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Oral—lyn口腔胰岛素喷雾剂-治疗1型和2型糖尿病
首个非注射的胰岛素Oral—lyn
【关键词】胰岛素制剂 Oral 厄瓜多尔 非注射 生物技术公司 2型糖尿病 口腔喷雾剂 糖尿病患者 自己注射 顺应性
【文 摘】首个非注射的胰岛素制剂，Generex生物技术公司的口腔喷雾剂Oral—lyn（Oralin）在厄瓜多尔批准用于治疗1型和2型糖尿病，给每日需要自己注射的糖尿病患者带来了方便，改善了顺应性。
口腔喷入型胰岛素显示有用
2009年10月23日（蒙特娄） -根据发表于国际糖尿病联盟（国际糖尿病联合会，以色列国防军）第20届世界糖尿病研讨会的研究，每天经口腔喷入12个单位的胰岛素，有助于葡萄糖耐受异常（糖耐量低减）病患维持可接受的血糖值。这种胰岛素给药模式，为第1和第2型糖尿病的非注射型胰岛素给药方式带来新希望。
发表人，第一作者尼古拉那不勒斯博士向Medscape糖尿病和内分泌表示，我们实验新的胰岛素给药途径，因为糖尿病患最重要的问题是使用注射剂，这是胰岛素治疗的最大限制，并非所有病患都接受注射剂，注射时会痛且比较难管理。那不勒斯博士来自义大利罗马生物医学生大学内分泌与代谢科。
【人类胰岛素口腔喷剂】
那不勒斯博士等人研究雷克斯制造的口腔，林恩这个胰岛素口腔喷剂的效果与安全性。该装置将胰岛素喷到口咽黏膜，所以不会进入肺部，且吸收很好，给药后10分钟就达最高值。给药器中，与注射剂同为中性pH值值的缓冲液中，溶有常态型人类DNA的胰岛素。给药器还含有吸收促进剂，稳定剂与非氟氯化碳的推动剂。
确认为糖耐量低减的31名病患，随机分派接受分成2个剂量的4,6或12个单位的口腔喷入型胰岛素。在标准的75克口服葡萄糖耐受测试前给予1个剂量，测试后30分钟给予另一次剂量。每一喷相当于1单位的胰岛素。之后在30,60,90,120和180分钟时检测葡萄糖和胰岛素值。
【12喷获得较低的血中葡萄糖值】
相较于没接受治疗的病患，使用4或6喷者的血中葡萄糖值没有改变，使用12喷这一组则有影响。喝下葡萄糖后2小时，使用12喷这组病患的血中葡萄糖值平均比没有接受任何治疗者低29.6％性（P“0.05）。3小时的时候，使用12喷这组病患的血中葡萄糖值低26.8％性（P”0.05）。将所有时间点一起分析，相较于没接受治疗的病患，使用12喷这组病患的血中葡萄糖值平均减少15.8％。使用12喷的剂量也和各时间点之胰岛素增加倾向有关，在30分钟时达到统计上的显著意义。研究中没有低血糖或其他副作用事件。
塔拉哈西（佛罗里达州首府）佛罗里达大学医学院小儿内分泌专家拉里长迪伯医师表示认同，认为发现其他的胰岛素给药途径是重要的。他表示，胰岛素给药是糖尿病患的一大问题。你必须克服恐惧，还有那些未按医嘱用药也还不至于致命的人。漏给胰岛素是第1和第2型糖尿病的重要问题之一。
【口腔给药的潜力】
他相信，口腔给药很有潜力。藉由这种产品，你比较不会高血糖。血中血糖值与时间变化表的曲线下面积也减少。他指出，需要以有更多病患，研究期间更久的大型研究，来确认这种小型短期研究的结果。
口腔喷剂已经在第1和第2型糖尿病的短期试验中成功检测。目前正在进行长期研究，那不勒斯博士等人目前对糖耐量低减病患进行1个这类型的长期研究。
那不勒斯博士的研究接受雷克斯赞助。迪伯医师宣告没有相关财务关系。
国际糖尿病联盟（IDF）为第20届世界糖尿病研讨会。摘要Ḏ- 0965。发表于2009年10月21日。
Generex Oral-Lyn
Generex Oral-lyn™, is an insulin spray for the treatment of Type I and Type II diabetes. Generex Oral-lyn™ is a safe, simple, fast, effective, and pain-free alternative to subcutaneous injections of prandial insulin and is conveniently delivered to the membranes of the oral cavity by a simple asthma-like device with no pulmonary (lung) deposition. As a pain-free and convenient method of insulin delivery, Generex Oral-lyn™ will allow individual patients to "fine tune" and then maintain their metabolism resulting in an improved quality of life. Accordingly, Generex Oral-lyn™ provides the opportunity for the establishment of a new and more efective diabetes treatment paradigm.
