【正文】
在糖尿病患者中檢測(cè)到在推進(jìn)劑吸入胰島素的穩(wěn)定懸浮液后 可 降低高血糖。 糖尿病發(fā)展于以每公斤體重 150毫克的劑量 在 動(dòng)物腹腔注射四氧嘧啶水合物 。 在某些動(dòng)物低血糖的臨床跡象 中 ,在許多情況下甚至 可以 觀察到:激勵(lì),競(jìng)爭(zhēng)能力, 以及 血糖水平的快速下降 和 抽搐 。由于 胰島素在脂質(zhì)體中 的 施用動(dòng)物的 健康狀況提高了 ,壽命增加了 (每批 被用于 胰島素脂質(zhì)體形式治療的動(dòng)物存活 率都明顯 超過(guò)對(duì) 照 組 )。每劑量 胰島素脂質(zhì)體在給藥后檢測(cè)出的陽(yáng)性作用與此外源激素滲透進(jìn)入有機(jī)體 有關(guān) ,因 為 C肽 含量在 血液中 的 增加是 不違背制劑給藥的背景的。 引入脂質(zhì)體胰島素 具有 顯 著 的降血糖作用,每天一次可以通過(guò)脂質(zhì)體的作用增加肝細(xì)胞對(duì)胰島素的敏感性,并通過(guò)大量的引入胰島素 直接到 肝臟的通道 ,這與 皮下注射的條件 是相反的 。 90%的動(dòng)物 24小時(shí)后的血糖水平明顯低于給藥之前。在患 重癥糖尿病 的 大鼠 中,在 嚴(yán)重的全身情況背景(發(fā)音為精神萎靡,口渴 ? 厭食,干燥的黏膜和毛發(fā))下, 大量的高血 糖和顯 著 的 高胰島素血癥 被記錄在案。 脂質(zhì)體是由磷脂酰膽堿和膽固醇于 8:2的摩爾比的混合物 由 Bangham方程方法 產(chǎn)生 , 在 每毫升懸浮液中的 10毫克脂質(zhì) 體 的基礎(chǔ)上 進(jìn)行的, 隨后 進(jìn)行 超聲處理 。 因此,例如, 大家已經(jīng) 認(rèn)為 用 胰島素制備的混合物在舌頭下被吸附具有血管舒張 作用; 然而,在一段長(zhǎng)時(shí)間 內(nèi) 使用大劑量的制劑的必要性阻止了 該方法的臨床實(shí)踐 。被包封的胰島素包裹在脂質(zhì)體雙分子層內(nèi)部 , 磷脂可促進(jìn)胰島素的吸收并 保護(hù)胰島素免受蛋白水解酶的破壞和免疫系統(tǒng)地降解 , 一定程度上提高了生物利用度 , 保證了療效 , 并可以使藥物通過(guò)磷脂雙分子層緩控釋放 , 可起到平穩(wěn)降血糖的作用。目前胰島素注射劑是臨床用于治療糖尿病的最有效的制劑 , 一般經(jīng) sc 或 im, 其主要缺點(diǎn)為注射部位吸收速度緩慢 , 長(zhǎng)期注射會(huì)給患者帶來(lái)許多痛苦和不便 , 甚至?xí)霈F(xiàn)炎癥、硬結(jié)、過(guò)敏等副反應(yīng)。 they became more active .It should be noted that in rats with alloxan diabetes mellitus, against the background of admininstration of insulin in liposomes, high levels of insulin in the blood serum were detected,evidently as a result of the release of insulin from the llposomes. This is demonstrated,on the one hand, by the absence of an increase in insulinemia in rats of the control groups,and on the other hand, by detection of low levels of blood serum Cpeptide, which is formed from proinsulin in equimolar amounts with insulin. The condition of the animals was improved against a background of administration of insulin in liposomes, and the lifetime was increased(in each lot the animals treated with the liposomal form of insulin survived significantly better than the controls). The introduction of pure liposomes (without insulin) or a mixture of insulin with liposomes without enclosure of the hormone inside did not give such a pronounced effect, although it did exhibit a small hypoglycemic action, which we are inclined to explain by an increase in the sensitivity of the peripheral tissues, in particular, the liver, to the action of circulating endogenous insulin, present in the organism in small amounts, in connection with the incorporation of the liposomal phospholipids into the hepatocyte membrane,and possibly the removal of excess cholesterol from it and a consequent decrease in the viscosity of the membranes. Thus, the administration of insulin in liposome s to the experimental animals per os has a positive effect on them, which is expressed in an improvement of their condition, a lowering of the hyperglycemia, and a substantial increasein insulinemia, although the level of the Cpeptide remains lowered. Evidently the results obtained associated with the release of insulin from the liposomes administered per os. The pronounced hypoglycemic action of the introduction of liposomal insulin once a day can be explained both by an increase in the sensitivity of the