and over 800 residents and clinical fellows, the hospital accommodates over 41,000 inpatient admissions and 600,000 outpatient visits annually. The patient population is derived from several sources, including a local inner city neighborhood, a suburban population, HMOs that serve a large, diverse primary care population, and an extensive tertiary care referral service. Relationships and collaborations among pathologists and clinicians are excellent.
作为毗邻的哈佛医学院最主要的教学实习医院，布赖海姆女子医院是一个拥有700张床位的总医院，并以其世界闻名的先进外科设施为病人关怀和研究提供高质量的服务。医院理有超过2400名全兼职的员工和超过800名的住院医师和门诊医师。医院每年可以向超过41，000的住院病人和超过600，000的门诊病人提供服务。病人们来自各种渠道，包括当地城区附近的人口，郊区人口，为大量不同的主要病人人口提供服务的卫生维护组织，及广泛的第三类转交护理的病人。医院的病理学者和临床医师之间的关系和协作是非常出色的。
The surgical services cover a wide range of surgical specialties, including general, oncologic, cardiac, thoracic, orthopedic, neurological, genitourinary, and gynecologic surgery, as well as transplantation services, including approximately 65 kidney, 30 heart, and 20 lung transplants per year. There is a separate bone marrow transplant service performing over 300 transplants per year. The medical services include internal medicine, rheumatology, oncology, hematology, dermatology, cardiology, endocrinology and gastroenterology. The gynecology and obstetrics services are extremely active, with over 9,800 births per year.
外科服务涵盖了广泛的外科领域，包括普通外科，肿瘤外科，心脏外科，胸外科，整形外科
神经系统外科，泌尿生殖系统外科和妇产外科。以及各种移植服务，包括每年大约要做65个肾移植，30个心脏移植和20个肺移植的手术。每年还要有做超过300个分离骨髓移植的手术。医疗服务包括内科病，风湿病，肿瘤，血液病，皮肤病，心脏病，内分泌疾病和肠胃疾病。妇科和产科的服务非常活跃，每年要接生超过9，800个新生儿。
The hospital supports an extensive research program, including over 500 investigators with approximately 670 funded research and training projects, and 330,000 square feet of research space, largely supported by over 240 million dollars annually in NIH and other funds.
医院支持广泛的研究计划，包括超过500名调查员带来的大约670个基金研究和训练项目，有330，000平方英尺的研究空间和每年从全国卫生研究所和其他基金所获得的超过24亿美元的大量资金支持。
Located in the Longwood Medical Area, the hospital is within easy commuting distance by public transportation of downtown Boston, the neighboring communities of Brookline, Jamaica Plain, Brighton and Cambridge; it is a short driving distance from most Boston suburbs.
医院座落于Longwood医学区，无论对于波士顿市区，布鲁克林邻近的社区，还是对于牙买加平地，布赖顿和剑桥地区的居民来说，都拥有非常合适的公共交通往返距离。从波士顿大多数郊区地区驾车来医院的距离都很短。
In late 1993, the Brigham and Women's Hospital and the Massachusetts General Hospital (MGH) began a collaboration to form an integrated health care network (the Partners Community Healthcare System [PCHI]), while taking steps to preserve and strengthen the research and teaching missions of these hospitals. Now mature and thriving, this close affiliation has enhanced patient services and clinical programs, research and training, and administrative and support services. This arrangement is not a merger. The training programs in Pathology at the BWH and MGH remain distinct and independently administered, with independent resident recruitment and selection, curriculum and rotations, leadership, and mentoring. Nevertheless, a byproduct of the BWH-MGH affiliation is the creation of enhanced opportunities for broadened residency and fellowship training, especially in sub-specialty electives.
在1993年底，布赖海姆女子医院和马萨诸塞州总医院开始协作从而形成了一个完整的健康服务体系（医疗保健系统的合作人共同体[PCHI]），同时在保持和加强这些医院间的研究和教学目标方面采取了各种措施。现在这种合作已经成熟和蓬勃发展起来，这种紧密联系已经进一步加强了对病人的服务和各种临床计划，研究和培训计划及行政管理上的服务支撑。这种管理不是合并式的，BWH和MGH两个医院在病理学的培训计划上保持着截然不同的和独立的管理。它体现各自独立的住院医师的招募选择，课程轮流制，领导阶层的独立和导师的独立性上。然而，这种BWH-MGH联盟的副产品就是为那些扩大了住院医师的实习期和带奖学金的各种培训，特别选择在非本专业的选修课学习的那些人们增加了机会。
History历史
1832 — Following fundraising appeals to individuals and various charitable organizations, the Boston Lying-In Hospital, one of the nation’s first maternity hospitals, opens its doors to women unable to afford in-home medical care.
1832年---随着向个人和各种慈善团体的筹款成功，全国第一家产科医院之一的波士顿产科医院向那些负担不起请医生的妇女们敞开了自己的大门。
1847 — Anesthesia is administered in childbirth for the first time (Boston Lying-In).
1847年---麻醉剂第一次被允许在分娩时使用。（波士顿产科医院）
1875 — The Free Hospital for Women is founded "for poor women affected with diseases peculiar to their sex or in need of surgical aid," according to its mission statement. Each of five beds is sponsored by a different charitable group.
1875年---“为那些感染了疾病的贫穷妇女特别是对于她们的性别上或者需要外科援助的人们提供援助”的对妇女免费的医院成立了。按照医院的使命，每五张住院床位就有一张是由不同的慈善组织赞助付费的。
1883 — Antiseptic techniques are introduced to ward off infection following childbirth, dramatically reducing the maternal/child death rate (Boston Lying-In).
1883年---为防止分娩时感染的防腐科技的引进。大量降低了母婴死亡率（波士顿产科医院）
1911 — The Peter Bent Brigham Hospital is established "for the care of sick persons in indigent circumstances" with a bequest from restauranteur and real estate baron Peter Bent Brigham.