Oral-Lyn - Oral Insulin for Types 1 and 2 Diabetes
Drug (Brand / Generic)Oral-Lyn Company / LicenseeGenerex BiotechnologyTherapy ClassInsulinsProduct DescriptionOral spray formulation of human insulinCurrent IndicationType 2 diabetic patients Market SectorDiabetesDevelopment StatusApproved Ecuador; phase III Europe and North America
Under development by Canadian company Generex Biotechnology, Oral-Lyn is an oral spray formulation of human insulin indicated for the treatment of type 1 and 2 diabetes.
Having secured regulatory approval in 2005 for clinical use of Oral-Lyn in type 2 diabetics in Ecuador, the company is keen to progress phase III trials in the major North American and European markets, where it hopes eventually to achieve comparable success
The announcement to start Phase III for Oral-Lyn in North America was made on 7 April 2008, beginning with patient screening. The first screening was carried out in Texas in late March 2008. Other clinical sites taking part in the study are located in Maryland, Minnesota, California and in the province of Alberta in Canada.
Non-injectable insulins may improve complianceAt present diabetics who require insulin to keep their blood sugar levels under tight control (target HbA1c levels of <7%) have to administer it by injection. The need for regular daily injections is a major drawback for diabetic patients and can reduce compliance with treatment.
Considerable research effort has been devoted to the development of alternative modes of insulin delivery which can deliver insulin safely and effectively without the need for injection. Various alternatives to injectable insulin have been investigated including:
Insulin patches
Insulin pumps
Inhaled insulin
Oral formulations designed to resist insulin digestion in the gastrointestinal tract
Oral formulations for buccal delivery
Generex's Oral-Lyn is a liquid formulation of human insulin that is sprayed into the mouth using its proprietary RapidMist device. In the mouth the insulin is absorbed via the buccal mucosa, an area with a rich vasculature. Generex believes that Oral-Lyn will provide an effective alternative to prandial insulin injections and improve patient compliance with insulin therapy.
"The need for regular daily injections is a major drawback for diabetic patients and can reduce compliance with treatment."
Evidence of efficacy in diabetic patientsApproval of Oral-Lyn by the Ecuadorian Ministry of Public Health was based on data from clinical trials conducted in Ecuador which involved more than 250 patients with type 2 diabetes. These showed that Oral-Lyn had comparable efficacy to prandial insulin injections in this patient population.
The company is also hoping to extend use of Oral-Lyn in Ecuador to type 1 diabetic patients and has already initiated a six-month study of its safety and efficacy in adolescent and young adult patients with type1 diabetes.
An earlier short-term study, in which Oral-Lyn was compared with short-acting subcutaneously injected pre-prandial insulin (Humulin), was considered successful. In this study Oral-Lyn was taken both before and after each meal.
The real test of the product's viability, however, will come from large-scale trials involving several thousand patients that will be required by regulatory authorities in North America and Europe. On 6 August 2008, Generex recieved approval to conduct an Oral-Lyn trial on patients diagnosed with or prone to developing impaired glucose tolerance. The approval was recieved from the Ethics Committe at University Campuse Bio Medico, Rome. The study was to help determine whether the glucose levels of patients drop when they are using Oral-Lyn.
Plans are underway for Phase III trials in Canada and Europe to be followed by similar large-scale studies in the US. On 11 March 2008 Generex announced that the labelling and packaging of cannisters for Oral-Lyn had been completed. The cannisters will be used for Phase III clinical trials in the US, Canada and Ukraine.
Diabetes represents a rapidly growing problem
Estimates from the World Health Organisation suggest that 150 million or more people have diabetes, of which type 2 accounts for the vast majority of cases. Worldwide, the costs associated with the treatment of diabetes and its complications are estimated to exceed $200 billion annually.
Adverse lifestyle changes which have seen an explosion in the incidence of obesity, an important risk factor for type 2 diabetes, are contributing to the continual rise in the number of new cases that occur each year. By 2025, preva lence of diabetes is expected to have more than doubled from today's figures.
"Generex's Oral-Lyn is a liquid formulation of human insulin that is sprayed into the mouth."
