兽用抗寄生虫药物新剂型及其新技术的研究进展

兽用抗寄生虫药物由于使用频繁,其给药技术研究一直备受重视.目前,兽用抗寄生虫药物新剂型和新技术的研究主要集中在缓释控释制剂和脂质体制剂,其次是透皮给药系统、微囊、微球、环糊精包合物、固体分散体等.但这些新剂型和新技术大多还处于研究阶段,在处方设计或制剂工艺方面都还存在一些问题,今后应加强这些新剂型的工艺和技术研究,以真正发挥这些新剂型的优点.     

小动物麻醉药物及麻醉技术研究进展

随着人们生活水平的提高,家庭饲养小动物日益增多,动物园中观赏性小动物也在增多.小动物饲养数量的增长,导致小动物临床疾病数量的增加.其中相当一部分病例需要进行手术治疗,从而小动物麻醉在疾病治疗中的作用越来越重要.小动物麻醉技术迅速发展,相应的麻醉药物也逐渐更新,为此,对小动物的麻醉药物及麻醉技术的最新进展进行综述,为临床...     

新型药物递送系统在兽药制剂领域的研究进展

新型药物递送系统在新药研发中的应用近年来在国内外受到了广泛的重视。兽用新型载药系统的研究,解决了兽用药物在动物体内半衰期短、靶向性差、药物利用率低以及药物溶解性特定要求等问题,可开发出新型、高效、安全的生物药物剂型。兽药新型递药系统已在兽药领域展现出广阔的前景,并成为兽药研发的新方向之一。本文就目前主要递药系统(如缓控释递药系统、纳米递药系统、靶向给药系统、透皮给药系统、生物粘附给药系统、植入控释给药系统以及自乳化给药系统等)在兽药制剂领域的研究进展进行综述,并分析和探讨了新型递药系统在兽医领域应用瓶颈、现有研究面临的挑战及未来的发展趋势,以期为新型递药系统在兽药领域的应用提供参考。     

Clinical evaluation of new products for small animals

Extract

The discovery and development of sulphonamides and antibiotics marked the beginning of serious efforts to study in depth the efficacy and other sequelae of therapeutic agents. Before the sulphonamide/antibiotic era, pharmacological tests earned out on laboratory animals were considered adequate for most medicaments. Now, more exact information is required about modern drugs used in man and animals. Staff of several disciplines are needed to devise laboratory techniques, controlled experiments, methods of measuring results, and their statistical analysis. Moreover, tests with laboratory animals were not enough, and the much more difficult task of clinical evaluation had to be devised. This has led to a specialization in the testing of drugs by clinicians in human and veterinary medicine. A new discipline, Clinical Pharmacology, has been established for the scientific evaluation of therapeutics.     

Advances in Exotic Mammal Clinical Therapeutics

It is imperative that the veterinarian treating exotic companion mammals stay abreast of the latest developments relating to medications and drug delivery approaches for safety and efficacy. Sustained-release formulations of commonly used drugs, as well as newer routes for administration of therapeutic agents, allow the veterinarian treating exotic companion mammals to reduce the stress associated with drug administration. Interactions can occur between vehicle and drugs when formulations are compounded; therefore, research studies are warranted regarding potential problems associated with these formulations. However, newer studies have been published that provide the basis for exploring the use of different vehicles, frequency of dosing, and drug delivery techniques for various classes of drugs in exotic mammals. The goals of this review are to not only evaluate new medications or uses for medications in companion exotic mammal patients but also review new methods of drug delivery that might be useful to the veterinarian who treats these animals.     

Nonsteroidal antiinflammatory drugs: a review

The increasing use of nonsteroidal antiinflammatory drugs (NSAIDs) in small animals has resulted in the development of new and innovative additions to this class of drugs. Examples of NSAIDs now available for use in small animals include aspirin, etodolac, carprofen, ketoprofen, meloxicam, deracoxib, and tepoxalin. The purposes of this article are to review the pathophysiology of prostaglandin synthesis and inhibition, the mechanisms of action, pharmacokinetics, pharmacological effects, and potential adverse reactions of aspirin and the newly released NSAIDs.     