1911年---利用从餐饮业和房地产业大亨彼得.本特.布赖海姆男爵那里得来的遗产建立了彼得.本特.布赖海姆医院。它的使命是“为那些在贫穷环境中的病人提供服务”
1914 — The Robert Breck Brigham Hospital, founded with a bequest from Peter Bent Brigham’s nephew, opens to serve patients with arthritis and other debilitating joint diseases.
1914年---继承了彼得.本特.布赖海姆侄子的遗产，罗伯特.布莱克.布赖海姆医院成立。它是为那些得关节炎和其他关节疾病病人服务的医院。
1926 — Drs. William Murphy, George Whipple and George Minot discover that liver extracts cure pernicious anemia. In 1934, they share the Nobel Prize for this work (Peter Bent Brigham Hospital).
1926年---威廉姆.莫菲博士, 乔治.惠普尔博士和乔治.迈诺特博士一起发现了肝脏榨取物可以治愈有害的贫血症。1934年，他们由于这项发现而分享了诺贝尔奖金。（彼得.本特.布赖海姆医院。）
1954 — The first successful human organ transplant, a kidney transplanted from one identical twin to another, is accomplished. Joseph Murray, MD, receives the Nobel Prize in 1990 for this work and the subsequent development of immunosuppressive drugs (Peter Bent Brigham Hospital).
1954年---第一例成功的人类器官移植完成了。一个肾从一对双胞胎中的一个人移植到另一个人体内。医学博士约瑟芬.墨里在1990年由于这项工作获得了诺贝尔奖金。随后又发展出了免抑制疫力的药物。（彼得.本特.布赖海姆医院。）
1966 — The Boston Hospital for Women is established through a merger of the Boston Lying-In Hospital and the Free Hospital for Women.
1966年---通过合并波士顿产科医院和妇女免费医院，波士顿妇女医院成立了。
1980 — The Brigham and Women’s Hospital opens its doors, welcoming patients to a new, state-of-the-art facility six years after the formal affiliation of three distinguished predecessors, the Boston Hospital for Women, the Peter Bent Brigham Hospital and the Robert Breck Brigham Hospital.
1980年---在三家著名的前辈医院——波士顿妇女医院，彼得.本特.布赖海姆医院和罗伯特.布莱克.布赖海姆医院正式合并后的第六年，布赖海姆女子医院敞开了它的大门，迎接病人们来这个崭新的，充满艺术级设备的医院来看病。
1985 — The Nobel Peace Prize is awarded to International Physicians for the Prevention of Nuclear War, an organization co-founded by BWH cardiologist Bernard Lown, MD.
1985年---为奖励在预防核战争中的努力，诺贝尔奖金颁发给了国际内科医师组织。这个组织是由布赖海姆女子医院的心脏病专家伯纳德.劳恩博士合作创办的。
1991 — BWH is acknowledged as having received more citations in scientific papers than any other hospital in the world for the period 1986 through 1990.
1991年---布赖海姆女子医院被公认为是从1986年到1990年期间在科学性报刊上所被引用的事例比世界上任何一家医院都要多。
1993 — BWH is selected by the National Institutes of Health as one of 16 Vanguard Centers nationwide to help lead the Women’s Health Initiative, the largest clinical trial ever undertaken in American women.
1993年---布赖海姆女子医院被全国健康学会推选为16家全国性先锋中心之一。这是由于它帮助引导了妇女健康计划——一个最大的在美国妇女中实施的临床试验性计划。
1994 — The 12-story Center for Women and Newborns opens. The facility, which in 1999 is named the Mary Horrigan Connors Center for Women’s Health, sets a new standard in obstetrical and newborn care, featuring home-like birthing suites, private postpartum and antepartum rooms that promote family-focused care, and a 46-bed Newborn Intensive Care Unit with overnight rooms for parents.
1994年---一个12层的妇女和新生儿中心成立了。这个设施在1999年被命名为玛丽.好里根.考纳中心并专门为妇女健康服务。这个中心建立了新标准的生产和对婴儿的关怀服务。他以家一般的出生套房，为产后及产前的妇女促进以家庭为中心的关怀服务，和拥有46张床位的为她们的父母们提供通宵房间的婴儿加强关怀单元为特色。
1994 — BWH joins with Massachusetts General Hospital to form Partners HealthCare System.
1994年---布赖海姆女子医院加入了马萨诸塞州总医院从而形成了健康关怀系统共同体。
1999 — Amid national discourse on the need to reduce errors in medicine, BWH researchers report that the hospital’s own computerized drug-order entry system reduces the incidence of serious medication-related errors by 55 percent, setting a new benchmark for the country.
1999年---在减少用药方面错误需要的全国性报告中，布赖海姆女子医院的研究员们报告说医院拥有了一套计算机化的药物订单条目系统。从而降低了55%的根药物有关的严重错误。同时为国家建立了一套新的基准。
Center for Clinical Excellence
临床优化中心
The Center for Clinical Excellence (CCE) is a dedicated department at Brigham & Women's Hospital responsible for facilitating the achievement of excellence in patient care throughout the hospital. The CCE embodies our hospital's commitment to continually improve the care provided to patients and their families.
临床优化中心是布赖海姆女子医院一个专门的部门负责推动整个医院在病人关怀方面上取得杰出的成就。临床优化中心把我们医院对不断改善病人及其他们家庭的医疗服务提供内容上更加具体化了。
The philosophy of the CCE is to examine clinical performance from a "balanced" perspective, viewing the aspects of customer service, efficiency, quality, safety, and innovation simultaneously. As a collaborative support department, the CCE relies on strong partnerships with clinical and administrative leaders to prioritize, lead, and evaluate clinical improvement activities.
