expiration be assessed by applying statistical tests of the equality of dating period granted on the basis of extrapolation should slopes and of zero time intercepts order 20mg deltasone free shipping allergy shots for hives. The level of signiﬁ- always be veriﬁed by actual stability data as soon as these cance of the tests, expressed in the P value, should be data become available. Computation of Expiration Date equality of intercepts do not result in rejection at a level of signiﬁcance of. The data generated in If the preliminary statistical test rejects the hypothesis support of the assigned expiration dating period should be of batch similarity because of unequal initial intercept val- from long-term studies under the storage conditions rec- ues, it may still be possible to establish that the lines are ommended in the labeling. If so, the data may only a month and year, the product should meet speciﬁ- be combined for the purpose of estimating the common cations through the last day of the month. E, the initial values and the common slope using appropriate should support at least a 1-year expiration dating period. If data from several batches are Exceptions do exist, for example, with short half-life combined, as many batches as feasible should be combined radioactive drug products. Extension of Expiration Dating Period expiration dating period will depend on the minimum time An extension of the expiration dating period based on full a batch may be expected to remain within acceptable limits. The expiration dating period may be extended The statistical methods for determining an expiration dating in an annual report only if the criteria set forth in the period beyond the observed range of time points are the approved stability protocol are met in obtaining and ana- same as for determining an expiration dating period within lyzing data, including statistical analysis if appropriate. To approval, it is feasible to extend the tentative expiration extend the retest period, full long-term data from a formal dating period based on full long-term data obtained from stability study on three production batches using a proto- these batches in accordance with the approved protocol, col approved in an application or found acceptable in a including statistical analysis if appropriate, through a Prior drug master ﬁle should be provided. However, the expiration dating Similar to the extension of an expiration dating period period thus derived remains tentative until conﬁrmed with for a drug product, a retest period for a drug substance full long-term data from at least three production batches. This can be achieved through an annual a Prior Approval Supplement before the change is made, report based on full long-term stability data (i. If the data are obtained under a a drug substance, it may be inappropriate to use a retest new or revised stability protocol, a Prior Approval Sup- date. Shortening of Expiration Dating Period When warranted, a previously approved expiration dating period may be shortened via a Changes Being Effected 3. The Intermediates supplemental application should provide pertinent infor- Intermediates such as blends, triturates, cores, extended- mation and the data that led to the shortening of the expi- release beads, or pellets may be held for up to 30 days ration dating period. The expiration dating period should from their date of production without being retested before be shortened to the nearest available real-time long-term use. An intermediate that is held for longer than 30 days test point where the product meets acceptance criteria. The should be monitored for stability under controlled, long- expiration dating period thus derived should be applied to term storage conditions for the length of the holding all subsequent production batches and may not be extended period. In addition, the ﬁrst production batch of the ﬁn- until the cause for the shortening is fully investigated, the ished drug product manufactured with such an intermedi- problem is resolved, and satisfactory stability data become ate should be monitored on long-term stability. When pre- available on at least three new production batches to cover vious testing of an intermediate or the related drug product the desired expiration dating period and are submitted in batches indicates that an intermediate may not be stable a Changes Being Effected Supplement. The frequency of testing of an intermediate’s stability A retest period for a drug substance may be established on is related to the length of the holding time. Where prac- the basis of the available data from long-term stability tical, testing should be done at a minimum of three time studies and, as such, can be longer than 24 months if sup- points after the initial testing of an intermediate. A retest date should be placed on the storage minimum, all critical parameters should be evaluated at container and on the shipping container for a bulk drug release of an intermediate and immediately before its use substance. A drug substance batch may be used without in the manufacture of the ﬁnished drug product. However, beyond In the event that the holding time for an intermediate the approved retest period, any remaining portion of the has not been qualiﬁed by appropriate stability