口蹄疫新型疫苗研究进展

口蹄疫是一种急性、热性、传染性强、致病率高的动物性疫病,对偶蹄动物威胁极大,每年都给畜牧业带来严重的经济损失。随着分子技术的发展,新型口蹄疫研究不断深入,文中就目前几种新型口蹄疫疫苗进行阐述。     

The consequences of generic marketing on antibiotic consumption and the spread of microbial resistance: the need for new antibiotics

In both human and veterinary medicine, it has been shown that flooding the market with different generics and/or ‘me‐too’ branded drugs has increased overall antibiotic consumption correlating with the emergence and spread of bacterial resistance to antibiotics. Another possible undesirable consequence of the promotion of generics is the promotion of an economic incentive that encourages the use of old drug products with very poor oral bioavailability, marketed with historical dosage regimens and extensively excreted in the environment. What veterinary medicine rather needs is new innovative and ‘ecofriendly’ antibiotics to actually enforce a more prudent use of antibiotics. For a pharmaceutical company, generics are inexpensive to manufacture and on a short‐term basis, the generic market is very appealing. However, on a long‐term basis, this marketing orientation provides a disincentive to the development of new and innovative products that will be required to meet the therapeutic needs of the veterinary community while being consistent with public health concerns. Indeed, for veterinary medicine, the key issue surrounding antibiotics is public health. It is the opinion of the authors that veterinary antibiotics and/or veterinary drug formulations should be innovative in terms of selectivity (no or minimal impact on the commensal gut flora), biodegradable (with minimal environmental disruption), and more expensive, with a strictly regulated market rather than unselective, cheap, and freely available drugs.     

Microbiological aspects of osteomyelitis in veterinary medicine: drawing parallels to the infection in human medicine

Osteomyelitis is a challenging infectious disease affecting humans and animals. It is difficult to diagnose because, in many cases, symptoms are non-specific and, for example in implant-related cases, can appear long time after surgery. In addition to this, it is also difficult to treat due to the need to find the appropriate antibiotic regime and delivery system to reach the site of infection and to avoid development of bacterial resistance. The central purpose of this review is to compare the microbiological aspects of osteomyelitis in human and veterinary medicine, with the aim of improving the microbiological diagnosis and treatment of this infection in animals. Furthermore, the study of osteomyelitis in animals may help to improve the development of animal models for testing new treatments in humans. Host factors and underlying conditions have been studied mainly in humans, although aspects as immunodeficiency have been described in some veterinary cases. Even when Staphylococcus aureus is still considered the most prevalent causing microorganism, this prevalence should be reviewed using molecular diagnostic techniques, and this could affect treatment options. New approaches to treatment include local delivery of antibiotics using different biomaterials, antimicrobial photodynamic therapy, and new antimicrobial compounds. We would like to remark the need of large, high-quality clinical trials and of the development of guides for the diagnosis and treatment of osteomyelitis in different animal species.     

Responsibilities of animal scientists and drug sponsors when conducting research with investigational new animal drugs

The Center for Veterinary Medicine of the Food and Drug Administration (FDA) is charged with implementing the Federal Food, Drug and Cosmetic Act as it pertains to animal drugs and food additives. Title 21 of the Code of Federal Register Part 500 contains the regulations promogulated by the FDA as it implements this Act. Investigational New Animal Drug (INAD) applications provide for the shipment of experimental drugs and provide for the establishment of reconditioning procedures so edible products from research animals may be used for food. The record-keeping requirements for holders of INAD and for researchers are described. Protocol development and importation of investigational new animal drugs are discussed.     