临床优化中心的哲学就是从“平衡”远景，察视客户服务，效率，质量，安全度和改革创新等多方面同时检查临床的履行。作为一个协作支撑部门，临床优化中心强烈依靠着和临床上及管理领导们的伙伴关系，对临床改善行为进行区分优先次序，领导和评估等工作。
A significant focus of the CCE's work is coordinating efforts across departments and divisions, as well as translating best practices between clinical areas. This work speeds the pace of learning and improvement within the hospital. The Center utilizes "continuous quality improvement" concepts and methodologies to fuel this ongoing work.
临床优化中心工作的重要焦点就是在部门和部门之间调整各自的成就，以及在各个临床领域转换最好的实践经验。这项工作加快了医院内部相互学习和改善的步伐。中心利用“不断的质量改善”的概念和方法论为正在进行中的工作提供不断进步的动力。
CCE goals include the following:
临床优化中心目标包括：
Expedite patient flow to minimize unnecessary delays in diagnosis and treatment (e.g., improve admission processes through the Emergency Department, reduce wait times for and during tests, eliminate delays on the day of discharge so that patients may leave when scheduled).
Improve patient satisfaction performance across all patient care settings, including ambulatory practices, outpatient testing and procedure sites, and inpatient units.
Support dedicated Performance Improvement Teams at all levels of the hospital.
Establish a hospital culture that promotes the safest possible work environment for patients and staff. This includes fostering a shared sense of responsibility and enthusiasm among staff for identifying adverse events or "near-misses" and developing subsequent improvements.
Maintain and continually enhance a hospital-wide clinical performance measurement and reporting system that helps administrative leaders and care providers identify improvement opportunities and track the impact of their improvement efforts.
Embrace opportunities to benchmark our quality and clinical performance against other institutions, including those within Partners HealthCare System and other national academic medical centers. This work allows evolving best practices to be rapidly identified and adopted.
加速病人的流动速度从而将在诊断和治疗方面的耽搁减到最少（举例，改进通过急诊允许入院的步骤，减少检验的等待时间，消除在清偿医疗费方面的耽搁使病人能够按时离开医院。）
通过对所有病人的关怀安置上改善病人满意度的履行，其中包括流动的具体实施，门诊病人的测试和旅行手续的场所，和住院病人的病房。
在医院所有的水平上面支撑到专有的履行改善团队。
建立一种医院文化为病人和医院员工们促成一个最为安全的工作环境。这包括在员工中培养一种共同的责任感和热情。使他们能鉴别各种不利事件或是“危险失误”从而在随后的工作中更加进步。
维持和继续增强一个医院范围的临床履行的度量制和报告体系。从而帮助行政管理者和关怀提供者们鉴别各种改进的机会。并且沿着他们的改进成果的效果继续前进。
抓住一切机会对照其他机构来规范我们的质量和临床履行，对照的对象包括那些健康关怀体系中的伙伴和其他全国性的学院级医疗中心。这项工作可以使我们发展出一种最好的习惯来进行快速的鉴别和采纳工作。
医药类产品说明书（英译中）
SEPPIC
1. General description of emulsions. 乳剂的概述
2. Mantanide ISA range Mantanide ISA 范围
3. Quality of the emulsions 乳剂的质量
4. Stability of the emulsions 乳剂的稳定性
5. Efficiency 功效
6. Safety of the emulsions 乳剂的安全性
7. Emulsions for human applications 乳剂对人类的应用
8. Bibliography on preclinical and clinical trails performed with ISA720 and ISA51
对于ISA720和ISA51在临床前和临床试验使用的参考书目
9．Manufacturing 制造
10．SEPPIC knowledge in adjuvant field 在辅药领域上SEPPIC的知识
SEPPIC is involved in the development of speciality chemicals for pharmaceutical applications. These chemicals are mainly surfactants used as solubilizers, emulsifiers or coating agents. Beyond these cativities, SEPPIC is involved in the development of adjuvants/vehicles for veterinary and human applications. These adjuvants/vehicles are mainly designed to achieve emulsions but others concepts are under development.
SEPPIC公司致力于对药用化学制剂专项研究的开发。这些化学制剂主要用于溶解剂、乳化剂和涂层作用剂的表面活性剂。SEPPIC公司还致力于医用兽用的佐剂和媒介物的开发。这些佐剂和媒介物的主要用于生产乳剂，其他的用途正处于开发之中。
Ⅰ- Emulsions
An emulsion is defined as a dispersion of a liquid called the dispersed phase in a second liquid called the continuous phase with which the first one is not miscible. In vaccine formulations, these phases are water (antigenic media) and oil. In order to stabilize the emulations, surfactants are added. A surfactant is a compound containing a polar group which is hydrophilic and a non polar group which is hydrophobic and often composed of a fatty chain.
Ⅰ- 乳剂
乳剂在一种溶液里呈现出溶胶液特性的，被称为分散相，且这种分散相是不可溶合的。在第二种溶液里被称为连续相。在疫苗配方中，这些相的成分由水（抗原介质）和油组成。为了使乳剂具有稳定性，需要添加表面活性剂。表面活性剂是一种包含亲水性极簇和通常由脂肪链组成的恐水非极簇的混合物。
Surfactants can be defined by their Hydrophilic/lipohilic Balance (HLB) value, which gives an information on their relative affinity with the both phases. According to the HLB value of the surfactant, different kind of emulsions can be achieved. Those having a low HLB value have a high affinity for oily phases and render W/O emulsions. In this case, the antigenic phase is made of droplets dispersed into the continuous oily phase. Those with a high HLB value have a high affinity for aqueous phase and render O/W emulsions, where the continuous phase is water and the dispersed phase is oil. At last, with certain specific surfactant systems, when the HLB value is intermediate, W/O/W emulsions can be achieved. In this case, the continuous phase is aqueous and the dispersed phase is oil. But inside the oil droplets, an entrapped aqueous phase is found.