evaluations, batch should be retested immediately before use. Retest of the expiration date assigned to the related ﬁnished drug different portions of the same batch for use at different product batch should be computed from the quality control times as needed is acceptable, provided that the batch has release date of the intermediate if this date does not exceed been stored under the deﬁned conditions, the test methods 30 days from the date of production of the intermediate. The purpose 30 days from the date that the intermediate is introduced of retest is to qualify a speciﬁc batch of a drug substance into the manufacture of the ﬁnished drug product. General weight of the dosage unit remains constant, bracketing The use of reduced stability testing, such as a bracketing may not be applicable unless justiﬁed. Such justiﬁcation design, may be a suitable alternative to a full testing pro- may include a demonstration of comparable stability pro- gram where the drug is available in multiple sizes or ﬁle among the different strengths based on data obtained strengths. This section discusses the types of products and from clinical and development batches, primary stability submissions to which a bracketing design is applicable batches, or production batches in support of primary sta- and the types of factors that can be bracketed. With this approach, the formulations should be identical or very closely related, and the container and closure system 2. Applicability should be the same between the supportive batches and The factors that may be bracketed in a stability study are the batches for which the bracketing design is intended. If the formulation is signiﬁcantly different among the The types of drug products and the types of submissions to different strengths (e. Types of Drug Product Because of the complexity in product formulation, Bracketing design is applicable to most types of drug applicants are advised to consult the appropriate chemistry products, including immediate- and modiﬁed-release oral review team in advance when questions arise in the above solids, liquids, semisolids, and injectables. In the case in which the strength and the container delivery systems, may not be amenable to, or may need or ﬁll size of a drug product both vary, bracketing design additional justiﬁcation for, bracketing design. Types of Submissions Where a range of container ﬁll sizes for a drug product A bracketing design may be used for primary stability of the same strength is to be evaluated, bracketing design batches in an original application, postapproval commit- may be applicable if the material and composition of the ment batches, annual batches, or batches intended to sup- container and the type of closure are the same throughout port supplemental changes. Such justiﬁcation should demonstrate that the batches, commitment batches, or production batches. Bracketing protocols to be applied to postap- in the same container and closure (with identical material proval commitment batches and annual batches, if pro- and size) is to be tested, bracketing design may be appli- posed, will be approved as part of the original application. If the weights of a common granulation, or a capsule range made new bracketing design is used to generate stability data to by ﬁlling different plug ﬁll weights of the same compo- support two different chemistry, manufacturing, or controls sition into different-size capsule shells. The phrase “very changes, the two proposed changes could be combined into closely related formulation” means a range of strengths one Prior Approval Supplement even though the latter may with a similar, but not identical, basic composition such otherwise qualify for a Changes Being Effected Supplement that the ratio of active ingredient to excipients remains or annual report under 314. In addition, ies, and subsequently submit the data to support the pro- data variability and product stability, as demonstrated posed change through the appropriate ﬁling mechanism. Physician Matrixing design is applicable to most types of drug prod- samples or bulk pharmacy packs intended to be repack- ucts, including immediate- and modiﬁed-release oral sol- aged should be excluded from the bracketing protocol for ids, liquids, semisolids, and injectables. Where a large number ery systems may not be amenable to, or may need addi- (for example, four or more) of sizes or strengths is tional justiﬁcation for, matrixing design. Factors diates or three batches of the middle size or strength in the bracketing design is recommended. Where the ultimate Some of the factors that can be matrixed include batches, commercial sizes or strengths differ from those bracketed strengths with identical formulation, container sizes, ﬁll in the original application, a commitment should be made sizes, and intermediate time points. With justiﬁcation, to place the ﬁrst production batches of the appropriate additional factors that can be matrixed include strengths extremes on the stability study postapproval. Such differ- with closely related formulation, container and closure ences should, however, be justiﬁed. Where additional jus- suppliers, container and closure systems, orientations of tiﬁcation for the bracketing design is needed in the original container during storage, drug