Network on veterinary medicines initiated by the European Federation For Pharmaceutical Sciences

The European Federation for Pharmaceutical Sciences (EUFEPS) was founded 25 years ago by more than 20 national pharmaceutical societies and faculty members. As a pan‐European organization, it brings together pharmaceutical societies as well as academic, industrial and regulatory scientists engaged in drug research and development, drug regulation and education of professionals working in these fields. EUFEPS represents pharmaceutical sciences in Europe and is recognized as such by both the European Commission and the European Medicines Agency. EUFEPS cooperates with the European Federation of Pharmaceutical Industries and other European organizations and maintains global connections with agencies such as the US Food and Drug Administration and the American Association of Pharmaceutical Scientists. EUFEPS has established specified networks forming the basis of its activities. The creation of a Network on Veterinary Medicines is prompted by the manifold problems resulting from the use of veterinary drugs and its inherent interconnections with human medicine, environmental and public health. A long‐term goal of this initiative was to expand the spectrum of available therapeutics for use in animals, including the development of innovative delivery systems.     

兽用抗菌增效剂制剂的研究进展

抗菌增效剂属于人工合成的二氨基嘧啶类药物，此类药物与抗菌药物联合使用时会以特定的机制来增强抗菌药的药物活性。近年来，由于抗生素的广泛使用甚至滥用导致细菌耐药的问题日益显现，通过加入抗菌增效剂而研制出的新制剂可以提高抗菌药在动物体内的利用率、降低药物用量、增强药物疗效、降低兽药残留及减少细菌耐药性。文章分析了近年来甲氧苄啶、二甲氧苄啶和艾地普林与各类抗生素的联合使用制备的制剂产品，发现其对疾病的治疗效果普遍优于单独使用抗生素。同时，配合中药的使用对细菌耐药的问题有显著改善，为后期抗菌增效剂的研究打开新的局面。随着对兽药制剂的研究，其不再局限于简单的剂型，通过运用新技术、新材料研制出的制剂，针对不同的给药部位和给药途径可以对病患进行更精准的治疗，减少药物达到靶部位的时间，增加患病部位的药量，此思路可为后续的研发方向提供支持和参考。文章将对抗菌药-抗菌增效剂联用制剂的研发情况进行综述。     

前列腺素F2α及其类似物对哺乳动物生殖影响的研究进展

前列腺素F_2α(prostaglandin F_2α,PGF_2α)是一种黄体溶解因子,广泛用于母猪的同期发情和分娩启动。近年来还陆续发现PGF_2α的新功能,内源性PGF_2α可作为哺乳动物的妊娠识别信号,与胎体和子宫内膜PGF_2α受体(PGF_2α receptor,FP)结合,启动下游信号通路,对早期胚胎发育、着床、妊娠维持发挥重要作用,缺乏或合成不足会导致妊娠中断或流产。鉴于PGF_2α对母畜繁殖活动的促进作用,兽药中心研发了多种PGF_2α药物,如氯前列醇钠、地诺前列腺素F_2α等,被广泛用来启动分娩和促进发情。根据氯前列醇钠的旋光性,可分为D-型和L-型两种对映体,其中D-型结构是氯前列醇钠的主要活性成分。外源性PGF_2α药物不仅可以诱导母猪同期发情与同步分娩、促进产后健康,提高断奶母猪发情率,还可以改善母猪泌乳力与初乳质量,提高仔猪活力等生产性状。作者综述了近几年国内外PGF_2α的研究进展,包括PGF_2α对周期黄体的双重作用,PGF_2α对早期胚胎的发育、着床、分娩的影响,PGF_2α对母猪泌乳力及仔猪活力等方面的重要作用等,同时也综述了几种PGF_2α及其类似物对母畜繁殖性能等方面的影响,旨在为PGF_2α及其类似物的合理运用提供依据。     