表面活性剂的特性可以用亲水亲油平衡值（HLB值）来解释，即从表面活性剂对两种极簇的相对亲和力上能过得知：根据表面活性剂的HLB值，可以生产出不同种类的乳剂。如果HLB值低，可以生产出对油相亲和力高的水包油（W/O）型乳剂。在这种情况下，抗原相由分散成一系列的油相小滴组成。如果HLB值高，则可以生产出对水相亲和力高的油包水（O/W）型乳剂。该乳剂的连续相是水，分散相是油。最后根据某种特殊表面活性剂的规律，使HLB值居中，则可以生产出水包油包水（W/O/W）型乳剂。就这种情况来说，虽然连续相是水，分散相是油。但是在油滴当中，仍然可以见到水相的存在。
Ⅱ- MONTANIDE? ISA are ready to use adjuvants which allow the manufacture of emulsions. They are the results of an appropriate formulation of several components. They can be based on mineral oil, non mineral oil or a mix of them. Mineral oil is known to be efficient but can induce local reaction with some antigens. Non mineral oils are better tolerated but are less efficient. A blend of the both oils can be in some case a good balance between efficacy and safety.
工业结构标准倾向于允许乳剂产品使用佐剂。要使几种成分配方适当。乳剂可以基于矿物油、非矿物油或者包含二者的混合物。矿物油公认是高功效的但是有可能引起某些抗原的局部不良反应。非矿物油虽然耐受性更强，但是功效低。就某种情况来说，两者的混合油可以在功效性和安全性上起到很好的调和作用。
Montanide ISA range is presented here according to the type of oil, the type of emulsion and the ratio in weight between adjuvant phase and antigenic phase. Those mentioned in pink are specifically dedicated for human applications.
工业结构标准的范围，根据油的种类，乳剂的种类以及辅助相和抗原相的比重的不同来制定。这些在pink中提及过是专门致力于医用的。
Ⅲ- Quality
The quality of emulsions is an important parameter as it has a direct impact on the efficacy and the the safety of adjuvants. The characterization of an emulsion can be defined by various parameters such as droplet test, conductivity, viscosity, particle size and stability at various temperatures.
Ⅲ- 品质
乳剂的品质直接影响到佐剂的功效性和安全性，因此是非常重要的界定因素。乳剂的品质鉴定可以通过多种不同的参数，比如小滴测试、传导率、粘滞性、粒子大小以及在不同温度下的稳定性。
Droplet test and conductivity characterizes cation of the type of emulsion. When a droplet of a W/O emulsion is introduced into a beaker containing water, it will stay at the surface. On the opposite, an O/W emulsion will spread into the water.
小滴测试和传导率描述了乳剂类型的阳离子特征。当W/O型乳剂的小滴注入到一个有水的烧杯时，小滴将浮在水的表面，与此相反，O/W型乳剂将扩散到水中。
The viscosity of the emulsion is closely linked to the surfactant structure and its HLB value. Non optimized HLB render viscous and unstable W/O emulstion rendering it difficult to inject. Fluid W/O emulsions can be achieved with surfactants having an optimised HLB value called required HLB, which depend on the nature of the oil. The viscosity can be then decreased by 10 to reach about 200mPa.s. W/O/W emulstions and O/W emulsions have a lower viscosity respectively of around 50 and 10mPa.s
乳剂的粘滞性将表面活性剂的结构及其HLB值紧密地联系在一起。非优化的亲水亲油平衡呈现出粘滞的液体，不稳定的W/O型乳剂使得该液体难以注入。这种乳剂可以根据油的自然属性，用含有优化HLB值即必要亲水亲油平衡的表面活性剂来制成。粘滞度有可能随后降低10从而达到200 mPa.s。W/O/W型乳剂和O/W型乳剂的粘滞性比较低，分别是50和100mPa.s.
The particle size is also an important parameter influenced by an adequation of the surfactant system and the emulsification process. It is generally recognized that emulsions having a small particle size and a homogeneous distribution are more stable.
粒子的形状同样是一个重要的参数并且受到表面活性剂系统拉直和乳化作用过程的影响。乳剂通常被公认为有一个小的粒子形状并且同类的分区会更加稳定。
Ⅳ- Stability
Stability is very important and various parameters can have an influence on it.
- Mineral, vegetal, animal or synthetic oils can be used alone or in combination, but their required HLB surfactant adjustment.
乳剂的稳定性是非常重要的，各种界限因素对其均产生影响。
- 矿物质、植物、动物、和合成油都可以单独或者联合使用。但是使用品需要做表面活性剂亲水亲油平衡的调整。
- The non respect of the ratio defined for initial optimisation betweeen the oil phase and antigenic phase can have a negative effect on the stability of the final emulsion. The ratio between the continuous phase and the dispersed phase has a strong influence on the viscosity. An increase of the dispersed phase leads to an increase of the viscosity of the final emulsion, due to droplets close pack network. The continuous phase must increase in order to decrease viscosity. Hence when water in oil emulsion are achieved with adjuvants adapted for a ratio of 70%of oil and 30%of aqueous phase, the viscosity can decrease to reach 50mPa.s, whereas a similar optimised formula for a ratio 50/50 will have a four time highter viscosity.
如果不考虑比率对油相与抗原相初始最优化的限定，则可能对乳剂最终的稳定性产生反作用。连续相与分散相的比率对其粘滞性有着很强的影响。一个分散相的增加会导致乳剂最终稳定性的增加，从而引起小滴靠拢成为网状群集。连续相必须为减少粘滞性而增加。因此，在使佐剂适合于比率为70％油相30％水相的W/O型乳剂时，粘滞性可能减少致50mPa.s。然而，如果是同样的优化配方，比率为50/50，其粘滞性则比原来强四倍。
- antigenic media often contain proteins or compounds which have surfactant properties, as they are constituted of polar and non polar groups. This can modify the global HLB inducing poor stability. In this case, specific HLB adjustments need to be done.