substance manufacturing application, one or more of the ﬁrst production batches of sites, and drug product manufacturing sites. Data evaluation including open-dish experiments) and to be so stable that the protective nature of the container and closure system The stability data obtained under a bracketing protocol made little or no difference in the product stability should be subjected to the same type of statistical analysis (through supportive data). The same principle and pro- onstrated, if appropriate, that there is no difference in the cedure on poolability should be applied (i. If the statistical assess- ensure that the matrixing protocol would lead to a suc- ments of the extremes are found to be dissimilar, the cessful prediction of the expiration dating period when intermediate sizes or strengths should be considered to be two otherwise different container and closure systems are no more stable than the least stable extreme. General excipients or different active and excipient ratios), and The use of reduced stability testing, such as a matrixing storage conditions. Data Variability and Product Stability gram where multiple factors involved in the product are being evaluated. This section provides further guid- batches depends on the product stability and data variabil- ance on when it is appropriate to use matrixing and how ity demonstrated through clinical or developmental batches. Applicability It is assumed that there is very little variability in the The types of drug products and the types of submissions analytical methods used in the testing of stability samples. The factors that can be indicate that the product exhibits excellent stability with 48 Handbook of Pharmaceutical Manufacturing Formulations: Semisolid Products very small variability.
The committee recognizes that many poor-quality medicines also in- fringe on registered trademarks buy 5mg deltasone allergy testing list. At times discount deltasone 10 mg without prescription allergy treatment guidelines, trademark infringement can become a public health problem 10 mg deltasone allergy medicine 9\/3, but it is not a public health problem in itself generic 5mg deltasone visa best allergy medicine for 5 yr old, even insomuch as it pertains to medicines. Competing Meanings of the Term Counterfeit The contentious history of drug patent and trademark enforcement col- ors discussions of drug quality, particularly the use of the term counterfeit. Nevertheless, the word counterfeit, like material and harmless, means one thing to lawyers and judges and something else in common discourse. Its proponents rightly observe that this is what most people understand the word to mean anyway. This defnition has at its center the effort to distinguish between deliberate and accidental problems. The manufacturer is not to blame if a drug is sold after the expiry date or if it has been kept in conditions that encourage rapid degradation. The 2008 contamination of Baxter heparin was a reminder that even expert companies sometimes pro- duce bad products, but the failure was not intentional (Attaran and Bate, 2010). The regulatory system typically punishes such mistakes, whereas the law enforcement system punishes intentional crimes. In practice, however, it is extremely diffcult to distinguish accidental Copyright © National Academy of Sciences. Making the distinction, like determining trademark infringement, is a matter for the courts. Further- more, competing meanings of the word counterfeit—one narrow, meaning infringement on a registered trademark, and one broad, meaning intention- ally deceptive—frustrate many. Generics companies may be vulnerable to accusations of trademark infringement or even deception. When a generic and an innovator drug company market bioequivalent medicines under similar-sounding names or with similar-looking pills, it is debatable whether or not these characteristics are copied or made with an intention to deceive the consumer. Counterfeit is a word that almost everyone uses to talk about bad medicines, but as Tables 1-1 and 1-2 indicate, often with widely divergent meanings. The use of the word counterfeit to describe any poor-quality drug does not serve the cause of intellectual precision or pro- ductive discussion. The committee accepts the narrow, legal meaning of a counterfeit drug as one that infringes on a registered trademark. Trademark infringement is not a problem of public health concern, nor, in most cases, is it even readily identifable. Drug companies, both innovator and generic, have the legal right to challenge counterfeiting; sorting out the nuances of trademark infringement should be left to the courts. This report is about drug quality as a public health problem; it is not concerned with trademark infringement. Therefore, this report does not discuss the problem or solutions to the problem of drug counterfeiting, or make mention to counterfeit drugs, except in cases where to do otherwise would be a misrepresentation of someone else’s work. Scientifc literature and public health campaigns, especially those more than 2 or 3 years old, often describe poor-quality drugs as counterfeit. The committee hopes that all parties will break this habit but believes that most speakers who use the term use it broadly with no