弓形虫病治疗药物的研究进展

弓形虫病是一种呈全球分布的重要的人兽共患寄生虫病,能感染包括人在内的所有温血动物。目前对该病的防控主要依赖药物。临床上联合使用磺胺嘧啶与乙胺嘧啶是目前治疗弓形虫病的黄金标准,但该疗法具有一定的毒副作用,且长期使用易产生耐药性。因此,针对弓形虫病的药物研究一直是研究热点。螺旋霉素、甲氧苄啶－磺胺甲噁唑等常作为替代药物用于弓形虫病的治疗,但均具有不同的局限性。因而,人们将研究重点转移到天然产物上。研究以植物提取物为主,通过筛选具有抗弓形虫的活性分子,并对其进行适当的化学修饰,可增强抗虫活性,降低毒副作用。在动物提取物中,某些动物的毒液具有抗弓形虫活性,可作为候选药物。随着研究手段的提升,一些原有药物的新活性不断被发现。在"旧"药新用研究方向,一方面以亲缘关系为标准,针对其他抗寄生虫药物进行抗弓形虫活性探索;另一方面以药物作用靶点为标准,对治疗其他疾病的药物进行抗弓形虫活性研究。文章对弓形虫病临床用药史、天然产物的开发及"旧"药新用这3个方面进行综述,以期为抗弓形虫病药物的研究提供新的思路。     

New methods of drug application for control of helminths

Several new ways have been developed of delivering anthelmintics to ruminants aimed particularly at reducing labour. For single doses, these include a semi-automatic rumen injector for giving insoluble drugs to cattle more conveniently and efficiently than by oral dosing, and the dermal application of levamisole which is, however, subject to seasonal variation in absorption. Sustained administration offers potentially a high level of preventive control but carries a greater risk of developing drug resistance. Even with the best available methods of group administration in feed supplements or drinking water, there remains some uncontrollable variation in individual intake. Intraruminal sustained release devices largely overcome this problem and constitute the most important new technology. They are represented at present by the commercially successful morantel sustained release bolus, and the more versatile Laby capsule which is under development for anthelmintic delivery. Other new applications include the possible development of synergists, potentiators and drug combinations, the special features of drugs which bind strongly to plasma proteins, and the new possibilities offered by a drug highly effective against all stages of Fasciola hepatica. In the general approach to anthelmintic application in helminth control, there have been advances in knowledge of helminth population biology which can lead to better timing of strategic dosing programs, which show that single treatments can have persistent benefits without a simultaneous reduction in infection rate, and which question the conventional view that control schemes require the treatment of all animals in the group.     

伊维菌素药动学研究进展

综述了伊维菌素在动物体内的吸收、分布、代谢、排泄过程以及其药代动力学研究进展,以期为伊维菌素的临床用药和新兽药开发提供依据。     

Comparative cardiovascular and pulmonary effects of sedatives and anesthetic agents and anesthetic drug selection for the trauma patient

Objective: To integrate and compare the effects of tranquilizer/sedatives and anesthetic drugs on various parameters of cardiovascular function in normal dogs and in dogs stressed by hypovolemia, anemia, and endotoxemia, and to discuss the relative merits and appropriate precautions of anesthetic drugs with respect to specific patient physiologic complications. Data sources: Personal data and experiences in conjunction with veterinary and human clinical and research studies. Human and veterinary data synthesis: Drugs that produce calming, sedation, muscle relaxation, analgesia, and loss of consciousness have the potential to produce marked cardiorespiratory effects particularly in hemorrhaged, hypovolemic‐traumatized animals. Acute but key cardiovascular components that are affected by sedative and anesthetic drugs include heart rate and rhythm, venous return (preload), systemic vascular resistance (afterload), and myocardial contractile (inotropic) and relaxation (lusitropic) properties. In addition, all sedative and anesthetic drugs alter or depress normal baroreceptor reflex activity, thereby inhibiting or eliminating the animal's normal physiologic response to decreases in arterial blood pressure and predisposing to tissue hypoperfusion, decreased oxygen delivery, and oxygenation. Oxygen delivery needs to be adequate to meet the metabolic (oxygen) requirements of the patient. Decreases in oxygen delivery to tissues increases oxygen extraction, thereby maintaining tissue oxygenation (supply‐independent oxygen consumption phase) until compensatory processes reach their limit and any further decrease in oxygen delivery causes a decrease in oxygen consumption (supply‐dependent oxygen consumption phase). The critical oxygen delivery that defines the transition between these 2 phases is generally higher in the anesthetized state than in the awake state. The effect of anesthetics on critical oxygen delivery at comparable anesthetic dosages is pentobarbital=ketamine>alfentanil>etomidate=propofol>inhalational anesthetics. Anesthetics generally decrease oxygen consumption from the awake, baseline state; exceptions are ketamine and ether. Ketamine, however, increases oxygen delivery and oxygen extraction. Conclusions: The transition from the awake to the anesthetized state is a huge imposition on the physiology of animals and, therefore, should be accomplished with great care and proper vigilance. Rapid, ‘crash’ induction of anesthesia should be avoided in hypotension‐prone animals and slow, prolonged induction should be avoided in animals with respiratory disorders. It is not recommended to implement an unfamiliar protocol in critical patients, even if it might be pharmacologically preferable. Familiarity with an anesthetic drug is a very important reason for its selection.     

