糖尿病患的15%须用胰岛素，其治疗窗口窄，剂量不足难以抑制糖化血红蛋白，防止并发症；剂量过高则有生命之虑；了解血糖水平是胰岛素精准给药的前提。市售血糖仪依赖有创取血，患者抵抗感限制了测试频率和剂量调控。在研的无创测试无法取得与血液相通的内分泌体液，误差过大。申请人运用自己发明并在胰岛素透皮给药上成功的相转化微针技术，提出微创式血糖连续监测贴剂及其指导胰岛素给药的研究。相转化微针用于血糖连续监测的独特优势是：1、微针刺透表皮吸收真皮层体液溶胀却不溶解，持续保持着葡萄糖扩散通道；2、使得针体不溶的内部交联靠非化学反应的冷冻微晶化实现，葡萄糖显色剂可安全地置于微针针体的最佳处，不被破坏。近年来，“智能刺青”连续监测血糖的研究提供了用真皮层葡萄糖反映血糖的方案。相转化微针将其血糖可逆显色位点由表皮之下移至表皮之上，避免了指示剂的流失、毒性、和更换不便。研究中，血糖贴剂将与胰岛素贴剂联用，考察药效。

The critical challenge in insulin treatment to diabetes is that the blood sugar must be maintained in a narrow window to avoid hyperglycemic complications and the danger for hypoglycemia by insulin overdose. Continuous monitoring blood sugars will, if feasible, greatly improve the efficacy and safety for insulin administration to the patients who have to take insulin. The currently available blood sugar detectors require sampling blood, for which the patient resistance limits the measuring frequency and correspondent insulin administration. The so-called non-invasive detecting is unable to sample the endocrine interstitial fluid that connected with blood, for which the measurement accuracy is compromised. The applicant propose to utilize phase-transition microneedle patch, a technology invented by the team and proven to be effective in insulin transdermal delivery, to achieve continuous monitoring of blood sugar. The phase-transition microneedles are superior that other microneedles in that 1) the swollen but insoluble needle tips after absorbing the interstitial fluid ensues continuous diffusion path for glucose; 2) the needle’s anti-dissolution cross-linking is achieved by freezing induced micro-crystallization, a mild process for which the glucose indicating agents may be loaded in the needle tips for responding rate optimization. The recently reported “smart tattoos” suggest the feasibility of monitoring the glucose in the dermis interstitial fluid as an indication of blood sugar. Phase-transition microneedle patch may relocate the sugar-detecting site from sub-epidermis to the top of epidermis to avoid leaking, toxicity and the difficulty of replacement of the glucose-sensing agents. In the proposed study, the blood sugar monitoring patch will be developed and its application in directing insulin administration in animal models.