ulterior motives or ill will toward generics. There is consensus among most organizations that substandard drugs are those that fail to meet established quality specifcations. When regu- lators approve a drug, they approve a quality standard, outlined in the accepted pharmacopeia or in the manufacturer’s approved dossier. As Table 1-3 indicates, the emphasis on national standards is a rela- tively recent change to the defnition of a substandard drug. Before 2009, the emphasis was on an offcial pharmacopeia, not the national standard. Critics of the addition point out that the regulatory authority is responsible for approving national drug standards, a job that exceeds its capacity in many low- and middle-income countries (Ravinetto et al. Accept- ing the national standard might appear to endorse multiple, possibly inad- equate standards (Ravinetto et al. On the other hand, an emphasis on national standards improves the precision of the defnition. There are many internationally accepted phar- macopeias; some give, for example, different acceptable ranges for drug concentration. It is more practical to let the national regula- tory authority name the standard for a drug and test against that standard. In any case, most countries use standards set out in the large, international pharmacopeias. The regu- latory agency can then take corrective action with the manufacturer and recall other products from the same batch. During this process, the manu- facturer may prove with verifed records and batch samples that the poor- 4 For amodiaquine hydrochloride tablets, the acceptable drug concentration range under U. The committee considers a drug falsifed when there is false represen- tation of the product’s identity or source or both. The producer’s intention is theoretically important to the understanding of a falsifed drug, though in practice it is often impossible to known what these intentions were. That is, when a licensed manufacturer makes bad drugs, the deliberateness of the mistake is at least debatable. When an underground producer makes a bad-quality product there is not even a pretense of adhering to drug quality standards. Manufactur- ers may produce substandard drugs because they failed to adhere to good manufacturing practices or because their internal quality systems failed. Degraded or expired products are also substandard; in some ways, failure to pull these drugs from the market is a quality system failure. Inspection of the manufacturer’s records can usually distinguish between a degraded or expired drug and one that left the factory already outside of specifcations. Drug regulators have no authority over underground manufacturers; nothing can be said about The Indian generics house V. It is unlikely, though not unheard of, that an illegal manufacturer would go to the trouble of making a quality-controlled medicine from quality-assured substrate. Distinguishing between falsifed and substandard drugs is a necessary frst step when discussing the problem in any depth. In many parts of the world, drugs are sold without proper packaging and emphasis on label claims has no practical value. Pharmacopeia, for example, gives a dissolution standard; the British Pharmacopoeia, widely used in the Commonwealth, often does not (British Pharmacopoeia, 2012b; Paleshnuik, 2009). Critics of these defnitions might also point out that drug labels usually reference the pharmacopeial standard. The defnitions proposed can inevitably be caught on exceptions, but the committee believes that public discourse is best advanced by considering two main types of bad drugs: falsifed and substandard. Defning the products of interest is valuable only insomuch as it advances the discussion of the root causes and solutions of the problem; making defnitions is not an end in itself. Sometimes bilateral trade negotiations end in large shipments of unregistered medicines in a country (Morris and Stevens, 2006; Newton et al. In a conceptual illustration of the problem, Attaran and colleagues show that unregistered drugs may be of good quality (see Figure 1-1). This fgure shows drug quality standards on the y-axis and registration on the x-axis. In this framework, drugs that fail to meet the regulatory authority’s standards are divided into failures of negligence (substandard drugs) and willful failures (falsifed drugs).
Qui n’avance pas recule buy discount deltasone 40 mg online allergy medicine mood swings, et si nous ne voulions pas suivre la marche en avant des professions voisines de la nôtre cheap 40 mg deltasone otc allergy forecast victoria bc, nous serions bientôt tellement loin en arrière buy deltasone 40mg free shipping new allergy medicine 2014, que l’on fnirait par ne plus se souvenir de nous buy deltasone 20 mg visa allergy symptoms malaise, et nous serions à jamais rayés du nombre des professions de l’art de guérir. Il est donc de toute nécessité de relever le niveau intellectuel de la profession, et c’est le but que s’est donnée la Fédération Nationale des Herboristes de France et des Colonies…en créant par ses propres moyens cette magnifque École nationale d’Herboristerie. Its early history was actually linked to the invention and patenting of a device designed to “displace” the active components of medicinal plants in order to prepare