外用氢化可的松醋丙酯对实验性犬跳蚤过敏性皮炎的治疗效果 ...

王帆

 

Therapeutic efficacy of topical hydrocortisone aceponate in experimental flea-allergy dermatitis in dogs

外用氢化可的松醋丙酯对实验性犬跳蚤过敏性皮炎的治疗效果

 

作者：S Bonneau, V Skowronski, A Sanquer, L Maynard and HM Eun

翻译：王帆

 

Objective To evaluate the treatment efficacy of a topical spray containing hydrocortisone aceponate (HCA) on dogs with flea-allergy dermatitis (FAD).

Design A controlled clinical study was conducted on dogs with experimentally induced FAD. Sixteen laboratory beagles with mild to moderate clinical signs were divided into two groups. The test group received HCA by topical spray once daily for 7 days, while the control group did not. Pruritic events (time and frequency) were videotaped and then scored. Clinical signs (erythema, papules, excoriation and alopecia) present on four anatomical regions were monitored and their severity directly assessed.

Results After 2 days, pruritus was reduced by 94% in the treatment group and by 24% in the control group (P = 0.014) in cumulative time, and by 86% versus 34% (P = 0.034) in frequency. The HCA spray also resulted in significant improvements in overall clinical signs: 23% versus 0% in the control group (P = 0.0006) on day 3 and 43% versus 15% in the control group (P = 0.0006) on day 7. During the 7-day trial, no drug-related adverse effects were observed.

Conclusions Topical treatment with HCA showed a rapid and potent antipruritic effect on dogs with FAD. HCA also demonstrated significant overall therapeutic effects on FAD-associated skin lesions.

摘要

目的-评价含氢化可的松醋丙酯(HCA)外用喷雾剂对犬跳蚤过敏性皮炎(FAD)的治疗效果。

设计-对实验性诱发FAD的犬进行对照临床研究。将16只临床症状轻至中度的实验室比格犬分为两组。试验组给予HCA外用喷雾剂，每日1次，连用7天，对照组不给予。瘙痒事件(时间和频率)被录像，然后评分。监测四个解剖区域的临床症状(红斑、丘疹、抓痕和脱毛)，并直接评估其严重程度。

结果-2天后，治疗组瘙痒时间减少94%，对照组瘙痒时间减少24% (P = 0.014)，次数减少86%，对照组瘙痒次数减少34% (P = 0.034)。HCA喷雾也导致总体临床症状的显著改善:第3天，23%对0%的对照组(P = 0.0006)，第7天，43%对15%的对照组(P = 0.0006)。在7天的试验中，未观察到与药物相关的不良反应。

结论-外用HCA治疗对FAD患犬显示出快速有效的止痒作用。HCA对FAD相关的皮肤病变也显示出显著的整体治疗效果。

 

Keywords

关键词

dermatitis; dogs; flea allergy; hydrocortisone; skin; topical therapy

皮肤病;犬;跳蚤过敏;氢化可的松醋丙酯;皮肤;外部治疗

Abbreviations

缩写

FAD, flea-allergy dermatitis; HCA, hydrocortisone aceponate

FAD-跳蚤过敏性皮炎;HCA-氢化可的松醋丙酯

 

 

Flea-allergy dermatitis (FAD) is a pruritic dermatitis with skin inflammation and associated lesions in dogs and cats that have been sensitised to the bites of fleas. Although prevalence varies depending on season and geography, FAD is among the most significant skin disease motivating veterinary consultations. Despite this, effective treatment and control of FAD still remain a considerable challenge.

跳蚤过敏性皮炎(FAD)是一种瘙痒性皮炎，伴有皮肤炎症和相关病变，发生在对跳蚤叮咬敏感的犬和猫上。尽管流行率因季节和地理而异，但FAD是促使兽医咨询的最重要皮肤病之一。尽管如此，有效治疗和控制FAD仍然是一个相当大的挑战。

 

Current treatments for FAD hinge on two major strategies. The first basic strategy is direct control of infesting fleas by means of insecticides.  The second strategy is anti-inflammatory/antipruritic therapy based on antihistamines, glucocorticoids and other immunomodulatory drugs. The two strategies are complementary, and concomitant treatments are highly useful in controlling FAD.