Left untreated or poorly controlled, diabetes can lead to serious complications such as retinopathy, cardiovascular disease, nephropathy, neuropathy and peripheral vascular disease as well as premature death.
Insulin injections revolutionised the treatment of diabetes when first introduced into clinical practice in the 1920s. The advent of non-injectable insulins, such as Oral-Lyn, have the potential to be just as revolutionary and to make regular insulin therapy much more acceptable to diabetic patients.
Marketing commentary
In addition to all type 1 diabetic patients, for whom insulin is essential therapy, there are about 40-50 million type 2 diabetic patients who also need insulin to control their blood sugar levels effectively. However, the thought of having to self-inject several times a day leads many patients to fail to take their insulin treatment regularly, exposing them to the risk of diabetes-related complications.
Insulin therapies have evolved over recent years to include rapid-acting insulin analogues, analogue mixtures and long-acting insulin analogues. Non-injectable insulins are now poised to enter the market, with analysts predicting that these new insulin formulations could achieve sales in excess of $5bn by the end of the decade.
Generex has recieved approval for commercial sale of Oral-Lyn in several countries. In India, approval was obtained in November 2007. The first commercial order was made by Generex's Indian distributor Shreya Life Sciences in March 2008 for 210,000 cannisters of Oral-Lyn.
On 1 April 2008, Generex signed a licence and distribution agreement with SciGen. Under this agreement, SciGen will acquire approvals for importing, marketing, distributing and selling Oral-Lyn in China, Hong Kong, Indonesia, South Korea, Malaysia, the Philippines, Singapore, Thailand and Vietnam. SciGen will use its own recomnibant human insulin product for the sale of Oral-Lyn in these countries.
On 14 May 2009, Oral-Lyn was launched in Lebanon by Benta SAL. It is available on the market as a box containing one canister and one actuator. The cannister contains 400IU of recombinant human insulin, while an actuator is a device that is used for managing the drug.
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There are a range of symptoms that may be suggestive of diabetes, including excessive thirst and tiredness.
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Typical day-to-day patterns of blood glucose levels in several individuals.
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Risk factors for diabetic complications.
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Age of onset of type 1 diabetes, formerly known as insulin-dependent diabetes.
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Management of diabetes requires not only good glycaemic control but also control of blood pressure and blood lipid levels. Effective control significantly reduces the risk of diabetes-related complications.
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Type 2 diabetes accounts for the vast majority of cases.
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吸入型胰岛素可能用于治疗2型糖尿病
近日，一项新的研究结果显示，在难治性2型糖尿病患者中，吸入型胰岛素制剂在降低血糖水平方面与胰岛素注射剂同样有效，且副作用较少。
在6月的美国糖尿病协会年会中公布了这篇报告，并已将研究结果发表在《柳叶刀》上。研究者在来自10个不同国家、18-80岁年龄段的2型糖尿病患者中，对两种不同胰岛素剂型的治疗效果进行了比较。纳入的研究对象为不吸烟且已接受胰岛素治疗但仍有血糖控制不佳的患者。观察组共有211名患者，给予吸入型胰岛素联合甘精胰岛素（一种长效胰岛素注射剂，睡前注射以控制血糖）治疗；对照组237名患者，给予胰岛素注射剂治疗。
经过一年的治疗后，研究人员发现：两组间血糖水平相似；观察组中22%患者HbA1c水平达到7%及以下，而对照组达标人数为27%。应用吸入型胰岛素的患者体重增加（糖尿病患者较为关心的问题）较少。观察组平均增重2磅，而对照组为5.5磅。
与对照组相比，应用吸入型胰岛素的患者较少发生低血糖症（血糖突然降低）。其发生频率在观察组与对照组分别为31% 和 49%。
观察组的主要副作用为咳嗽和上呼吸道感染。咳嗽大多数发生在吸入后的前十分钟内，主要集中在治疗的第一周，随着治疗的继续而减少。
既往二甲双胍（一种常见的口服降糖药物）用药史对两组间的结果没有影响。
该研究的研究人员Julio Rosenstock博士及其同事认为，“我们的研究结果显示，吸入型胰岛素加甘精胰岛素单独或联合一种口服降糖药物如二甲双胍，可作为一种有效的替代方案，用于传统混合胰岛素治疗控制不良的2型糖尿病。吸入型胰岛素加甘精胰岛素不仅可以更好地控制血糖，增加体重可能性更小，同时还可降低许多2型糖尿病患者发生低血糖症的几率。” |
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