dried – rather than soft – extracts, namely a machine for mixing up slowly the water or the solvents used to concentrate the active principles, while keeping the minced and dried parts of the plant under constant temperature and pressure conditions. One common feature of all the procedures introduced within the Dausse factory located in Ivry, a southern suburb of Paris, was a strong interest in the relationship between mechanical innovations aiming at an accelerated transformation of plant material and the preparation culture of pharmacists, namely the search for extracts that would not only be “potent,” but above all stable, not to diffcult to store, and easy to administrate. Goris, then professors of pharmacology and materia medica at the Paris Faculty of Pharmacy and regular associates of Dausse. In tune with the strong interest of the times in diastases, the basic idea was to avoid spontaneous fermentation, which alters the plant material, by placing the dried organs or the powder resulting from their mincing in boiling alcohol for 10 minutes, in order to eliminate the enzymes involved in the oxidation of the active principles. An aspect of the industrialization of medicinal plants that attracted the attention of medicinal-plant vendors as well as plant therapists was the development of farming as a means to ensure a more regular supply of raw materials. Although many medicinal plants did not breed very well, Dausse’s agricultural production reached 600 tons by the end of World War I. Interests in the replacement of collections in the wild by greenhouse or feld growth were not only linked to issues of productivity and mass production. The question of the integrity of a plant as a prerequisite for potency and physiological effect played a critical role in the understanding of what could be a good – and salable – drug that was shared by Dausse and the herbalists. In addition to the (not-so-common) extracts prepared on the basis of purifcation procedures listed in the Codex, Dausse was actually promoting the making of other preparations, called plant intraits (“intracts” rather than extracts). Intraits were mixtures obtained from stabilized fresh plants, later distilled under vacuum, and dried after the elimination of chlorophyll and 8 A. Dausse, Mémoire sur la préparation de tous les extraits pharmaceutiques par la méthode de déplacement au moyen d’un appareil approuvé par la société de pharmacie contenant un procédé nouveau pour faire les extraits des plantes aromatiques suivi d’un tableau donnant exactement les quantités d’extrait fournies par chaque plante, Paris, 1836. Brissemoret, Essais sur nos préparations galéniques, Paris: Laboratoires Dausse, 1908. In contrast to most drug manufacturers, Dausse did not emphasize the purity and chemical nature of its products. Stressing the botanical origins of the preparations was not simply a way to signal their naturalness, it was also a means to link effcacy and complexity. Looking for pure active principles was taken to be very important in the laboratory, a good way to acquire knowledge, but a rather poor therapeutic practice. In contrast to “what many doctors had been trained to believe, purifcation did not improve or increase the clinical effciency of drugs. As a result, the preparations of stable specialties faced two problems: a) that of avoiding the inactivation of fragile active principles induced by many mechanical treatments; and b) to avoid the separation or the elimination of compounds acting in complementary or combined ways. Industrial preparations should not target the simplifcation of plant material, but its stabilization in order to facilitate storage, circulation, regular supply, and easy dosage. Even if Dausse’s catalogue mentioned pure or crystallized substances, advice to doctors always mentioned the advantages of combinations. Dausse’s intrait of digitalis was for instance documented as having better and less dangerous effects than pure digitaline. Unfortunately, a whole generation of physicians has been accustomed to accept as self-evident the idea that isolated active principles are equivalent to the plants just because science has proved able to purify specifc substances, eventually crystallized, and granted them with a formula and a structure. It is current knowledge that digitalis does not reproduce the action of Digitalis’ extracts, that morphine does not reproduce the action of opium, that quinine does not replace extracts of cinchona, that conicine does not calm pains the way a plaster of hemlock’s extract can do it. Joanin, Les Remèdes Galéniques, Paris: Laboratoires Dausse, 1er fascicule 1921, dernier fascicule 1939. L’extrait est la somme des principes utiles de la plante, lorsqu’il a été bien préparé. Malheureusement, toute une génération de médecins a été amenée à considérer les principes actifs isolés comme s’ils étaient équivalents aux plantes, sous le prétexte que l’on a retiré de celles-ci des corps, cristallisés parfois, à formule établie et à constitution souvent élucidée. Scientifc advertisement for the frm rather took the form of a Codex-like encyclopedia of its own preparations. The second edition of its Remèdes galéniques was a 3,000-page book circulated in isolated chapters throughout the 1930s. Dausse’s masterpiece was