目前对FAD的治疗取决于两个主要策略。第一个基本策略是通过杀成虫剂直接控制跳蚤。第二种策略是基于抗组胺药、糖皮质激素和其他免疫调节药物的抗炎/止痒治疗。这两种策略是互补的，同时治疗对控制FAD非常有用。

 

In canine pruritic dermatoses, antipruritic/anti-inflammatory therapy is the first-aid therapy bringing instant relief to the distressed animal. The need for such relief therapy is compelling, even after complete elimination of infesting fleas, because pruritus and other FAD-associated clinical signs can persist for 1 week or more. Indeed, it is not uncommon that complete resolution of clinical signs is attained only after 2 to 3 months of symptomatic therapy. Antipruritic/ anti-inflammatory therapy is also useful and sometimes necessary as an adjunct therapy to allergen-specific immunotherapy for atopic dermatitis.  Corticosteroid molecules, such as betamethasone, dexamethasone and other prednisolone-derivatives, are frequently administered by the topical and systemic routes for the treatment of dermatoses in general and FAD in particular. The glucocorticoids have a range of local and systemic adverse effects that render glucocorticoid therapy highly complex and/or restricted to short-term management of dermatological disorders. Recently, new generation topical corticosteroids have been developed, featuring potent pharmacological activity with low risk–benefit ratios. These have the potential to be the basis of effective and safe treatment of atopic dermatitis and other allergic reactions. The present study was undertaken to evaluate the therapeutic efficacy and profile of a topical formula of hydrocortisone diester (17,21-hydrocortisone aceponate (HCA)) for canine FAD.

在犬瘙痒性皮肤病中，止痒/抗炎治疗是一种首要疗法，可以立即缓解动物的痛苦。这种缓解治疗的必要性是迫切的，即使在完全消除了跳蚤感染之后，因为瘙痒和其他FAD相关的临床症状可以持续一周或更长时间。事实上，仅仅经过2到3个月的对症治疗，临床症状的完全缓解并不罕见。对于特应性皮炎，作为过敏原特异性免疫治疗的辅助治疗，止痒/抗炎治疗也是有用的，有时是必要的。皮质类固醇分子，如倍他米松、地塞米松和其他泼尼松衍生物，通常通过外部和全身途径给药，用于治疗常见皮肤病，特别是FAD。糖皮质激素具有一系列外用和全身不良反应，使得糖皮质激素治疗非常复杂和/或仅限于皮肤疾病的短期治疗。近年来，新一代外用皮质类固醇被开发出来，具有有效的药理活性和低风险-效益比。这些有可能成为有效和安全治疗特应性皮炎和其他过敏反应的基础。本研究旨在评估氢化可的松醋丙酯二酯(17,21-氢化可的松醋丙酯(HCA))外用配方治疗犬FAD的疗效和特点。

 

Materials and methods

材料与方法

The study was a randomised trial performed in accordance with the current ethics committee recommendations and Good Laboratory Practice guidelines of the Organization for Economic Co-operation and Development.

这项研究是一项随机试验，按照目前的伦理委员会建议和经济合作与发展组织的良好实验室规范指南进行的。

 

Animals

动物

The study used 16 beagle dogs (9 males, 7 females) with a mean age of 4.6 years and a mean weight of 11.2 kg. The animals were housed in individual pens under controlled environments (18°C, 55% relative humidity, 12-h dark/light cycle). Animals were fed once daily with a commercial pet food (Vet Complex Adult, Virbac A.H., Carros, France) and given free access to water.

该研究使用了16只比格犬(9只雄性，7只雌性)，平均年龄为4.6岁，平均体重为11.2公斤。在控制环境(18°C, 55%相对湿度，12 h暗/光循环)下，将动物饲养在单独的围栏中。动物每天喂食一次商业宠物食品，并给予自由饮水。

 