Overview of new vaccines and technologies

Molecular technology has given us a greater insight into the aetiology of disease, the functioning of the immune system and the mode of action of veterinary pathogens. The knowledge gained has been used to develop new vaccines with specific, reactive antigens which elicit protective immune mediated responses (humoral and/or cell mediated) in the host. These vaccines should not burden the immune system by initiating responses against non-essential antigens. However, the efficacy of these vaccines is only as good as the delivery technology or route used to present them to the immune system. Some vaccines, traditionally given by the parenteral route, are now given by the natural route; either orally or intranasally. Two major advantages, often interrelated, are the rapid onset of immunity and stimulation of the local, mucosal immunity. These new technologies are now making an impact on current vaccine development. The balance has to be found between what is technologically feasible and what will provide at least as good a protective immunity as current, conventional vaccines. As new and emerging diseases appear globally, new opportunities arise for molecular and conventional technologies to be applied to both the development and delivery of novel vaccines, as well as the improvement of vaccines in current use.     

Biological control of helminths in grazing animals using nematophagous fungi

For the last 50 years the control of gastro-intestinal nematodes (GIN) in grazing animals has almost entirely been alleviated by the use of anthelmintics. Due to development of resistance against the drugs, especially in the GIN of sheep and goats it has become necessary to develop new, innovative strategies such as the use of nematode destroying fungi. Despite experiments to employ various species against plant and animal parasitic nematodes were already attempted in the 1930's, it was not until the 1990's when selection by simulating passage through the gastro-intestinal tract of cattle led to isolation of the fungus Duddingtonia flagrans that a major breakthrough was achieved. This fungus, producing sticky three-dimensional network and now isolated world-wide, is special due to its capacity to prolifically produce high numbers of thick-walled resting spores, chlamydospores. These spores survive passage through the gastro-intestinal tract of grazing livestock and are capable of growing and subsequently trap nematodes, including larval stages of parasitic nematodes. The great potential of this fungus as a biological control agent has been demonstrated through numerous trials with cattle, sheep, horses, and pigs. But these trials have also pointed towards some potential limitations in the activity spectrum of the fungus (Dictyocaulus, Nematodirus) beside the whole group of parasites spreading through infective stages protected inside resistant eggs (e.g. Ascaris, Trichuris). So far, in the few reported studies conducted, no negative environmental impact has been found, but it is important that further studies are conducted on this important issue. Although the potential use of D. flagrans chlamydospores has been verified through numerous trials it is necessary to develop practical delivery systems such as slow release devices, feed-blocks or similar to be able to implement this tool in future integrated control strategies. Such control strategies could include the use of biological control, grazing management, smart use of existing drugs, parasite resistant animal breeds, bioactive forages, and possibly vaccines.