1、P131-Unit1314 制藥工程-專英作業(yè)Sterile product are dosage forms of therapeutic agents that are free of viablemicroorganismsTranslations:無菌產(chǎn)品是不含微生物活體的治療劑型。Principally ， theseincludeparenteral,ophthalmic,and。主要包括非腸道，眼藥，沖洗制劑Of these , parenteral products are unique among dosage forms of drugs because they are

2、injected through the skin or mucous membranes into internal bodycompartment.其中，腸外給藥在藥物劑型中是獨(dú)特的，因?yàn)樗鼈兪峭ㄟ^皮膚或粘膜注射到體內(nèi)的Thus, because they have circumvented the highly efficient first line of body defense,the skin and mucous membranes, they must be free from microbial, contamination and from toxic component

3、s as well as possess an exceptionally highly level ofpurity.須沒有微生物的污染和有毒成分，以及具有非常高的純度水平。原文：All compontents and processes involved in the preparation of these products must be selected and designed to eliminate,as much as possible,contamination ofalltypes,whether ofmicrobiologicorigin.翻譯：在產(chǎn)品制備中涉及的所有組

4、分和工藝流程必須要篩選和設(shè)計(jì)以物的。P131-6.Preparations for the eye , though not introduced into internal body cavities , are placed in contact with tissues that are very sensitive to contamination.眼用制劑，雖然沒有被引入體腔內(nèi)，但它仍然與對(duì)污染敏感的組織相接觸。Therefore, similar standards are required for ophthalmic preparation.因此，對(duì)眼藥制劑也要求類似的標(biāo)準(zhǔn)。I

5、rrigating solutions are now also required to meet the same standards asparenteralsolutionsbecauseduringanirrigationsubstantial amounts of these solutions can enter the bloodstream directly through open blood vessels of wounds or abraded mucous membranes.沖洗液現(xiàn)在也要求滿足到與非胃腸溶液一樣的標(biāo)準(zhǔn)，因?yàn)樵跊_洗過程血流。characteristi

6、cs and standards presented in this chapter for the production of large-volume parenteral solutions apply equally to irrigatingsolutions.同樣適用于沖洗液。Sterile products are most frequently solutions or suspensions,but may even be solid pellets for tissueimplantation.翻譯：無菌產(chǎn)品通常是溶液或者懸浮液，但是甚至也可以是用于組織植入的固體藥丸。Th

7、e control of a process to minimize contamination for a small quantity of such a product can be achieved with relativeease.對(duì)于少量的這種產(chǎn)品，使其污染降到最低的工藝控制可以相對(duì)容易的實(shí)現(xiàn)。As the quantity of product increases , the problem of controlling the process to prevent contaminationmultiply.Therefore ,the preparation of ster

8、ile products has become a highly specialized area in pharmaceutical processing.翻譯：因此,無菌產(chǎn)品的制備已經(jīng)成為藥品加工里一個(gè)高度特殊的區(qū)域。14：Thestandardsestablished,theattitudeofpersonnel,andprocesscontrol must be of a superiorlevel.翻譯：標(biāo)準(zhǔn)的建立、員工的態(tài)度和控制過程必須是高水平的。By far the most frequently employed vehicle for sterile products is

9、 water , since it is the vehicle for all natural bodyfluids.到目前為止，最長(zhǎng)被用于無菌產(chǎn)品的溶媒就是水，因?yàn)樗撬凶匀惑w液的溶媒。The superiorqualityrequiredforsuchuseisdescribedinmonograph on Water for Injection in the該用途要求的優(yōu)良特性在美國藥典的注射用水專題論文中有所描述。17 、 Requirements may be even more stringent for some products , however.譯：然而，對(duì)某些藥物的要

10、求可能會(huì)更苛刻。原 文 ： One of the most inclusive tests for the quality of water is the total solids content , a gravimetric evaluation of the dissociated and undissociated organic and inorganic substances present in the water.翻譯：水質(zhì)檢查的一種普遍的測(cè)試是固體總含量，一種對(duì)水中解離和不解離的有機(jī)物和無機(jī)物在重量上的評(píng)估。原 文 ：However, a less time-consumin

11、g test, the electrolytic measurement of conductivity of the water, is the one most frequently used.譯文：然而，一種用時(shí)較少的測(cè)試水導(dǎo)電性的電解測(cè)量則是最常用的測(cè)試方法，第 20 句Instantaneous measurements can be obtained by immersing electrodes in the water and measuring the specific conductance, a measurement that depends on the ionic

12、content of the water.一種基于水中離子含量的測(cè)量方法。The conductance may be expressed by meter scale as conductivity in micromhos,resistance inmegohms,orinoiccontent aspartsmillion(ppm) of sodiumchloride電動(dòng)率可以通過表頭刻度盤一電導(dǎo)，微歐姆，電阻，兆歐姆或者離子含量，ppmNacl 的形式顯示出來。The validity of this measurement as an indication of the purity