Induction of FAD

FAD的诱导

FAD was induced by controlled challenge infestation with fleas (Ctenocephalides felis, newly emerged, unfed adults) following an established two-step protocol developed in-house. Starting with 20 dogs, the first step consisted of sensitisation to flea bites by a series of four bi-weekly challenge infestations with 100 fleas/dog. This was followed by a rest period of 4 months in order to ensure that the dogs had no apparent FAD-associated clinical signs. The second step was hypersensitisation of the dogs and clinical development of the FAD signs, consisting of four successive challenge infestations on days −13, −9, −5, and −2. The objective was to induce sufficient yet moderate levels of pruritus and associated clinical signs, while avoiding excessive conditions of FAD. For this, the number of fleas was adjusted from 40 fleas/dog used in the first challenge to 5 to 30 fleas/dog for the second and successive ones. On day −2, pruritic status was assessed, and 16 dogs presenting minor to moderate signs of FAD were selected for the subsequent study program. Two dogs were excluded because of insufficient pruritus and two for having too severe clinical signs. The four excluded dogs received immediate antiparasitic treatment. The 16 participating dogs were then randomly assigned to two groups: HCA-treated and untreated (control), according to sex using the permutation tables. On day 0, the dogs were given oral antiparasitic tablets (Capstar®, Novartis A.H., Basel, Switzerland) to remove infesting fleas. Day 0 also corresponded to the first day of treatment with the HCA formulation.

FAD是通过跳蚤(猫栉首蚤，新孵化，未喂养的成虫)的可控挑战侵扰，按照内部制定的既定两步方案诱发的。从20只犬开始，第一步包括对跳蚤叮咬敏感，每两周一次，每只犬有100只跳蚤。随后是4个月的休息期，以确保犬没有明显的FAD相关临床症状。第二步是犬的超敏化和FAD症状的临床发展，包括在- 13、- 9、- 5和- 2天连续四次感染。目的是诱导足够但适度的瘙痒和相关临床症状，同时避免过度的FAD。为此，跳蚤数量从第一次的40只蚤/犬调整为第二次和后续的5到30只蚤/犬。在第2天，评估瘙痒状况，并选择16只出现轻微至中度FAD症状的犬进行后续研究。2只犬因瘙痒不足被排除，2只犬因临床症状过于严重而被排除。被排除在外的四只犬立即接受了抗寄生虫治疗。16只参与实验的犬被随机分为两组:HCA治疗组和未治疗组(对照组)，根据性别使用排列表。第0天，给犬口服抗寄生虫片(诺普星)，以清除跳蚤感染。第0天也对应于HCA制剂治疗的第一天。

 

Treatment formulation

治疗配方

The test substance was an HCA formulation containing 0.0635% (w/w) HCA (or 0.584 mg HCA/mL) in propylene glycol methyl ether (Cortavance®, Virbac A.H.). This product is designed to be used as a topical spray, each pump activation delivering 130 μL to an area of 10 × 10 cm when maintained at a distance of 10 cm from the skin.

试验物质为丙二醇甲醚中含有0.0635% (w/w) HCA(或0.584 mg HCA/mL)的HCA配方(皮乐美)。本品设计为外用喷雾，每次泵时，在距离皮肤10厘米的距离下，向10 × 10厘米的区域输送130 μL。

 

Treatment

治疗

The dogs were kept in individual pens in a room throughout the study. They were treated with the HCA once daily for 7 consecutive days with two complete pump activations on four regions of the body (lumbodorsal, sacrocaudal, ventral abdomen and ventral thorax). Each dog received a mean dose of 4.7 mL/day; control dogs received none. The study director dispensed the treatment in a manner blinded to all other study personnel. The treatment was given after monitoring on the day of assessing pruritus and clinical signs.

在整个研究过程中，这些犬被关在一个房间里的单独围栏里。他们接受HCA治疗，每天1次，连续7天，在身体的四个区域(腰背、骶尾、腹侧腹部和腹侧胸部)进行两次喷药。每只犬的平均剂量为4.7 mL/天;对照组的犬则没有。研究主任以一种对所有其他研究人员不知情的方式分配治疗。在评估瘙痒和临床症状当天进行监测后给予治疗。

 

Pruritus scoring

瘙痒评分

Pruritus was assessed by counting the number and duration of pruritic events including chewing, scratching, biting, licking, rolling and rubbing. The pruritic activities of each dog were observed for a 45-min period at a fixed time (from 10 am) of days −2, 2 and 7, and videotaped via closed-circuit video recorders in groups of four dogs. Pruritic events (time and frequency) of each dog were then evaluated by a trained group of observers. The pruritic time was defined as the cumulative time of the pruritic events recorded in the 45-min period on the given day, and the frequency as the number of pruritic events recorded in the same 45-min period.