organized according to plant species even if it included more general entries such as “biology” or “tests. The entry on Atropa belladonna (Figure 1) thus described the form of the plant, its fruits, its botanical location, and its varieties. The book then presented the conditions under which Dausse cultivated the plant on its medicinal farm, emphasizing the agricultural experimentation conducted with A. Goris, who correlated various forms of fertilization with the alkaloid concentration of the leaves. The active principles were accordingly taken as the basis for the value of the plant, and a summary was offered of the colorimetric methods used for measuring their global concentration in the leaves. A second section, called “Pharmacodynamie” (pharmaceutical dynamics), presented collected data on toxicity and the effects on animals and humans. The core of the discussion was the question of dosage, thresholds, and sensibility. Belladonna were active at low concentration levels and poisonous when given in too large amounts, the book recalled experiments with animal models showing variable effects, but not a single clinical report was included. At stake was not only the defnition of dangerous (if not lethal) doses, but also the inventory of physiological effects, which included changes in eye activity, inhibition of gland secretions, vasoconstriction, and accelerated cardiac rhythm, all of these mimicked by two alkaloids isolated in the plants, thus leaving the reader uncertain as to the supposed synergies involved in the clinical use of the plant. The next section was a Codex-like defnition of the right way to handle the extracts with the defnition of indications (targeting symptoms rather than diseases), legitimated by the physiological study of the plant (A. Belladonna could be employed: as an antispasmodic in cases of coughing, asthma, epilepsy; as an inhibitor of gastric secretion in cases of ulcer; as a regulator of the vagus nerve in cases of nausea and vomiting) followed by the presentation of the appropriate dosage of Belladone Dausse. The fnal section (called “Pharmacology”) was a long discussion of the various preparations combining all the forms and receipts mentioned in the Codex. The form of research associated with this professional/pharmacological perspective was marginally chemical. The frst one was a chemical laboratory involved in testing activities such as the evaluation of the quality of the raw material, while the second conducted pharmacological experimentation. Their role was not to produce new substances, but to assess the properties of plants already being used and to contribute to 14 Op. Assays of purity were not based on tests of chemical structure or composition but on what Dausse’s scientists called “assays of identity,” combining observation of the forms and colors of the plants, microscopic examination, qualitative chemical reactions, and measurement of dried weight for separate but nonetheless mixed principles. The measurement of physiological effects was included in the panoply but mentioned only when toxicity and potency were closely related, raising the delicate problem of establishing a dosage that would avoid heavy side effects, or of course acute poisoning. This was the case for extracts of Digitalis, for which in- house standardization became a routine procedure based on Dausse’s adaptation of the classical assay on a frog’s heart developed by academic physiologists. Dausse’s management thus aligned their products on the most convenient and “modern” presentation of drugs, expanding their facilities to transform plants into pills or ampoules rather than vials. As pointed out by Michèle Ruffat in her history of Sanof-Synthélabo,15 this culture would not resist the postwar transformation of French pharmacy: Dausse’s activities in the 1950s and 1960s reveal a gradual alignment on the screening model of innovation, a slow transition toward a regime dominated by the characterization and manipulation of therapeutic molecules rather than preparations. Pharmacists benefted from a monopoly on sales of all extracts included in the pharmacopoeia, which, ideally, they prepared themselves. In addition, a standing commission composed of physicians and apothecaries was in charge of listing prescription remedies. The frst is that in Germany, fewer plants required a prescription to be sold than in France, where herbalists could moreover only sell the so-called simples, thus excluding all plants considered as toxic at a given dosage. In Germany only roughly one-third of the plant preparations listed in the Arzneibuch fell into the jurisdictions of prescribing physicians. A second specifcity is that in Germany, after 1900, administrative control of “galenic” remedies – those originating in changes in either the mode of preparation or in the combination of drugs already included in the pharmacopoeia – became a permanent source of conficts between the pharmaceutical profession and the industry. This point is illustrated by a 1906 debate on the possibility of the government’s passing a “Galenika-Verordnung. Opposed by Cepha, the alliance of the German chemical-pharmaceutical industry, this proposal was never turned into law, the ministry of commerce arguing that such a measure would threaten German exports.