在抗原介质中通常含有蛋白质或者由极簇和非极簇构成的含有表面活性剂性质的混合物。这些混合物可以全面改善HLB，包括稳定性方面的欠缺。就这种情况看来，需要做好HLB的精确调节工作。
- the manufacturing process is also important. Indeed, W/O emulsions require high shear homogenisation and then specific device to get stable formulations. The same process applied to make a W/O/W eulsion will render it unstable.
乳剂的生产工序也同样重要。的确，W/O型乳剂要求高 以及获取稳定配方的特殊仪器。同样的工序如果应用于W/O/W型乳剂的生产，则无法实现其稳定性。
Ⅴ- Efficiency
Their action is not yet clear and relies on different mechanisms. The first one is the depot effect and the slow release of the antigen from the injection site. According to the type of emulsion, the kinetic release of the antigen varies. Experimentation where the inverted dialysis tube method is employed to assess the invitro kinetic release of a protein form an emulsion clearly shows differences according to the type of emulsion.
Ⅴ- 功效性
佐剂的效果不甚明显，依赖于不同的机理。第一种是贮存效果，抗原从注射处缓慢的释放。根据乳剂不同的种类，动力释放的抗原也不尽相同。利用逆向分离管方法的试验，在人造环境内从一种乳剂中动力释放出一种蛋白质，由此根据乳剂的种类就可以清楚的区分其差别。
Whereas the protein without adjuvant is immediately released, O/W emulsions allow a slight delay, but the protein is quickly released. W/O emulsions induce very slow release of antigen. This is correlated with the stability of the emulsion and as soon as the emulsion breaks, large amounts of antigen are released, but slower than O/W emulsions. W/O/W emulsions have an intermediate behaviour.
然而，不含佐剂的蛋白质会立即释放，O/W型乳剂允许有稍微的延迟，但是蛋白质仍然会很快地释放。W/O型乳剂诱发抗原释放缓慢。这与乳剂的稳定性及其突变有相互关系。虽然W/O型乳剂能释放大量的抗原，但其速度要比O/W型乳剂慢。W/O/W型乳剂则两者的特性均有。
The depot effect is not the only mechanism as Freund have demonstrated that the excision of the material at the injection site does not suppress the adjuvant effect. Microdiffusion of oil droplets to the draining lymph nodes can partly explain this observation. Emulsions also protect the antigen form a rapid degradation by enzymes and could modify the electric charge of the antigen becoming then, more immunogenic.they create also an inflammtion and stimulate the recruitment of antigen presenting cells such as macrophages, but also lymphocytes.
贮存效果不是唯一的装置，象弗罗因德氏佐剂那样证明在注射处切除材料而不抑止佐剂效应。油小滴的微扩散至淋巴节点可以在某种程度上地解释此种观测。乳剂同样用生化酶保护抗原防止其极度退化，并且可以将抗原的导电电荷改善得更能产生免疫性。乳剂也能制造炎症，刺激抗原补充巨噬细胞和淋巴细胞。
They can also facilitate the uptake of antigens by APC and this can be explained by the interactions between the surfactant and the cellular membrane. Lymphocyte trapping is another mechanism of action of oil adjuvants. They stimulate the accumulation of lymphocytes in draining lymph nodes and limit the recirculation hence facilitating cell association. Finally specific cytokines can be induced according to the type of emulsion selected.
乳剂还能使由APC抗原的摄取更便利，可以通过表面活性剂和细胞膜之间的相互作用对其加以说明。淋巴细胞的俘获是另一个油佐剂的机理作用。乳剂刺激位于淋巴节点的淋巴细胞堆积物并且限制其流通，进而促进细胞的缔合。最后，根据所选乳剂的种类，可以诱发特殊的细胞素。
Ⅵ- Safety
Traditional oil adjuvants can induce local and general reactions like granuloma, abscesses or fever, but they depend on different parameters. The origin of the oil is important. Indeed, highly purified non mineral oils are well tolerated as they are rapidly metabolized and eliminated from the injection site inducing a weak and transient inflammation. But this is to the detriment of their efficacy. Mineral oils stay at the injection site and are progressively eliminated by competent cells like macrophages. They can be also partially metabolized in fatty acids, triglicerids, phospholipids or sterols. In fact a very low level of real hydrocarbons is found outside the injection site. Bollinger et al demonstrate that 30%of the mineral oil disappear during the first month and majority of the oil found outside the injection site is in the liver and fatty tissues in the form of phospholipids and fatty acids.
传统的油佐剂可能诱发局部或者全身的不良反应，例如肉芽肿瘤、脓肿和发烧。但这还要根据界定因素的不同来判断。油的来源非常重要。的确，高纯度的非矿物油耐受性强，能从注射处诱发微弱且短暂的炎症从而迅速产生代谢变化和排泄，但是这将会损害其功效性。矿物油留在注射处象巨噬细胞这样有反应能力的细胞使得排泄量日益增多。矿物油还能在脂肪酸、甘油三酯、磷脂和固醇中产生部分代谢变化。实际上在注射处外部会发现有一种标准低的碳氢化合物。柏林格氏体及其它证明在第一个月内将有30％的矿物油消失，绝大多数在注射处外部发现的油是以磷脂和脂肪酸形式存在于肝脏和脂肪组织中。
The mineral oils are a mix of several hydrocarbons with different length of carbon chain. Stewarttull et al clearly show the direct impact of the length on the safety of adjuvants. Small chains are efficient but induce local reactions, whereas longer chains (>C14) are safer but less efficient. The solubilizing and detergent properties of small chains are probably responsible for these local reactions.