通过计算瘙痒事件的次数和持续时间来评估瘙痒症，包括咀嚼、抓、咬、舔、滚和摩擦。在第2天、第2天和第7天的固定时间(上午10点开始)对每只犬进行45分钟的瘙痒活动观察，并以4只犬为一组，通过闭路录像机进行录像。每只犬的瘙痒事件(时间和频率)然后由一组训练有素的观察者进行评估。瘙痒时间定义为当天45分钟内记录的瘙痒事件的累积时间，频率定义为同一45分钟内记录的瘙痒事件的次数。

 

Clinical signs and severity scoring

临床症状及严重程度评分

A single veterinarian assessed FAD-associated skin lesions on days −1, 3 and 7. The veterinarian, unaware of the grouping status of the dogs, also performed daily inspection of the dogs for general welfare conditions. Clinical signs were monitored with a focus on four parameters (erythema, papules/pustules, excoriation/erosion, and alopecia/epilation) present on the four body regions. Clinical scores were assigned according to a dual scale in which the severity of lesions and the extent of affected area were taken into account (Table 1). The score ranged from 0 (absence) to 6 (severe and >50% of the observed area affected).

一名兽医在第1、3和7天评估FAD相关的皮肤病变。兽医在不知道犬的分组情况的情况下，也每天检查犬的一般福利状况。监测临床症状，重点关注四个身体区域的四个参数(红斑、丘疹/脓疱、抓痕/糜烂和脱毛/脱毛)。临床评分根据双重评分，其中病变的严重程度和范围被考虑(表1)。评分范围从0(没有)到6(严重和>50%的观察区域患病)。

 

 

 

 

Safety assessment

安全评估

Animals were checked daily by the veterinarian for morbidity, body weight, food consumption, vomiting, diarrhoea, polyuria and polydipsia.

兽医每天检查动物的发病率、体重、食物消耗、呕吐、腹泻、多尿和多饮。

 

Statistical analysis

统计分析

The two groups were compared on day −2 for pruritus scores (time and frequency) and on day −1 for FAD clinical scores and general/ physical parameters. The calculations were made using Student’s t test, Wilcoxon rank sum test and Fisher’s exact test, depending on the validity of assumptions. The pruritic time and frequency on days 2 and 7 were compared between groups by an analysis of covariance using the values on day −2 as covariates. FAD clinical scores on days 3 and 7 were compared between groups by an analysis of covariance using the FAD scores on day −1 as covariates. For analyses of covariance, non-significance of the interaction term was tested and if it was non-significant, it was discarded from the model. In the case of significance of the interaction, no adjustment of day −1 values was made, and the groups were compared using Student’s t test or Wilcoxon rank sum test. All statistical analyses were performed using S-PLUS® 6.2 software (Insightful France, Paris, France). Differences were considered statistically significant at P < 0.05.

两组在第2天比较瘙痒评分(时间和频率)，第1天比较FAD临床评分和一般/身体参数。根据假设的有效性，使用Student 's t检验、Wilcoxon秩和检验和Fisher精确检验进行计算。以第2天和第7天的瘙痒时间和频率为协变量，通过协方差分析比较两组之间的瘙痒时间和频率。以第1天的FAD评分为协变量，通过协方差分析比较各组间第3天和第7天的FAD临床评分。对于协方差分析，检验交互项的不显著性，如果不显著，则将其从模型中丢弃。在相互作用显著的情况下，不调整day - 1值，并使用Student 's t检验或Wilcoxon秩和检验对组进行比较。所有统计分析均使用S-PLUS®6.2软件(洞察力法国，巴黎，法国)进行。P < 0.05认为差异有统计学意义。

 

Results

结果

Baseline status

基线状态

The HCA and control group animals were indistinguishable in their basal general/physical parameters (sex, age and weight) and also in their FAD clinical parameters (pruritic time, pruritus frequency and total lesion scores) (Table 2). Erythema and papules were the most prominent signs, with respective mean baseline scores of 10.4 and 9.7 (of maximum 24) (Table 3). Alopecia and excoriation were relatively mild, with mean scores ranging from 3.2 to 4.4. Clinical scores were observed in the order of ventral abdomen (10.8), sacrocaudal (9.4), ventral thorax (5.2), and lumbodorsal (2.5).