13、of the water is inferential in that methods of producing high-purity water,such asdistillationandreverseosmosis,canbeexpectedtoundissociated substances along with those that aredissociated.作為水純度的指示，這種測(cè)量方法的準(zhǔn)確性只是推理性的，比如蒸餾和反滲透，可以將不解離的物質(zhì)同那些解離的物質(zhì)一起除去。Undissociated substances such aspyrogens, however, cou

14、ld be present in the absence of ions and not be disclosed by thetest.翻譯：但是不解離的的物質(zhì)如熱原，可以不以離子的形式存在，因而不能被這種方法檢測(cè)出來。Thereforeforcontaminantsotherthanionsadditionaltestsshould be performed.測(cè)。Additional tests for quality of Water for Injection with permitted limits are described in the USPmonographs.具有特殊用途

15、的注射用水的水質(zhì)附加測(cè)試在美國藥典中有專篇描述。 comparingthe totalsolids permittedfor Water for Injection with that for Sterile Water for Injection, one will note that considerably higher values are permitted for Sterile Water for Injection.翻譯：當(dāng)把注射用水和無菌注射用水所允許的總固體含量作比較時(shí)， 你會(huì)發(fā)現(xiàn)無菌注射用水允許有相當(dāng)高的值This is necessary because the lat

16、ter product has been sterilized, usually by a thermal method , in a container that has dissolved to some extent in the water.這是必要的，因?yàn)楹笳呤墙?jīng)過滅菌的，通常是通過一種熱途徑，在一定程度上溶解于水的容器中。Therefore,the solids content will be greater than forthenonsterilized product.因此，其固體含量會(huì)比沒有滅菌的產(chǎn)品要高的多On the other hand,the 10 ppm tota

17、l solids officially permitted for Water for Injection may be much too high when ues as the vehicle for manyproducts另一方面，官方對(duì)于注射用水所允許的 10ppm 的固體總含量，對(duì)于許多產(chǎn)品來說作為溶媒其值可能太高了。In practice,waterforInjectionnormallyshouldnothavea conductivityofmorethan 1 micromho (1 megohm，approximately1ppmNaCl).事實(shí)上,注射用水其電導(dǎo)一般不應(yīng)

18、該超過 1 微歐姆（1 兆歐，大約ppmNaCl）31 原文:Substances added to aproduct to enhance its stability are essential for almost everyproduct.翻譯:添加到產(chǎn)品當(dāng)中用以提高產(chǎn)品穩(wěn)定性的物質(zhì)，對(duì)于幾乎每種產(chǎn)品來說都是必不可少的。Such substances include solubilizers , antioxidants , chelating agents,buffers , tonicity contributors , antibacterial agents , antifung

19、al agents , hydrolysisinhibitors,antifoammgagents,andhumeroussubstances for specializedpurposes.這樣的物質(zhì)包括增溶劑、抗氧劑、螯合劑、緩沖劑、張度調(diào)節(jié)劑、抗At the same time , these agentsmustbepreventedfrom affecting theproduct.同時(shí)，這些組分不能對(duì)產(chǎn)物有不利影響。In general , added substances must be nontoxic in the quantity administered to thepa

20、tient.一般來說，添加劑必須在病人的給藥量范圍是無毒的They should not interfere with the therapeutic efficacy nor with the assay of the active therapeuticcompound.它們（輔料）不應(yīng)該干擾療效，也不能干擾有效活性化合物的測(cè)定。they must also be present and active when needed throughout the useful life of theproduct翻譯：在產(chǎn)品的整個(gè)有效期內(nèi)，需要他們時(shí)，他們必須存在并且有效。.agents must

21、 be selected with greatcare ，and they must be evaluated as to their effect upon the entireformulation.的影響也必須進(jìn)行評(píng)估An extensive review of excipients used in parenteral products upon and the means for adjusting PH of these products has recently been published and should be referred to for more detailed

22、information.一篇關(guān)于用在非腸道用產(chǎn)品中的賦形劑和調(diào)節(jié)這些產(chǎn)品 pH 的方法的綜述，最近已經(jīng)出版，更多的詳細(xì)信息可參閱之。The formulation of a parenteral product involves the combination of oneormoreingredientswithamedicinalagenttoenhanceconvenience ,acceptability ,or effectiveness of theproduct.非腸道用產(chǎn)品的處方涉及一個(gè)或者更多組成部分間的結(jié)合，這些組成（各自有效成分。Rarely is it preferab

23、le to dispense a drug singly as a sterile dry powder unless the formulation of a stable liquid preparation is notpossible.（人們）很少愿意把藥物僅僅以一種無菌的、干燥的粉末（的形式）配售，除非（把它做成）穩(wěn)定的液體制劑處方，否則是行不通的。On the other hand,a therapeutic agent is a chemical compound subject to the physical and chemical reactions characteris