矿物油是一种混合物，由长短不一的碳链和几个碳氢化合物混合而成。史特沃氏及其它清楚地表明碳链长度对安全佐剂的直接效果。碳链短的有效力，但是可能诱发局部不良反应；反之，碳链长（>C14）更安全，但是效力不大。碳链短的溶解性和清洁特性或许是发生这种局部不良反应的原因。
The quality of the surfactant is also very important. Hardegree et al demonstrate that the toxic effect of non ionic sugar ester surfactants is correlated with free fatty acid level. Optimisation of specific chemical synthesis now allows a low residual fatty acid level. Checking various parameters, like acid value, saponification value or iodine value into very narrow range allows the control of the reproducibility and consistency of the surfactants form batch to batch. Their tendency to oxidize can be avoid by an appropriate storage under inert gas (such N2) and a control of the peroxide index.
表面活性剂的品质同样重要。 证明非离子糖酯表面活性剂的毒素作用与脂肪酸标准有相互关系。目前，特定的化学合成最优化可以允许用一种低标准剩余脂肪酸。校验各种界定因素，例如酸值、皂化值、碘值，在小范围内控制其再生性以及确保每一批表面活性剂的一致性。其氧化倾向可以通过使用惰性气体（如氮气）适量存储或者适量调节过氧化物来避免。
The antigen has also a strong influence on the safety of the vaccine formulation. Bacterial crude extracts often induce strong local reactions when administered in emusion. This can be explained by their structure, which can contain immunostimulating compounds like LPS structures or peptidoglycan fragments, responsible for the induction of secondary reactions. Viral antigens are generally safer but in order to avoid side effects, purified antigens or synthetic peptides can be used.Antigenic concentration and vaccine dose are also important, as side effect.
抗原对疫苗配方的安全性有着较大的影响。在乳剂中实施细菌的天然萃取通常会诱发局部不良反应，其原因是该结构与LPS结构和肽聚糖碎片相似，都包含免疫促进混合物。这些混合物导致了继发性不良反应的产生。病毒性抗原一般比较安全，但是为了避免产生副作用，可以利用提纯抗原和合成缩氨酸。抗原含量以及疫苗剂量和副作用都是同等重要的。
Ⅶ- Emulsions for human applications
The adjuvants authorized in human vaccines till now are aluminium compounds, however they do not fit all the requirements to get efficient and safe vaccines. They are known to enhance the humoral immune response but not cellular immunity and they do not induce a long term immunity. Therefore several others type of adjuvants are currently assessed in preclinical or clinical trial. Beyond these W/O, emulsions are assessed in human field for therapeutic applications such as aids, malaria or cancer immunotherapy.
Ⅶ- 医用乳剂
佐剂经认可用于疫苗至今一直使用铝化物，但是这并不能满足生产既有功效又安全的疫苗的所有必备条件。除了非细胞的免疫性，佐剂的作用是增强温性免疫反应，同时又不能诱发长期的免疫性。因此，有些其他类型的佐剂目前还处于临床使用前的评估和临床试验阶段。除了这些W/O型以外，乳剂还在对人类治疗应用领域用于艾滋病、疟疾和癌症的免疫治疗。
Since 1945 more than one million of persons have been vaccinated with mineral oils. First trials reveal some sterile abscesses or cysts but they were related to the quality of the surfactant or the oil. With the development of new grades of surfactants and oils avoiding free fatty acids, and short fatty chain, J.Salk has realised between 1951 and 1953 vaccination trials against flu on 18000 soldiers with incomplete Freund adjuvant and compared to 22000 soldiers vaccinated with classical formulation. The follow-up during 35 years reported first by Salk , then by Beebe and finally by Page demonstrate the safety and non carcinogenicity of these formulations.
自1945年以来，已经有一百多万人接种了含矿物油成分的疫苗。首次试验结果显示，有无菌脓肿或囊肿产生，这与表面活性剂以及油的品质有关系。通过表面活性剂新品级的开发以及将油中自由脂肪酸消除。美国细菌学家索尔克在1951到1953年间开展了一项流感疫苗试验：用弗氏不完全佐剂给18000名士兵接种，用传统配方给22000名士兵接种。通过对比发现了短脂肪链。继索尔克首先发布，后来又有Beebe,最后由佩奇证明了这些配方中的安全性和不可致癌性。
Then, SEPPIC has developed ready to use adjuvants specifically dedicated for human applications Montanide ISA51 and Montanide ISA720. they are based on highly refined surfactants and oils rendering W/O emulsions.
跟着，SEPPIC公司倾向专门致力于佐剂的医用Montanide ISA51 and Montanide ISA720的开发。基于高纯度的表面活性剂和油类来生产W/O型乳剂。
Today more than 1000 people have been vaccinated with formulations containing Montanide ISA 51 which is a mineral oil based emulsion and various publications report the very good tolerance of this adjuvant. Montanide ISA 720, based on non mineral oil, is also in current human clinical trials and phase Ⅰ and Ⅱ demonstrate the good tolerance of the product.
目前，有1000多人接种了包含基于矿物油的乳剂Montanide ISA 51疫苗，许多出版物发表的报告都指出这种佐剂有很好的耐受性。Montanide ISA 720，基于非矿物油，现在同样用于临床试验，相Ⅰ和相Ⅱ证明了该产品良好的耐受性。
Description:
Montanide ISA 51 is an oily adjuvant composition of a highly refined mannide oleate (Montanide 80)in a mineral oil solution (Drakeol 6VR). It is designed for the production of water in oil injectable emulsions. It is a ready to use product which can be mixed directly with an aqueous medium to provide stable formulations. The recommended ratio is 50/50(weight/weight)
Montanide ISA 51是一种在一种矿物油溶液中经过高度提炼的mannide油酸盐的油性辅药合成物（Drakeol 6VR）。它被设计成适合油包水的可注射的乳液剂产品。它已经准备应用于一种能够直接被水媒介所融合并提供稳定公式的产品。被推荐的比率是50/50（重量/重量）
Characteristic:
It is a clear yellow liquid stable at room temperature and 4C. Its viscosity is about 50mpas at 20C and its density is about 0.85.