HCA组和对照组动物在基本的一般/身体参数(性别、年龄和体重)以及FAD临床参数(瘙痒时间、瘙痒频率和总病变评分)方面没有区别(表2)。红斑和丘疹是最突出的症状，平均基线得分分别为10.4和9.7(最高24分)(表3)。脱毛和抓痕相对较轻，平均得分在3.2到4.4之间。临床评分依次为腹侧(10.8分)、骶尾部(9.4分)、胸侧(5.2分)、腰背侧(2.5分)。

 

Time course of pruritus

瘙痒的时间过程

The time course of pruritus is shown in Figure 1. Compared with the baseline values (on day −2), the control group showed a reduction in pruritic time by 24.3% and 45.3% on days 2 and 7, respectively. In the meantime, the HCA group showed reductions of 94.2% (P = 0.014) and 96.3% (P = 0.001), respectively.

瘙痒的时间过程如图1所示。与基线值(第2天)相比，对照组在第2天和第7天瘙痒时间分别减少了24.3%和45.3%。同时，HCA组分别减少94.2% (P = 0.014)和96.3% (P = 0.001)。

 

Regarding pruritus frequency (Figure 2), the control group showed reductions of 33.6% and 63.7% on days 2 and 7, respectively, while the HCA group showed reductions of 86.1% (P = 0.034) and 94.8% (P = 0.001), respectively.

关于瘙痒频率(图2)，对照组在第2天和第7天分别减少了33.6%和63.7%，而HCA组分别减少了86.1% (P = 0.034)和94.8% (P = 0.001)。

 

Time course of clinical scores

临床评分的时间过程

The HCA formulation resulted in statistically significant therapeutic effects on clinical signs (Figure 3a). Compared with the baseline scores (on day −1), the total clinical scores of the control group decreased by 0% and 15% on days 3 and 7, respectively, while those of the HCA group decreased by 23.3% and 43.0% (both P = 0.0006)

HCA配方对临床症状的治疗效果具有统计学意义(图3a)。与基线评分(第1天)相比，对照组的临床总评分在第3天和第7天分别下降了0%和15%，而HCA组的临床总评分在第3天和第7天分别下降了23.3%和43.0% (P均= 0.0006)。

 

 

 

 

 

 

Erythema showed the most prominent therapeutic effect (Figure 3b). On day 3, the score of the HCA group showed a reduction of 21%, and the control group showed an increase of 16% (P < 0.0001). On day 7, erythema scores were reduced by 45% and 4% in the HCA and control groups, respectively (P = 0.035).

治疗效果最显著的是红斑(图3b)。第3天，HCA组评分下降21%，对照组评分上升16% (P < 0.0001)。第7天，HCA组和对照组的红斑评分分别降低了45%和4% (P = 0.035)。

 

Papules also showed a significant score reduction on day 3 (Figure 3c): 35% in the HCA group versus 5% in the control group (P = 0.033), respectively. On day 7, they were reduced by 57% and 36% in the HCA and control groups, respectively (P = 0.13). The effect of HCA treatment on excoriation was indistinguishable between the groups because of the relatively high background scatter of the data (Figure 3d).

丘疹在第3天也显示出显著的评分降低(图3c): HCA组35%，对照组5% (P = 0.033)。第7天，HCA组和对照组分别减少57%和36% (P = 0.13)。由于数据的背景散点相对较高，HCA治疗对抓痕的影响在两组之间难以区分(图3d)。

 

Alopecia continued to increase during the test period; however, the HCA treatment tended to reduce the rate by 20% (P = 0.17) and 30% (P = 0.10) on days 3 and 7, respectively (Figure 3e).

试验期间脱毛持续增加;然而，在第3天和第7天，HCA治疗倾向于分别降低20% (P = 0.17)和30% (P = 0.10)的发生率(图3e)。

 

Adverse events

不良事件

No adverse events were observed in any of the dogs during the trial period.