24、tic of the class of compounds to which itbelongs.翻譯：另一方面，一個(gè)藥物制劑是一個(gè)遵從物理和化學(xué)反應(yīng)支配特性的化合物。（藥物的有效成分物理和化學(xué)反應(yīng)特性的一種化合物。Therefore ,a careful evaluation must be made of every combination Of two or more ingredients to ascertain whether or not adverse interaction occur ,and if they do, of ways to modify the formul

25、ation so that the reactions are eliminated orminimized.因此對(duì)每一個(gè)兩種或更多組成部分間的結(jié)合都必須有一個(gè)仔細(xì)的評(píng)以使反應(yīng)消除或者降低到最小。the formulation of sterile products is challenging,therefore ,to the kno wledge and ingenuity of the personsresponsible.翻譯：無菌產(chǎn)品的制定是具有挑戰(zhàn)性的，因此，需要具有學(xué)問和聰明的人負(fù)責(zé)。因此，無菌產(chǎn)品的配方是對(duì)負(fù)責(zé)人員知識(shí)和獨(dú)創(chuàng)性的一個(gè)挑戰(zhàn)。the amount of infor

26、mation available to the formulator concerning the physical and chemical properties of a therapeutic agent,particularly if it i s a new compound,is often quitemeager.可用的信息量配方設(shè)計(jì)師關(guān)于治療劑的物理和化學(xué)性質(zhì) ,特別是如果這是一個(gè)新的化合物,通常是很微薄的（藥物的有效成分質(zhì)的信息量通常是很少的，尤其當(dāng)治療藥物是一種新的化合物時(shí)。Information concerning basic properties muse be ob

27、tained, including molecular weight, solubility, purity, colligative properties , and chemical reactivity, before an intelligent approach to formulation canbegin.溶解性、純度、依數(shù)性等信息關(guān)于（治療劑）基本性質(zhì)的信息，包括分子量、溶解度、純度、依數(shù)性和化學(xué)反應(yīng)性必須在一種好的組建配方的方法可以開始之前得到46.Improvementsinformulationareacontinuingprocess,since important p

28、roperties of a drug or of the total formulation may not becomeevident untiltheproduct hasbeenstored orusedfora prolongedtime.翻譯：改進(jìn)處方是一個(gè)持續(xù)的過程，因?yàn)橐环N藥物或者一種處方的重要性質(zhì)直到這種藥品被存放或者使用了很長(zhǎng)時(shí)間才會(huì)變得明顯。處方的改進(jìn)是一個(gè)持續(xù)的過程，因?yàn)樗幬锘蛘w配方的一些重要性質(zhì)只有在貯存或者使用了很長(zhǎng)時(shí)間之后才可能會(huì)變得明顯。47.However,because of the extensive test documentation require

29、d by the U.S. Food and DrugAdministration,onlyoutstanding formulations can be justified for continuance to the state of a maketed product. 然而由于美國食品和藥物管理局要求的廣泛的測(cè)試文件只有優(yōu)的制劑才能被證明能夠持續(xù)產(chǎn)品的狀態(tài)。（使得）只有那些杰出的配方才能繼續(xù)發(fā)展成為上市產(chǎn)品48 The production process includes all of the steps from the accumulation and combining of

30、the ingredients of the formula to the enclosing of the product in the individual container for distribution.生成過程包括從配方的各個(gè)組成部分的積聚和結(jié)合到產(chǎn)品封裝用于分售的單個(gè)包裝內(nèi)的所有步驟。生產(chǎn)過程包括從配方的各個(gè)組成部分的積累和結(jié)合到產(chǎn)品封裝入用于分售的單個(gè)包裝內(nèi)的所有步驟。Intimately associated with these processes are the personnel who carry them out and the facilities in whi

31、ch they areperformed與這些過程密切相關(guān)的是執(zhí)行它們的人員和執(zhí)行它們的設(shè)施和這些過程有緊密聯(lián)系的是搬運(yùn)人員和執(zhí)行這些步驟的設(shè)備。The most ideally planned processes can be rendered ineffective by personnel who do not have the right attitude or training, or by facilities that do not provide an efficiently controlledenvironment.最理想的計(jì)劃過程，可以使無效的人員沒有正確的態(tài)度或培訓(xùn)，或

32、設(shè)施，不提供有效的控制環(huán)境。計(jì)劃出來的最理想的過程也會(huì)因?yàn)闆]有正確態(tài)度或沒有接受正確培訓(xùn)的人員或者不能提供一個(gè)有效的控制環(huán)境的設(shè)備而變得無效。To enhance the assurance of successful manufacturing operation , all process steps must be carefully reduced to writing after being shown to beeffective加強(qiáng)生產(chǎn)操作成功的保證,所有流程步驟必須被小心地減少到標(biāo)準(zhǔn)下被證明是有效的后都要仔細(xì)地歸納成書面材料，These written procee steps are offen called sta