特征：
在室温或者是4度的情况下，它是一种稳定的清澈黄色液体。在20度的时候它的粘性大约是50mpas, 密度大约是0.85
Identification
Infra red spectrum: conform to the reference (spectrum 1)
Saponification value USP NF 19<401>: 16-20
Hydroxyl value USP NF 19 <401>: 9-13
Conductivity of the emulsion containing Montanide ISA 51 (50%) / Saline (50%) in weight: The conductivity is less than 10Scm-1
辨别：
以下红色的光谱：与参考值一致（光谱1）
皂化值 美国药典 国家处方集 19<401>: 16-20
羟基单价原子值 美国药典 国家处方集 19<401>: 9-13
乳液剂在分量上包含Montanide ISA 51(50%)/盐（50%）的传导率：传导率小于 10Scm-1
Impurities
Heavy metals (not routine test-PE2.4.8): 20ppm max
Acid value [USP NF 19<401>]: 0,5 max
Water content USP NF 19 <921-1>: 4% max
Residue on ignition (not routine test): 0.1% max
杂质
重金属（不是例行试验-PE2.4.8）: 最大量百万分之20
酸值[美国药典 国家处方集 19<401>]：最大量 0.5
水容量 美国药典 国家处方集 <921-1>：最大量 4%
在燃烧后的渣滓 （不是例行试验）：最大量0.1%
Assay
Peroxide value USP NF 19<401>]: 2 max
Iodine value USP NF 19<401>]: 5-9
Refractive index 25 C: NF60212: 1.461-1.463
Colour VCS (S52-150B): 0-2
PH 10% NFT 73206: 4.5-6.5
Emulsifying properties (S571N001-internal SOP): Pass
Endotoxins (EP2.6.14):<7UE/ml
Abnbormal toxicity(EP2.6.9): Pass
化验
过氧化物值 美国药典 国家处方集 19<401>：最大值 2
碘值 美国药典 国家处方集 19<401>：5-9
25度下的折射指数 国家处方集60212：1.461-1.463
颜色的VCS （S52-150B）:0-2
PH值10% NFT73206: 4.5-6.5
使乳化特性 （S571N001-内部的标准操作程序）：合格
内毒素 （EP2.6.14）:<7UE/ml
不正常毒性 （EP2.6.9）:合格
Storage:
Store in an airtight container. Current shelf life is 2 years.
储存
在密封包装中储存。保质期两年
Packaging:
Montanide ISA 51 is delivered in 500ml amber glass type I flasks. Sterile grade is available in 3ml ampoules.
包装
Montanide ISA 51装在500毫升的琥珀色一型长颈瓶中进行运输。消毒等级在3毫升一次用量的针剂中适用。
Manufacturing process
The water in oil emulsion is obtained by mixing 50% of Montanide ISA 51 with 50% of aqueous phase (w/w). A high shear mixing is neccessary to obtain a stable emulsion. A detailed manufacturing process is available on request. MANUFACTURE OF THE WATER IN OIL EMULSIONS
Homogeneizer: Silverson L4RT Stirring speed: 4000tr/min x 3min
制造过程
在油乳剂中的水通过融合50% Montanide ISA 51 加上50%的水定相获得。一种高质量的修剪混合物对于获得稳定的乳剂是必要的。一个详尽的制造过程一经要求即可提供。在油乳剂中水的制造
纯一化：Silverson L4RT 搅拌速度：4000tr/min x 3min
Standard quality controls of the emulsion
The quality of the emulsion is controlled by several parameters.
乳剂的标准质量控制
乳剂的质量由几个参数控制
Parameters 参数
Values on placebo emulsion 安慰剂乳剂的值
Type of emulsion
乳剂类型
W/O (Droplet test (S57 IN 001) 水包油（滴液试验）
Viscosity 粘性
1500 mpas (brookfield DVI-spindle 2-Speed 30)
1500mpas (布鲁克菲尔德DVI-轴2-速度 30)
Microscopic aspect
用显微镜看到的景象
Fine emulsion having refracting droplets with a diameter around 1 micron. The particle size distribution can be measured by laser scattering (see below) 精炼的乳液经折射的滴液直径约为1微米。粒子大小的分布状态可以通过激光散射测量到。（看下面）
Conductivity传导率
Less than 10 us.cm-1 少于 10us.cm-1
Stability* 4C在4度情况下的稳定性
2 years minimum 最少两年
Stability Room temperature 在室温下的稳定性
1 month minimum 至少一个月
Stability 37C在37度时的稳定性
More than 2 weeks 超过两周
*: Emulsion is considered as stable when no visual critical defaults are observed.
Granulometric profile of an emulsion made with Montanide ISA 51
在没有视觉鉴定默认值被观测到的时候，乳剂被认为是稳定的。
乳剂的颗粒测定的剖面 由Montanide ISA 51制造。
Description:
Montanide ISA 720 is an oily adjuvant composition containing a natural metabolizable oil and a highly refined emulsifier based on mannide oleate. It is designed for the production of water in oil injectable emulsions. It is a ready to use product which can be mixed directly with an aqueous medium to provide stable and very fluid formulations. The recommended ratio is 70% of adjuvant for 30% of aqueous media (weight/weight)
描述
Montanide ISA 720是一种包含着自然可代谢的油和在mannide油酸盐的基础上经过高纯度提炼的乳化剂合成的油性辅剂。它被设计成适合油包水的可注射的乳液剂产品。它已经准备应用于一种能够直接被水媒介所融合并提供稳定和流动的公式产品。被推荐的比率是70%的辅剂对30%的水媒介（重量/重量）
Characteristic:
It is a clear yellow liquid stable at room temperature and 4C. Its viscosity is about 50mpas at 20C and its density is about 0.85.