在试验期间，没有观察到任何犬的不良事件。

 

 

 

Discussion

讨论

The present study was undertaken to evaluate the efficacy and safety of a topical HCA formulation in the treatment of pruritus and other clinical signs associated with FAD, under the specific conditions of the dispensing mode.

本研究旨在评估外用HCA制剂在特定配药模式下治疗瘙痒和其他与FAD相关的临床症状的有效性和安全性。

 

A prerequisite for such a study, and other studies of pruritic dermatitis in general, is an accurate, consistent, and reliable scoring system for pruritus on the one hand and for other clinical signs on the other. Indeed, developing a standard scale for assessing pruritus has been quite challenging and controversial.  Developing a standard severity scale for skin lesions is another matter, with its own complexities related to the diverse clinical manifestations (multiple symptoms and affected areas) and assessor subjectivity. The recently developed scoring system, CADESI (Canine Atopic Dermatitis Extent and Severity Index), is perhaps the most comprehensive and well suited to field clinical trials, but as such, it may be too complicated to be directly useful in the laboratory setting. Our present model involved a single breed of dogs in which FAD was induced by controlled flea-challenge infestation. The relative homogeneity and simplicity of the model under the controlled environment allowed the development and use of a better adapted, streamlined scoring system for the clinical signs (Table 1). The experimental conditions also permitted relatively accurate scoring of pruritus by direct timing and counting of pruritic events. Although straightforward and relatively bias-free, the assessment of pruritus and clinical signs was highly labour-intensive, the reason why baseline values could not all be taken on day 0 (elimination of fleas and first treatment), but also included those obtained on day −1 (clinical scores) and day −2 (pruritus scores).

这项研究以及其他一般瘙痒性皮炎研究的先决条件是一个准确、一致和可靠的瘙痒和其他临床症状评分系统。事实上，制定一个评估瘙痒的标准量表一直是相当具有挑战性和争议性的。制定皮肤病变的标准严重程度量表是另一回事，其复杂性与不同的临床表现(多种症状和受影响区域)和评估者的主观性有关。最近开发的评分系统CADESI(犬特应性皮炎程度和严重程度指数)可能是最全面的，非常适合现场临床试验，但因此，它可能过于复杂，无法在实验室环境中直接使用。我们目前的模型涉及单一品种的犬，其中FAD是通过控制跳蚤攻击感染诱导的。在受控环境下，模型的相对同质性和简单性允许开发和使用一个更好的适应，简化的临床症状评分系统(表1)。实验条件也允许通过直接计时和计数瘙痒事件相对准确地评分瘙痒症。虽然简单且相对无偏倚，但瘙痒和临床症状的评估是高度劳动密集型的，原因是基线值不能全部在第0天(消除跳蚤和首次治疗)获得，但也包括第1天(临床评分)和第2天(瘙痒评分)获得的基线值。

 

Overall, the baseline clinical scores (on day −1) were mild to moderate, with even group distribution (Table 3). With regard to clinical signs, the scores were in the order of erythema ≥ papules/pustules > alopecia/epilation ≈ excoriation/erosion. With regard to anatomical region, the scores were distributed in the order of ventral abdomen ≥ sacrocaudal > ventral thorax > lumbodorsal. These clinical features generally corresponded to those of the early phase of FAD and thus fitted the purpose of the present trial. As such, however, they were slightly different from those observed in veterinary clinics where excoriation and lichenification tend to be the next highest scorers to erythema. The main reason for this is that dogs presented to clinics generally have longer histories and/or recurrent episodes of dermatological problems, not to mention their diverse origins.

总体而言，基线临床评分(第1天)为轻度至中度，组间分布均匀(表3)。在临床症状方面，评分顺序为:红斑≥丘疹/脓疱>脱毛/脱毛≈抓痕/糜烂。从解剖区域来看，得分依次为腹侧≥骶尾部>腹侧胸>腰背。这些临床特征通常与FAD的早期阶段相对应，因此符合本试验的目的。然而，就其本身而言，它们与兽医诊所观察到的情况略有不同，在兽医诊所中，抓痕和苔藓化往往是仅次于红斑的最高评分。这种情况的主要原因是，到诊所就诊的犬通常有更长的病史和/或反复发作的皮肤病问题，更不用说它们的起源不同了。

 

Under the present experimental conditions, daily topical spray of the HCA formulation exerted immediate and substantial therapeutic effects on pruritus, resulting in approximately 90% reduction in both pruritic time and frequency after only 2 days’ treatment. Although less pronounced than for pruritus, the therapeutic effect of the HCA was also significantly manifest on other clinical signs, especially erythema and somewhat for papules. Compared with the pruritic events, which reflect behavioural modifications and consequent rapid response to the treatment, the skin lesions, for their physical characters and associated healing process, turned out to be more slowly responsive to the same treatment. It is also important to note that the therapeutic effects of topical HCA are not limited to FAD. Indeed, our preliminary data from field clinical trials on dogs with pruritic dermatoses indicate that 92% of the HCA-treated dogs responded favourably while only 47% of the dogs were diagnosed as FAD cases (unpublished data).

在本实验条件下，每日外喷HCA制剂对瘙痒具有立竿见影的显著治疗效果，治疗2天后瘙痒时间和次数均减少约90%。虽然不像瘙痒那么明显，但HCA的治疗效果在其他临床症状上也很明显，尤其是红斑和丘疹。与瘙痒事件相比，瘙痒事件反映了行为改变和随后对治疗的快速反应，皮肤病变由于其物理特征和相关的愈合过程，对相同治疗的反应更为缓慢。值得注意的是，外用HCA的治疗效果并不局限于FAD。事实上，我们对患有瘙痒性皮肤病的犬进行的现场临床试验的初步数据表明，92%的HCA治疗的犬反应良好，而只有47%的犬被诊断为FAD病例(未发表的数据)。

 

As a new generation dermocorticoid, HCA has a potent pharmacological activity and yet, unlike other corticosteroids of similar or higher potency, has remarkably low adverse effects. These advantageous characteristics are attributed to the balanced hydrophilicity and lipophilicity of the HCA molecule. Compared with the parent drug, hydrocortisone, the enhanced lipophilicity of HCA is derived from the esterifications at C21-acetate and C17- propionate, which provide the HCA molecule with important double benefits: a higher capacity to permeate the stratum corneum and a lower propensity to reach the blood circulation, thereby accumulating in the epidermis–dermis in a high concentration and exerting potent antipruritic/anti-inflammatory activity.

作为新一代皮肤类固醇，HCA具有强大的药理活性，但与其他类似或更高效力的皮质类固醇不同，它的不良反应非常低。这些有利的特性是由于HCA分子的亲水性和亲脂性平衡。与母体药物氢化可的松相比，HCA的亲脂性增强来自于C21 -乙酸酯和C17-丙酸酯的酯化，这为HCA分子提供了重要的双重好处:更高的渗透角质层的能力和更低的进入血液循环的倾向，从而在表皮-真皮中高浓度积累，并发挥有效的止痒/抗炎活性。

 

Under the protocol conditions, the repeated use of the HCA formulation elicited no observable adverse reactions in the dogs. Under normal conditions of use, the 7-day treatment with the HCA formulation should be sufficient to bring immediate relief from pruritus and accelerate clinical recovery. Whereas prompt and potent antipruritic activity of HCA can be generally expected in FAD and other pruritic dermatoses, the therapeutic effects on skin lesions may be less pronounced, especially for dogs with hardened skin or chronic clinical signs. Ideally, HCA therapy for pruritic dermatitis should be prescribed in conjunction with other treatments aimed at eliminating the underlying cause such as bacteria, parasites, fungal infection, insects, arachnids and/or environmental allergens.

在方案条件下，重复使用HCA制剂在犬上没有引起可观察到的不良反应。在正常使用条件下，7天的HCA制剂治疗应足以立即缓解瘙痒，加速临床恢复。尽管在FAD和其他瘙痒性皮肤病中，HCA通常具有迅速而有效的止痒活性，但对皮肤病变的治疗效果可能不太明显，特别是对皮肤变硬或慢性临床症状的犬。理想情况下，对瘙痒性皮炎的HCA治疗应与其他治疗结合使用，旨在消除潜在的原因，如细菌、寄生虫、真菌感染、昆虫、蛛形纲动物和/或环境过敏原。

 

 

 

 

 

zhangenzyme

杨先生

南海

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