特征：
在室温或者是4度的情况下，它是一种稳定的清澈黄色液体。在20度的时候它的粘性大约是50mpas, 密度大约是0.85
Identification
Infra red spectrum: conform to the reference (spectrum 2)
Conductivity of the emulsion（S571N001）: Prepare an emulsion containing Montanide ISA 720 (70%) / Saline (30%) in weight: The conductivity is less than 10Scm-1
辨别：
以下红色的光谱：与参考值一致（光谱2）
乳剂的传导率：（S571N001）: 预备一种乳液剂在分量上包含Montanide ISA 720(70%)/盐（30%传导率小于 10Scm-1
Impurities
Heavy metals (not routine test-PE2.4.8): 20ppm max
Acid value [USP NF 19<401>]: 0,5 max
Water content USP NF 19 <921-1>: 0.5% max
杂质
重金属（不是例行试验-PE2.4.8）: 最大量百万分之20
酸值[美国药典 国家处方集 19<401>]：最大量 0.5
水容量 美国药典 国家处方集 <921-1>：最大量 0.5%
Assay
Saponification value[USP NF 19<401>]: 17-21
Hydroxyl value [USP NF 19<401>]: 9-12
Peroxide value [USP NF 19<401>]: 5 max
Iodine value [USP NF 19<401>]：320-350
Refractive index 25C: NF60212: 1,4900-1,4930
Colour VCS (S52-150B): 0-2
PH 10% NFT73206: 5-7
Emulsifying properties (S571N001-internal SOP): Pass
Endotoxins (EP2.6.14):<7UE/ml
Abnbormal toxicity(EP2.6.9): Pass
化验
皂化值 美国药典 国家处方集 19<401>：17-21
羟基值 美国药典 国家处方集 19<401>：9-12
过氧化物值 美国药典 国家处方集 19<401>：最大值 5
碘值 美国药典 国家处方集 19<401>：320-350
25度下的折射指数 国家处方集60212：1，4900-1，4930
颜色的VCS （S52-150B）:0-2
PH值10% NFT73206: 5-7
使乳化特性 （S571N001-内部的标准操作程序）：合格
内毒素 （EP2.6.14）:<7UE/ml
不正常毒性 （EP2.6.9）:合格
Storage:
Store in an airtight container under nitrogen as it can be damaged by oxidation. Current shelf life is 2 years.
储存
由于它容易被氧化损坏因此在氮气的密封包装中储存。保质期两年
Packaging:
Montanide ISA 720 is delivered in 500ml amber glass type I flasks. Sterile grade is available in 3ml ampoules.
包装
Montanide ISA 720装在500毫升的琥珀色一型长颈瓶中进行运输。消毒等级在3毫升一次用量的针剂中适用。
Manufacturing process
The water in oil emulsion is obtained by mixing 70% of Montanide ISA 720 with 30% of aqueous phase (w/w). A high shear mixing is neccessary to obtain a stable emulsion. A detailed manufacturing process is available on request. MANUFACTURE OF THE WATER IN OIL EMULSIONS
Homogeneizer: Silverson L4RT Stirring speed: 4000tr/min x 3min
制造过程
在油乳剂中的水通过融合70% Montanide ISA 720 加上30%的水定相获得。一种高质量的修剪混合物对于获得稳定的乳剂是必要的。一个详尽的制造过程一经要求即可提供。在油乳剂中水的制造
纯一化：Silverson L4RT 搅拌速度：4000tr/min x 3min
Standard quality controls of the emulsion
The quality of the emulsion is controlled by several parameters.
乳剂的标准质量控制
乳剂的质量由几个参数控制
Parameters 参数
Values on placebo emulsion 安慰剂乳剂的值
Type of emulsion
乳剂类型
W/O (Droplet test (S57 IN 001) 水包油（滴液试验）
Viscosity 粘性
50 mpas (brookfield DVI-spindle 2-Speed 30)
50mpas (布鲁克菲尔德DVI-轴2-速度 30)
Microscopic aspect
用显微镜看到的景象
Fine emulsion having refracting droplets with a diameter around 1 micron. The particle size distribution can be measured by laser scattering (see below) 精炼的乳液经折射的滴液直径约为1微米。粒子大小的分布状态可以通过激光散射测量到。（看下面）
Conductivity传导率
Less than 10 us.cm-1 少于 10us.cm-1
Stability* 4C在4度情况下的稳定性
2 years minimum 最少两年
Stability Room temperature 在室温下的稳定性
3 month minimum 至少一个月
Stability 37C在37度时的稳定性
More than 2 weeks 超过两周
*: Emulsion is considered as stable when no visual critical defaults are observed.
Granulometric profile of an emulsion made with Montanide ISA 51
在没有视觉鉴定默认值被观测到的时候，乳剂被认为是稳定的。
乳剂的颗粒测定的剖面由Montanide ISA 51制造。
临床检测报告
The development of medical devices which get in contact with physiological fluids is a rapidly increasing field of study.However, different reactions of devices’ surfaces in contact with blood components are still important factors setting limitations to usage of synthetic polymeric materials in contact with blood.The first contact of these materials with blood produces deposition of plasma proteins as albumine, fibrinogen, immunoglobuline, coagulation factors and complement components. In a second time fibrinogen surface adsorption produces phenomena of platelets adhesion, activation and aggregation. This reactions cascade is induced also by other cellular adhesion proteins like fibronectine,vitronectine and von Willebrand factor.
译文：与体液相接触医疗器械的发展，已经成为学术研究中快速发展的领域。然而，器械表面与血液成分接触时所产生的各种不同反应仍然是限制合成聚合材料与血液接触使用的重要因素。当此类材料与血液首次接触时，会产生血浆蛋白质的沉淀反应，如白蛋白、纤维蛋白原、免疫球蛋白、凝血因子和补体成分等。而当再次接触时，纤维蛋白原表面吸附，则会产生血小板粘着，激活进而产生聚集现象。这一连串的反应也可以通过其它细胞吸附蛋白诱导而来，如纤维连接蛋白、体外粘连蛋白和冯威勒布兰德因子（von Willebrand）等。
关键词:医学翻译|医疗翻译|医疗器械翻译|医学翻译公司
